Caris Life Sciences and Elevation Oncology Announce Joint Discovery and Development Collaboration Focused on Oncogenic Fusions and Driver Mutations -…

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Two precision medicine innovators to leverage genomic data from leading molecular diagnostics platform to identify actionable driver alterations, and jointly discover and develop therapeutics to target them

IRVING, Texas, and NEW YORK, June 15, 2021 /PRNewswire/ -- Caris Life Sciences, a leading innovator in molecular science and artificial intelligence focused on fulfilling the promise of precision medicine, and Elevation Oncology, a clinical stage biopharmaceutical company focused on the development of precision medicines for patients with genomically defined cancers, announced today a strategic collaboration to jointly identify oncogenic fusions and mutations that are driver alterations. Together, Caris and Elevation Oncology will discover and develop therapeutics targeting these newly identified alterations.

Under the terms of the agreement, Caris and Elevation Oncology will jointly evaluate potential targets, some of which are not currently actionable by an existing therapeutic, identified on an ongoing basis by analyzing Caris' Whole Transcriptome Sequencing (WTS) and Whole Exome Sequencing (WES) data. The companies can then elect to initiate a novel drug discovery program for those targets, or pursue licensing or product acquisitions, while retaining exclusive access to all targets selected by the parties.

"Caris is dedicated to advancing precision oncology for patients. We are thrilled to build upon our strategic relationship with Elevation Oncology and deepen the connection between molecular diagnostics and clinical development," said David Spetzler, M.S., Ph.D., MBA, President and Chief Scientific Officer of Caris Life Sciences. "By pairing our unique insight into potential genomic driver alterations gained through Caris' market-leading molecular profiling capabilities with Elevation Oncology's strength in executing innovative clinical oncology programs in genomically-defined populations, we aim to further close the gap between target identification and clinical investigation for potential new therapeutics."

"Through this collaboration between Elevation Oncology and Caris, we hope to demonstrate how biopharmaceutical and molecular medicine companies can work hand in hand to realize visions that are shared across the precision oncology community," said Shawn M. Leland, PharmD, RPh, Founder and Chief Executive Officer of Elevation Oncology. "At Elevation Oncology, we believe every cancer patient deserves the opportunity to be matched with an actionable, purposely selected therapeutic that is precisely targeted to their tumor's unique genomic biomarkers. In Caris, we have found a collaborator who both shares this vision as a leader in genomic testing and who can provide real-world insights into emerging or underserved genomically-defined patient populations. Together, we believe we are pioneering a platform to accelerate the development of precision therapeutics and build toward a future where patients have the option of a matched therapy for every driver alteration no matter how rare."

Caris Molecular Intelligence, the company's proprietary, comprehensive tumor profiling approach assesses all 22,000 genes in both DNA and RNA, and proteins unique to an individual's cancer to reveal a molecular blueprint in order to guide more precise and individualized treatment decisions. Caris' CODEai is the most comprehensive data solution in the industry, with cancer treatment information and clinical outcomes data for over 244,000 patients covering over 1,000,000 data points per patient. The analysis of oncogenic fusions and mutations that are driver alterations for assessment under the collaboration will be conducted on both the historical dataset that has been compiled by Caris, and on an ongoing basis from the future tumor profiling data routinely generated from Caris' platforms over the term of the agreement.

Therapeutics selected by the parties, and subsequent companion diagnostics, will be developed on a cost-sharing basis with revenue being shared on any approved therapeutics.

About Caris Life SciencesCaris Life Sciences is a leading innovator in molecular science and artificial intelligence focused on fulfilling the promise of precision medicine through quality and innovation. The company's suite of market-leading molecular profiling offerings assesses DNA, RNA and proteins to reveal a molecular blueprint that helps physicians and cancer patients make more precise and personalized treatment decisions. MI Exome whole exome sequencing with 22,000 DNA genes, and MI Transcriptome whole transcriptome sequencing with 22,000 RNA genes along with cancer-related pathogens, bacteria, viruses and fungi analysis run on every patient provides the most comprehensive and clinically relevant DNA and RNA profiling available on the market.

Caris is also advancing precision medicine with Caris Artificial Intelligence, combining its market leading service offering, Caris Molecular Intelligence with its proprietary artificial intelligence analytics engine, DEAN, to analyze the whole exome, whole transcriptome and complete cancer proteome. This information, coupled with mature clinical outcomes on thousands of patients, provides unmatched molecular solutions for patients, physicians, payers and biopharmaceutical organizations.

Caris Pharmatech is changing the paradigm and streamlines the clinical trial process by connecting biopharma companies with research-ready oncology sites for clinical trials. With over 423 research sites within the Caris Pharmatech Just-In-Time (JIT) Oncology Network, biopharma companies can identify and enroll more patients, faster. Caris Pharmatech Just-In-Time Clinical Trial Solutions focus on rapid site activation and patient enrollment to streamline the drug development process. By implementing Caris' Just-In-Time Trial-Matching System, Caris will automatically match patients to clinical trials and sites can be activated and eligible to enroll patients within one week.

Headquartered in Irving, Texas, Caris Life Sciences has offices in Phoenix, Denver, New York, and Basel, Switzerland. Caris provides services throughout the U.S., Europe, Asia and other international markets. To learn more, please visit CarisLifeSciences.com or follow us on Twitter (@CarisLS).

About Elevation OncologyElevation Oncology is founded on the belief that every patient living with cancer deserves to know what is driving the growth of their disease and have access to therapeutics that can stop it. We aim to make genomic tests actionable by selectively developing drugs to inhibit the specific alterations that have been identified as drivers of tumor growth. Together with our peers, we work towards a future in which each tumor's unique genomic test result can be matched with a purpose-built precision medicine to enable an individualized treatment plan for each patient. Our lead candidate, seribantumab, is intended to inhibit tumor growth driven by NRG1 fusions and is currently being evaluated in the Phase 2 CRESTONE study for patients with solid tumors of any origin that have an NRG1 gene fusion. Details on CRESTONE are available at http://www.NRG1fusion.com. For more information visit http://www.ElevationOncology.com.

Caris Life Sciences Business Development Contact:Brian D. Lamon, Ph.D.Chief Business Officer+1 (609) 955-8883blamon@carisls.com

Caris Life Sciences Media Contact:Lindsey Bailys, GCI Health+1 (212) 798-9884Lindsey.Bailys@GCIHealth.com

Elevation Oncology Media Contact:David Rosen, Argot Partners+1 (716) 371-1125media@ElevationOncology.com

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SOURCE Caris Life Sciences; Elevation Oncology

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Biological Dynamics to Participate in the Nephron Research Liquid Biopsy Innovation Symposium – Business Wire

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SAN DIEGO--(BUSINESS WIRE)--Biological Dynamics, Inc., a next-generation liquid biopsy company focused on detecting cancers at the earliest stages, will participate in the Nephron Research Liquid Biopsy Innovation Symposium.

CEO Raj Krishnan, Ph.D. and CFO Kevin Han, will be joined by Dr. Dave Hoon, Professor and Director, Translational Molecular Medicine and Genome Sequencing at Saint John's Cancer Institute to collaborate in a panel discussion, Novel Approaches for Early Cancer Detection, on Wednesday, June 16, 2021, at 12:10 p.m. ET / 9:10 a.m. PT.

Biological Dynamics will discuss a transformative approach to cancer screening using a proprietary platform that enables the isolation and evaluation of non-DNA biomarkers, such as exosomes, exo-proteins, and surfaceomes. The company will also discuss how the access to these differentiated biomarkers from blood can empower cancer detection at the earliest stages.

About Biological Dynamics

Biological Dynamics, Inc. is a healthcare company committed to improving global health outcomes by detecting diseases at their earliest stages. The company's proprietary platform simplifies access to native-state biomarkers and nanoparticles, enabling differentiated multiomics applications. The company is applying its platform technology along with machine learning to detect cancers in blood. For more information, please visit http://www.biologicaldynamics.com and follow us at @BiodynSD on Twitter.

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Viewpoint Molecular Targeting(TM) Chief Scientific Officer, Dr. Michael Schultz, Discusses the Promise of Image-Guided 212Pb Alpha-Particle…

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Presented data highlights the performance of Viewpoint's chelation technology

CORALVILLE, IA / ACCESSWIRE / June 15, 2021 /Viewpoint Molecular Targeting, Inc. ("Viewpoint" or the "Company"), a radiopharmaceutical company developing precision lead-212-based -particle oncology therapeutics and complementary diagnostic imaging agents, today announced that Michael K. Schultz PhD, Chief Science Officer of Viewpoint presented at The Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting, held virtually June 11-15, 2021.

Dr. Schultz presented on Saturday, June 12, 2021, as part of the Continued Education (CE) session titled, "Imaging of Therapeutic Radionuclides for Dosimetry." As part of the session, Dr. Schultz discussed the 203Pb/212Pb image-guided radionuclide therapy paradigm and key innovations that are advancing the approach. Key data presented substantiates the potential of 203Pb imaging as a surrogate for 212Pb therapeutics and the performance of Viewpoint's chelation technology for delivering radiation specifically to tumors.

Viewpoint is currently advancing its new, proprietary class of personalized 212Pb-based alpha-particle radiopharmaceuticals to transform the treatment landscape of radiotherapies for cancer. Through its unique theranostic approach, the Company's technology provides the ability to diagnose the tumor and then treat it. This two-step, personalized medicine process helps to identify patients that are more likely to respond to the Company's therapy and potentially improve efficacy. At the same time, the use of imaging to personalize treatments has the potential to minimize potential toxicities associated with many other types of cancer treatments.

The Company's image-guided targeted alpha therapies (TAT) leverage specialized targeting peptides to deliver the diagnostic 203Pb and cancer-killing 212Pb directly to the tumor. Targets are carefully selected to ensure they are overexpressed on cancer cells and minimally expressed on normal healthy cells. When the peptide is radiolabled with the Company's diagnostic 203Pb, the patient can be imaged (i.e., SPECT/CT) to reveal cancer cells in the body. When the peptide is radiolabeled with 212Pb (alpha-particle emitting radiation) the target-peptide binding delivers powerful, yet locally deposited, cancer-killing alpha-particle radiation directly to cancer cells. This targeting mechanism allows for maximized therapeutic effects while minimizing off-target toxicities.

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For more information about the Company's precision oncology therapeutics and complementary diagnostic imaging agents, visit viewpointmt.com.

About The 2021 SNMMI Annual Meeting

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting is recognized as the premier educational, scientific, research, and networking event in nuclear medicine and molecular imaging. The four day event, taking place each June, provides physicians, technologists, pharmacists, laboratory professionals, and scientists with an in-depth view of the latest research and development in the field as well as providing insights into practical applications for the clinic. For more information, visit http://www.snmmi.org

About Viewpoint

Viewpoint Molecular Targeting is a radiopharmaceutical company developing precision oncology therapeutics and complementary diagnostic imaging agents. The Company's proprietary technology utilizes lead-212 to deliver powerful alpha radiation specifically to cancer cells via specialized targeting peptides. Viewpoint is also developing complementary imaging diagnostics that incorporate the same targeting peptides which provide the opportunity to personalize treatment and optimize patient outcomes. This "theranostic" approach enables the ability to see the specific tumor and then treat it to potentially improve efficacy and minimize toxicity associated with many other types of cancer treatments.

The Company's melanoma (VMT01) and neuroendocrine tumor (VMT--NET) programs are entering Phase 1 imaging studies, to be followed by Phase 1/2a therapy trials for the treatment of metastatic melanoma and neuroendocrine tumors at two leading academic institutions. The Company has also developed a proprietary lead-212 generator to secure isotope supply for clinical trial and commercial operations. For more information, please visit the Company's website viewpointmt.com.

Investor Inquiries:Jenene ThomasChief Executive OfficerJTC Team, LLCT: 833.475.8247viewpoint@jtcir.com

SOURCE: Viewpoint Molecular Targeting, Inc.

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AWS leader talks about technologies needed to take precision medicine to the next level – Healthcare IT News

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One of the most significant challenges to the advancement of precision medicine has been the lack of an infrastructure to support translational bioinformatics, supporting organizations as they work to uncover unique datasets to find novel associations and signals.

By supporting greater interoperability and collaboration, data scientists, developers, clinicians and pharmaceutical partners have the opportunity to leverage machine learning to reduce the time it takes to move from insight to discovery, ultimately leading to the right patients receiving the right care, with the right therapeutic at the right time.

To get a better understanding of challenges surrounding precision medicine and its future, Healthcare IT News sat down with Taha Kass-Hout, director of machine learning at AWS.

Q: You've said that one of the most significant challenges to the advancement of precision medicine has been the lack of an infrastructure to support translational bioinformatics. Please explain this challenge in detail.

A: One of the challenges in developing and utilizing storage, analytics and interpretive methods is the sheer volume of biomedical data that needs to be transformed that often resides on multiple systems and in multiple formats. The future of healthcare is so vibrant and dynamic and there is an opportunity for cloud and big data to take on a larger role to help the industry address these areas.

For example, datasets used to perform tasks such as computational chemistry and molecular simulations that help de-risk, and advance molecules into development, contain millions of data points and require billions of calculations to produce an experimental output. In order to bring new therapeutics to market faster, scientists need to move targets through development faster and find more efficient ways to collaborate both inside and outside of their organizations.

Another challenge is that large volumes of data acquired by legacy research equipment, such as microscopes and spectrometers, is usually stored locally. This creates a barrier for securely archiving, processing and sharing with collaborating researchers globally. Improving access to data, securely and compliantly, while increasing usability is critical to maximizing the opportunities to leverage analytics and machine learning.

For instance, Dotmatics' cloud-based software provides simple, unified, real-time access to all research data in Dotmatics and third-party databases, coupled with integrated, scientifically aware informatics solutions for small molecule and biologics discovery that expedite laboratory workflows and capture experiments, entities, samples and test data so that in-house or multi-organizational research teams become more efficient.

