Monthly Archives: June 2022

Enterovirus isolation

Three isolates were obtained from the clinical samples of the patients involved in the small outbreak. One was obtained from the hepatic biopsy of patient 1, here referred to as Iso_pt1_L, while the others were obtained from the serums of patient 2 and patient 3, named Iso_pt2_S and Iso_pt3_S respectively (see Table 3).

The Enterovirus strains involved in this small outbreak were typed, basing on VP1 partial sequences and all resulted belonging to E-11. Moreover, the phylogenetic analysis performed comparing the VP1 sequences with a set of E-11 strains retrieved from GenBank shows that our strains strictly correlated and segregated in a unique and well separated clade which belongs to the D5 genotype of E-11 according to Li et al. [31], thus confirming the epidemiological link between the Enterovirus infections described here. (Additional file 3).

To further characterize the RNA genome, the EVs isolated in cell culture (Iso_pt1_L, Iso_pt2_S and Iso_pt3_S) and the virus from the liver biopsy of patient 1 (Pt1_L) were entirely sequenced. All nucleotide sequences were then aligned using Clustal W and the amino acid sequences of the polyproteins were compared. As expected, all viral strains revealed a high identity at nucleotide level (median=99.87%, ranging from 99.83 to 100%); two schematic tables of the nucleotides and amino acid differences respectively found, are provided in Additional file 4. Moreover, comparing the Liver Enterovirus strain (Pt1_L) with the corresponding Liver isolate (Iso_pt1_L), no amino acid differences were observed, while the sequence of Iso_pt2_S compared to Enterovirus strains of pt1, shows one amino acid substitution, C1677 L, located in the P3 region of the polyprotein. Specifically, it maps in the region encoding for the protein complex of 3BCD that is the precursor of the non-structural proteins 3B (Vpg primers for RNA transcription), 3C (protease) and 3D (viral polymerase). Similarly, we compared the amino acid sequence of Iso_pt3_S with those of pt1 (Iso_pt1_L and pt1_L) and we found the following four substitutions: D478G localized in the P1 portion of the polyprotein encoding for capsid proteins; T1898A, G2100V and E2101T, located in the portion encoding for the viral RNA polymerase 3D. Furthermore, comparing the amino acid sequence of the virus described here with 35 polyprotein sequences of other E-11 strains downloaded from Genbank, we found 25 amino acid substitutions (V101I, E115D, I310V, V572A, T651V, E895D, Q1031H, C1033S, L1938F, I1084V, T1122A, Q1185H, S1213E, S1365N, T1418S, S1429N, N1536S, P1539L, A1533S, V1558I, L1298I, T1868N, I2135V and D2140N). To date, no biological significance associated with any of these substitutions have been described.

Despite the typing of the VP1 gene assigned our virus to an E-11, the phylogenetic analysis of the full-genome sequence of ECHO11_INMI against a set of 123 sequences retrieved from the Picornavirus homepage, showed an unexpected pattern: ECHO11_INMI strain did not segregate with E-11 serotypes, but with a CV-B1 (Acc N: MG845887) (Fig.2). This finding led us to hypothesize that ECHO11_INMI could be a chimeric strain, maybe originating from a recombination event between an E-11 (Acc N: AY167103) and CV-B1 (Acc N: MG845887).

Unfortunately, we were not able to sequence the entire genome of the virus infecting Pt 0 (index case) due to the low quantity of virus in residual material, as the liver bioptic sample (Pt0_L) was fixed in paraffin which badly conserved the nucleic acid. However, we were able to obtain two amplicons of the sequence by RT-PCR that localized upstream and downstream from the recombination breakpoint respectively. Both amplicons were sequenced and show a high identity (median value=99.78% and 98.17% of upstream and downstream fragment, respectively) both with the sequences of the three isolates and the virus detected in the liver of patient 1 (Pt1_L), therefore suggesting that the recombination had already occurred in the virus infecting the source (Pt0).

The phylogenetic tree of the full genome sequences (data not shown) shows that ECHO11_INMI, segregates with the CV-B1 (MG845887.1). To better define the phylogenetic relationships, we analyzed separately the P1, containing the VP1 gene, and the P3 region as it locates close to 3 end of the genome and far from P1 (Fig.1). The phylogenetic tree of the P1 region (Fig.2) shows that our ECHO11_INMI sequence clusters together with all E-11 types while CV-B1 (MG845887.1) segregates with CV-B1 type in a separate clade. The P1 region contains the sequence coding for the capsid proteins, VP4, VP2, VP3 and VP1. In particular, it is well known that VP1 is the most antigenic protein and its sequence is used for the typing of Enterovirus genus as it has been shown to correlate very well with the classical serotype [32]. Indeed, phylogenetic studies on VP1 sequences of the genus have clearly shown that strains of the same serotype always cluster together [33].

Phylogenetic trees. Phylogenetic trees constructed on the basis of P1 region [nucleotide positions from 726 to 3253 referring to Human echovirus 11 prototype strain Kust/86 (Accession N GenBank: AY167105.1)] and of the P3 region [nucleotide positions from 6956 to 7256 referring to Human echovirus 11 prototype strain Kust/86 (Accession N GenBank: AY167105.1)]. The nodes defining the clade including ECHO11_INMI strain are indicated with a black dot (Bootstrap value in a, b, and c tree are: 99, 100 and 94 respectively). ECHO11_INMI strain are reported in red, Echo 11 types are reported in blu and CVB1 types are reported in green

Therefore, this result confirms that our sequence belongs to the E-11 type. The last tree (Fig.2), constructed on the basis of the P3 region of the genome, shows that the ECHO11_INMI segregates close to the CV-B1 (MG845887.1). This result is consistent with the hypothesis that recombination occurred in the P2 region of the genome, between P1 and P3.

