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Top: A person is infected by the Alpha variant of SARS-CoV-2. Within a few weeks, antibodies are made that protect the person against the Alpha variant as well as Beta and Gamma variants which are very similar to the Alpha variant. Bottom: A person who (1) has recovered from COVID-19 and who (2) has received mRNA vaccine with components of the Alpha variant develops a strong immune response within a few weeks. The antibodies that are made in the body protect against the Alpha variant, the closely related Beta and Gamma variants as well as the more distantly related Delta and Omicron variants. People who have recovered from COVID-19 and then received the mRNA vaccine are also protected against new variants of SARS-CoV-2. Ill: Gerda Kaynova

Credit: Gerd Kaynova

Vaccines help boost the production of antibodies, providing effective protection against serious illness and death, says Mona Hyster Fenstad.

Fenstad is a senior consultant at the blood bank at St. Olavs Hospital in Trondheim.

We are already well into autumn, and the COVID-19 virus is rife all over Norway. The Norwegian Institute of Public Health recommends people in risk groups to get vaccinated.

They point out that elderly people in particular will be vulnerable to serious illness if they are infected with COVID-19. However, since the vast majority of us have already had COVID-19 at least once, do we really need to think about getting vaccinated?

Yes, say the scientists.

The saying what doesnt kill you makes you stronger is not true in this context. The inflammation that occurs in the body during infections such as influenza, COVID-19 and pneumonia can be harmful. Especially for people with heart or lung disease, or where other risk factors are involved, says Fenstad.

Fenstand and her international colleagues have recently published a study that looked at the effect of vaccination on people who became ill with COVID-19 before vaccines were available. This work has been closely linked to the search for antibodies that can be used as medicine against COVID-19.

At the beginning of 2020, the World Health Organization (WHO) asked scientists and therapists around the world to look for treatments for COVID-19. Among the treatments proposed was convalescent plasma therapy, which uses plasma from blood donors who have recovered from the illness. Along with colleagues from NTNU (the Norwegian University of Science and Technology), we chose to take a closer look at how the antibodies in this plasma were able to neutralize new virus variants that emerged, says Fenstad.

While big pharmaceutical companies were working hard to develop vaccines and medicines, scientists had already begun to look at the use of blood plasma from COVID-19 patients as a possible treatment.

Many of these patients had large amounts of antibodies in their blood. Plasma containing these antibodies was therefore given to seriously ill patients to help them fight the virus. It turned out that convalescent plasma therapy was primarily effective in patients who had immunodeficiencies, says Fenstad.

We were looking for so-called super-neutralizers, people who develop specific antibodies that effectively neutralize different variants of SARS-CoV-2, says Denis Kainov, a professor in NTNUs Department of Clinical and Molecular Medicine who was part of the research team.

These antibodies were eventually cultivated and cloned, and then turned into medicines used to fight COVID-19.

In Norway, the first COVID-19 outbreak occurred in February 2020. The first Alpha variant was quickly followed by new, mutated variants named Beta and Delta. Omicron, which is currently the prevailing variant, was first reported in late 2021.

By April 2020, blood banks across Norway had begun collecting blood plasma from patients who had recovered from COVID-19. At St. Olavs Hospital, 72 patients were selected for a more detailed study of the antibodies in their blood plasma.

It turned out that half of these patients had serum containing antibodies that effectively neutralized the Beta variant, says Kainov.

Kainov has been searching for active substances to use in the treatment of COVID-19 and other viral diseases.

He is now looking for antibodies that could provide wider protection, including against new COVID-19 variants that might emerge.

They noticed that four patients had antibodies that effectively neutralized the COVID-19 variant that was dominant in Trondheim at the time.

We followed up by taking new samples from these patients and found that their antibodies also neutralized other COVID-19 variants. In fact, they were also effective on new virus variants, says Kainov.

The conclusion is thus that it is a good idea to get vaccinated even if you have already had COVID-19 and even if the virus has mutated since the vaccine was made.

Out of the four patients, the scientists picked the one whose antibodies had been least effective against the Omicron variant. This patient had received their first vaccine dose four months after recovering from COVID-19. The efficacy of the vaccine was striking.

The vaccine boosted the production of immune cells and antibodies against all tested variants of the virus, including Omicron, says Kainov.

Kainovs colleagues in Estonia could then proceed with blood plasma from the patient, cloning and cultivating antibodies that neutralised COVID-19 viruses on a wide scale.

The results have also provided the scientists with useful knowledge about the effect of the vaccine on convalescents.

When it comes to vaccines, it is always a race. The virus is always one step ahead, and the vaccines and medicines will never be completely up to date, Fenstad said

Our study is an in-depth study of just one patient, and it constitutes only a tiny piece of research in this field. However, large studies in other countries confirm our findings. Vaccines boost the production of antibodies that are also effective against new variants of the virus, she said.

The finding demonstrate that it is a good idea to get vaccinated even if you have already had COVID-19 and even if the virus has mutated since the vaccine was made. It may not prevent you from being reinfected, but it will provide protection against serious illness and death.

When you get sick with COVID-19, you develop antibodies, but the effects of these diminish and are gone after six to nine months. This is why people can get infected again and again by new variants of SARS-CoV-2. The virus mutates to avoid the immune response we have developed through previous infections or vaccines, says Kainov.

That is why vaccination is important now that we are heading towards winter.

The studies we have conducted here on COVID-19 patients are extremely important, because there will be new outbreaks of the virus. Almost seven million people have died from COVID-19. We must avoid getting into the same situation again, says Kainov.

