tbuckley/cabot-search huggingface dataset:
HiNT: a computational method for detecting copy number variations and translocations from Hi-C data
Authors: Su Wang, Soohyun Lee, Chong Chu, Dhawal Jain, Peter Kerpedjiev, Geoffrey M. Nelson, Jennifer M. Walsh, Burak H. Alver, Peter J. Park
Journal: Genome biology (2020)

The three-dimensional conformation of a genome can be profiled using Hi-C, a technique that combines chromatin conformation capture with high-throughput sequencing. However, structural variations often yield features that can be mistaken for chromosomal interactions. Here, we describe a computational method HiNT (Hi-C for copy Number variation and Translocation detection), which detects copy number variations and interchromosomal translocations within Hi-C data with breakpoints at single base-pair resolution. We demonstrate that HiNT outperforms existing methods on both simulated and real data. We also show that Hi-C can supplement whole-genome sequencing in structure variant detection by locating breakpoints in repetitive regions.
Molecular characterization of SARS-CoV-2 in the first COVID-19 cluster in France reveals an amino acid deletion in nsp2 (Asp268del)
Authors: A. Bal, G. Destras, A. Gaymard, M. Bouscambert-Duchamp, M. Valette, V. Escuret, E. Frobert, G. Billaud, S. Trouillet-Assant, V. Cheynet, K. Brengel-Pesce, F. Morfin, B. Lina, L. Josset
Journal: Clinical Microbiology and Infection (2020)
A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent β-Thalassemia
Authors: M. Domenica Cappellini, Vip Viprakasit, Ali T. Taher, Pencho Georgiev, Kevin H.M. Kuo, Thomas Coates, Ersi Voskaridou, Hong-Keng Liew, Idit Pazgal-Kobrowski, G.L. Forni, Silverio Perrotta, Abderrahim Khelif, Ashutosh Lal, Antonis Kattamis, Efthymia Vlachaki, Raffaella Origa, Yesim Aydinok, Mohamed Bejaoui, P. Joy Ho, Lee-Ping Chew, Ping-Chong Bee, Soo-Min Lim, Meng-Yao Lu, Adisak Tantiworawit, Penka Ganeva, Liana Gercheva, Farrukh Shah, Ellis J. Neufeld, Alexis Thompson, Abderrahmane Laadem, Jeevan K. Shetty, Jun Zou, Jennie Zhang, Dimana Miteva, Tatiana Zinger, Peter G. Linde, Matthew L. Sherman, Olivier Hermine, John Porter, Antonio Piga
Journal: New England Journal of Medicine (2020)

Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients.
Boosting the Ranks of American Indian and Alaska Native Physicians
Authors: Bridget M. Kuehn
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Tocilizumab in symptomatic calcium pyrophosphate deposition disease: a pilot study
Authors: Augustin Latourte, Hang-Korng Ea, Aline Frazier, Anne Blanchard, Frédéric Lioté, Hubert Marotte, Thomas Bardin, Pascal Richette
Journal: Annals of the Rheumatic Diseases (2020)

Calcium pyrophosphate (CPP) deposition disease (CPPD) is a prevalent condition characterised by the presence of CPP crystals in articular tissues, especially hyaline cartilage and fibrocartilage. It is most frequently idiopathic, but CPPD may also be associated with other metabolic disorders, such as primary hyperparathyroidism, hereditary hemochromatosis or hypomagnesemia (eg, in a context of Gitelman’s disease).1 Some mutations, such as in ANKH , have also been described in familial forms of the disease.2

CPPD is a cause of acute or chronic inflammatory arthritis. The management of CPP crystal–induced arthritis has been extrapolated from that of gout flares and includes colchicine, non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroids.1 In cases of failure of or contraindications to these drugs, case series suggested that the interleukin 1 (IL-1) inhibitor anakinra was an alternative, especially in acute CPP arthritis.3 However, IL-1 inhibitors may be ineffective or induce …
EHA Endorsement of ESMO Clinical Practice Guidelines for Marginal Zone Lymphomas
Authors: Marco Ladetto, Martin Dreyling
Journal: HemaSphere (2020)