Today we are seeing a rising wave of healthcare organizations moving to the cloud, which is enabling researchers to unite R&D data with information from across the value chain, while benefiting from compute and storage options that are more cost-effective than on-premises infrastructure.

For large datasets in the R&D phase, large-scale, cloud-based data transfer services can transfer hundreds of terabytes and millions of files at speeds up to 10 times faster than open-source tools. Storage gateways ensure experimental data is securely stored, archived and available to other permissioned collaborators. Uniting data in a data lake improves access and helps to eliminate silos.

Cloud-based hyperscale computing and machine learning enable organizations to collaborate across datasets, create and leverage global infrastructures to maintain data integrity, and more easily perform machine learning-based analyses to accelerate discoveries and de-risk candidates faster.

For example, six years agoModerna started building databases and information-based activities to support all of their programs. Today, they are fully cloud-based, and their scientists don't go to the lab to pipette their messenger RNA and proteins. They go to their web portal, the Drug Design Studio that runs on the cloud.

Through the portal, scientists can access public and private libraries that contain all the messenger RNA that exists and the thousands of proteins they can produce. Then, they only need to press a button and the sequence goes to a fully automated, central lab where data is collected at every step.

Over the years, data from the portal and lab has helped Moderna improve their sequence design and production processes and improve the way their scientists gather feedback. In terms of research, all of Moderna's algorithms rely on computational power from the cloud to further their science.

Q: You contend that by supporting greater interoperability and collaboration, data scientists, developers, clinicians and pharmaceutical partners have the opportunity to leverage machine learning to reduce the time it takes to move from insight to discovery. Please elaborate on machine learning's role here in precision medicine.

A: For the last decade, organizations have focused on digitizing healthcare. In the next decade, making sense of all this data will provide the biggest opportunity to transform care. However, this transformation will primarily depend on data flowing where it needs to, at the right time, and supporting this process in a way that is secure and protects patients' health data.

It comes down to interoperability. It may not be the most exciting topic, but it's by far one of the most important, and one the industry needs to prioritize. By focusing on interoperability of information and systems today, we can ensure that we end up in a better place in 10 years than where we are now. And so, everything around interoperability around security, around identity management, differential privacy is likely to be part of this future.

Machine learning models trained to support healthcare and life sciences organizations can help automatically normalize, index and structure data. This approach has the potential to bring data together in a way that creates a more complete view of a patient's medical history, making it easier for providers to understand relationships in the data and compare this to the rest of the population, drive increased operational efficiency, and have the ability to use data to support better patient health outcomes.

For example, AstraZeneca has been experimenting with machine learning across all stages of research and development, and most recently in pathology to speed up the review of tissue samples. Labeling the data is a time-consuming step, especially in this case, where it can take many thousands of tissue-sample images to train an accurate model.

AstraZeneca uses a machine learning-powered, human-in-the-loop data-labeling and annotation service to automate some of the most tedious portions of this work, resulting in at least 50% less time spent cataloging samples.

It also helps analysts spot trends and anomalies in the health data and derive actionable insights to improve the quality of patient care, make predictions for medical events such as stroke or congestive heart failure, modernize care infrastructure, increase operational efficiency and scale specialist expertise.

Numerate, a discovery-stage pharmaceutical, uses machine learning technologies to more quickly and cost-effectively identify novel molecules that are most likely to progress through the research pipeline and become good candidates for new drug development.

The company recently used its cloud-based platform to rapidly discover and optimize ryanodine receptor 2 (RYR2) modulators, which are being advanced as new drugs to treat life-threatening cardiovascular diseases.

Ryanodine 2 is a difficult protein to target, but the cloud made that process easier for the company. Traditional methods could not have attacked the problem, as the complexity of the biology makes the testing laborious and slow, independent of the industry's low 0.1% screening hit rate for much simpler biology.

In Numerate's case, using the cloud enabled the company to effectively decouple the trial-and-error process from the laboratory and discover and optimize candidate drugs five times faster than the industry average.

Machine learning also is helping power the entire clinical development process. Biopharma researchers use machine learning to design the most productive trial protocols, study locations, recruitmentand patient cohorts to enroll. Researchers not trained as programmers can use cloud-based machine learning services to build, train and deploy machine learning algorithms to help with pre-clinical studies, complex simulations and predictive workflow optimization.

Machine learning can also help accelerate the regulatory submission process, as the massive amounts of data generated during clinical trials can be captured and effectively shared to collaborate between investigators, contract research organizations (CROs) and sponsor organizations.

For example, the Intelligent Trial Planner (ITP) from Knowledgent, now part of Accenture, uses machine learning services to determine the feasibility of trial studies and forecast recruitment timelines. The ITP platform enables study design teams at pharma organizations to run prediction analysis in minutes, not weeks, allowing them to iterate faster and more frequently.

Powered by machine learning, real-time scenario planning helps to facilitate smarter trial planning by enabling researchers to determine the most optimal sites, countries and/or protocol combinations.

By eliminating poor performing sites, trial teams have the potential to reduce their trial cost by 20%. And by making data-driven decisions that are significantly more accurate, they can plan and execute clinical trials faster, leading to hundreds of thousands in cost savings for every month saved in a trial.

Additionally, purpose-built machine learning is supported by cost-effective cloud-based compute options. For example, high-performance computing (HPC) can quickly scale to accommodate large R&D datasets, orchestrating services and simplifying the use and management of HPC environments.

Data transformation tools can also help to simplify and accelerate data profiling, preparation and feature engineering, as well as enable reusable algorithms both for new model discovery and inference.

The healthcare and life sciences industry has come a long way in the last year. However, for progress and transformation to continue, interoperability needs to be prioritized.

Q: The ultimate goal of precision medicine is the right patients receiving the right care, with the right therapeutic, at the right time. What do healthcare provider organization CIOs and other health IT leaders need to be doing with machine learning and other technologies today to be moving toward this goal?

A: The first things IT leaders need to ask themselves is: 1) If they are not investing yet in machine learning, do they plan to this year? And 2) What are the largest blockers to machine learning in their teams?

Our philosophy is to make machine learning available to every data scientist and developer without the need to have a specific background in machine learning, and then have the ability to use machine learning at scale and with cost efficiencies.

Designing a personalized care pathway using therapeutics tuned for particular biomarkers relies on a combination of different data sources such as health records and genomics to deliver a more complete assessment of a patient's condition. By sequencing the genomes of entire populations, researchers can unlock answers to genetic diseases that historically haven't been possible in smaller studies and pave the way for a baseline understanding of wellness.

Population genomics can improve the prevention, diagnosis and treatment of a range of illnesses, including cancer and genetic diseases, and produce the information doctors and researchers need to arrive at a more complete picture of how an individual's genes influence their health.

Advanced analytics and machine learning capabilities can use an individual or entire population's medical history to better understand relationships in data and in turn deliver more personalized and curated treatment.

Second, healthcare and life sciences organizations need to be open to experimenting, learning about and embracing both cloud and technology and many organizations across the industry are already doing this.

Leaders in precision medicine research such as UK Biobank, DNAnexus, Genomics England, Lifebit, Munich Lukemia Lab, Illumina, Fabric Genomics, CoFactor Genomics and Emedgene all leverage cloud and technology to speed genomic interpretation.

Third, supporting open collaboration and data sharing needs to be a business priority. The COVID-19 Open Research Dataset (CORD-19) created last year by a coalition of research groups provided open access to the plenary of available global COVID-19 research and data.

This was one of the primary factors that enabled the discovery, clinical trial and delivery of the mRNA-based COVID-19 vaccines in an unprecedented timeframe. Additionally, our Open Data Programmakes more than 40 openly available genomics datasets accessible, providing the research community with a single documented source of truth.

Commercial solutions that have leveraged machine learning to enable large-scale genomic sequencing include organizations such as Munich Leukemia Lab, who has been able to use the Field Programmable Gate Array-based compute instances to greatly speed up the process of whole genome sequencing.

As a result, what used to take 20 hours of compute time can now be achieved in only three hours. Another example is Illumina, which is using cloud solutions to offer its customers a lower-cost, high-performance genomic analysis platform, which can help them speed their time to insights as well as discoveries.

Twitter:@SiwickiHealthITEmail the writer:bsiwicki@himss.orgHealthcare IT News is a HIMSS Media publication.

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What makes us sneeze? Washington University School of Medicine in St. Louis – Washington University School of Medicine in St. Louis

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Molecules, nerve cells in brain trigger sneezes; understanding may point to ways to quell spread of infectious viruses

What exactly triggers a sneeze? A team led by researchers at Washington University School of Medicine in St. Louis has identified, in mice, specific cells and proteins that control the sneeze reflex. Better understanding of what causes us to sneeze specifically how neurons behave in response to allergens and viruses may point to treatments capable of slowing the spread of infectious respiratory diseases.

A tickle in the nose can help trigger a sneeze, expelling irritants and disease-causing pathogens. But the cellular pathways that control the sneeze reflex go far beyond the sinuses and have been poorly understood. Now, a team led by researchers at Washington University School of Medicine in St. Louis has identified, in mice, specific cells and proteins that control the sneeze reflex.

Better understanding what causes us to sneeze specifically how neurons behave in response to allergens and viruses may point to treatments capable of slowing the spread of infectious respiratory diseases via sneezes, said Qin Liu, PhD, an associate professor of anesthesiology and the studys senior investigator.

The findings are published June 15 in the journal Cell.

We study the neural mechanism behind sneezing because so many people, including members of my own family, sneeze because of problems such as seasonal allergies and viral infections, said Liu, a researcher in the universitys Center for the Study of Itch and Sensory Disorders. Our goal is to understand how neurons behave in response to allergies and viral infections, including how they contribute to itchy eyes, sneezing and other symptoms. Our recent studies have uncovered links between nerve cells and other systems that could help in the development of treatments for sneezing and for fighting infectious respiratory diseases.

Sneezing is the most forceful and common way to spread infectious droplets from respiratory infections. Scientists first identified a sneeze-evoking region in the central nervous system more than 20 years ago, but little has been understood regarding how the sneeze reflex works at the cellular and molecular level.

In the new study, Liu and her team established a mouse model in an attempt to identify which nerve cells send signals that make mice sneeze. The researchers exposed the mice to aerosolized droplets containing either histamine or capsaicin, a pungent compound made from chili peppers. Both elicited sneezes from the mice, as they do in people.

By examining nerve cells that already were known to react to capsaicin, Lius team was able to identify a class of small neurons linked to sneezing that was caused by that substance. The researchers then looked for molecules called neuropeptides that could transmit sneeze signals to those nerve cells, and found that a molecule called neuromedin B (NMB) was required for sneezing.

Conversely, when they eliminated the NMD-sensitive neurons in the part of the nervous system that evoked sneezes in the mice, they blocked the sneeze reflex. Those neurons all make a protein called the neuromedin B receptor. In mice without that receptor, sneezing again was greatly reduced.

Interestingly, none of these sneeze-evoking neurons were housed in any of the known regions of the brainstem linked to breathing and respiration, Liu said. Although we found that sneeze-evoking cells are in a different region of the brain than the region that controls breathing, we also found that the cells in those two regions were directly connected via their axons, the wiring of nerve cells.

The researchers also found they could stimulate the sneeze reflex by exposing part of the mouse brain to the NMB peptide. Further, the animals began to sneeze even though they had not been exposed to any capsaicin, histamine or other allergens.

Because many viruses and other pathogens including the majority of human rhinoviruses and coronaviruses such as Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2, the coronavirus that causes COVID-19 are spread in part by aerosolized droplets, Liu said it may be possible to limit the spread of those pathogens by targeting NMB or its receptor to limit sneezing in those known to be infected.

A sneeze can create 20,000 virus-containing droplets that can stay in the air for up to 10 minutes, Liu explained. By contrast, a cough produces closer to 3,000 droplets, or about the same number produced by talking for a few minutes. To prevent future viral outbreaks and help treat pathological sneezing caused by allergens, it will be important to understand the pathways that cause sneezing in order to block them. By identifying neurons that mediate the sneeze reflex, as well as neuropeptides that activate these neurons, we have discovered targets that could lead to treatments for pathological sneezing or strategies for limiting the spread of infections.

Li F, et al. Sneezing reflex is mediated by a peptidergic pathway from nasal sensory neurons to brainstem respiratory neurons. Cell, published online June 15, 2021.

This work was supported by the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Eye Institute of the National Institutes of Health (NIH). Grant numbers R01 AI125743, R01 EY024702, K08 AR065577, R01 AR07116, and R01 AR77007. Additional funding was provided by the Pew Scholar Research Award, the American Skin Association and the Doris Duke Charitable Foundation.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, consistently ranking among the top medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Rising Preference of Electrical Pulse as opposed to Drug-based Intervention will Boost Growth of Bioelectric Medicine Market: Fact.MR – BioSpace

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Increasing prevalence of cardiac diseases and neurological disorders is encouraging pharmaceutical players to discover bioelectric medicines

The global bioelectric medicine market is expected to exhibit a steady growth owing to the increasing demand for advanced electroceuticals. As per a study by Fact. MR, the bioelectric market is estimated to surpass a valuation of more than US$ 28.5 Bn through 2031.

A rising number of geriatric population is in need of bioelectric medicine. Aging population are often vulnerable to medical disorders such as depression, epilepsy, Alzheimers disease, Parkinsons disease, and cardiac arrhythmias. These disorders usually demand advanced electroceutical treatment such as spinal cord stimulator, cardiac pacemakers, cochlear implants, and implantable cardioverter defibrillators.

According to Centers for Disease Control and Prevention (CDC), around 610,000 people die of heart attack and around 370 people die of coronary heart disease (CHD) in the United States.