Reference: Mona Hyster Fenstad et al.:Boosted production of antibodies that neutralized different SARS-CoV-2 variants in a COVID-19 convalescent following messenger RNA vaccination a case study.International Journal of Infectious Diseases. Volum 137, December 2023 https://doi.org/10.1016/j.ijid.2023.10.011

International Journal of Infectious Diseases

Experimental study

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Boosted production of antibodies that neutralized different SARS-CoV-2 variants in a COVID-19 convalescent following messenger RNA vaccination - a case study

1-Nov-2023

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Why you should be vaccinated even if you have had COVID-19 - EurekAlert

Lyudmila A. Bazhenova, MD

With the integration of neoadjuvant, adjuvant and perioperative chemoimmunotherapy approaches into the nonsmall cell lung cancer (NSCLC) treatment paradigm, it is increasingly vital for clinicians to accurately identify patients with unresectable disease displaying key oncogenic drivers, such as EGFR and ALK mutations, before deciding on a therapeutic approach, according to Lyudmila A. Bazhenova, MD.

Its important to highlight that [genetic] testing is necessary for patients [with unresectable lung cancer], and remember that the phase 3 PACIFIC trial [(NCT02125461) regimen] is the standard of care [SOC] right now in this space, Bazhenova said regarding a recent OncLive Institutional Perspectives in Cancer webinar on lung cancer, which she chaired.

In an interview with OncLive, Bazhenova, who is a medical oncologist and professor of medicine at the University of California San Diego (UCSD) Moores Cancer Center in California, expanded on key topics in lung cancer that were discussed by her colleagues at UCSD Health. This included key considerations when navigating the use of perioperative immunotherapy for patients with or without oncogenically-driven lung cancers, the importance of collaboration between oncologists and other specialists when deciding on a treatment plan, and the need for increased and earlier implementation of biomarker testing in all patients with lung cancer.

Bazhenova: 2023 has been a very busy year in lung cancer and several important publications have been presented. Many [of the emerging agents presented] do not have FDA approvals yet, so its hard to apply these data to current practice. However, it is important to be aware of what agents are coming down the lineonce they are FDA approved, we can utilize that treatment modality.

Its important to know which cancers are resectable and which are unresectable. It is very important to work with your multidisciplinary team to make that decision. [Clinicians should not] forget that durvalumab [Imfinzi] is the SOC for patients with unresectable disease. I would not consider durvalumab for patients with oncogenic drivers, especially EGFR and ALK mutations.

The challenge with this approach is the fact that there is no consensus because we have options for our patients. You can give them adjuvant, neoadjuvant or perioperative immunotherapy. We do not have any randomized trials telling us what the right thing to do is, so whatever works [at a given clinicians] institution is appropriate. At UCSD, we are believers in neoadjuvant and perioperative immunotherapy, so thats what we offer our patients. Again, like with unresectable disease, multidisciplinary care is vital. Clinicians should make sure to discuss [the patients situation] with a radiation oncologist as well as surgeon and determine a treatment plan in the beginning once all the specialists have evaluated the patient.

For patients with EGFR mutations and ALK rearrangements, we know that immunotherapy generally does not work very well. For those patients, I would not consider neoadjuvant chemoimmunotherapy or adjuvant immunotherapy. Those patients will generally go to surgery. One could consider neoadjuvant chemotherapy if theyre dealing with a stage III cancer where this approach would be appropriate. After the completion of neoadjuvant treatment, it is important to make sure that [clinicians] offer those patients adjuvant osimertinib [Tagrisso], which is currently FDA approved.

Although adjuvant alectinib [Alecensa] has not yet been FDA approved, the phase 3 ALINA trial [NCT03456076] is very important. I hope that adjuvant alectinib will eventually become an FDA-approved option. It is also important to make sure that clinicians test patients for those abnormalities; ideally, one would want to test patients before selecting a neoadjuvant approach because your decision depends on the presence or absence of given mutations.

At UCSD, we have the [phase 2 TRUST-II study (NCT04919811)] with taletrectinib for ROS1rearranged lung cancer. The preliminary efficacy [data] showed a high response rate [with the agent] and responses appear to be durable. The interesting fact about taletrectinib is that it does not inhibit trkB. So the adverse effect profile is different, and in my opinion better, than the safety profile of entrectinib (Rozlytrek) and repotrectinib (Augtyro).

My main message is biomarkers, biomarkers, biomarkers! [Clinicians should] make sure that patients are being tested for molecular abnormalities and should understand the difference between DNA testing and RNA testing. [We should understand] the additional benefit that RNA testing brings, especially for patients with gene fusions, which are common in lung cancer.

[Lastly], we need to know the issues surrounding cell-free DNA. Its a great tool for patients, but approximately 30% of cell-free DNA tests will produce a false negative. If an oncologist performs a liquid biopsy and didnt discover the mutation, it is not appropriate to stop there. We want to make sure that tissue next-generation sequencing is being performed so we dont miss patients who display oncogenic drivers.

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Multidisciplinary Collaboration and Molecular Testing Are Integral to ... - OncLive

A map of Stony Brook University marked with the locations of crimes that occurred on campus from Saturday, Nov 18. to Friday, Nov 24. ILLUSTRATED BY BRITTNEY DIETZ/THE STATESMAN

All reports are taken directly from the University Police Department and cannot be independently verified by The Statesman.

On Saturday, Nov. 18, there was a report of missing kitchen scissors last seen on Oct. 30 in Chapin Hall. The case was closed by investigation.

On Monday, Nov. 20, a patient struck another patient in Stony Brook University Hospital. The case was closed after the victim refused to cooperate.

On Monday, Nov. 20, there was a report of a phone scam in the Centers for Molecular Medicine. The case was closed and referred to another agency.

On Tuesday, Nov. 21, there was a report of a missing pair of jeans and dorm key in the Walter J. Hawrys Campus Recreation Center. The case is still open.

On Tuesday, Nov. 21, a dispute was reported between a motorist and pedestrian in a motor vehicle accident at Circle Road and Engineering Drive. An MV-104 was completed, and no injuries were reported. The case was closed after the victim refused to cooperate, and there was a student referral.

On Wednesday, Nov. 22, a social media scam was reported in Greeley Hall. The case is still open, and the victim was transported to the Comprehensive Psychiatric Emergency Program.

On Wednesday, Nov. 22, there was a report of a vehicle driving through a gate arm, damaging the Stony Brook University Hospital parking garage. The case is still open.