To confirm the presence of a recombination breakpoint in our strains, we performed a recombination detection analysis, using RDP4 software (Fig.3). Specifically, the analysis recognized that ECHO11_INMI was a chimeric strain of E-11 (AY167103) and CV-B1 (MG845887); it also identified the breakpoint of recombination between nucleotide 4083 and 4201 of ECHO11_INMI sequence without gap, with 99% certainty (p values 5.259*1024, as reported by RDP4).

Recombination analysis results using RDP4. The plot shows the pairwise identity between ECHO11_INMI (accession no: KX527626) and the Human E-11 strain Hun/90 (accession no: AY167103.1) or CV-B1 (accession n. MG845887), represented in green and purple line respectively. While the yellow line shows the pairwise identity between E-11 strain Hun/90 and CV-B1. Each polymorphic site detected in the sequence dataset analyzed, was marked with a black bar. Then, the long black lines above the plot equivalent to the high number of nucleotide variation among sequences; the white spaces identify regions where the polymorphism are absent

The recombination site is located in the region encoding for P2 of the polyprotein that is the precursor of three non-structural proteins involved in the replication process: 2Apro, 2B and 2C.

To confirm that the virus in our samples is a new variant originating from a recombination event between an E-11 and a CV-B1, and to exclude the hypothesis of a co-infection with both viruses, we designed four sets of primers. Two of them were specific for E-11 serotype, targeting respectively the region upstream and downstream of the breakpoint (E11 2F-E11 2R, E11 3F-E11 3R); in the same way we designed two sets of primers specific for CV-B serotypes, targeting respectively the region upstream and downstream from the recombination site (CVB 2F-CVB 2R, CVB 3F-CVB 3R). Figure1 shows a schematic representation of the EVs genome and details of experimental design for RT-PCR amplification of both E-11 and a CV-B1.

Pt1_S and all isolates were tested with all sets of primers described and we obtained similar results(Additional File 5). The amplification resulted positive with the set E112F-E112R, that targets the region upstream of the recombination breakpoint, and with the set CVB 3F-CVB 3R, that targets the region downstream of the breakpoint, instead the other sets of primers, CVB 2F-CVB 2R and E11 3F-E11 3R, that map at 5 and 3 of the genome, respectively, gave negative results (Fig.4).

RT-PCR performed with specific sets of primers for E-11 and CV-B on Pt1_S and Iso_PT1_S

These findings are consistent with the recombination hypothesis and confirm the presence of only the recombinant variant in the examined samples; in addition the presence of the same pattern of amplification obtained by the analysis of the virus in serum sample and the one isolated from cell culture, revealed that the recombination was not generated by the isolation procedure.

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Detection of recombinant breakpoint in the genome of human enterovirus E11 strain associated with a fatal nosocomial outbreak - Virology Journal -...

It has been almost 44 years years since the first in vitro fertilisation (IVF) procedure was successfully performed in 1978 in Lancashire, England. Since then, more than 8 million babies have been born worldwide to assisted reproductive technologies, such as IVF.

But despite its increasing use, the success rate of IVF still remains relatively low, at around 30%. There may be a number of reasons for this. In our recent paper, we argue that this low rate is partially due to the many unfavourable genetic changes that we carry in our DNA.

Genetic changes happen when mutations in our genes replace, insert or delete sections of DNA. More of these mutations are occurring now in humans because were having babies at a later age. As we get older, more mutations are likely to accumulate meaning older parents are more likely to pass on genetic mutations to their children than younger parents. Mutations may also be caused by environmental factors (such as ultraviolet radiation in sunlight), or lifestyle choices (for example, smoking).

All of the genetic changes we inherit or develop throughout our lifetime constitute whats known as our genetic load. This genetic load can impact our ability to reproduce. And as our study suggests, this may also affect our ability to reproduce via methods such as IVF.

Genetic mutations make evolution possible. They provide the new material for natural selection that allows species to adapt and evolve. While most of these mutations have no effect, some are slightly harmful. Such harmful mutations may cause diabetes or breast cancer, for example or they may disrupt the healthy development of an embryo.

Human DNA carries more than 1,000 harmful mutations, most of which happened many generations ago. Yet, even though they are harmful, they have not (yet) been removed, because natural selection is a very slow process.

In addition to the large number of old mutations, new mutations also enter the population every generation. On average, every person acquires approximately 70 new mutations during their lifetime. But since some of these mutations are harmful, they need to be removed by natural selection, so that they arent passed on to future offspring. One of the most important times this happens is during natural conception.

When a child is conceived naturally, the body has many mechanisms in place to remove some of these harmful mutations.

For example, the female reproductive system is designed in such a way that only the fittest sperm cells can reach the egg for fertilisation. Although evidence is scarce, animal studies suggest that the sperm that reach the fertilisation site have a better DNA quality and potentially fewer mutations.

Mature eggs also undergo a sort of quality check during fertilisation. This too helps purge some of the genetic load. The implantation stage (where a fertilised embryo implants itself in the mothers womb) is also important, as many embryos with severe genetic abnormalities tend to be lost naturally during pregnancies.