This has resulted in increased demand for improved bioelectric medicine for treating chronic illnesses. Major players such as GlaxoSmithKline plc have invested in the bioelectric medicine industry whereas, organizations such as the National Institutes of Health (NIH) in the United States have shown strong interest in the industry.

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Increasing investment in the development of advanced bioelectric medicine is bolstering the growth of electroceutical market. For instance, Medtronic in 2016, invested approximately US$ 2.224 mn in research and development activities to develop advanced products.

The company tapped in to capitalize the opportunity of people witnessing cluster headache and came up with FDA cleared product namely, gammaCore, and a non-invasive VNS therapy that helps in managing painful adult headaches.

There is high focus on research and development among key players. This will result in product launches, which is expected to aid the overall expansion of the market, said a Fact.MR analyst.

Key Takeaways

Key Drivers

Key Restrains

Competitive Landscape

The key players operating in the global bioelectric medicine market are Medtronic, Abbott, Boston Scientific Corporation, Cochlear Ltd., LivaNova PLC, Sonova, BIOTRONIK SE & Co. KG, NEVRO CORP., Second Sight, electroCore, Inc., BioElectronics Corporation, GlaxoSmithKline plc, Wright Medical Technology, Inc., and others. The key players in the market are adopting numerous strategies such as regional expansion, collaboration, new product development, and mergers & acquisition to acquire more income share in the sector.

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More Insights into Bioelectric Medicine Market

Fact.MR offers unbiased analysis of the bioelectric medicine market. In order to understand the global market potential, its growth, and scope, the market is segmented on the basis of product type (Implantable cardioverter defibrillators, cardiac pacemakers, cochlear implants, spinal cord stimulators, deep brain stimulators, transcutaneous electrical nerve stimulators, sacral nerve stimulators, vagus nerve stimulators, and other bioelectric medicines), device type (implantable devices and non-implantable devices), application (arrhythmia, pain management, sensorineural hearing loss, Parkinsons disease, tremor, depression, treatment-resistant depression, epilepsy, urinary and faecal incontinence, and others), end user (hospitals, ambulatory surgical centres, speciality clinics, home care settings, and other), and region (North America, Latin America, Europe, South Asia, East Asia, Oceania, and Middle East & Africa).

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Drug Discovery Services Market - The expansion of drug discovery services can be attributed to an increase in research and development efforts and expenditures, as well as leading pharmaceutical companies' shift to outsourcing. The use of improved technology in the drug discovery process is also a major market growth factor. With stringent regulations in some regions on drug discovery services, high cost involved in the discovery of drug and development and usage of animals in testing are hampering the market growth.

Drug Delivery Systems Market - The ongoing COVID-19 pandemic will bolster medication delivery system chances. In the field of medication delivery systems, several advances have been accomplished. The introduction of three-dimensional printing is the most significant of them (3D-printing). 3D printing is a one-of-a-kind medication delivery prototyping method. It can readily overcome the challenges of delivering strong medicines, peptides, and multi-drugs that are less water soluble.

Ocular Drug Delivery Technology Market - In the global ocular drug delivery technology market, North America is likely to maintain hegemony. According to projections, the ocular drug delivery technology market will account for more than half of the whole market. Furthermore, the introduction of new formulation types and lower R&D expenses are expected to boost growth possibilities. During the projected period, the North American market is expected to grow by 1.4x according to Fact.MR research study.

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Rising Preference of Electrical Pulse as opposed to Drug-based Intervention will Boost Growth of Bioelectric Medicine Market: Fact.MR - BioSpace

Phigenix, Inc. Announces Issuance of US Patent Covering Precision Medicine Diagnostic and Novel Therapeutic for Treating – GlobeNewswire

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ATLANTA, June 15, 2021 (GLOBE NEWSWIRE) -- Phigenix, Inc. Pharmaceutical and Biomedical Research Company, a molecular oncologist-led, biopharmaceutical company focused on identifying, developing, and commercializing innovative and differentiated therapies to address significant unmet needs in diagnosing and precision treatment in oncology, today announced that the United States Patent and Trademark Office (USPTO) has issued U.S. Patent No. 11,033,628, which is directed to methods related to the use and administration of certain PAX2 inhibitors for treating drug-resistant breast cancer. Drug resistance of metastatic breast cancersto first-line chemotherapies, either single or a combination ofdrugs, occurs in 30-70% of cases.

U.S. Patent No. 11,033,628 also covers the use of a diagnostic test that assesses the expression status of PAX2 and Human Beta Defensin-1 (DEFB1) in addition to the current standard of care molecular markers to determine the best course of treatment of breast cancer. Additional issued claims pertain to methods of using anti-PAX2 compositions to treat particular resistant breast cancers. This newly issued patent is owned by Phigenix, Inc and is the latest U.S. patent issued in connection with Phigenix's PAX2 robust drug and diagnostics development program for cancer detection and treatment.

"We are extremely pleased with the addition of this new patent to our portfolio to extend our cutting-edge, next-generation medical innovations. This new issuance continues to expand the breadth and depth of our PAX2 intellectual property portfolio covering methods of use for certain PAX2 inhibitors and diagnostic tests for effective breast cancer disease treatment and management. The technology covered in this patent has the potential to revolutionize how physicians determine the most effective course of treatment for breast cancer patients. Ultimately, this new technology may make treatment more affordable and save thousands of lives, said Dr. Carlton D. Donald, Founder, President and Chief Executive Officer of Phigenix, Inc.

About Phigenix, Inc.

Phigenix, Inc. is a molecular oncologist-led biopharmaceutical company committed to identifying, developing, and commercializing innovative therapies to address significant unmet needs in diagnostic and therapeutic oncology and cancer drug resistance. Phigenix possesses and is developing an impressive patent portfolio that covers compounds that suppress the expression or activity of the PAX2 cancer-causing protein, and subsequently increases DEFB1 levels, which is a component of the immune system and cancer suppressor. The technology includes diagnostic tests for precision medicine to be utilized for the determination of the best course of treatment of cancer and proprietary inhibitors of the PAX2 oncogene and the subsequent PAX2-mediated cancer cell survival and drug resistance. This portfolio includes the recently issued U.S. patent discussed above, as well as issued U.S. and foreign patents directed to methods and drugs for treating cancer by blocking the expression of PAX2 and the subsequent re-expression of DEFB1 to fight cancer. Phigenix is also developing RNA-based cancer vaccines that increase the expression of the tumor suppressor Human Beta Defensin-1 (DEFB1), a critical component of the innate immune system and regulator of the anti-tumor response. The targeted anti-PAX2 and DEFB1 therapies represent a novel and first-in-class approach to treating cancer.

Phigenix is focused on advancing cancer disease management by utilizing molecular signature-based diagnostic tests and precision medicine-driven novel therapeutics. Phigenix is based in Atlanta, GA. More information can be found by visiting the Phigenix website at http://www.phigenix.com.

Cautionary Note Regarding Forward-Looking Statements

Certain information set forth in this presentation contains "forward-looking information", including "future-oriented financial information" and "financial outlook", under applicable securities laws (collectively referred to herein as forward-looking statements). Except for statements of historical fact, the information contained herein constitutes forward-looking statements and includes, but is not limited to, the (i) projected financial performance of the Company; (ii) completion of, and the use of proceeds from, the sale of the shares being offered hereunder; (iii) the expected development of the Company's business, projects, and joint ventures; (iv) execution of the Company's vision and growth strategy, including concerning future M&A activity and global growth; (v) sources and availability of third-party financing for the Company's projects; (vi) completion of the Company's projects that are currently underway, in development or otherwise under consideration; (vi) renewal of the Company's current customer, supplier and other material agreements; and (vii) future liquidity, working capital, and capital requirements. Forward-looking statements are provided to allow potential investors the opportunity to understand management's beliefs and opinions in respect of the future so that they may use such beliefs and opinions as one factor in evaluating an investment.

These statements are not a guarantee of future performance and undue reliance should not be placed on them. Such forward-looking statements necessarily involve known and unknown risks and uncertainties, which may cause actual performance and financial results in future periods to differ materially from any projections of future performance or result expressed or implied by such forward-looking statements.

Phigenix Contact Charles A. West, Ph.D.Head of Business DevelopmentCorporate Strategy/Investor Relations404-946-1811cawest@phigenix.com

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Phigenix, Inc. Announces Issuance of US Patent Covering Precision Medicine Diagnostic and Novel Therapeutic for Treating - GlobeNewswire

Is A Fully Vaccinated Person With No Antibodies Safe From Covid-19? – Outlook India

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Many people havent developed any antibodies despite taking both doses of either of the two vaccines Covishield and Covaxin.

There have been many reports in which vaccine beneficiaries have got their antibodies tested and didnt find the presence of any immunity against the virus.

Gyaneshwar Chaubey, a professor of genetics at Banaras Hindu University (BHU), who is researching antibody formation among vaccinated and naturally infected people, says that many of the elders didnt develop any antibodies even after two doses.

This is quite intriguing. After testing 2309 individuals we didnt find even a single naturally recovered individual who didnt develop Sars-Cov-2 specific antibodies but it is not true for all vaccinated people, Prof Chaubey said.

As antibody is associated with a persons ability to fight against Covid-19, people are worried about their safety.

Their concern seems genuine as there are a few reported cases of death due to breakthrough infections (post-vaccinated infection).

One of the most prominent faces in the country who lost the battle against Covid-19 was well-known cardiologist Dr KK Aggarwal who was fully vaccinated but hadnt developed any antibody.

Some government doctors working in Covid wards have shared anecdotal experiences with Outlook in which they confirmed that there are more cases in the country one like Dr Aggarwal.

We dont know whether the virus or its mutants are virulent enough to overpower the bodys immune system or there was no immunity in the body post-vaccination to fight against the disease, a doctor in a government Covid ward, said.

Now the question is, Since a significant number of people are not showing any antibody, are they safe from Covid-19?

Before answering this question, lets first understand how our immune system works against the virus.

How immune system works?

Immunologists say that when a person is naturally infected, his immune system produces two types of response, humoral and cellular.

Under humoral response, different types of antibodies are formed such as a general antibody, neutralizing antibody, anti-spike antibody to name a few. These antibodies fight against the virus.

At the same time, the cellular response also gets activated which is also known as a T-cell response.

T cells recognize the virus and help (T helper cells) B cells to produce antibodies. In another direction, some of them become CTL and offer an immunity by killing the virus-infected cells of our body. That is how viremia settles down, Prof RM Pitchappan, a well-known name in human immunogenetics and also a visiting professor at Madurai Kamaraj University said.

Prof Gobardhan Das from Special Centre for Molecular Medicine, Jawaharlal Nehru University says that along with providing protection, T-cells also memorize the antigen so that next time when the same antigen attacks the immune system, it can help develop antibodies faster.

These experts also say that while humoral immunity response disappears after a few months, cellular immunity remains for a longer duration. The research is going on in the West that how long this Cellular immunity sustains in the body. Some studies have hinted that it can sustain for a few years to the rest of the life as well.

Can a vaccinated person develop only T-Cells but not antibodies?

Now the next important question is, Is there a possibility that after vaccination the human body develops cellular-mediated response without developing any humoral response?

The Ministry of Health and Family Welfare has answered in affirmative on several occasions in its regular press conferences to dispel the fear among such vaccine beneficiaries.

In a recent government release, Dr VK Paul, Member (Health), NITI Aayog, was quoted as saying, Some people seem to be thinking of getting an antibody test done post-vaccination. But that is not required to be done for the simple fact that antibodies alone do not indicate the immunity of a person.

This is so because of T-cells or memory cells; these undergo certain changes when we receive the vaccine, they become stronger and gain resistance power. And T-Cells are not detected by antibody tests as these are found in bone marrow, Dr Paul added.

Dr Paul hasnt quoted any research done anywhere to find out if a vaccinated person can develop a strong and resistant T-cell without developing any type of initial humoral response or antibodies.

Interestingly, during the Phase II clinical trial of both the vaccines, it was found that both Covishield and Coivaxin develop humoral as well as cellular immune responses.

There is no instance in which they develop only cellular response and not the humoral response.

Many health experts say that they are not aware of any study done to look at this particular aspect of the vaccine.

In the case of other viral diseases like HIV, this is true that the body develops a cell-mediated response, Prof Pitchappan said.

He added, However, I have no idea, whether anybody in ICMR, CSIR or various hospitals handling Covid patients have done any research to find out if vaccines develop cellular immune response without forming any kind of antibody,

Prof Pitchappan also clarifies that T-cells reside in lymph nodes and there are about 460 such lymph nodes in a human body.

Dr. D Nageshwar Reddy, Chairman, Asian Institute of Gastroenterology, Hyderabad, which recently conducted a study to show how a Single Dose of vaccine sufficient for those already infected with COVID-19, says, There is no research done to find out that a person can develop cellular-mediated response without having humoral response initially.

Since there is no evidence-based research, experts views vary.

I believe that the body may make T-cell without developing any antibody at the initial stage, Dr Reddy said.

Prof Chaubey says, To me, it looks like there are three broad categories of people. First, who develop antibodies; second, who didnt develop antibodies but do develop B and T cells and third who dont develop anything and this is possibly due to their genetic makeup.

Dr Sanjay Rai, Professor at the Centre for Community Medicine, AIIMS agrees with Dr Choubey and says, There are two possibilities. The higher possibility is that such people have neither developed any humoral response nor cellular response. The second probability is that they might have developed the cellular response without showing any sign of humoral response, i.e. antibody.

Since there are two contradictory hypotheses, the important question is how to protect such vaccinated beneficiaries from falling prey to Covid-19?

Protecting vaccinated people with no antibody

Immunologists and other health experts say that it is easy to test the cellular-mediated response of these categories of the vaccinated population by the government and take a corrective step.

Prof Gobardhan Das from Special Centre for Molecular Medicine, Jawaharlal Nehru University, says that like antibody the government can also find out whether the person has developed any cellular immunity, B-Cell or T-Cell, response after vaccination.