On Thursday, Nov. 23, a patient slapped a staff member on the arm in Stony Brook University Hospital. The case was closed after the victim refused to cooperate.

On Friday, Nov. 24, a patient struck three employees in Stony Brook University Hospital. The case was closed after the victims refused to cooperate.

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SBU Crime Watch: Nov. 18 Nov. 24 The Statesman - Stony Brook Statesman

CHICAGO -- GE HealthCare (GEHC) brought new CT and MRI scanners and a range of AI software applications to McCormick Place for RSNA 2023.

CT

In CT, GEHCshined the spotlight on its Revolution Ascend scanner, which was first introduced at ECR in March. With onsite detector upgrades, Ascend can be upgraded from a 20-mm coverage system for routine scanning to a 40-mm coverage system that delivers better low-contrast detectability, according to the vendor.

The scanner also comes with True Enhance DL, an AI-based application that generates deep learning-based monochromatic-like images from a single-energy x-ray acquisition. This capability is designed to increase contrast resolution and is especially useful for challenging oncology exams, GEHC said.

GE HealthCare's new Revolution Ascend CT scanner.

GEHC also pointed to upgrades for its Revolution Apex scanner, including ECG-less Cardiac for acquiring cardiac images without the need for an ECG signal or trace. Whats more, GEHC has launched Tube Watch, which uses digital twin technology to remotely monitor and predict tube failures or potential issues in Apexs x-ray generation chain.

In addition, the vendor said that its TrueFidelity DL software is available on both Apex and Ascend. Based on a deep neural network, TrueFidelity DL is designed to generate high-definition, low-noise CT images. TrueFidelity DL features for the lung and extremity are available exclusively, however, on the Apex.

Both Apex and Ascend come with GEHCs Effortless Workflow CT workflow automation software and Smart Subscription services for easy software updates.

In photon-counting CT technology developments, GEHC said that researchers at Stanford Medicine have begun scanning human subjects using its photon-counting CT prototype. The research will produce technical feedback to assist GEHC in assessing the systems reconstruction methods, image presentation workflow, and clinical benefits for specific pathologies and disease types.

MRI

GEHC unveiled Signa Champion, a 1.5-tesla, wide-bore scanner that features AI-supported workflow features such as the firms AIR Recon DL image reconstruction software and Sonic DL software for accelerating image acquisition. The company also highlighted the patient comfort benefits of Champions wide bore and short scan times. Notably, Champion has the smallest footprint and is the most power-efficient among GEHCs wide-bore systems.

GE HealthCare's Signa Champion 1.5-tesla scanner.

Via a partnership with Brazilian automation technology provider Ionic Health, GEHC has also added remote scanning capability as part of anew version of its Digital Expert Access software. Ionic Healths nCommand Lite technology, which is currently pending U.S. Food and Drug Administration (FDA) 510(k) clearance, is designed to support vendor-agnostic remote scanning capabilities

As a result of the new technology, remote clinical users can currently initiate a scan on GEHCs MR devices from inside or outside the radiology suite or at any clinical facility, according to the firm.

Informatics/AI

GEHC featured App Orchestrator, an AI application orchestration platform for facilitating integration of multiple third-party apps into existing workflow. App Orchestrator is compatible with most major PACS, according to the company.

The company also unveiled Theranostics Pathway Manager Tile, an application designed to aid in coordinating the theranostics care pathway, as well as identifying and tracking potential theranostics candidates. Its available on GEHCs Command Center Software Platform.

GEHC also introduced version 2.0 of its Imaging 360 for Operations platform. The latest release supports operational analytics, remote scan assistance, protocol management, dose management, and scheduling.

Interventional

In image-guided surgery activities, GEHC showcased two new AI applications previously presented at ECR 2023. Embo Assist AI automatically segments vascular structures to facilitate embolization workflow planning, while Liver Assist Virtual Parenchyma 3D provides AI-based virtual parenchymography.

Interact Touch is a new feature for GEHCs Allia image-guided surgery platform that enables clinicians to control up to three different third-party devices including Avvigo+ multimodality guidance system from Boston Scientific -- through one single touch panel.

GEHC has also added an interventional augmented reality (AR) application via a partnership with MediView for OmnifyXR Interventional Suite, which allows users to simultaneously display up to four customized holographic projections of liver imaging. 3D volume images can also be displayed in AR for improved anatomy visualization.

In addition, the company said it has continued its collaboration with Centerline Biomedical for its Intra-Operative Positioning System (IOPS) and has also partnered with Proximie to incorporate real-time collaboration and access to data insights.

Molecular imaging

In molecular imaging, GEHC emphasized the launch of its Precision DL for PET/CT imaGEHC processing software, which is now available on its Omni Legend PET/CT scanner.

GEHC has also brought its Effortless Workflow technology to its molecular imaging portfolio. Available on GEHCs Omni PET/CT and StarGuide SPECT/CT scanners, the AI-based Effortless Workflow service automates patient positioning and suggests protocols to enable time savings for molecular imaging studies, according to the firm.

In theranostics developments, GEHC has formed a collaboration with cancer treatment center BAMF Health to provide its PETtrace Solid Target gallium production platform; Omni Legend; Signa PET/MR AIR scanner; StarGuide SPECT/CT scanner; and software such as Precision DL, AIR Recon DL, and Q.Thera AI.

GEHC also displayed its Signa PET/MR AIR system, which was introduced at the annual Society of Nuclear Medicine and Molecular Imaging (SNMMI) conference in June.

Ultrasound

In ultrasound developments, GEHC discussed the addition of Caption Guidance AI software to its Venue family of point-of-care ultrasound systems. With Caption Guidance, even healthcare providers without specialized training or experience can perform cardiac ultrasound exams and acquire diagnostic-quality cardiac images, according to the vendor.

GEHC acquired caption guidance developer Caption Health earlier this year and said it plans to integrate the software into other ultrasound systems in its portfolio, including handheld units.