However, IVF bypasses some of these natural mechanisms. During IVF, multiple eggs are harvested from the womans ovaries and fertilised with sperm in a laboratory. After they have been fertilised, the embryos are then returned to the womb. This reduces the opportunity for natural selection, which may therefore make IVF less efficient in reducing the genetic load. This could potentially increase the likelihood that harmful variants of genes may be passed onto the next generation.

So, the genetic load has two big implications for human reproduction. First, the genetic load of parents affects their ability to successfully reproduce. This is true both for natural conception, as well as for IVF. Second, by relaxing natural selection, IVF may let more mutations slip through the net. As such, it could slowly increase our genetic load in future generation. But there may be a solution.

Fertility rates have suffered an unprecedented decline in recent decades. In fact, sperm count has fallen by about 50 to 60% between 1973 and 2011. Its unclear why this is, but if this trend continues it could mean more people turn to IVF to conceive.

Yet we still know surprisingly little about human reproduction and the selective processes operating during natural conception. We must understand natural conception first if we want to improve assisted reproduction methods, including IVF. But recent technological advances in assisted reproductive technologies mean that we may soon be better able to counteract some of the genetic load in humans. For example selection at sperm level in the IVF process has been shown to improve the offspring fitness in animal models. In particular, selection of longer-lived sperm in zebrafish results in healthier offspring that live longer.

Advances in genomic technologies also have the potential to affect human evolution. Already, genomic data is effectively being used in clinical care, and the genomic bases of thousands of human diseases are now known. Furthermore, changes to our environment and our lifestyle are affecting the genetic load and human health. Most often, these changes have a negative effect, which makes these technological advances ever more important. As new advances are made, it will also be important to consider the potential consequences of using assisted reproductive technologies if these become the norm.

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IVF: heres how genetics may be affecting its success new insights - The Conversation Indonesia

Using DNA extracted from blood, tissue or skin samples, researchers looked for 566 mutations linked to disease, including 84 for cancer, 77 for heart conditions, and others affecting responses to medicines

Image: Reuters)

Whole genome sequencing could be offered to all adults on the NHS within five years to help millions cut their risk of conditions such as cancer and heart disease, experts have revealed.

Thousands of lives could be saved annually if the tests - which read a persons entire genetic code - were widely available, it was said.

In a study of 102 healthy patients at a GP surgery, one in four were found to carry actionable mutations.

These were changes to their genes which increased risk of certain diseases but could be mitigated through lifestyle changes, extra monitoring or other preventative measures.

Six in ten carried an inherited mutation in a recessive gene, meaning they were not affected by a condition but could pass it on to their children.

Detecting such mutations can guide healthcare decisions and enable more personalised treatment.

Study leader Professor Ros Eeles, an expert in oncogenetics at The Institute of Cancer Research in London, said the results could spark a revolution in healthcare, paving the way for testing to be rolled out to anyone who wants it in the next two to five years.

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No countries are yet offering genome tests on this scale.

Prof Eeles added: Our findings suggest that integrating whole-genome sequencing into primary care could change the way most patients and their families are managed by their GPs.

Health Secretary Sajid Javid said genomics was changing the future of healthcare.

He added: This study shows the potential for genome sequencing in enabling patients with life-changing diseases to receive early diagnoses just by visiting their GPs in future.

The UK continues to lead the way in genomics expertise and this exciting collaboration between the Institute of Cancer Research, the NHS and the wider health sector has the potential to save lives by increasing the detection and prevention of diseases such as cancer and heart disease.

The study was the first to trial offering the tests at GP surgeries and recruited participants from The London Genetics Centre, at 90 Sloane Street.

A human genome contains around 20,000 genes made up of 3.2 billion letters of DNA.

Using DNA extracted from blood, tissue or skin samples, researchers looked for 566 mutations linked to disease, including 84 for cancer, 77 for heart conditions, and others affecting responses to medicines.

Some 26 patients had potentially actionable genetic variants, 61 had a recessive gene that could be passed on should their partner also carry it, and 38 had changes linked to medicine responses.

Dr Eeles, also a cancer consultant at The Royal Marsden NHS Foundation Trust, said the most common action taken as a result was more frequent screening for patients at risk of cancer.

One woman found to be at elevated risk of ovarian cancer chose to have her ovaries removed.

Another who frequently travelled discovered she was at high risk of deep vein thrombosis and now uses an injectable anticoagulant before flights to prevent blood clots.

Other possible benefits include the ability to select drugs that cause less side effects, or earlier prescribing of statins for people predisposed to have high-cholesterol.

People with mutations that could be passed onto their children can be offered IVF with embryo screening.

Around 70 per cent of those with actionable mutations would not have been identified through normal checks and family history.

Whole genome sequencing is available for certain conditions including some cancers and rare diseases.

Dr Eeles said her team was in discussions with NHS England and the tests could eventually become a routine part of GP registration.

She added: The power of new genetics really needs to be enhanced for healthcare and this is the first study along the way.

Its definitely coming. Theres a huge impetus in genome integration into healthcare in the UK.

Sequencing each patients genome cost 1,800 but researchers believe this can be cut to under 1,000 for the NHS.

Dr Eeles added: It sounds like a lot but to treat somebody with metastatic [cancer] you could be talking about 200,000 for two years of immunotherapy treatment.

Patients were not told about their risk of diseases with no known treatments, such as dementia. Specially trained staff helped them understand their results and deal with any concerns.

The findings will be presented at the American Society of Clinical Oncologys Annual Conference in Chicago.