Prof Das highlights another important aspect as he says, Another cause for concern is that we have no idea that even if there is a cellular immune response, it is quantitatively high to provide adequate protection.

Merely saying that they have developed cellular-mediated response doesnt serve any purpose. They are like a lame duck who is as vulnerable to infection as a nave person, Rahul Bhargava, Head of Hematology Dept, Fortis Gurgaon said.

Very few hospitals have facilities in their labs to test the presence of B-Cells or T-Cells and it is done mainly for research purposes.

There is no private lab in India that conducts tests to check the presence T-Cell and its neutralizing capabilities against Sars_Cov_2.

Big diagnostic labs say that it cost about Rs 20 lakh to have the whole set-up and then each test costs about Rs 6000. So even if an individual wants to get his cellular immunity tested, he cant get it done in India.

Besides, there is no clarity on regulation that if an individual can be allowed to get his cell-mediated response test done, so private labs havent started any such facility in India, Dr Bhargava said.

Health experts also say that a common man doesnt need to go for any T-cell test and the government should take care of these issues on the research level.

It adds on another test and burden to the public. I dont think it is required for a common man to go for it. Let the government take care of such people who have issues in developing antibodies. They should be given an additional booster dose, a prominent doctor in a government hospital said.

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Is A Fully Vaccinated Person With No Antibodies Safe From Covid-19? - Outlook India

Oxford spinout spies the hidden mechanics of DNA and disease with single-pair resolution method – FierceBiotech

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A spinout from the University of Oxford has found a new way to depict and analyze DNA with super-fine resolution, allowing them to peer into what they describe as the dark matter of the human genome and the molecular basis of many diseases.

Nucleome Therapeutics is working on a method known as micro-capture-C, or MCC, to provide a three-dimensional view of the famously twisting double-helix structure, with the ability to zoom in on individual base pairs.

Previous methods of determining the large-scale 3D genome structure within cells have been unable to resolve it much below 500 to 1,000 base pairs, said co-founder James Davies, who helped develop the technology at Oxfords MRC Weatherall Institute of Molecular Medicine alongside Danuta Jeziorska, who serves as Nucleomes CEO.

Nucleome plans to use its technique to identify the genes at play behind severe COVIDas well as find new drug targets for diseases such as rheumatoid arthritis and multiple sclerosiswith additional reports in the near future. Its latest work on 3D genome mapping was published this week in Nature.

RELATED: Google, Oxford study projects benefits to coronavirus-tracing smartphone apps, even at low levels of adoption

The researchers equate the process with looking at a citys skyline, representing the full strand of DNA within a cell. While before they could only make out the shape of small buildings from a distance, now they can see how its built up from individual brickswith all 6 billion of them representing a single letter of the genetic code.

3D genome analysis is key to understanding the largely untapped dark matter of the genome, Jeziorska said. Better resolution of 3D genome maps improves the accuracy and confidence of linking disease-relevant genetic changes to genes.

This could include the coronavirus pandemic and may help provide a better understanding of why some people require intensive care while others may show no symptoms at all.

RELATED: Oxford, Prenetics to take their COVID-19 rapid testing tech to other infectious diseases

For example, at the moment we know that there is a genetic variant which doubles the risk of being severely affected by COVID-19, Davies said. However, we do not know how the genetic variant makes people more vulnerable to COVID-19.

By providing a more detailed view into DNAs larger structure, drugs aimed at these genetic targets may have a better chance of making it through clinical trials, he added.

In the Nature publication, the researchers report that MCC could spot the physical interactions between gene-regulating proteins and the DNA code itself at base-pair resolutioneven though one targeted string may be controlled by genes located tens of thousands to millions of base pairs further along the chainor maybe a mile away, by bricks in a wall on the other side of the city.

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Oxford spinout spies the hidden mechanics of DNA and disease with single-pair resolution method - FierceBiotech

Using ivermectin in treating of patients with mild COVID-19 | IJN – Dove Medical Press

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Introduction

Coronaviruses (CoV) include a large number of viruses causing diseases ranging from mild common cold to severe Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). Coronaviruses are zoonotic viruses; SARS-CoV was transmitted from civet cats to humans and MERS-CoV from dromedary camels to humans.1 The worldwide pandemic of Coronavirus Disease 2019 (COVID-19), is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), first discovered in Wuhan, China in 2019.24

Common manifestations of COVID-19 infection include respiratory symptoms, cough, fever, breathing difficulties and anosmia. Severe cases result in pneumonia, severe acute respiratory syndrome, kidney failure and even death. WHO recommendations to prevent infection spread include frequent hand washing, covering nose and mouth when sneezing and coughing, and avoiding close contact with anyone showing symptoms of respiratory symptoms such as coughing and sneezing.1

There is currently no specific drug therapy or vaccine available to treat COVID-19. Antimalarial drugs such as hydroxychloroquine and azithromycin, as well as antifilarial drugs such as ivermectin and antiviral drugs such as favipiravir, remdesivir, and umifenovir, have been studied. Many study groups around the world are looking into their potential effectiveness against COVID-19.5 Additionally, SARS-CoV and other viral infections are believed to be inhibited by a variety of medicinal plants and natural products such as ilimaquinone (marine sponge metabolite), which have been shown to act on the ACE-2 receptor as well as other viral protein targets.6,7 When compared with other cell-based therapies, which may experience challenges such as the cells sticking to the respiratory tract epithelia during administration, mesenchymal stem cells (MSCs) and their exosomes (MSCs-Exo) have shown promise in clinical trials as a therapeutic tool for severely affected COVID-19 patients.8

Ivermectin is an FDA-approved broad-spectrum anti-parasitic agent that in recent years has shown to have anti-viral activity against a broad range of viruses.9,10 The mechanism of action of this drug against COVID-19 is unclear, though researchers suggest it works in the same way as it does against other viruses.9 It is proved to inhibit integrase protein (IN) nuclear import and HIV-1 replication,11 as it inhibits interaction between the importin (IMP) /1 heterodimer responsible for IN nuclear import and human immunodeficiency virus-1 (HIV-1) integrase protein.11 Ivermectin is proved to limit infection caused by some Ribonucleic Acid (RNA) viruses such as West Nile viruses, influenza and dengue virus.12 It is reported that ivermectin inhibits the replication of SARS-CoV-2 in vitro, and causes reduction about 5000-fold in SARS-CoV-2 viral RNA at 48 hours.13 In addition, the binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein to the human cell membrane may be hindered by ivermectin docking.14 Nanosuspension is a very fine dispersed drug particle in an aqueous vehicle for either topical and oral use or pulmonary and parenteral administration.15 Nanosuspensions have high chemical stability, high drug loading capacity and low toxicity. Intranasal administration needs localization of drug in the nasal cavity for a prolonged time for absorption.16 So, nanoparticles must be incorporated into mucoadhesive formulations that maintain the properties of nanosizing simultaneously with localization inside the nasal cavity.17

Because olfactory disturbances (anosmia/hyposmia) are frequently presenting manifestations of COVID-19,18 and many patients could still have these disturbances for variable times (days to months) after complete cure from SARS-CoV-2, which can significantly affect their psychological status, we studied the local use of ivermectin as a mucoadhesive nanosuspension intranasal spray (where a large viral load is found at the early stages of the infection) to explore its possible effect in curing mild COVID-19 patients, with special concern on assessment of the possible efficacy in curing the olfactory manifestations based on clinical, biochemical and molecular data of the included patients, as previous clinical trials regarding local nasal use of ivermectin in humans are limited.

This is a prospective clinical trial which included 114 patients diagnosed as mild COVID-19 who presented to the outpatients clinic, Qena University Hospital, Upper Egypt, during the period from February to March, 2021. Ethical approval from the Ethics Committee, Faculty of Medicine South Valley University was taken before starting the study (code: SVU 2021/1/120). Written informed consents were obtained from the included patients regarding the approval to use the drug and performing the required investigations and the study was conducted in accordance with the Declaration of Helsinki. The patients with mild COVID-19 were divided randomly into two groups; group A included 57 patients with mild COVID-19 who received ivermectin nanosuspension nasal spray twice daily plus the Egyptian protocol of treatment for COVID-19 and group B included 57 patients with mild COVID-19 who received the Egyptian protocol for COVID-19 only.

The diagnosis of COVID-19 was based on history of exposure, the presence of respiratory manifestation and/or fever, radiological signs suggestive of COVID-19: ground glass opacity GGO, changes in total leucocytic count and lymphocytic count (normal or reduced).19 All cases were confirmed by real-time PCR test positive for SARS-CoV-2 using upper respiratory tract swabs.

Regarding illness severity, severe or critical COVID-19 was diagnosed by the presence of one or more of the following; (1) respiratory rate 30 cycles per minute or more, (2) resting room air oxygen saturation of 93% or less, (3) PaO2/FiO2 is 300 mmHg or less, (4) respiratory failure requiring mechanical ventilation, shock, organ dysfunction syndrome and ICU admission. COVID-19 patients who did not meet these specifications yet had a positive COVID-19 nucleic acid test were considered to have a mild disease level.20,21 A mild case of COVID-19 is defined as symptomatic case with lymphopenia or leucopenia with no radiological signs for pneumonia, according to the Egyptian management Protocol for COVID-19.22

All patients with severe COVID-19 or patients indicated to receive systemic ivermectin according to the Egyptian management protocol for COVID-19 patients,22 were excluded from this study. Also chronic ENT disorders such as chronic sinusitis, nasal allergy, patients using nasal spray preparation, systemic or local use of steroids due to any cause, or allergic to ivermectin were excluded.

The Egyptian protocol for treatment of mild COVID-19 includes:

Demographic data were recorded for all patients including age, sex, BMI, comorbidities, and smoking, clinical manifestations including fever, cough, dyspnea, anosmia and gastrointestinal tract (GIT) symptoms such as diarrhea, vomiting and/or abdominal pain. Full laboratory investigations were done in all patients and chest CT performed.

Follow-up of all included patients until complete recovery from COVID-19 and the recovery durations of all symptoms for all included patients were recorded in days. Follow up of routine laboratory tests was conducted 7 days after starting ivermectin nanosuspension nasal spray. Group A patients were followed also for any side effects of the ivermectin nanosuspension nasal spray.

Poloxamer 407 and Poloxamer 188 were obtained from Sigma Chemicals Co. (St. Louis, MO, USA). Sodium alginate was supplied by General Chemical and Pharmaceutical Co. Ltd, Sudbury, UK. Hydroxypropyl methylcellulose 15,000 (HPMC) was obtained from El-Gomhouria Co., Cairo, Egypt. Carbopol 974P (CP) was obtained from Lubrizol Co., Cleveland, OH, USA.

Ivermectin nanosuspension was developed using a nanoprecipitation method followed by ultrasonication as reported in the literature.23 A specified amount of ivermectin was dissolved in a small amount of acetone to form the solvent phase (120 mg/L). Poloxamer 407 and Poloxamer 188 as stabilizers were dissolved in distilled water at concentrations of 2 and 1% w/v, respectively to form antisolvent phase. The drug solution was then added dropwise to the aqueous stabilizer solution using a suitable syringe under continuous stirring on magnetic stirrer at 25C (3000 rpm for 30 min). The resultant homogenous suspension was immediately subjected to ultrasonication using a probe-type sonicator (Cole-Parmer, Vernon Hills, IL, USA) for 10 min at 5 spauses and amplitude pressure 50% for further control of particle aggregation. After sonication, the nanosuspension was placed on a magnetic stirrer for 2 h to ensure the complete evaporation of solvent.

For the preparation of the mucoadhesive nasal formulation of ivermectin nanosuspension, mucoadhesive polymer mixture (HPMC K15M (0.3% w/v), Carbopol 974P (0.1% w/v) and sodium alginate (0.2% w/v)) were added to the prepared nanosuspension with continuous stirring until an homogenous viscous dispersion was obtained. To this formulation other ingredients such as sodium benzoate (0.01%w/v) and glycerol (1.0%w/v) as preservatives were added and mixed well. Finally, the prepared formulation was filled into nasal spray containers. Concentration of ivermectin per puff was 70 g/mL.

The judging points regarding the efficacy of Ivermectin nanosuspension nasal spray in improving patients with mild COVID-19 were as follows (Figure 1):

Figure 1 Flow chart of the study design.

Data entry and data analysis were done using SPSS version 26 (Statistical Package for Social Science). Data were presented as a number, percentage, the mean and standard deviation for parametric data, the median and inter-quartile range for non-parametric data. Chi-square test and Fisher exact test were used to compare qualitative variables. MannWhitney test was used to compare between two quantitative variables and KruskalWallis test was used to compare between more than two quantitative variables for non-parametric data. Independent t-test was used to compare between two quantitative variables for parametric data. P-value was considered statistically significant when <0.05.

This prospective study included 114 patients with mild COVID-19; 82 males (71.9%) and 32 females (28.1%) with mean age 45.1 18.9. All patients showed no signs suggestive of moderate or severe COVID-19 on CT chest. Co-morbidities were present in 47 patients of all patients (41.2%) in the form of chronic obstructive pulmonary disease [1 case (0.9%)], cerebrovascular stroke [4 cases (3.5%)], diabetes mellitus [14 cases (12.3%)], hypertension [20 cases (17.5%)], bronchial asthma and interstitial pulmonary fibrosis [3 cases for each, (2.7%)]. Both groups were age and sex matched. Group A (ivermectin nanosuspension nasal spray treated group) included 40 males (70.2%) and 17 females (29.8%) and group B included 42 males (73.7%) and 15 females (26.3%) with no significant difference (P = 0.7). The mean age (years) of group A is 44.8 19.2 versus 45.5 18.8 in group B, with no significant difference (P = 0.8). Neutrophil/lymphocyte ratio before treatment was 3.1 1.3 in group A versus 3.1 1.2 in group B with P = 0.9. Also the median values of CRP, D-dimer, and serum ferritin were not significantly different between the two study groups (P = 0.9, 0.5, and 0.7 respectively). There were no significant differences regarding the history of contact cases which was found in 30 patients of group A (52.6%) versus 28 patients of group B (49.1%) with P = 0 0.7. As regards the frequency of different blood groups, there were no statistically significant differences between both groups, P = 0.9 (Table 1). There was no statistical significant difference between both groups regarding frequency of cough, dyspnea, anosmia, and GIT symptoms, as shown in Table 1.