GE also introduced bkActive, an ultrasound system that provides real-time surgical visualization and improved control over procedures supporting surgeons and clinicians in urology, neurosurgery, hepato-pancreato-biliary surgeries, colorectal and pelvic floor surgeries, and laparoscopic surgeries. The system was developed by GEHC company BK Medical.

Other ultrasound scanners on display included GEHCs Logiq E10, Fortis, Invenia ABUS 2.0, Vscan AIR SL, and Voluson Expert systems. The company also showed its Vivid series of cardiovascular ultrasound scanners.

Additionally, GE pointed to its Verisound suite of ultrasound software applications, including Verisound Reporting, Verisound Fleet Management, Verisound Collaboration, and Vscan Digital Tools.

Meanwhile, a new version of GEs ViewPoint software, 6.14, enables data to be distributed directly from the ultrasound scanner to populate reports.

Womens imaging

GEHC introduced MyBreastAI Suite, an AI platform that currently integrates three AI applications from partner iCAD, including the following: ProFound AI for DBT, PowerLook Density Assessment, and SecondLook for 2D Mammography.

To help practices start a new contrast-enhanced mammography program, GEHC has launched Pristina Bright, which combines SenoBright HD, Pristina Serena, and Serena Bright with an education program that provides dedicated onsite support, CME-accredited self-assessment, and access to a user club to collaborate with experts around the globe, the firm said.

X-ray

In radiologys oldest modality, GEHC once again emphasized Definium 656 HD, an overhead tube suspension system with the highest weight capacity in the companys fixed x-ray portfolio. At RSNA 2023, the firm announced upgrades to Definium 656 HD aimed at improving image quality and consistency, reducing acquisition errors, and streamlining workflows.

The company also debuted Precision CRF, a fluoroscopy system featuring an overhead tube suspension, digital detectors, intelligence exposure control, and image processing software. It supports both radiography and fluoroscopic imaging.

Another introduction, Definium Pace, is a fixed x-ray system available at a value price point, according to GEHC. It comes with a range of automation and enhanced workflow features, the company said.

In other news, GE announced that users of its legacy AMX 200, 220, or 240 systems can now be upgraded to an AMX fixed-column configuration, as well as a modern user interface and software functionalities.

Pharmaceutical diagnostics

The company pointed to a recent study that validated the use of AI models for predicting patient response to therapy. In research presented at the Society for Immunotherapy of Cancer in San Diego in November, the AI models yielded 70%-80% accuracy for predicting treatment response.

Cardiology

In cardiology, GEHC introduced CardioVision for AFib, a software tool for management of patients with atrial fibrillation. The software automatically compiles longitudinal data for disease progression from multiple data sources and generates therapy recommendations based on guidelines, according to the vendor.

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New CT, MR scanners and AI top GE HealthCare highlights at ... - AuntMinnie

Daniel Muoz, MD, MPA

by Matt Batcheldor

Daniel Muoz, MD, MPA, associate professor of Medicine, and Francis Miller, MD, professor of Medicine, have been named interim directors of the Division of Cardiovascular Medicine at Vanderbilt University Medical Center. Their appointments are effective Dec. 1.

Muoz, also the executive director of Vanderbilt Heart and Vascular Institute (VHVI), will be responsible for clinical affairs. Miller, a physician-scientist investigator in the Division of Cardiovascular Medicine and chief of Cardiology at the VA Tennessee Valley Healthcare System, will be responsible for academic affairs.

Muoz and Miller will assume the directorship duties of Jane Freedman, MD, professor of Medicine, who has been named to serve as interim chair of the Department of Medicine and physician-in-chief for VUMC, also effective Dec. 1.

Muoz graduated from Princeton University with a bachelors degree in Economics. He went on to receive his medical degree from Johns Hopkins University and his masters degree in Public Administration from Harvard Universitys John F. Kennedy School of Government in 2005. He continued to serve in the Johns Hopkins Hospital and Health System, where he completed his residency in 2008, chief residency in 2010 and cardiology fellowship in 2011. After completing a research fellowship at Duke University, he came to Vanderbilt for further subspecialty training, after which he joined the faculty in 2013.

In his decade on the VUMC faculty, Muoz has served in various leadership roles, including medical director of the Cardiovascular Intensive Care Unit (CVICU), medical director for Quality at VHVI and as interim division co-director for Clinical Affairs from 2020-2021.

Muoz currently serves as an attending physician in the CVICU, where he is known as an effective teacher and a skilled clinician. His outpatient practice is focused on the realms of preventive and general cardiology.

His research has focused on developing innovative strategies for lowering cardiovascular risk and improving patient outcomes in high-risk primary prevention settings. This includes widely recognized work with the polypill in underserved areas of the rural South. This research, published in The New England Journal of Medicine, demonstrated that a polypill approach to the management of hypertension and cholesterol could effectively improve these measurements of cardiovascular health in an underserved population.

Miller obtained his bachelors degree in Biology and a medical degree from the University of Iowa. He completed an internal medicine residency at the University of Texas Southwestern Medical Center in Dallas before returning to the University of Iowa for a cardiology fellowship. He remained at the University of Iowa as a faculty member, rising to professor before relocating to Duke University and the Durham VA Medical Center in 2016 as a professor of Medicine. In 2020, Miller became the chief of Cardiology at the Salisbury VA Medical Center and a professor at Wake Forest University. He joined VUMC and VA Tennessee Valley Healthcare System in 2022.

Miller has served on several national committees, including as a member of the board of directors of the Federation of American Societies for Experimental Biology, committee chair for the Society for Redox Biology and Medicine, chair of an oversight advisory committee for the American Heart Association, and president of the American Federation for Medical Research.

He has contributed to several editorial boards and study sections. and is a deputy editor of Circulation Research. His research has been funded by the National Institute of Health, National Science Foundation, Department of Defense, Department of Veterans Affairs, and American Heart Association.

The central goal of Millers research is to understand the molecular and cellular roles of reactive oxygen species in cardiovascular disease. His work on NADPH oxidases in the blood vessels has received international recognition.