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Genome sequencing could be offered to all adults on NHS in bid to defeat cancers - The Mirror

According to a new report published by Grand View Research, the future market potential of genomics in newborn screening programs, emerging companies like Counsyl and Natera have launched various genetic tests to maintain their competitive edge in the market.

Genomics Industry Overview

The global genomics market size was valued at USD 20.1 billion in 2020 andis expected to reach USD 62.9 billion by 2028, expecting to expand at a CAGR of 15.35%during forecast period.

The scientific community has tried to address genetic susceptibility and severity to SARS-CoV-2 infection by combining research efforts using existing genetic databases. Multiomic-based approaches and genome-wide association studies (GWAS) have been employed to uncover biological networks and common variants underlying host-pathogen interactions. Similarly, data derived from genomes, such as polygenic risk scores (PRS), ABO blood groups, and HLA haplotypes, can be potentially used to decipher COVID-19 complications, resistance, and susceptibility. Moreover, biobanks that link electronic health records (EHRs) to genomic data can be leveraged to study the impact of genomic factors on the clinical course of patients infected with SARS-CoV-2.

Gather more insights about the market drivers, restrains and growth of the Global Genomics Market

The COVID-19 Host Genetics Initiative launched by researchers from the Finnish Institute for Molecular Medicine (FIMM) aims to inspire the human genetics community to analyze, share, and generate data to interpret determinants of COVID-19 outcomes, severity, and susceptibility. deCODE genetics, a genomics solutions provider in Iceland, has used SARS-CoV-2 genomic analysis to monitor the viral spread.

In addition, the company has partnered with the Government of Iceland to conduct genome sequencing of viral hosts. Similarly, the government of Greece funded the COVID-19-GR initiative to genotype 3,500 COVID-19 patients, conduct WGS on the SARS-CoV-2 genome obtained from these patients, and conduct immunogenomic analyses. The complete set of this data along with detailed clinical information is available and can be retrieved from the Greek COVID-19 registry.

In the near future, prenatal genetic screening programs are likely to grow at a significant pace. This is because these programs help expectant mothers identify chromosomal anomalies in their offspring. Moreover, it is anticipated that in the next 10 years, every newborns genome would be sequenced and stored in the electronic medical record. Gauging the future market potential of genomics in newborn screening programs, emerging companies like Counsyl and Natera have launched various genetic tests to maintain their competitive edge in the market.

Genomics Market Segmentation

Based on the Deliverable Insights, the market is segmented into product ad services

Based on the Application and Technology Insights, the market is segmented into functional genomics, pathway analysis, biomarker discovery, epigenetics and others

Based on End-use Insights, the market is segmented into pharmaceutical and biotechnology companies, hospitals and clinics, academic and government institutes, clinical research and other end users

Based on the Regional Insights, the market is segmented into North America, Europe, Asia Pacific, Latin America, and Middle East & Africa

Market Share Insights:

Key Companies Profile:

Companies are increasingly focusing on the development and launch of new products and collaboration with other entities to increase their market share.

Some prominent players in the global genomics market include:

Order a free sample PDF of the GenomicsMarket Intelligence Study, published by Grand View Research.

About Grand View Research

Grand View Research is a full-time market research and consulting company registered in San Francisco, California. The company fully offers market reports, both customized and syndicates, based on intense data analysis. It also offers consulting services to business communities and academic institutions and helps them understand the global and business scenario to a significant extent. The company operates across multitude of domains such as Chemicals, Materials, Food and Beverages, Consumer Goods, Healthcare, and Information Technology to offer consulting services.

Web: https://www.grandviewresearch.com

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Genomics Market Size Is Expected To Reach $62.9 Billion By 2028, Based on High Demand For Advanced Gene-Editing Tools From Biotechnology Companies |...

NEWCASTLE, United Kingdom Scientists at Newcastle University report the discovery of a new hereditary disease called TULP3-related ciliopathy. Caused by a faulty inherited gene, this condition can result in either liver or kidney failure among both adults and adolescents.

Both kidney and liver failure, of course, can stem from a number of different causes. Organ failure can be life-threatening if left untreated, but many patients find it difficult to get an accurate diagnosis. As one can imagine, this makes settling upon the best possible treatment option near impossible.

Study authors have found that a faulty gene is the catalyst for increased fibrosis in both the liver and kidney. More fibrosis often results in the patient needing a transplant.

Our finding has a huge implication for better diagnosis and management of kidney and liver disease in some patients, says Professor John Sayer, Deputy Dean of Clinical Medicine at Newcastle, in a university release. What we are now able to do is give some patients a precise diagnosis, which allows their treatment to be tailored to their needs for the best possible outcome.

Researchers reviewed each studied patients clinical symptoms, and also collected biopsies and genetic sequencing data. Ultimately, the team identified 15 patients from eight families as having the new disease. They then utilized urine collected from those 15 patients to grow cells in a lab setting. Analysis of those lab-grown cells helped the team investigate the precise defect behind TULP3-related ciliopathy.

Over half of all study participants needed a liver or kidney transplant. Before this work, the original cause for their organ failure was a mystery.

We were surprised at how many patients we were able to identify with TULP3-related ciliopathy and this would suggest that the condition is prevalent within those with liver and kidney failure, Prof. Sayer explains. We hope to provide a proper diagnosis for many more families in the future. This work is a reminder that it is always worth investigating the underlying reasons for kidney or liver failure to get to the bottom of the condition.