Table 1 Comparison Between Demographic Data of Both Study Groups

In the ivermectin-treated group (group A) 54 patients (94.7%) achieved 2 consecutive negative PCR nasopharyngeal swabs in comparison to 43 patients (75.4%) in the control group, P = 0.004, as shown in Table 2. Patients who progressed to more severe disease were only 3 (5.3%) cases in the ivermectin-treated group and 14 (24.6%) cases in group B. No side effects were recorded in the ivermectin nanosuspension nasal spray treated group.

Table 2 COVID-19 PCR Negative Conversion Achievement in Ivermectin and Control Group

The durations (days) of fever, cough, dyspnea, anosmia, and GIT manifestations were assessed in the improved patients in both groups. Ivermectin-treated group (group A) exhibited significantly shorter mean duration of fever, cough, dyspnea, and anosmia compared with group B: 5 1.7 days versus 13.6 2.7 days; 5 1.9 days versus 14 2.6; 4.4 2.7 days versus 10.1 3.4; 0.5 0.9 versus 1.6 3.2, respectively with P = 0.0001 for all (Table 3). As regards gastrointestinal symptoms duration there was no significant difference between both groups, P = 0.884, as shown in Table 3. In this study no patients in both groups showed persistent anosmia or gastrointestinal manifestation, even those who failed to achieve negative PCR.

Table 3 Comparison Between Both Groups as Regards Duration of Fever, Cough, Dyspnea, Anosmia, GIT Symptoms and Duration to PCR Negative Conversion

Mean duration taken for nasopharyngeal swab to be negative was significantly shorter in group A than in group B (8.3 2.8 days versus 12.9 4.3 days; P = 0.004) (Table 3).

All laboratory parameters [neutrophil/lymphocyte ratio, CRP (mg/dl), D-dimer (ng/mL), and ferritin (ng/mL)] of both groups showed reduction towards normality references 7 days after diagnosis with more significant reduction in group A compared with group B. The median values and inter-quartile ranges in group A versus group B were [1.5 (0.53.5) versus 1.9 (0.64.2); 6 (396) versus 15 (2120); 250 (100900) versus 310 (10900); 199 (762020) versus 253 (752100) respectively] (Table 4).

Table 4 Comparison Between Both Groups as Regard Laboratory Parameters Changes 7 Days After Diagnosis

There is no definite drug therapy for COVID-19 up till now. Several drugs are under clinical trials for treatment of this serious disease, Ivermectin is one of these drugs.10,24 Ivermectin previously has been used in treatment of lymphatic filariasis, and Onchocerca volvulus.2 It is proved to have antiviral activity against a number of viruses in in vitro investigations3,2527 and is also found to limit viral infections such as influenza, West Nile viruses, and dengue fever. An in vitro study reported that ivermectin inhibits SARS-CoV-2, with a single addition to Vero/hSLAM cells 2-h post infection and reduces viral RNA ~5000- at 48 h.2,3,10,11,26,27 Recent studies that examined the efficacy of ivermectin have shown antiviral activity for many viral infections.28

Caly et al. found that a single dose of 5 M ivermectin can inhibit SARS-CoV-2 in vitro with 99.98% reduction of viral RNA in 48 h.10 The FDA-approved dose of ivermectin for other diseases is 150200 mcg/kg. But Caly et al. used a single large dose 30 times greater than the FDA-approved one.6 This study showed that mean age of mild COVID-19 patients is 45.1 18.9 years, which is in agreement with Ghweil et al., who reported that severe COVID-19 was more frequent in older age groups, while mild to moderate infection was more frequent in younger age groups;29 this is also reported by other investigators.3034

In this study the most common comorbidities were diabetes mellitus and hypertension which is similar to results reported by Ghweil et al.29 Astudy done by Marhl et al. reported that a higher risk for COVID-19 among diabetic patients may be due to associated dysregulation of angiotensin-converting enzyme 2 (ACE2), liver dysfunction, and chronic inflammation;35 Singh et al. reported the same results.36 In a randomized trial done by Shouman et al., ivermectin was used as a chemoprophylactic agent for contacts of COVID-19 patients and they found that ivermectin is a safe and effective chemoprophylactic agent in prevention of COVID-19.37

A randomized, double-blind trial was done in Dhaka, Bangladesh in which oral ivermectin alone (12mg once daily for 5 days) or in combination with doxycycline (12mg ivermectin single dose and 200mg doxycycline day-1 followed by 100mg 12-hourly for next 4 days) was compared with placebo among patients with COVID-19 infection. Negative PCR was earlier in the 5-day ivermectin treatment group versus the placebo.38 A recent study done in Florida, USA, reported that COVID-19 patients given ivermectin with other treatments (e.g., azithromycin and hydroxychloroquine) showed lower mortality rate than COVID-19 patients who did not receive ivermectin.39

Various studies have reported the nasal delivery of nanosuspensions. Saindane et al. incorporated a carvedilol-containing nanosuspension into in situ gel,40 and Alshweiat et al. prepared a loratadine-based nasal nanosuspension to improve bioavailability.12 SARS-CoV-2 invades the oropharynx and nasopharynx, from which it transmits even before any signs appear. The first symptoms (odynophagia, anosmia, dry cough, fever) and lung parenchyma colonization occur when the virus replicates in this region. The use of a nasal ivermectin spray to deposit the drug in the upper respiratory tract may be a useful method for exposing the SARS-CoV-2 virus (or the cells that contain the viral particles) to high ivermectin concentrations. As a result, early in the infection, the viral load is reduced, preventing extensive viral replication, transmission, and disease aggravation.41

No previous study has used ivermectin in a nanosuspension nasal spray. In this study we tried to decrease the viral load in the nose and nasopharynx in early COVID 19 patients by the direct action of an ivermectin nanosuspension nasal spray. Administration of nanosuspension by nasal spray provides uniform distribution of the drug through the nasal mucosa. Mucoadhesive polymers such as hydroxypropyl methylcellulose 15,000 (HPMC K15M), carbopol 974P and sodium alginate were used in a mixture to increase the residence time of formulation at site of action.12,13

In this study, COVID-19 patients treated with an ivermectin mucoadhesive nanosuspension nasal spray showed shorter duration of fever, dyspnea, cough, and anosmia but not GIT symptoms duration. Additionally, the findings of the current study revealed that patients with COVID-19 treated with ivermectin showed more significant reduction in measured hematological and biochemical parameters towards normal values with rapid viral clearance as evidenced by conversion of nasopharyngeal swab to negative. Further studies should be done to assess the ivermectin nanosuspension nasal spray in prophylaxis of close contacts to COVID-19 patients.

Local use of ivermectin mucoadhesive nanosuspension nasal spray is safe and effective in treatment of mild COVID-19 patients, with rapid viral clearance and recovery of respiratory manifestations (anosmia, cough, and dyspnea). The result of efficacy of ivermectin in reducing patients symptoms can promote the current protocols of COVID-19 treatment. Further studies should be done to assess the possible role of ivermectin mucoadhesive nanosuspension nasal spray as a prophylaxis against COVID-19 infection.

The current studys main limitation was the lack of a multi-dose design of ivermectin to assess the potential dose-effect relationship, which could be designed in future studies.

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

This research was partially funded by South Valley University, Faculty of Medicine, Qena 83523, Egypt.

No potential conflicts of interest between authors to be declare.

1. El-Sayed, A., Kamel, M. Coronaviruses in humans and animals: the role of bats in viral evolution. Environ Sci Pollut Res. 2021;28:1958919600. doi:10.1007/s11356-021-12553-1

2. Gonzlez Canga A, Sahagn Prieto AM, Diez Libana MJ, et al. The pharmacokinetics and interactions of ivermectin in humansa mini-review. AAPS J. 2008;10(1):4246. doi:10.1208/s12248-007-9000-9

3. Gtz V, Magar L, Dornfeld D, et al. Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import. Sci Rep. 2016;6:23138. doi:10.1038/srep23138

4. Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin /-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J. 2012;443(3):851856. doi:10.1042/BJ20120150

5. Siddiqui AJ, Jahan S, Ashraf SA, et al. Current status and strategic possibilities on potential use of combinational drug therapy against COVID-19 caused by SARS-CoV-2. J Biomol Struct Dyn. 2020;114. doi:10.1080/07391102.2020.1802345

6. Siddiqui AJ, Danciu C, Ashraf SA, et al. Plants-derived biomolecules as potent antiviral phytomedicines: new insights on ethnobotanical evidences against coronaviruses. Plants. 2020;9(9):1244. doi:10.3390/plants9091244

7. Surti M, Patel M, Adnan M, et al. Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing, docking and molecular dynamics simulation study. RSC Adv. 2020;10(62):3770737720. doi:10.1039/D0RA06379G

8. Alzahrani FA, Saadeldin IM, Ahmad A, et al. The potential use of mesenchymal stem cells and their derived exosomes as immunomodulatory agents for COVID-19 patients. Stem Cells Int. 2020;2020:8835986. doi:10.1155/2020/8835986

9. Wagstaff KM, Rawlinson SM, Hearps AC, Jans DA. An AlphaScreen-based assay for high-throughput screening for specific inhibitors of nuclear import. J Biomol Screen. 2011;16(2):192200. doi:10.1177/1087057110390360

10. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved]drug ivermectin inhibits the replication of SARS-CoV-2 invitro. Antiviral Res. 2020;178:104787. doi:10.1016/j.antiviral.2020.104787

11. Ketkar H, Yang L, Wormser GP, Wang P. Lack of efficacy of ivermectin for prevention of a lethal Zika virus infection in a murine system. Diagn Microbiol Infect Dis. 2019;95(1):3840. doi:10.1016/j.diagmicrobio.2019.03.012

12. Alshweiat A, Cska I, Tmsi F, et al. Nasal delivery of nanosuspension-based mucoadhesive formulation with improved bioavailability of loratadine: preparation, characterization, and in vivo evaluation. Int J Pharm. 2020;579:119166. doi:10.1016/j.ijpharm.2020.119166

13. Alshweiat A, Ambrus R, Csoka I. Intranasal nanoparticulate systems as alternative route of drug delivery. Curr Med Chem. 2019;26(35):64596492. doi:10.2174/0929867326666190827151741

14. Lehrer S, Rheinstein PH. Ivermectin docks to the SARS-CoV-2 spike receptor-binding domain attached to ACE2. In Vivo. 2020;34(5):30233026. doi:10.21873/invivo.12134

15. Rodriguez-Morales AJ, Gallego V, Escalera-Antezana JP, et al. COVID-19 in Latin America: the implications of the first confirmed case in Brazil. Travel Med Infect Dis. 2020;35:101613. doi:10.1016/j.tmaid.2020.101613

16. Rodriguez-Morales AJ, Snchez-Duque JA, Hernndez-Botero S, et al. Preparacin y control dela enfermedad por coronavirus 2019 (COVID-19) en Amrica Latina. Acta Medica Peruana. 2020;37(1):37. doi:10.35663/amp.2020.371.909

17. Gallego V, Nishiura H, Sah R, Rodriguez-Morales AJ. The COVID-19 outbreak and implications for the Tokyo 2020 Summer Olympic Games. Travel Med Infect Dis. 2020;2020:101604. doi:10.1016/j.tmaid.2020.101604

18. Abdelmaksoud AA, Ghweil AA, Hassan MH, et al. Olfactory disturbances as presenting manifestation among egyptian patients with COVID-19: possible role of zinc. Biol Trace Elem Res. 2021:18. doi:10.1007/s12011-020-02546-5

19. Wang YY, Jin YH, Ren XQ, et al. Updating the diagnostic criteria of COVID-19 suspected case and confirmed case is necessary. Mil Med Res. 2020;7(1):13. doi:10.1186/s40779-020-00245-9

20. Li L, Li R, Wu Z, et al. Therapeutic strategies for critically ill patients with COVID-19. Ann Intensive Care. 2020;10(1):45. doi:10.1186/s13613-020-00661-z

21. Zhang J, Wang X, Jia X, et al. Risk factors for disease severity, unimprovement, and mortality in COVID-19 patients in Wuhan, China. Clin Microbiol Infect. 2020;26(6):767772. doi:10.1016/j.cmi.2020.04.012

22. Ministry of Health and Population. Egyptian national guidelines for COVID-19. 2020. Available online: https://hiph.alexu.edu.eg/images/egyptian_national_guidelines_covid-19.pdf. Accessed December 1, 2020.

23. Xia D, Quan P, Piao H, et al. Preparation of stable nitrendipine nanosuspensions using the precipitationultrasonication method for enhancement of dissolution and oral bioavailability. Eur J Pharm Sci. 2010;40(4):325334. doi:10.1016/j.ejps.2010.04.006

24. Hegazy AA, Hegazy RA. COVID-19: virology, pathogenesis and potential therapeutics. Afro-Egypt J Infect Endem Dis. 2020;10(2):9399. doi:10.21608/AEJI.2020.93432

25. Mastrangelo E, Pezzullo M, De Burghgraeve T, et al. Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug. J Antimicrob Chemother. 2012;67(8):18841894. doi:10.1093/jac/dks147

26. Lundberg L, Pinkham C, Baer A, et al. Nuclear import and export inhibitors alter capsid protein distribution in mammalian cells and reduce venezuelan equine encephalitis virus replication. Antiviral Res. 2013;100(3):662672. doi:10.1016/j.antiviral.2013.10.004

27. Azeem S, Ashraf M, Rasheed MA, Anjum AA, Hameed R. Evaluation of cytotoxicity and antiviral activity of ivermectin against newcastle disease virus. Pak J Pharm Sci. 2015;28(2):597602.