As a practicing cardiologist, he strives to unite findings in the research lab with human disease. His current research has resulted in several patents using synthetic RNA ligands as novel therapies. Miller is an avid supporter of the physician-scientist and has received awards for house staff teaching and mentorship of graduate students.

I am delighted with Drs. Muoz and Millers appointments to serve as joint interim directors of the Division of Cardiovascular Medicine, Freedman said. I am confident that their expertise and experience in academic, clinical and educational affairs will support the division during an exciting time of ongoing growth and expansion.

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Daniel Muoz and Francis Miller named interim directors of the ... - VUMC Reporter

At left is Hyeong-Reh Kim, Ph.D., with her lab members in the School of Medicine Department of Pathology.

The National Cancer Institute has awarded the Wayne State University School of Medicine $3,032,353 over five years to fund a study that holds the potential to introduce a new class of drugs tailored for patients with therapy-resistant cancers.

Professor of Pathology Hyeong-Reh Kim, Ph.D., is the principal investigator on the project, A novel AR degrader in castrate-resistant prostate cancer.

The goal is to develop a new class of drugs that effectively degrade both wild-type androgen receptor (AR) proteins and AR variants in prostate cancer. The Kim laboratory has been working to uncover the molecular and cellular mechanisms underlying human cancer progression and metastasis, to identify therapeutic targets and to develop novel therapeutics for patients with therapy-resistant cancers, including advanced head and neck cancers and castrate-resistant metastatic prostate cancer.

The receptors for androgens, the group of male sex hormones, play a critical role in all stages of prostate cancer. While many prostate cancer patients initially respond to hormone therapies, significant numbers of patients develop castrate-resistant prostate cancer.

Clinical studies have shown that castrate-resistant prostate cancer often involves androgen receptor variants that lack the ligand binding domain, making this hormone receptor constitutively active and resistant to hormone therapy.

The innovations in our study include the development of a new therapeutic platform usingautophagy-targetingchimera (AUTOTAC)for oncoprotein degradation, she said.This novel therapeutic platform is composed of a target-binding small molecule linked to an autophagy ligand. The AUTOTAC brings the targeted oncoprotein to the protein degradation machinery, involving autophagosome and lysosome, leading to the efficient removal of oncoproteins.

Using a natural ligand or a synthetic small molecule that binds the protein of interest, the AUTOTAC can be utilized for the removal of unwanted proteins. Our study will help establish the foundation for arevolutionary drug development platform in a wide array of human diseases, Dr. Kim added.

In collaboration with Radiation Oncology Professor Harold Kim, M.D., and Associate Professor Joseph Rakowski, Ph.D., and the new Barber Integrative Metabolic Research Team, the Kim laboratory is engaged in the development of radiosensitizers utilizing the AUTOTACplatform or inducers of lipolysis.

This is a truly collaborative project involving many co-investigators, including Dr. Yong Tae Kwon at Seoul National University; and Drs. Elisabeth Heath (Oncology), Seongho Kim (Oncology), Dongping Shi (Pathology), Michael Cher (Urology), Lisa Polin (Oncology) and Sijana Dzinic (Oncology) at the Wayne State University School of Medicine. In my laboratory, Drs. Abdo Najy and Tri Pham, Alaleh Zamiri, M.D. a Ph.D. student and Jenna Poole will work on this project. We hope to recruit more student and post-doctoral fellows to work on this project, Dr. Kim said.

The number for this National Institute of Health award is R01CA282040.

Originally posted here:

School of Medicine's Kim lab secures more than $3 million from ... - Wayne State University

Request for Information on Themes for the NIAMS Strategic Plan for Fiscal Years 2025-2029

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) supports research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. NIAMS is updating its Strategic Plan to help guide the research, training, and information dissemination programs it supports between fiscal years 2025 through 2029. The new Plan will focus on cross-cutting thematic research opportunities that position the Institute to make a difference in the lives of all Americans.Because public input is a crucial step in this effort, the Institute issued a Request for Information (NOT-AR-22-023) and hosted a meeting attended by approximately 160 researchers, patient representatives, and staff from other Federal entities to gain insight into topics that could be included in the new Strategic Plan.

Through this Request for Information, NIAMS invites feedback from researchers in academia and industry, health care professionals, patient advocates and health advocacy organizations, scientific or professional organizations, Federal agencies, and other interested members of the public on the Institutes distillation of the input received to date. Professional societies and patient organizations are strongly encouraged to submit a single response that reflects the views of their entire membership.

Please provide your perspective on the following potential cross-cutting themes, examples, and bold aspirations. NIAMS is particularly interested in suggestions for additional or alternative:

Examples:

Bold Aspirations:

Examples:

Bold Aspiration:

Note: Efforts to identify and reduce health disparities and provide all Americans with equitable access to clinical and epidemiologic studies and healthcare should be considered for NIAMS-funded research projects whenever possible.

Examples:

Bold Aspirations:

Examples:

Bold Aspiration:

Note: Consistent with the note under Health disparities and health equity, studies of lifestyle factors and environmental exposures should include efforts to identify and reduce health disparities and provide all Americans with equitable access to clinical and epidemiologic studies and healthcare whenever possible.

Examples:

Bold Aspiration:

Note: Consistent with the note under Health disparities and health equity, clinical and epidemiologic research should include efforts to identify and reduce health disparities and provide all Americans with equitable access to clinical and epidemiologic studies and healthcare whenever possible.

Examples:

Bold Aspiration:

Examples:

Bold Aspiration:

Note: Training and workforce efforts are essential for the pursuit of all cross-cutting thematic research areas in the new NIAMS Strategic Plan.

Examples:

Bold Aspiration:

Examples:

Bold Aspirations:

Responses to this RFI must be submitted electronically at https://rfi.grants.nih.gov/?s=654a7bc81e7ccb6f7d03d792.

Responses must be received by Monday, January 1, 2024.