Finding a genetic cause of liver or kidney failure has huge implications for other family members, especially if they are wishing to donate a kidney to the patient, the researcher adds.

Moving forward, the team at NU will keep working on this topic. They plan to analyze cell lines taken from relevant patients, and test more potential new treatments for TULP3-related ciliopathy.

Linda Turnbull, one of the 15 patients identified as having the new condition, received a new liver decades ago. Now in her 60s, doctors diagnosed Linda with liver failure at just 11 years-old. All these years later, she finally has a better idea of what happened.

It is brilliant to finally have an answer to my life-long questions: Why has this happened to me and why do I have this condition, she comments. Its fantastic that this research has been led in Newcastle and it means that people in the future will have information regarding their condition and how best to treat it.

The study is published in the American Journal of Human Genetics.

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New disease affecting the kidneys and liver discovered - Study Finds

Doctors were significantly less likely to order colorectal cancer screening with the at-home test Cologuard (Exact Sciences Corp) for Black patients and were more likely to order the test for Asian patients, new evidence reveals.

Investigators retrospectively studied 557,156 patients in the Mayo Clinic health system from 2012 to 2022. They found that Cologuard was ordered for 8.7% of Black patients, compared to 11.9% of White patients and 13.1% of Asian patients.

Both minority groups were less likely than White patients to undergo a follow-up colonoscopy within 1 year of Cologuard testing. Cologuard tests the stool for blood and DNA markers associated with colorectal cancer.

Although the researchers did not examine the reasons driving the disparities, lead investigator Ahmed Ouni, MD, told Medscape Medical News that "it could be patient preferences...or there could be some bias as providers ourselves in how we present the data to patients."

Ouni presented the findings on May 22 at Digestive Disease Week (DDW) 2022, held in person in San Diego and virtually.

"We looked at the specialty of physicians ordering these because we wanted to see where the disparity was coming from, if there was a disparity," said Ouni, a gastroenterologist at Mayo Clinic in Jacksonville, Florida.

Just over half (51%) of the patients received care from family medicine physicians, 27% received care from internists, and 22% were seen by gastroenterologists.

Family physicians ordered Cologuard testing for 8.7% of Black patients, compared to 16.1% of White patients, a significant difference (P< .001). Internists ordered the test for 10.5% of Black patients and 11.1% of White patients (P< .001). Gastroenterologists ordered Cologuard screening for 2.4% of Black patients and 3.2% of White patients (P=.009).

Gastroenterologists were 47% more likely to order Cologuard for Asian patients, and internists were 16% more likely to order it for this population than for White patients. However, the findings were not statistically significant for the overall cohort of Asian patients when the researchers adjusted for age and sex (P = 0.52).

Black patients were 25% less likely to have a follow-up colonoscopy within 1 year of undergoing a Cologuard test (odds ratio [OR], 0.75; 95% CI, 0.60 0.94), and Asian patients were 35% less likely (OR, 0.65; 95% CI, 0.52 0.82).

Of the total study population, only 2.9% self-identified as Black; according to the 2020 US Census, 12.4% of the population of the United States are Black persons.

When asked about the relatively low proportion of Black persons in the study, Ouni replied that the investigators are partnering with a Black physician group in the Jacksonville, Florida, area to expand the study to a more diverse population.

Additional plans include assessing how many positive Cologuard test results led to follow-up colonoscopies.

The investigators are also working with family physicians at the Mayo Clinic to examine how physicians explain colorectal cancer screening options to patients and are studying patient preferences regarding screening options, which include Cologuard, fecal immunochemical test (FIT)/fecal occult blood testing, CT colonography, and colonoscopy.

"We're analyzing the data by ZIP code to see if this could be related to finances," Ouni added. "So, if you're Black or White and more financially impoverished, how does that affect how you view Cologuard and colorectal cancer screening?"

"Overall this study supports other studies of a disparity in colorectal cancer screening for African Americans," John M. Carethers, MD, told Medscape Medical News when asked to comment. "This is known for FIT and colonoscopy, and Cologuard, which is a genetic test in addition to FIT, appears to be in that same realm.

"Noninvasive tests will have a role to reach populations who may not readily have access to colonoscopy," said Carethers, John G. Searle Professor and chair of the Department of Internal Medicine and professor of human genetics at the University of Michigan in Ann Arbor. "The key here is if the test is positive, it needs to be followed up with a colonoscopy."

Carethers added that the study raises some unanswered questions, for example, Does the cost difference between testing options make a difference?

"FIT is under $20, but Cologuard is generally $300 or more," he said. What percentage of the study population were offered other options, such as FIT? How does insurance status affect screening in different populations?

"The findings should be taken in context of what other screening options were offered to or elected by patients," agreed Gregory S. Cooper, MD, professor of medicine and population and quantitative health sciences at Case Western Reserve University and a gastroenterologist at University Hospitals Cleveland Medical Center in Ohio.

According to guidelines, patients can be offered a menu of options, including FIT, colonoscopy, and Cologuard, Cooper told Medscape Medical News.

"If more African Americans elected colonoscopy, for example, the findings may balance out," said Cooper, who was not affiliated with the study. "It would also be of interest to know if the racial differences changed over time. With the pandemic, the use of noninvasive options, such as Cologuard, have increased."

"I will note that specifically for colonoscopy in the United States, the disparity gap had been closing from about 15% to 18% 20 years ago to about 3% in 2020 pre-COVID," Carethers added. "I am fearful that COVID may have led to a widening of that gap again as we get more data.