28. Jabeen T, Khader MA, Jabeen S. A review on the antiparasitic drug ivermectin for various viral infections and possibilities of using it for novel severe acute respiratory syndrome coronavirus 2: new hope to treat coronavirus disease-2019. Asian J Pharm Clin Res. 2020;13:2127. doi:10.22159/ajpcr.2020.v13i8.38357

29. Ghweil AA, Hassan MH, Khodeary A, et al. Characteristics, outcomes and indicators of severity for COVID- 19 among sample of ESNA Quarantine Hospitals Patients, Egypt: a retrospective study. Infect Drug Resist. 2020;13:23752383. doi:10.2147/IDR.S263489

30. Liu K, Chen Y, Lin R, Han K. Clinical features of COVID-19 in elderly patients: a comparison with young and middle-aged patients. J Infect. 2020. doi:10.1016/j.jinf.2020.03.005

31. Mahase E. Covid-19: death rate is 0.66% and increases with age, study estimates. BMJ. 2020;369:m1327. doi:10.1136/bmj.m1327

32. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:9195. doi:10.1016/j.ijid.2020.03.017

33. Kumar S, Singh R, Kumari N, et al. Current understanding of the influence of environmental factors on SARS-CoV-2 transmission, persistence, and infectivity. Environ Sci Pollut Res Int. 2021;28(6):62676288. doi:10.1007/s11356-020-12165-1

34. Aly MH, Rahman SS, Ahmed WA, et al. Indicators of critical illness and predictors of mortality in COVID-19 patients. Infect Drug Resist. 2020;13:19952000. doi:10.2147/IDR.S261159

35. Marhl M, Grubelnik V, Magdi M, Markovi R. Diabetes and metabolic syndrome as risk factors for COVID-19. Diabetes Metab Syndr. 2020;14(4):671677. doi:10.1016/j.dsx.2020.05.013

36. Singh AK, Gupta R, Ghosh A, Misra A. Diabetes in COVID-19: prevalence, pathophysiology, prognosis and practical considerations. Diabetes Metab Syndr. 2020;14(4):303310. doi:10.1016/j.dsx.2020.04.004

37. Shouman WM, Hegazy AA, Nafae RM, et al. Use of ivermectin as a potential chemoprophylaxis for COVID-19 in Egypt: a randomised clinical trial. J Clin Diagn Res. 2021. doi:10.7860/JCDR/2020/46795.0000

38. Alam MT, Murshed R, Bhiuyan E, Saber S, Alam R, Robin R. A case series of 100 COVID-19 positive patients treated with combination of ivermectin and doxycycline. J Bangladesh Coll Phys Surg. 2020;38:1015. doi:10.3329/jbcps.v38i0.47512

39. Rajter JC, Sherman MS, Fatteh N, Vogel F, Sacks J, Rajter JJ. Use of ivermectin is associated with lower mortality in hospitalized patients with coronavirus disease 2019: the ivermectin in COVID nineteen study. Chest. 2021;159(1):8592. doi:10.1016/j.chest.2020.10.009

40. Saindane NS, Pagar KP, Vavia PR. Nanosuspension based in situ gelling nasal spray of carvedilol: development, in vitro and in vivo characterization. Aaps Pharmscitech. 2013;14(1):189199. doi:10.1208/s12249-012-9896-y

41. Errecalde J, Lifschitz A, Vecchioli G, et al. Safety and pharmacokinetic assessments of a novel ivermectin nasal spray formulation in a pig model. J Pharm Sci. 2021;110(6):25012507. doi:10.1016/j.xphs.2021.01.017

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Using ivermectin in treating of patients with mild COVID-19 | IJN - Dove Medical Press

Cyberpunk 2077 developer says its hacked data is circulating online – The Verge

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Hacked data stolen from CD Projekt is circulating online, the company says. The studio behind Cyberpunk 2077 and The Witcher 3 says it can not confirm the exact contents of the data being circulated, but believes it relates to its games, contractors, and both current and former employees. It also warned that the data may have been manipulated or tampered with.

The disclosure comes four months after the studio first announced that it had fallen victim to a ransomware attack. It initially said hackers had managed to access certain data from the company. CD Projekt posted the ransom note it received in which the hackers claimed to have access to source code from its games including Cyberpunk 2077, The Witcher 3, and Gwent. The note also said the hacked data included details relating to its HR, accounting, and other internal operations.

The company said it would not give in to the hackers demands, and days later the attackers claimed to have sold the data online. However the nature of the sale, in which the hackers claimed to have found a buyer outside of a hacking forum auction, raised questions about whether they were able to find a buyer at all. Writing in a blog post, Emsisoft threat analyst Brett Callow said he thought it was likely that the hackers were just claiming to have found a buyer to save face after having failed to monetize the hack.

CD Projekt has previously admitted that hackers were able to encrypt some of its employee data on its network. But the company said its investigation had found no evidence that the data had been transferred out of the companys systems.

The hack followed the troubled launch of the studios latest blockbuster title, Cyberpunk 2077. Although it sold well and was initially well-received by critics, players quickly discovered that the game was riddled with bugs, and almost unplayable on older consoles. The situation was so bad that the game was pulled from the PlayStation Store. As of this writing, it is yet to return.

CD Projekt says its continuing to work with law enforcement and outside experts as it responds to the hack, and said it is committed and prepared to take action against anyone sharing the stolen data.

See the article here:

Cyberpunk 2077 developer says its hacked data is circulating online - The Verge

CD Projekt says Cyberpunk 2077 will return to Sonys PlayStation Store on June 21st – The Verge

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CD Projekt says Cyberpunk 2077 will return to Sonys PlayStation Store on June 21st, slightly more than six months after being removed. As Polygon notes, the news came in a regulatory disclosure by Cyberpunk 2077s developer, CD Projekt Reds parent company, saying Sony had agreed to reinstate the game.

A CD Projekt Red spokesperson declined further comment about Cyberpunk 2077s return, including what potential bug fixes or other updates the new version offers. In a statement to Polygon, Sony confirmed the news but said that it still doesnt recommend playing the game on PlayStation 4. Users will continue to experience performance issues with the PS4 edition while CD Projekt Red continues to improve stability across all platforms. [Sony Interactive Entertainment] recommends playing the title on PS4 Pro or PS5 for the best experience, a spokesperson said.

CD Projekt executives have said they frequently updated Sony on fixes for Cyberpunk 2077s myriad bugs and performance issues since the game was pulled from the store on December 17th, 2020. The studio has released numerous patches for its console, PC, and Google Stadia editions; in late May, joint CEO Adam Kiciski told investors thered been visible progress on stabilizing the game. But Kiciski said Sony would have to make the final call.

Cyberpunk 2077 was released in December to strong sales but severe technical problems. The game struggled to run on last-generation Xbox One and PlayStation 4 consoles, and players faced numerous (and frequently hilarious) bugs on every platform. Microsoft and Sony both offered refunds for the game, and Microsoft added a warning label for Xbox One owners on its Xbox store. Sony took the more drastic step of pulling Cyberpunk 2077 from its PlayStation Store entirely. Console owners could still buy physical discs, but CD Projekt has said that the digital versions absence may have slowed down sales on Xbox and PC as well as PlayStation.

CD Projekt Red spent nearly a decade designing Cyberpunk 2077, and it calls the game a long-term investment that it can sell for years to come. The studio has backed away from plans for a standalone multiplayer mode, saying it would focus on adding online features to all its games instead. But its promised downloadable content for Cyberpunk 2077s single-player campaign, plus a major upgrade for new consoles including the PlayStation 5 in the second half of this year.

Update June 15th, 2:00PM ET: Added comment from Sony via Polygon and response from CD Projekt Red.

Continued here:

CD Projekt says Cyberpunk 2077 will return to Sonys PlayStation Store on June 21st - The Verge

Cyberpunk RPG The Ascent coming to Game Pass at launch in July – Rock Paper Shotgun

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Cyberpunk action RPG The Ascent is queued up to launch next month and it's just popped up with a fresh trailer. Developers Neon Giant have let on an extra quick look at some more co-op cyberpunk shoot 'em upping here in the new video. Good news for the subscription service fans as well. The Ascent has announced that it will be joining Xbox Game Pass for PC on its launch day in July.

You'll play as a worker for The Ascent Group which unexpectedly shuts down, threatening the survival of your corpo-owned distrct. It'll be up to you, RPG hero, to grab your cyberpunk guns and figure out why. The Ascent kicked off a new running and gunning cyberpunk-y trailer during Microsoft's E3 showcase. You can catch the explosions and co-op hijinx right here.

Ed got the chance to play The Ascent just last month. He was impressed by its rusty, seedy cyberpunk world but was a little disappointed that the combat wasn't equally messy and loud.

"In many ways, it was a lot more controlled than I was expecting. I mixed and matched between a revolver, assault rifle, submachine gun, and shotgun, all of which felt punchy, sure, but a bit too grounded for me," Ed explains, but also adds a moment from a later fight. "That's maybe a bit harsh, because in its best moments The Ascent is wild. I fought against these two big baddies with hammers and tremor attacks I had to dodge roll to avoid, finally introducing something other than bullets!"

The new trailer up top there does include some explosions and lasers and some area of effect stuff so perhaps The Ascent saved its best tricks for launch day.

You can find the Ascent over on Steam where it will launch on July 29th. It will be on 10% discount through August 5th. It'll also be coming to Game Pass on PC, console, and cloud on its launch day.

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Cyberpunk RPG The Ascent coming to Game Pass at launch in July - Rock Paper Shotgun

What is the Fifth Amendment?

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THE defense rested their case on Thursday, April 15 in the murder trial of Derek Chauvin in the death of George Floyd.

The defense presented a total of two days of testimony to the prosecution's two weeks.

Read our Derek Chauvin trial live blog for the latest updates

5

The Fifth Amendment to the United States Constitution addresses criminal procedure as well as other aspects of the Constitution.

The Fifth Amendment applies to every level of the government, including the federal, state and local levels, in regard to a US citizen or resident of the US.

One provision of the Fifth Amendment requires thatfeloniesbe tried only uponindictmentby agrand jury.

Another provision, theDouble Jeopardy Clause, provides the right of defendants to be tried only once in federal court for the same offense.

5

Theself-incriminationclause provides various protections against self-incrimination, including the right of an individual to not serve as a witness in a criminal case in which they are the defendant.

"Pleading the Fifth" is a colloquial term often used to invoke the self-incrimination clause when witnesses decline to answer questions where the answers might incriminate them.

The Fifth Amendment reads as followed: "No person shall be held to answer for a capital, or otherwise infamous crime, unless on a presentment or indictment of a Grand Jury, except in cases arising in the land or naval forces, or in the Militia.

"When in actual service in time of War or public danger; nor shall any person be subject for the same offence to be twice put in jeopardy of life or limb; nor shall be compelled in any criminal case to be a witness against himself, nor be deprived of life, liberty, or property, without due process of law; nor shall private property be taken for public use, without just compensation."

5

As the defense side drew to a close on April 15, Chauvin removed his Covid-19 face mask and informed the judge that he would not testify, saying he would invoke his Fifth Amendment right not to take the stand.

"Is this your decision not to testify?" Judge Peter Cahill asked Chauvin.

"It is, your honor," Chauvin told the judge.

There was speculation whether Chauvin would testify.

Charges against Chauvin include second-degree murder, third-degree murder and second-degree manslaughter.

An expert told the Star Tribune that it was too risky for Chauvin, whose actions were caught on video, to testify.

"Chauvin doesn't come across as a character that you want to root for because of the video," Joseph Daly, emeritus professor at Mitchell Hamline School of Law, told the Star Tribune.

5

"[Prosecutors will] take him through every single second of that video and have him testify.

"In cross-examination he'll just get beat up. It'll be horrible for him. The risk is so immense for him to testify."

Floyd's loved oneswanted to see Chauvin take the stand.

" He won't be able to handle what's thrown at him, because how can you explain that you had your knee on a man's neck for nine minutes? How can you explain that? There's no way to explain. You can't,"brother Philonise Floydtold the Star Tribune.

"So it will be a good thing [if he testifies], but I know that's not going to happen."

The high profile case is expected to end sometime next week.

5

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Chauvin's decision not to testify has competed the case for both the defense and prosecution's side, which sets up the stage for closing arguments and deliberation Monday, April 19.

The three other fired officers who assisted in Floyd's arrest - J Alexander Kueng, Thomas Lane and Tou Thao - are scheduled to be tried in August on charges of aiding and abetting murder and manslaughter.

See more here:

What is the Fifth Amendment?

Prosecution rests in 2nd trial of officers accused of assaulting Black colleague by again focusing on texts – KSDK.com

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Also Monday, both officers invoked their Fifth Amendment right not to testify as they did during the first trial

ST. LOUIS Prosecutors trying to convict two former St. Louis police officers for assaulting one of their own as he worked undercover as a protester rested its case Monday with perhaps its most powerful evidence against them: text messages.

In the messages, former Officer Dustin Boone uses the n-word and sends a lengthy apology to the victim in the case, Detective Luther Hall. In one, he tells a friend, I feel bad, we obviously didn't know he was a policeman.

In others, former Officer Christopher Myers writes, Lets whoop some (expletive) as the protests were about to start in 2017 after a judge acquitted a white St. Louis police officer of murdering a Black man.

The jury also heard from a doctor who treated Hall, and said his injuries are consistent with the alleged assault because he did not complain or experience any neck or back problems before it.

Patrick Kilgore, who is representing Boone, suggested the neck issues could be degenerative.