Responses to this RFI are voluntary. Do not include any proprietary, classified, confidential, trade secret, or sensitive information in your response. The responses will be reviewed by NIAMS staff, leadership, and Advisory Council members. Individual feedback will not be provided to any respondent. NIAMS will use the information submitted in response to this RFI at its discretion and will not provide comments to any respondents submission. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted.The Government reserves the right to use any submitted information on public NIH websites, in reports, in summaries of the state of the science, in any possible resultant solicitation(s), grant(s), or cooperative agreement(s), or in the development of future funding opportunity announcements.

This RFI is for information and planning purposes only and shall not be construed as a solicitation, grant, or cooperative agreement, or as an obligation on the part of the Federal Government, the NIH, or individual NIH Institutes and Centers to provide support for any ideas identified in response to it. The Government will not pay for the preparation of any information submitted or for the Governments use of such information. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Governments use of such information.

We look forward to your input and hope that you will share this RFI document with your colleagues.

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NOT-AR-23-022: Request for Information on Themes for the NIAMS ... - National Institutes of Health (.gov)

image:

When human biliary tract cancer cells are transfected with miR-451a, cell proliferation within the cell aggregates is inhibited. Researchers from Okayama University Hospital, Japan, show this occurs due to the suppression of PI3K/AKT pathway, partially through the downregulation of MIF.

Credit: Dr. Koichiro Tsutsumi from Okayama University Hospital, Japan

Biliary tract cancers (BTCs) including cholangiocarcinoma (CCA) and gallbladder cancer (GBC) are becoming more prevalent globally. An effective chemotherapeutic agent for the treatment of BTCs is gemcitabine. Other novel molecular targeted drugs have also been developed; however, they are only effective at treating a few cases of BTCs. In addition, very few drugs are effective against GEM-resistant BTCs. While surgery is the best option for the treatment of BTCs, many patients are diagnosed late, due to a lack of symptoms. Another challenge for physicians treating BTCs is identifying an appropriate treatment approach due to the complexity of the hepatobiliary-pancreatic system. Therefore, developing novel treatment strategies for BTCs, especially for GEM-resistant BTCs, is the need of the hour.

Nucleic acid-based therapies built around microRNAs (miRNAs) are the next frontier of cancer treatment. miRNAs play a role in gene expression, and their dysregulation is believed to contribute to cancer pathogenesis. Now, researchers from Japan are exploring the prospects of microRNA-451a (miR-451a), a miRNA identified in gallbladder tissue, as a viable targeted nucleic acid BTC therapy. The team, led by Assistant Professor Koichiro Tsutsumi, along with Dr. Taisuke Obata and Dr. Motoyuki Otsuka, all from the Department of Gastroenterology Okayama University Hospital, Japan, recently uncovered the mechanism of miR-451as antineoplastic effects. Their findings were published in Molecular Therapy: Nucleic Acids on 28 October 2023.

Apart from gemcitabine, very few effective drugs are available for the treatment of BTCs. Therefore, there is an urgent need for new therapies. Additionally, we dont know a lot about the miRNA targets that can be used to improve the prognosis of BTCs, especially in the context of resistance to GEM, explains Dr. Tsutsumi while discussing his motivation behind this research. The team had evidence from previous experiments that miR-451a was downregulated in patients with GBC, and they decided to build on other research that showed that the miRNA inhibited cell proliferation when introduced into human GBC cells. They transfected miR-451a into GBC, gemcitabine-resistant GBC (GR-GBC), and gemcitabine-resistant CCA (GR-CCA) cells to understand its effects on tumor progression. They also studied the gene expression profile in these three groups following transfection, to gauge how cell-signaling pathways were altered by miR-451a.

Under experimental conditions that mimicked those of the cancer environment, we found that miR-451a significantly diminished cell proliferation, induced cell death, and reduced the occurrence of chemoresistant cell types in GBC, GR-CCA, and GR-GBC cells, says Dr. Tsutsumi. He adds, One of the factors known to promote metastasis and chemoresistance was the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. This pathway was suppressed partially through the downregulation of macrophage migration inhibitory factor (MIF) after the transfection of miR-451a. These findings underpin miR-451as use as a replacement therapy for GEM-resistant BTCs. miR-451as effects at the molecular level were reflected in 2D or 3D cell culture experiments where GR-CCA and GR-GBC cells were rendered less viable following treatment.

Dr. Tsutsumi is looking to the future, and the group is planning future studies to evaluate the effective delivery of miR-451a and validate its clinical application. He concludes, Nucleic acid-based treatments are not mature enough to be considered first-line treatments for BTCs, so chemotherapy and immunotherapy still have their place. However, given miR-451as antineoplastic activity against GEM-resistant BTCs, I anticipate them to be mainstream alternatives with further developments.

About Okayama University, Japan As one of the leading universities in Japan, Okayama University aims to create and establish a new paradigm for the sustainable development of the world. Okayama University offers a wide range of academic fields, which become the basis of integrated graduate schools. This not only allows us to conduct the most advanced and up-to-date research, but also provides an enriching educational experience. Website: https://www.okayama-u.ac.jp/index_e.html

About Assistant Professor Koichiro Tsutsumi from Okayama University, Japan Dr. Koichiro Tsutsumi is an Assistant Professor in the Department of Gastroenterology at Okayama University Hospital. He earned his Doctor of Medicine from Tohoku University in 2001, and Doctor of Philosophy from Okayama University in 2013. His research explores themes across gastroenterology, tumor diagnostics and therapeutics. Dr. Tsutsumi has published over 120 peer-reviewed articles since 2003 and received the Japanese Biliary Society International Exchange Encouragement Award in 2016.

Molecular Therapy Nucleic Acids

Experimental study

Cells

MicroRNA-451a inhibits gemcitabine-refractory biliary tract cancer progression by suppressing the MIF-mediated PI3K/AKT pathway

28-Oct-2023

The authors declare no competing interests.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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A novel targeted molecular therapy for drug-resistant biliary tract ... - EurekAlert

Researchers at the University of California (UC) San Diego School of Medicine have made significant discoveries in understanding the complex relationship between bacterial vaginosis and adverse sexual and reproductive health outcomes.