"It is important that noninvasive tests for screening be a part of the portfolio of offerings to patients, as about 35% of eligible at-risk persons who need to be screened are not screened in the United States," Carethers said.

The study was not industry sponsored. Ouni and Carethers report no relevant financial relationships. Cooper has received consulting fees from Exact Sciences Corp.

Digestive Disease Week (DDW) 2022: Abstract Su1012. Presented May 22, 2022.

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and critical care. Follow Damian on Twitter: @MedReporter.

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At-Home Colorectal Cancer Testing and Follow-Up Vary by Ethnicity - Medscape

NEW YORK & SAN ANTONIO--(BUSINESS WIRE)--3DBio Therapeutics (3DBio), a clinical-stage regenerative medicine company, and the Microtia-Congenital Ear Deformity Institute announced they have conducted a human ear reconstruction using the AuriNovo implant, an investigational, patient-matched, 3D-bioprinted living tissue ear implant. The groundbreaking reconstructive procedure in the first-in-human Phase 1/2a clinical trial is evaluating the safety and preliminary efficacy of AuriNovo for patients with microtia, a rare congenital deformity where one or both outer ears are absent or underdeveloped. Microtia affects approximately 1,500 babies born in the US annually1,2. This transformational implant procedure was performed by a team led by Arturo Bonilla, M.D., a leading pediatric ear reconstructive surgeon specializing in microtia and the founder and director of the Microtia-Congenital Ear Deformity Institute in San Antonio, Texas.

AuriNovo is a patient-specific, living tissue implant created using 3D-bioprinting technology for surgical reconstruction of the outer ear in people born with microtia Grades II-IV. AuriNovo is designed to provide a treatment alternative to rib cartilage grafts and synthetic materials traditionally used to reconstruct the outer ear of microtia patients. The U.S. Food and Drug Administration (FDA) has granted AuriNovo Orphan Drug and Rare Pediatric Disease Designations.

As a physician who has treated thousands of children with microtia from across the country and around the world, I am inspired by what this technology may mean for microtia patients and their families, said Dr. Bonilla. This study will allow us to investigate the safety and aesthetic properties of this new procedure for ear reconstruction using the patients own cartilage cells. My hope is that AuriNovo will one day become the standard-of-care replacing the current surgical methods for ear reconstruction requiring the harvesting of rib cartilage or the use of porous polyethylene (PPE) implants. The AuriNovo implant requires a less invasive surgical procedure than the use of rib cartilage for reconstruction. We also expect it to result in a more flexible ear than reconstruction with a PPE implant. The AuriNovo living tissue implant is designed to provide a better solution for patients born with microtia by transforming their appearance and building their confidence and self-esteem.

Daniel Cohen, Ph.D., 3DBio Chief Executive Officer and Co-founder, and his team have built a comprehensive, proprietary technology platform to deliver living tissue implants to patients. This is a truly historic moment for patients with microtia, and more broadly, for the regenerative medicine field as we are beginning to demonstrate the real-world application of next-generation tissue engineering technology. It is the culmination of more than seven years of our company's focused efforts to develop a uniquely differentiated technology platform meeting the FDAs requirements for therapeutic manufacturing of reconstructive implants, said Dr. Cohen. We believe that the microtia clinical trial can provide us not only with robust evidence about the value of this innovative product and the positive impact it can have for microtia patients, but also demonstrate the potential for the technology to provide living tissue implants in other therapeutic areas in the future.

Our initial indications focus on cartilage in the reconstructive and orthopedic fields including treating complex nasal defects and spinal degeneration, continued Dr. Cohen. We look forward to leveraging our platform to solve other high impact, unmet medical needs like lumpectomy reconstruction and eventually expand to organs.

In addition to the Microtia-Congenital Ear Deformity Institute, the AuriNovo Phase 1/2a clinical trial is enrolling patients at Cedars-Sinai Medical Center in Los Angeles, CA under the direction of John Reinisch, M.D., Director of Craniofacial and Pediatric Plastic Surgery.

AuriNovo Clinical Trial

The Phase 1/2a clinical trial is a multicenter, single arm, prospective, open-label, staged study of the AuriNovo living tissue ear implant for surgical reconstruction of the external ear in patients born with unilateral microtia. The clinical trial will collect safety data on microtic ear reconstruction using AuriNovo and assess preliminary efficacy data which will be measured by overall satisfaction scores from Surgical Outcomes and FACE-Q Kids questionnaires. Following 3D scanning of the opposite ear to specifically match the patients ear geometry, AuriNovo incorporates the patients own auricular cartilage cells into a 3D-bioprinted, living, full-sized ear construct designed to replace the patients microtia-affected ear. The trial expects to enroll 11 patients and is being conducted in sites in Los Angeles, California and San Antonio, Texas. For more information on the clinical trial, visit clinicaltrials.gov.

Proprietary 3D-Bioprinting Technology

3DBio has developed unique capabilities enabling the creation of living tissue implants for therapeutic applications. The Company not only created the first 3D-bioprinted living tissue implant, but it also created an entire suite of processes and engineering solutions required to support the technology platform. The platform is purpose-built to meet the FDAs requirements for therapeutic manufacturing and includes: proprietary cell processes to rapidly expand cells in sufficient quantity; ColVivo therapeutic grade bio-ink to preserve key biological and rheological properties; GMPrint 3D-bioprinter to enable a sterile workflow combined with exceptional quality and speed; and Overshell technology to add non-permanent structural support to biological implants.