One noticeable absence from the prosecutions witness list is former Officer Randy Hays. He has already pleaded guilty to his role in the alleged assault and is awaiting sentencing.

He testified during the first trial and changed his recollection of what the officers did during the alleged assault.

This is the second time these officers are on trial for their role in this assault.

A jury returned partial verdicts following a two-week trial in March.

Boone is facing the most serious of charges in this case, aiding and abetting in the deprivation of civil rights. It carries a sentence of 10 years in prison.

Myers is charged with tampering with evidence to impede an investigation for allegedly destroying Halls cellphone.

The government must prove Boone knew he was aiding and abetting in the deprivation of Halls civil rights. His defense has focused heavily on how Boone assumed his fellow officers had probable cause to make the arrest, and thats why he held Hall down by putting a knee in his back and pushed his head back down to the ground.

The same can be said for Myers.

The government must prove Myers is the one who struck the phone, and that he knew there was a criminal investigation he needed to impede.

His defense has focused heavily on creating reasonable doubt around who actually destroyed the phone, suggesting at one point Monday that an officer who stepped on it could have shattered the screen and a pebble in that officers shoe could have created the circular shape of the cracks.

The prosecution has said the crack to the phone clearly came from an asp and went through photographs taken by a newspaper photographer and Halls own cellphone to demonstrate its theory.

The defense also spent hours going through the images, and the corresponding timestamps, showing their clients were not near Hall during the alleged assault.

Prosecutors have said the last few frames caught on Halls cellphone show an officer raising a baton before striking the phone and the audio cuts off. Defense attorneys suggested Myers was not near Hall at the moment the phone was struck.

Myers face can be seen in the last few moments before the phone cuts off entirely. His attorneys say he picked it up, saw blood on it, and threw it out of the way. Before Hall was taken away, Myers put the phone back in Halls backpack another move his attorneys say prove he had no intention of destroying evidence.

Also Monday, both officers invoked their Fifth Amendment right not to testify as they did during the first trial.

The defense called four officers to the stand and is expected to call additional officers Tuesday.

Lt. Joe Crews was among the officer called. He said he saw Hall at police headquarters holding a towel to his bloody lip and asked him what happened.

He told me he was running with the (expletives), the worst of the worse, when the police got him.

First Assistant U.S. Attorney Carrie Costantin reminded Crews of his statement to the FBI in which he said Hall told him he was running with everyone and got his (expletive) beat by the police.

The defense is expected to call at least two more witnesses Tuesday, and the jury could start deliberations Tuesday afternoon.

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Prosecution rests in 2nd trial of officers accused of assaulting Black colleague by again focusing on texts - KSDK.com

Right to Due Process: Overview | Constitution Annotated …

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Fifth Amendment:

No person shall be held to answer for a capital, or otherwise infamous crime, unless on a presentment or indictment of a Grand Jury, except in cases arising in the land or naval forces, or in the Militia, when in actual service in time of War or public danger; nor shall any person be subject for the same offence to be twice put in jeopardy of life or limb; nor shall be compelled in any criminal case to be a witness against himself, nor be deprived of life, liberty, or property, without due process of law; nor shall private property be taken for public use, without just compensation.

Standing by itself, the phrase due process would seem to refer solely and simply to procedure, to process in court, and therefore to be so limited that due process of law would be what the legislative branch enacted it to be. But that is not the interpretation which has been placed on the term. It is manifest that it was not left to the legislative power to enact any process which might be devised. The article is a restraint on the legislative as well as on the executive and judicial powers of the government, and cannot be so construed as to leave Congress free to make any process due process of law by its mere will. All persons within the territory of the United States are entitled to its protection, including corporations, aliens, and presumptively citizens seeking readmission to the United States, but States as such are not so entitled. It is effective in the District of Columbia and in territories which are part of the United States, but it does not apply of its own force to unincorporated territories. Nor does it reach enemy alien belligerents tried by military tribunals outside the territorial jurisdiction of the United States.

Early in our judicial history, a number of jurists attempted to formulate a theory of natural rightsnatural justice, which would limit the power of government, especially with regard to the property rights of persons. State courts were the arenas in which this struggle was carried out prior to the Civil War. Opposing the vested rights theory of protection of property were jurists who argued first, that the written constitution was the supreme law of the State and that judicial review could look only to that document in scrutinizing legislation and not to the unwritten law of natural rights, and second, that the police power of government enabled legislatures to regulate the use and holding of property in the public interest, subject only to the specific prohibitions of the written constitution. The vested rights jurists thus found in the law of the land and the due process clauses of the state constitutions a restriction upon the substantive content of legislation, which prohibited, regardless of the matter of procedure, a certain kind or degree of exertion of legislative power altogether. Thus, Chief Justice Taney was not innovating when, in the Dred Scott case, he pronounced, without elaboration, that one of the reasons that the Missouri Compromise was unconstitutional was that an act of Congress that deprived a citizen of the United States of his liberty or property, merely because he came himself or brought his property into a particular territory of the United States, and who had committed no offence against the laws, could hardly be dignified with the name of due process of law. Following the war, with the ratification of the Fourteenth Amendments Due Process Clause, substantive due process interpretations were urged on the Supreme Court with regard to state legislation. First resisted, the arguments came in time to be accepted, and they imposed upon both federal and state legislation a firm judicial hand that was not to be removed until the crisis of the 1930s, and that today in non-economic legislation continues to be reasserted.

It may prevent confusion, and relieve from repetition, if we point out that some of our cases arose under the provisions of the Fifth and others under those of the Fourteenth Amendment to the Constitution of the United States. Although the language of those Amendments is the same, yet as they were engrafted upon the Constitution at different times and in widely different circumstances of our national life, it may be that questions may arise in which different constructions and applications of their provisions may be proper. The most obvious difference between the two Due Process Clauses is that the Fifth Amendment clause as it binds the Federal Government coexists with other express provisions in the Bill of Rights guaranteeing fair procedure and non-arbitrary action, such as jury trials, grand jury indictments, and nonexcessive bail and fines, as well as just compensation, whereas the Fourteenth Amendment clause as it binds the states has been held to contain implicitly not only the standards of fairness and justness found within the Fifth Amendments clause but also to contain many guarantees that are expressly set out in the Bill of Rights. In that sense, the two clauses are not the same thing, but, insofar as they impose such implicit requirements of fair trials, fair hearings, and the like, which exist separately from, though they are informed by, express constitutional guarantees, the interpretation of the two clauses is substantially, if not wholly, the same. Save for areas in which the particularly national character of the Federal Government requires separate treatment, this book's discussion of the meaning of due process is largely reserved for the section on the Fourteenth Amendment. Finally, some Fourteenth Amendment interpretations have been carried back to broaden interpretations of the Fifth Amendments Due Process Clause, such as, for example, the development of equal protection standards as an aspect of Fifth Amendment due process.

Due process under the Fifth and Fourteenth Amendments can be broken down into two categories: procedural due process and substantive due process. Procedural due process, based on principles of fundamental fairness, addresses which legal procedures are required to be followed in state proceedings. Relevant issues, as discussed in detail below, include notice, opportunity for hearing, confrontation and cross-examination, discovery, basis of decision, and availability of counsel. Substantive due process, although also based on principles of fundamental fairness, is used to evaluate whether a law can be applied by states at all, regardless of the procedure followed. Substantive due process has generally dealt with specific subject areas, such as liberty of contract or privacy, and over time has alternately emphasized the importance of economic and noneconomic matters. In theory, the issues of procedural and substantive due process are closely related. In reality, substantive due process has had greater political import, as significant portions of a state legislatures substantive jurisdiction can be restricted by its application.

Although the extent of the rights protected by substantive due process may be controversial, its theoretical basis is firmly established and forms the basis for much of modern constitutional case law. Passage of the Reconstruction Amendments (13th, 14th, and 15th) gave the federal courts the authority to intervene when a state threatened fundamental rights of its citizens, and one of the most important doctrines flowing from this is the application of the Bill of Rights to the states through the Due Process Clause. Through the process of selective incorporation, most of the provisions of the first eight Amendments, such as free speech, freedom of religion, and protection against unreasonable searches and seizures, are applied against the states as they are against the federal government. Though application of these rights against the states is no longer controversial, the incorporation of other substantive rights, as is discussed in detail below, has been.

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Right to Due Process: Overview | Constitution Annotated ...

There are instances in which the government can take your home. Heres how. – WKMG News 6 & ClickOrlando

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Did you know that there are some instances in which the United States, state and municipal governments can come take your property, even without your consent?

Its a legal right called eminent domain, and if you have never heard of it or want to know more, here are some key questions as to how it happens and how to deal with it.

Eminent domain is the Fifth Amendment right of a government entity to take your property for a public purpose. The government has to provide proof that the property will have a beneficial use to the public, and also has to make a fair value offer for the property.

There is a wide range of situations, but the most common ones are for construction of roads/highways and public buildings, supplying water to a community or for defense purposes.

There are cases when it can be. If the government makes an offer for more than the property is worth or if a property owner doesnt owe much more money on a loan, eminent domain can be great for that owner. But it can work the other way, also. If an owner owes more money on a property than is offered by the government, it can be a crushing blow.

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If someone is unhappy about an eminent domain offer from the government, an owner can retain the services of a lawyer and fight for a better offer. As part of the process, that lawyer can also hire a forensics appraiser that can evaluate the value of a property and testify in front of a judge in defense of that evaluation.

Roughly 95% of cases are settled before going to court, according to Rick Dreggors, a forensic appraiser in Orlando with 34 years of experience in the industry. But there are instances in which cases arent settled, and a judge will decide the true value of an offer and what an owner should be getting from the government.

On this most recent episode of You Have Real Estate With Justin Clark, attorney Justin Clark chats about eminent domain with Dreggors.

To watch the full segment, hit play on the video above.

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There are instances in which the government can take your home. Heres how. - WKMG News 6 & ClickOrlando

History Book – The right to remain silent – WORLD News Group

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NICK EICHER, HOST: Today is Monday, June 14th. Good morning! This is The World and Everything in It from listener-supported WORLD Radio. Im Nick Eicher.

MARY REICHARD, HOST: And Im Mary Reichard. Next up: The WORLD History Book. Today, stealth technology, the constitutional rights of the accused, and the death of a traitor. Heres senior correspondent Katie Gaultney.

SONG: Hush, Joy Williams and Matt Berringer, from AMCs Turn

KATIE GAULTNEY, SENIOR CORRESPONDENT: Benedict Arnold, a name synonymous with betrayal. After the Americans uncovered his treason, he escaped, defecting to the British. But he couldnt escape death. Arnold died of natural causes 220 years ago, on June 14, 1801.

Arnold rose to the rank of major general in the American Continental Army. Motivated by the promise of 20,000 British poundsand at his wifes urgingArnold plotted to gain command of the American fortress of West Point, New York, then turn it over to the British. West Point was so critical, soldiers called it the key to the colonies. Losing it would cut the colonies in halfand cut off access to important supplies, sabotaging the revolutionary effort.

Papers outlining Arnolds scheme fell into the hands of American militia forces, who alerted Washington.

U.S. Army Lieutenant General Dave Palmer shared with Biography how Americas top brass regarded Arnold.

PALMER: Right after his treason, George Washington decreed that the name Benedict Arnold would never be mentioned again in anything written about the army or about the country.

But the British didnt welcome him either, despite that he made a home among them. They provided for his needs, setting Arnolds wife, Peggy, up with a pension for life. But Arnold was largely shunned socially. He developed a nervous disorder that would ultimately claim his life. The Biography channel reenacted one of Arnolds last wishes. He asked his wife, Peggy

CLIP: Let me die in my old American uniform, the uniform in which I fought my battles. God forgive me for ever putting on another. Benedict Arnold, 1801.

He died at age 60 in London on June 14, 1801, followed not long after by his wife. She was just 44 years old.

DETECTIVE: You have the right to remain silent. Anything you say can and will be used against you in a court of law. You have the right to an attorney. If you cannot afford an attorney, one will be provided for you at no cost.

Any fan of Law & Order knows those familiar words: the Miranda rights. But they arent just a trope of crime procedurals. They came as the result of a U.S. Supreme Court decision 55 years ago. On June 13, 1966, the nations highest court ruled in Miranda v. Arizona that police must inform suspects of their rights before questioning them.

A man named Ernesto Miranda faced charges of kidnapping and rape in 1963. He didnt have a lawyer during his two-hour police interrogation. During questioning, he confessed to both crimes. A lengthy jail sentence followed. But, he appealed his conviction, saying he didnt know he had the right to remain silent.

The Fifth Amendment says No person... shall be compelled in any criminal case to be a witness against himself, nor be deprived of life, liberty, or property, without due process of law. And the Sixth Amendment protects the right of those facing criminal prosecution to have the assistance of counsel for his defense.

In a 5-4 decision, the Supreme Court ruled that prosecutors could not use Mirandas confession against him. They said investigators had not informed Miranda of his right against self-incrimination or his right to an attorney. Ultimately, they said an accused persons rights dont mean much if he doesnt know he has them. So, the Miranda Warning was born. It aims to protect people from self-incrimination when their lives are on the line.

After the Supreme Court decision, Miranda stood trial again. The second time, a jury convicted him without the confession.

And well top off todays History Book with top-secret technology.

SONG: Danger Zone, Kenny Loggins

Lockheeds F-117 Nighthawk made its maiden flight on June 18, 1981, after six years of development at the Pentagon. The plane was the first operational aircraft designed around stealth technology. The Defense Department finally admitted the planes existence in 1988. In the early 1990s, the plane proved to be a valuable asset during Operation Desert Storm. Colonel Rick Wright of Holloman Air Force Base.

WRIGHT: You notice the airplane has a pretty strange shape to it. It doesnt have any curves on it, its in a faceted shape like a diamond or some kind of jewel.

And that unusual shape is the key to its stealth technology. A Russian scientist determined in the 1960s that sharp edge configuration decreases an object's radar signature.