Bacterial vaginosis, a common condition affecting nearly 29 percent of women between the ages of 14 and 49 in the United States, has long been associated with pregnancy loss, preterm birth, postsurgical infections, pelvic inflammatory disease, and sexually transmitted infections. Reporting in Science Translational Medicine, researchers are now shedding light on the mechanisms by which certain bacterial species disrupt the delicate balance of the vaginal microbiome, leading to these severe health complications.

Bacterial vaginosis is known to be linked to pregnancy loss, preterm birth, postsurgical infections, pelvic inflammatory disease, and sexually transmitted infections, emphasized Warren G. Lewis, an assistant professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at UC San Diego School of Medicine. The study not only highlights the severity of the conditions associated with bacterial vaginosis but also provides a deeper understanding of its underlying molecular mechanisms.

The researchers analyzed epithelial cells that line the vagina as crucial players in the interaction between bacteria and the human body. These cells are densely coated with sugar chains known as glycans, which play pivotal roles in cell biology and disease. The team discovered that in bacterial vaginosis, specific bacteria release enzymes called sialidases, which partially dismantle protective glycan molecules on the surface of epithelial cells. Remarkably, they were able to induce a bacterial-vaginosis-like state in normal epithelial cells by treating them directly with sialidase enzymes produced in the laboratory.

Amanda Lewis, a professor in the Department of Obstetrics, Gynecology & Reproductive Sciences, said, The fact that we were able to replicate some of the effects of bacterial vaginosis suggests that we may be on the right track to finding a common cellular origin for the various complications associated with this condition. According to the researchers, this breakthrough opens the door to potential diagnostic advancements, as studying the surface of vaginal epithelial cells at such a detailed biochemical level could aid in identifying subsets of individuals at the greatest risk for negative health outcomes, including recurrence.

While the study provides a blueprint of the glycans present on vaginal epithelial cells, Warren Lewis acknowledges that further research is needed to fully comprehend the functions of glycans in the vaginal epithelium and how bacterial vaginosis impacts these functions. As this research progresses, clinicians are urging individuals with vaginas to be vigilant about the symptoms of bacterial vaginosis and to refrain from practices such as douching or using scented products, which may exacerbate microbial imbalances.

In unraveling the complexities of the vaginal microbiome, this research not only contributes to our understanding of bacterial vaginosis but also holds the promise of more effective diagnostics and targeted interventions for individuals at risk. The authors believe that the implications of this study reach beyond gynecology, touching on broader aspects of reproductive health and paving the way for innovative approaches to tackle related complications.

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Understanding the Vaginal Microbiome's Impact on Health and ... - Inside Precision Medicine

Leading University of Cape Town (UCT) scholar and scientist Professor Kelly Chibale has been awarded an honorary doctorate from the Faculty of Science at the University of Basel, Switzerland a world-leading research university and one of the oldest in Europe.

Professor Chibale was one of seven scholars who received honorary doctorates during the Dies Academicus ceremony in Basel on 24November. But his was the only one awarded by the universitys Faculty of Science.

The annual Dies Academicus celebration is held in St Martins Church on the last Friday of each November and commemorates the opening of the university on 4April1460 at the Basel Minster. The ceremony is also an occasion to honour early-career researchers for their achievements through awards sponsored by companies, foundations or associations.

The University of Basel is the oldest university in Switzerland; its goal is to remain one of the best research universities worldwide and to make important contributions to research and social development through scientific knowledge and innovation.

Exceptional and inspiring

Chibale is a South African National Research Foundation A-rated scholar and holds the Neville Isdell Chair in African-centric Drug Discovery and Development at UCT. He isthe founder and director of H3D, UCTs drug discovery and development centre based in the Department of Chemistry and the Institute of Infectious Disease and Molecular Medicine (IDM).

The commendation for his honorary doctorate reads: At the Dies Academicus of the University of Basel, the faculties award honorary doctorates to outstanding personalities in science or society. I am delighted to inform you that the Faculty of Science has decided to award you with this years honorary doctorate.

It is to honour your exceptional and inspiring curriculum vitae, your outstanding academic achievements and last, but not least, your continuous and ongoing support of the Swiss Tropical and Public Health Institute, an associate Institute of the University of Basel.

It continues: Professor Kelly Chibale [is] one of the most influential scientists in the research and development of new drugs for malaria, tuberculosis and understudied tropical diseases. The researcher, who is currently working in South Africa, was part of the Next Generation Scientist program run by Novartis and the University of Basel for over a decade.

Speaking to UCT News after the event, Chibale said, The ceremony at a packed church was movingly symbolic as a church is a place of worship for me. I was there in the church worshiping, thanking, and giving glory to God for being the source of this award given to me.

The celebratory banquet that followed was out of this world and the largest I have ever attended.

After the event, Chibale presented a Novartis public lecture titled Fostering drug discovery in Africa at the breathtakingly impressive Novartis Pavillon.

It was a fantastic day of celebrations with my Swiss friends. In the process I boosted the economy of Switzerland with the many Swiss chocolate gifts I was presented with by my Swiss friends who in turn boosted the South African economy with the South African wine I took to Switzerland for them.

With the Royal Society Africa Prize and Schmidt Futures AI2050 Senior Fellowship, the two other individual awards already received this year, this honorary doctorate is like icing on the cake. An individual award like this is also an opportunity for me to thank my present and past team members (both in my academic group and H3D), as well as research and funding partners because as the saying goes, It takes a village to raise a child.

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Honorary doctorate for Kelly Chibale in Switzerland - University of Cape Town News

Research Education & Training is excited to welcome Dr. Haley du Bois back to campus as a new postdoctoral fellow in the lab ofDr. Conor Lynch. Dr. du Bois first visited campus in May as part of the inaugural cohort of the Moffitt Innovators of Tomorrow (MIOT) Symposium, our newest postdoctoral recruitment program.