About AuriNovo

AuriNovo is a patient-specific, supportive living tissue implant created using 3D-bioprinting technology for surgical reconstruction of the external ear (auricle) in people born with microtia Grades II-IV. The construct is a 3D-bioprinted collagen hydrogel scaffold encapsulating the patient's own auricular cartilage cells (chondrocytes). The construct is printed in a size and shape matching the patients opposite ear for implantation. AuriNovo was granted Orphan Drug and Rare Pediatric Disease Designations by the FDA for reconstruction of the outer ear in patients with microtia.

About the Microtia-Congenital Ear Deformity Institute

Founded in 1996 by Dr. Arturo Bonilla, the Microtia-Congenital Ear Deformity Institute helps children born with microtia and other ear deformities. It is one of the largest clinics in the world specializing in pediatric microtia reconstruction surgeries and has performed thousands of procedures to help children born with this ear deformity. The Microtia-Congenital Ear Deformity Institute is based in San Antonio, Texas. For more information visit: https://www.microtia.net/.

About 3DBio Therapeutics

3DBio Therapeutics (3DBio) is a clinical-stage regenerative medicine company solving medical challenges by pioneering custom-engineered, patient-specific, 3D-bioprinted, living tissue implants. 3DBios groundbreaking approach develops living tissue implants with structural and functional integrity using a full suite of features to meet the FDAs requirements for therapeutic manufacturing including novel and proprietary 3D-bioprinter (GMPrint), bio-ink (ColVivo), specialized cell culture system, and implantable protective Overshell technology. 3DBios first investigational product, AuriNovo, is currently being evaluated in a Phase 1/2a clinical trial for ear reconstruction in patients with microtia and has been granted Orphan Drug and Rare Pediatric Disease designation by the FDA. For more information visit: http://www.3dbiocorp.com

REFERENCES:

1 Luquetti, D.V., et al., Microtia: epidemiology and genetics. American Journal of Medical Genetics Part A, 2012. 158(1): p. 124-139.2 Luquetti, D.V., E. Leoncini, and P. Mastroiacovo, Microtia-anotia: a global review of prevalence rates. Birth Defects Res A Clin Mol Teratol, 2011. 91(9): p. 813-22.

Certain information set forth in this press release may constitute forward-looking statements under applicable securities laws. There are a number of factors that could cause actual results or outcomes to differ materially from those addressed in such forward-looking statements. Thus, forward-looking statements are provided only as an opportunity to understand managements beliefs and opinions in respect to the companys future prospects.

For additional resources (photos, b-roll, video statements, biographies, headshots, etc.) and access to the media room, please email 3dbio@lavoiehealthscience.com.

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3DBio Therapeutics and the Microtia-Congenital Ear Deformity Institute Conduct Human Ear Reconstruction Using 3D-Bioprinted Living Tissue Implant in a...

Our Father is difficult to watch, especially if youve suddenly discovered as an adult that you have a never-known family of half-siblings, cousins, nieces, and nephews thanks to a long-ago sperm donation. One review dubs the series Netflixs most gruesome real-life documentary yet.

It tells the tale of Indianapolis fertility physician Donald Cline, who used his sperm to inseminate at least 96 women (and counting) between 1979-1986. After years of being in the dark, the offspring have found each other thanks to diligent sleuthing by some of the half-siblings and DNA testing.

The majority of us live in a 25-mile radius, some within minutes of Cline. I walk around and I could be related to anyone. Ive probably met half sibs and we dont even know it, said a son named Guy.

Dr. Cline told many of his patients that he would be using sperm from a medical student or resident, and that no donor would be used for more than three women. The nefarious donations went on for so long in the small town that he used his sperm to inseminate his own daughter!

The Our Father series is in part a detective storythe sleuthing work of Jacoba Ballard, a young woman who was the first to uncover the physicians deception. When aDNA test revealed she had seven relatives in nearby parts of Indiana, she knew something was wrong.

It was a sick feeling, Jacoba said. What she unraveled was shocking: besides finding sisters and brothers with whom she shared a quarter of their DNA, each victim had a mother whod sought fertility treatment from Dr. Cline.

How did these suddenly-bonded young adults unravel the rest of the mystery? Figuring out familial relationships begins with more sleuthing than science. Newbie sibs zero in on the donor by identifying relatives whove tested and with whom everyone matches. Then, they trace backwards and start asking older relatives questions.

Things got complicated at times. Jacoba identified a second cousin they all matched with on 23andMe whos related to someone with the same surname as Dr. Clines mothers maiden name. Dr. Cline was indeed the cousins cousin, and yes, hes a doctor.

Right then my stomach dropped because she confirmed what we already knew but were hoping wasnt true, that Dr. Donald Cline could be our biological father, she says in the documentary. I was in shock. So many emotions, so many questions. He lied about a donor being used. Why did he do it? How long did he do it? How many siblings do we have? Jacoba recalls.

Our Father is also the story of local FOX 59 TV journalist Angela Ganote. She began unearthing the story in February 2015. At first she had great difficulty getting information from local authorities. But once the station began airing her interviews with Jacoba, at least one half-sib stared at her screen and thought she was looking at a twin. Many of them share blond hair and blue eyes.

The documentary opens with a hallway lined with photos of babies. Objects and imagery from Christianity are everywhere; the doctor was a marriage counselor and Sunday school teacher. A placard quotes Jeremiah 1:5,

God Knew Me Before I Was Born: Before I formed you in the womb I knew you, and before you were born, I consecrated you; I appointed you a prophet to the nations.