WRIGHT: The shape of the airplane bounces radio signals so they dont return back to the transmitter, and then any signals that do bounce back are attenuated by the skin of the airplane so that they come back much smaller

The Air Force retired the F-117 in April 2008 as other advanced stealth aircrafts joined its fleet. Still, some Nighthawks remain airworthy, and people have reported sightings as recently as last year.

Thats this weeks History Book. Im Katie Gaultney.

WORLD Radio transcripts are created on a rush deadline. This text may not be in its final form and may be updated or revised in the future. Accuracy and availability may vary. The authoritative record of WORLD Radio programming is the audio record.

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History Book - The right to remain silent - WORLD News Group

In His Wild Bid to Stop Leaks to the Press, Trump Even Spied on His Own Lawyer – Truthout

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From the Nothing New Under the Sun files, I bring you a former president whose concern over leaks to the press eventually blew his entire administration straight to hell.

President Nixons staffers formed the White House Plumbers, explains Time, a secret unit tasked with digging up dirt on Pentagon Papers leaker Daniel Ellsberg. The Plumbers went on to commit crimes for the Committee for the Re-Election of the President, including the Watergate burglaries. Although Nixon denied knowledge of the Plumbers activities, tapes subpoenaed during the Watergate investigation revealed years of political espionage and illegal surveillance. The Smoking Gun tape revealed that Nixon was involved in the cover up. On August 8, 1974, Nixon became the only American president to resign the office.

Nothing so dramatic as that is in the offing today; Donald Trump whose own surveillance program against journalists, Democratic politicians and their families, and even his own lawyer, is roiling Washington, D.C., once again is already out of office. He has been quacking about getting reinstated as president from his funnel hole in New Jersey. Sure, put him back in, and then impeach him a third time. Maybe this one will stick.

The first reports of Trumps administration running its own ham-fisted Plumbers operation landed late last week with a rolling boom. As the Justice Department investigated who was behind leaks of classified information early in the Trump administration, it took a highly unusual step: Prosecutors subpoenaed Apple for data from the accounts of at least two Democrats on the House Intelligence Committee, aides and family members, reported The New York Times. One was a minor.

The roll call of people affected is a perfect match to another Nixonian throwback, the enemies list. Atop Trumps effective corollary to Nixons list was House Intelligence Committee Chairman Adam Schiff, who was a regular target of Trumps tirades. All told, Apple received subpoenas that covered 73 phone numbers and 36 email addresses. A number of the people swept up in this metadata search were not in government, including the aforementioned minor.

Along with the subpoena came a nondisclosure order which barred Apple from informing its customers that the Justice Department was digging into their data. The nondisclosure order was extended three times, reports CNN, each time for a year, Apple said. When it was not extended for a fourth time, Apple said it informed the affected customers on May 5, 2021.

Concurrently, the Trump administration also seized communications data from CNN, The New York Times and The Washington Post. This revelation landed more than a week ago, tangling the Biden administration up in the mess, because his Justice Department apparently continued this surveillance after Trump left office. The Biden White House has disavowed these activities, and the policy regarding leak investigations over at Justice has been changed.

The wildest revelation came this weekend, when it was revealed that one of Trumps targets was his own White House counsel, Doug McGahn. Apple told Mr. McGahn about the subpoena last month, said one of the people, who spoke on the condition of anonymity to discuss the matter. Mr. McGahns wife also received a similar notice from Apple, reports the Times.

The time frame for this is easy enough to recall. Not long after Trump took office, his administration sprang more leaks than a badly wrapped diaper. Nobody in the administrations lower echelons had the courage to resign in protest over the terrifying things they were seeing Anonymous, your table is ready but they were more than happy to spray that cheese into the wind for the news media to collect, and collect it they did.

There were weeks when one could not walk around the block without tripping over 10 heavily sourced news reports about White House shenanigans regarding the southern border, the ceaseless infighting within the administration that was usually inspired by Trump himself, and the administrations dealings with Russia both before and after the election. The Russia questions, it appears, hit a tender spot with Trump, initially prompting the broad and surreptitious data harvest.

Fallout from these revelations is just beginning. House Democrats intend to hold hearings on the matter and will subpoena any witnesses who dont come voluntarily. This includes former Attorney General William Barr, who was running Justice when all of this went down. Barr is trying to put as much daylight as he can between himself and these subpoenas, but that will be challenging.

In May of 2019, then-Sen. Kamala Harris asked Barr directly if the president or anyone at the White House ever asked or suggested you open an investigation into anyone? Barrs reply was a tap-dancing clinic, but if and when he appears at a hearing on this matter, he will not have many places to hide besides an invocation of his Fifth Amendment rights.

The House will not be the only entity involved in this investigation. The Justice Departments internal watchdog announced Friday that he would review how officials sought the data of reporters, lawmakers and others as part of an aggressive crackdown on leaks during the Trump administration, reports the Post, a day after it was revealed the department years ago had secretly obtained the data of two congressmen well known for their criticism of President Donald Trump.

For their part, congressional Republicans are putting on their best What, me worry? faces as these revelations continue to roll in, and why not? Few of them have paid a price for loyalty to Trump, even now that he is out of office. As far as the public stance of the GOP goes, its all blue skies.

but I do wonder. At present, the Republican Party has tasked itself to defeat several wildly popular pieces of Democratic legislation, bury the sacking of the Capitol by Trump supporters under a compost pile of They were just tourists excuses even as they block an investigation into the incident, and now this, a scandal straight out of central casting with an eerily familiar historical hook to boot. There are only so many running chainsaws a person can juggle before limbs start getting lopped off.

The reason this latest issue is so important is that it appears to show the executive branch of the government wielding presidential power to target the legislative branch, reports CNNs Stephen Collinson, and the Presidents personal political enemies. It would be hard to find a more clear and flagrant abuse of presidential power. This behavior would not only be a perversion of the DOJs critical role in ensuring the neutral and apolitical application of justice a key requirement for a democratic society. It would also mirror the actions of autocrats across the world, many of whom Trump openly admired.

The GOPs worst enemy in this? Trump himself, of course. Does anyone think he will sit quietly while this investigation unfolds daily on the television he watches relentlessly? I would be not at all surprised if at some point he winds up pulling a Colonel Jessup from A Few Good Men: Did you order the Code Red? YOURE GOD DAMNED RIGHT I DID!

One of these days not today or tomorrow, but someday I have to believe the GOP will be forced to wise up and toss this hot potato back into the pot. They are whistling past the political graveyard now because Trumps base still has the back of the loyal, but there are not enough voters in that base to make a winning national coalition. As these treacherous stories about the former president continue to pile up, that loyalty may come only to be worth the price of a bus ticket home.

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In His Wild Bid to Stop Leaks to the Press, Trump Even Spied on His Own Lawyer - Truthout

Young Workers Optimistic in Latin America and the Caribbean – Gallup

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Story Highlights

COVID-19 not only changed the workplace, but it also changed the world.

Gallup's most recent data show that the coronavirus situation affected 80% of people's lives globally at least "somewhat," with 45% saying it affected their lives "a lot." A great deal of the impact of COVID-19 was economic: Whereas 32% of people who were working at the time of the pandemic say they lost their job or business as a result of the pandemic, 50% claim to have received less money than usual from their employer or business because of COVID.

In this respect, Latin America and the Caribbean are no exception to the global trend. According to Gallup's State of the Global Workplace: 2021 Report, 45% of adults in the region say their lives have been affected a lot by the pandemic, and the percentage of workers who have lost a job or business (31%) mirrors the global average. Over half of those working at the time of the pandemic in Latin America and the Caribbean have lost pay (57%) and worked fewer hours (57%), while 58% say they temporarily stopped working.

Not only did COVID-19 put a strain on the region's formal economy, but it also put the informal sector -- which accounts for about half of all jobs in Latin America and the Caribbean -- against the ropes. According to the Center for Strategic and International Studies, estimations for real GDP contraction centered around 8.1%, higher than any other region in the world. But unlike other economic regions, the limited growth projections for 2020, coupled with the economic and social hardships brought about by the pandemic, created a perfect storm in the area.

Custom graphic. In Latin America and the Caribbean, 57% of employees say they have received less money than usual from their employer because of the pandemic, and 57% say they have lost a job or their business.

As the economy shrank, employee engagement declined by seven percentage points -- all the way back to 2015 levels -- to 24%. From Mexico to Argentina, almost every country in the region -- with some exceptions in Central America and the Caribbean -- saw the world's worst setbacks in employee engagement.

Custom graphic. 24% of employees in Latin America and the Caribbean are engaged. This latest reading shows that engagement has declined to 2015 levels.

One possible explanation may be the sudden shift to a work-from-home arrangement. Many leaders were not equipped to manage their teams remotely; failed to provide the necessary materials, support and expectations; and lacked the skills to effectively deal with the complexity of juggling their personal work-life balance, as well as that of their employees. In other cases, the infrastructure to effectively implement remote working was not there, such as proper internet connection, platforms and other IT requirements. Alternatively, it may also be a reflection of overall misery. Gallup found that in Latin America and the Caribbean, 61% of employees are categorized as struggling or suffering in their daily lives.

It may be no surprise, therefore, that workers in Latin America and the Caribbean have the highest rates of worry in the world -- 55%, compared with the global average of 41%.

What may come as a surprise, however, is that younger workers are far more optimistic than older workers.

This is surprising because younger workers in Latin America and the Caribbean report a heavier burden of economic concerns. Though younger adults were about equally affected by the coronavirus situation (46% of those aged 40 and older said their lives were affected a lot, as did 45% of those younger than 40) and were equally likely to say they'd lost pay (57% of both age groups did), employees younger than 40:

So, although Gallup finds that employees' overall life evaluation in the region is down seven percentage points from 2019, it's somewhat promising that younger workers are thriving at a much higher rate than older ones (43%, vs. 34% of those aged 40 and older) and suffering at a much lower rate (3%, compared with 10% of those aged 40 and older).

Though the rate of suffering among older generations is alarming, younger workers' experience should be read as auspicious. Never in its recorded history has Latin America and the Caribbean had such a large proportion of young people -- the region's median age is 31, which means the millennial and Gen Z age cohorts have enormous influence over their companies just from sheer size.

Although Gallup finds that employees' overall life evaluation in the region is down seven percentage points from 2019, it's somewhat promising that younger workers are thriving at a much higher rate than older ones.

The fact that younger Latin Americans -- who are beginning or in the thick of their professional lives -- have so much hope has the potential to change the shape of the region's future. And there's much leaders can do to help.

In hard-hit Latin America and the Caribbean, leaders may not be able to bolster workers' hope with higher pay or advancement, but our research shows that leaders who clearly communicate their plans and strategies strongly affect employees' perceptions about the future. But nothing improves workers' outlook like being engaged.

The most important factor behind employee engagement is the manager. But most managers aren't prepared to see to the 12 elements necessary for engagement -- the managerial approach in Latin America and the Caribbean tends toward paternalistic or command-and-control leadership -- nor to develop workers properly. Shifting from a figure of "boss" to a role of "coach" is a culture change that often requires a mandate from leadership. Regardless of the circumstances, this shift is possible.

The fact that younger Latin Americans -- who are beginning or in the thick of their professional lives -- have so much hope has the potential to change the shape of the region's future.

Where to start: Gallup's first recommendation is to change the paradigm of how businesses -- and, consequently, people -- strive for excellence, starting with using and developing talent. A new focus on strengths fundamentally changes how people interact with each other and provides the right conditions for collaboration, even in a remote setting. Developing talent may be a culture change, but it pays off.

Given the regional wellbeing picture -- where 61% of employees are categorized as struggling or suffering in their daily lives -- helping each person discover what they are naturally good at and positioning them to apply those talents productively will bring a positive impact at the micro and macro levels.

Next step: Gallup's second recommendation is to increase not only the quantity but also the quality of conversations between managers and employees. The topics will vary, but managers should always set expectations, clear obstacles, create accountability and demonstrate caring.

A manager's regular, meaningful feedback has a measurable effect on engagement and performance. But in this economic downturn, in which managers face increased pressure to hit their objectives, command-and-control management will further damage engagement and undermine people's sense of hope for the future.

A manager's regular, meaningful feedback has a measurable effect on engagement and performance.

Even before the pandemic, employees (particularly the younger generations) demanded development from their immediate supervisors -- not employee manuals -- and a clear set of expectations. These conversations must help employees feel inspired and motivated to do better work.

This is the motivation that the people of Latin America and the Caribbean need to set them up for success both inside and outside the workplace and to fuel their sense of hope.

And being hopeful is a very good attitude to have. Hope builds resiliency and is the wellspring of innovation. Gallup finds that employees who strongly agree that their leader makes them feel enthusiastic about the future (Gallup's measure of hope in the workplace) are 69 times more likely to be engaged in their work compared with employees who don't feel hopeful. Hope builds strong and prosperous organizations.

This time of economic hardship is, ironically, the perfect time to invest in employees' hope. Economists predict economic growth in Latin America in the near future and greater international competitiveness, especially in professional services, IT and risk management. Though the "blue economy" -- the sustainable use of ocean resources -- is a smart bet for economic diversification and growth in the Caribbean, many nations in the region are already broadening their economic base beyond tourism.

Inevitably, this will exert pressure on the demand for better managers. Young people have been leading that charge since before the pandemic -- and they're starting to move into leadership roles. Their numbers and the region's economic decline make younger workers' call for better, more modern management increasingly justified.

And as Gallup studies show that engaged workers are 18% more productive and 23% more profitable than less engaged workers, anything a business can do to support young workers' engagement affects their bottom line. But giving them a reason to hope will shape the future of Latin America and the Caribbean.

Hugo Ledesma is Regional Manager for Gallup in Latin America.

Jennifer Robison contributed to this article.

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Young Workers Optimistic in Latin America and the Caribbean - Gallup