The Office of Postdoctoral Affairs hosts the MIOT Symposium twice a year, each time bringing a cohort of 10 advanced doctoral researchers and recent graduates to campus to present their research, meet with Moffitt faculty and learn about postdoctoral fellowship opportunities. The attendees are competitively selected and represent top emerging talent in basic science, quantitative science and population science cancer research.

A large focus of the event is showcasing the collaborative research environment Moffitt offers, as well as the extensive scientific and professional support available to Moffitt postdocs through the Cores and Office of Postdoctoral Affairs.

Dr. du Bois received her PhD in Cellular Biology earlier this year from the New York University Grossman School of Medicine, where she studied under the direction of Dr. Amanda Lund. The Office of Postdoctoral Affairs interviewed Dr. du Bois as part of our new Meet the Postdocs series, to learn about her, her research and how the Innovators of Tomorrow Symposium helped bring her to Moffitt.

Can you tell us a bit about your doctoral research?

My graduate work was focused on understanding how a primary tumor communicates regionally and systemically with the host and how this long-range molecular communication may prime tissues for metastasis. Given that the lymph node is the most common site of metastasis for most solid tumors, I used a melanoma model to test whether the primary tumor secretes proteins that activate the lymph node as a pre-metastatic niche.

Testing this, I found that indeed tumor-secreted proteins are able to activate the pre-metastatic lymph node, even in the absence of extracellular vesicles. Using a chemical biology approach termed BONCAT (bioorthogonal non-canonical amino acid tagging), I was able to identify the melanoma-secreted proteins transported to a pre-metastatic lymph node. From these, I found that one such protein, CSPG4, is cleaved from the primary tumor cell surface and transported to the lymph node, priming it for metastasis. Furthermore, I found that CSPG4's chondroitin sulfate decorations were necessary for CSPG4-dependent lymph node pre-metastatic niche establishment, and that targeted removal of them can prevent lymph node metastasis.

Why did you decide to do your postdoc at Moffitt?

Attending MIOT was pivotal to my decision. I was incredibly fortunate to attend the inaugural MIOT symposium during a time in my graduate training that I was beginning to solidify my next goals. MIOT was a very comprehensive introduction to Moffitt's outstanding resources, exemplary faculty and innovative environment. The immersive experience showcased how collaborative and creative the teams here at Moffitt are and it was clear to me that this is a place where I would be supported to accomplish my goals.

Can you tell us a bit about yourself, what youre most looking forward to about your life in Tampa and your hobbies outside of the lab?

Coming from New York City, I am most looking forward to spending more time outside being active. I really enjoy gardening, hiking, and kayaking which are much more accessible here in Tampa. Aside from the outdoor activities I enjoy, I also like to cook and play board games with friends.

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Moffitt Innovators of Tomorrow Symposium Welcomes Its First ... - Moffitt Cancer Center

One person in the UK has been infected by a strain of flu similar to viruses spreading in pigs, health officials have announced.

But what is the strain, what are the symptoms in humans and are experts worried?

Heres what we know so far.

Influenza A(H1) viruses are native to swine populations in most regions of the world, but viruses in pigs can occasionally infect humans, usually after direct or indirect exposure to pigs or contaminated environments.

Influenza A(H1N2)v is similar to flu viruses currently circulating in pigs in the UK but this is the first detection of this particular strain of flu in a human in the UK.

Theres been a total of 50 human cases of influenza A(H1N2)v reported globally since 2005, but no human deaths from this strain have been reported.

Human infections with swine influenza viruses also known as swine flu occur sporadically, according to the UKs Health Security Agency (UKHSA). It becomes a variant influenza virus when detected in a person.

The infection found in the UK is slightly different from recent human cases of the flu strain globally, health officials say, but similar to viruses in UK pigs.

The case was detected as part of routine national flu surveillance undertaken by UKHSA and the Royal College of General Practitioners. The individual was tested by their GP after experiencing respiratory symptoms and influenza A(H1N2)v virus was detected. They experienced a mild illness and have fully recovered.

In 2009, there was a pandemic in humans caused by an influenza virus (official name: influenza A H1N1(pdm09)) commonly referred to as swine flu.

But that virus contained genetic material from viruses circulating in pigs, birds and humans in the 1990s and 2000s. Its now circulating in humans on a seasonal basis and is no longer referred to as swine flu.

It is distinct from the viruses currently circulating in pigs. The case of flu found in the UK is classed as swine flu because its influenza from a pig, but what was previously called swine flu in 2009 is now not referred to as that.

The source of the individuals infection has not yet been found and remains under investigation, but close contacts of the case are being followed up by the UKHSA and partner organisations, and will be offered testing and advised on any necessary further care if they have symptoms or test positive.

The UKs Chief Veterinary Officer, Dr Christine Middlemiss, said: In this case we are providing specialist veterinary and scientific knowledge to support the UKHSA investigation.

Pig keepers must also report any suspicion of swine flu in their herds to their local vet immediately.

People who are contacted and asked to test are encouraged to do so in order to assist in the detection of cases and assessment of transmission.

Those with any respiratory symptoms should continue to follow the existing guidance, including avoiding contact with other people while symptoms persist, particularly if the people they are coming into contact with are elderly or have existing medical conditions.

Martin Michaelis, professor of molecular medicine at the University of Kent, told FactCheck that as the pig influenza case detected in the UK was mild and efforts are ongoing to trace and break potential transmission chains, it does not seem very likely that this could be the beginning of a large, dangerous pig influenza outbreak in humans.

However, he added that you can never be entirely sure, because mutations can happen that change the nature of this virus strain, if it keeps spreading in humans.

But he noted that this pig H1N2 influenza virus infection of a human is a stark reminder that influenza viruses that spread between different species are posing a continuous risk to humans.

Paul Hunter, professor in medicine at the University of East Anglia, told the Science Media Centre: Overall the evidence is that influenza A(H1N2) does not cause any more severe disease than other more commonly circulating types of influenza.

Also, person to person transmission does not appear to be very efficient and sustained person to person transmission has not been reported so far.

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FactCheck: are experts worried about first UK 'pig' flu case? - Channel 4 News