Then the camera pans to a sterile exam room with illustrations of uteri festooning the walls. Photos of kids are tacked to bulletin boards; lots of little blonds a la The Boys from Brazil.

The story unfolds in interviews with parents, kids, and co-workers. Numbers interrupt the narrative as test results reveal more offspring, up to #96.

A nurse who worked for Dr. Cline from 1981 to 1994 tells how it all happened. She gave patients questionnaires about traits they desired in a donor. Then shed go across the way to a hospital to collect samples from medical residents. Some couples would bring in a sperm sample, perhaps told that that it would be used or mixed with donor sperm.

A former physician colleague backs up the stories from the nurse, patients, and offspring. He adds how the layout of the office suite enabled Dr. Cline to collect and deliver his donations.

But the hospital samples were never used. In fact, Cline would have had to masturbate somewhere nearby while the women were waiting insemination. He would likely still be experiencing the after-effects of arousal as he was inserting the semen, one daughter said.

She recalled that shed be the only patient in the office, and the doc would duck out while she arranged herself in the stirrups.

Hed place his semen into a syringe and then place it at the base of my cervix. The fact that he was still on an endocrine high from ejaculation has no place in a medical setting. When my sons DNA test came back, my first words were I was raped and didnt even know it.

Added Jacoba,

What made him wake up every day and go into work and masturbate and place it into women without their consent?

But if the goal was to make his patients pregnant, the doctor did. The fact that he used his specimen to impregnate me made me sick to my stomach. On the other hand, because of his skills, I have twin daughters who are absolutely delightful. You cant be angry when you have what you always dreamed of, said one former patient.

Jacobas half-siblings share their emotional ups and downs, their words eerily echoing my own as I have struggled to accept, beginning in September 2018, that I, too, have a mystery family, the result of mysterious sperm donations. Since then, Ive been on several Facebook groups for NPEs not parent expected and read many stories, but none on the scale of Our Father.

It helps to connect with others. Especially useful was a recent study in the American Journal of Human Genetics from Christi Guerrini JD, MPH, from the Center for Medical Ethics and Health Policy at Baylor College of Medicine, Family secrets: Experiences and outcomes of participating in direct-to-consumer genetic relative-finder services. I wrote about it here.

As I watched the progam and saw the numbers tick up for Dr. Clines offspring, my empathy for their angst began to ebb. Their reactions were overwhelmingly of anger and negativity, or at least that is what dominated Our Father. Perhaps it was like a Facebook page for people with the same disease dominated by those with the most dire experiences. I couldnt help but wonder without the horrifically egocentric fertility doctor, those half-siblings wouldnt exist.

Consider some of their comments:

Some of them recognize past clues and present commonalities:

Some of the siblings saw something more sinister. Every time we get a DNA match, we say it looks like one of the Cline boys or it looks like a Cline girl. Most of us have blond hair and blue eyes. I hate to say this, but it is almost like we are this perfect Aryan clan and its disgusting. The goal appeared to be to produce more whites because whites would eventually disappear.

All of the photos in the office were of Caucasian babies, said a sister named Julie. Added Jacoba, You wonder if the person who created you was a racist bigot who used my mom as a pawn, and he did it over and over and over again.

The Nazi hypothesis is as opposite as possible from the motivation behind some of the thousands of surprise-donor-conceived offspring like me from the New York City area, from the 1950s and 1960s. Our existence, in some cases, grew out of a desire to replace some of the six million Jews the Nazis killed during the second world war.

The number of Dr. Clines offspring may not even be known or knowable. But he did the deed. When forced to provide a DNA sample, the results showed that the probability that Jacoba is his biological child was beyond doubt: 99.9997 percent.

But in the end, he wasnt punished much. In 2016, Cline was only charged with two counts of obstruction of justice, to which he plead guilty. Technically, the court found, he wasnt sexually violating the women because they were his patients and had given permission. Although some of his offspring feel that their mothers had been raped, legally that claim couldnt hold up.

Dr. Cline was sentenced as a level 6 felon and fined $500, which is a slap in the fing face, said Jacoba.

But progress has been made. In 2018 illicit donor insemination became illegal in Indiana, although theres still no federal law. And dozens of more doctors have been caught using their own sperm.

My reactions to discovering one-half of my genetic parentage was different than the siblings in my father. Ive shared my story in Libby Copelands book The Lost Family, in several blog posts and articles for Genetic Literacy Project and with the New York Times Modern Love Podcast.

The feelings among my half-siblings vary.

Who was our biological father? Weve narrowed down our sperm donor to two of three brothers from a wonderful family that were excited to be part of, even in such a strange way. We look a lot alike. And well have an answer pretty soon, pending a recent match that filled in a few blanks, and also led to the discovery of a wonderful new cousin, half-niece, and possible brother or cousin.

Its weird, and adjusting took time, but Im thankful. Now that were at an age when we are starting to lose people, finding new siblings is a great gift. Thats no solace to many of the aggrieved victims of the deeply deceptive Dr. Cline. But it does illustrate that the proliferation of DNA tests can, in some circumstances, bring some joy and help expand a sense of family.

Ricki Lewis, PH.D is a writer for PLOS and author of the book The Forever Fix: Gene Therapy and the Boy Who Saved It. You can check out Rickiswebsiteand follow Ricki on Twitter@rickilewis

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Who is your real parent? Our Father on Netflix depicts the dark side of 'secret serial sperm donation'. My birth has a similar origin but with a more...