EHA and ESMO recently agreed to collaborate in the production of European Guidelines for different hematological malignancies. As a first step, a number of completed guidelines will be reviewed by the corresponding EHA Scientific Working Groups in a standardized review process. The ESMO guideline on Marginal Zone Lymphomas1 represents the first example of this collaboration and has been endorsed by the EHA LyG (www.ehalyg.org). The definition of marginal zone lymphoma (MZL) encompasses a number of different entities including extra nodal MZL (EMZL) of mucosa-associated lymphoid tissue (MALT), also known as MALT lymphoma, splenic MZL (SMZL) with or without villous lymphocytes and nodal MZL (NMZL) with or without monocytoid B cells. These entities and particularly MALT lymphoma are far from being homogeneous in terms of etiology, biology, clinical presentation, and treatment. Increasing knowledge has been accumulated on the biology and pathogenesis of several of these entities, and histological characterization appears straightforward compared to the past. Due to rarity and heterogeneity of this subgroup, very few randomized phase III clinical trials have focused on MZL. As a consequence, most of the evidence is still arising from retrospective or some clinical prospective experiences, as well as from studies enrolling multiple histological subtypes of indolent lymphomas. Nevertheless, substantial progress has been made over recent years including results from few well-conducted histotype-specific and (for EMZL) site-specific prospective clinical trials. The combination of rituximab and chlorambucil in EMZL or the benefit of ibrutinib in relapsed MZL are 2 prominent examples of recent practice-changing advances in the field. It should be noted that, until now, European guidelines have not been available for most MZL-related conditions. ESMO guidelines were limited to gastric EMZL and only few and often obsolete national guidelines have become available. The current MZL clinical practice guidelines1 are therefore an ambitious and unprecedented effort, as all MZL entities have been covered in detail. This is particularly relevant for SMZL where considerable heterogeneity among treatment choices exist ranging from splenectomy, antiviral treatment, immunotherapy and immunochemotherapy. The purpose of any guideline is to provide the best available clinical guidance in an easy and accessible way that could be effectively translated in the everyday practice. It must be realized that the field still lacks high levels of evidence in some critical points that impact the management of our patients. Nevertheless, hematologists, clinical oncologists, radiation oncologists, biologists and pathologists who work on the development of these guidelines have struggled to generate a balanced and effective tool that hopefully will be of substantial help for clinicians dealing with MZL in Europe and beyond.
No difference in hepatocellular carcinoma risk between chronic hepatitis B patients treated with entecavir versus tenofovir
Authors: Feng Su, Kristin Berry, George N Ioannou
Journal: Gut (2020)

Objective Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line agents for the treatment of chronic hepatitis B (CHB). Recent studies have challenged the assumption that these agents are equally effective at preventing hepatocellular carcinoma (HCC). We aimed to determine whether the risk of HCC and mortality differ in patients with CHB treated with ETV and TDF. Design We performed a retrospective cohort study of Veterans Affairs patients with CHB in the USA who initiated treatment with ETV or TDF between the dates of Food and Drug Administration approval of these medications and 1 January 2017. Multivariable Cox proportional hazards regression was used to determine the association between antiviral therapy and HCC risk as well as the risk of death or liver transplantation. Propensity score adjustment and competing risks analysis were performed. Results We identified 2193 ETV-treated and 1094 TDF-treated patients who were followed for a mean of 5.4 years. We found no difference in the risk of HCC in ETV-treated versus TDF-treated patients (adjusted HR (aHR) 1.00, 95% CI 0.76 to 1.32). Results were similar in propensity score adjusted and competing risks analysis, and in multiple sensitivity analyses. We also found no difference in the risk of death or liver transplantation (aHR 1.16, 95% CI 0.98 to 1.39). Conclusions We found no difference in the risk of HCC between patients with CHB treated with ETV versus TDF. Our results support current guideline recommendations that both agents are appropriate first-line options for the treatment of CHB.
A new 12-French plastic stent for unresectable distal malignant biliary obstruction
Authors: Pierre H. Deprez, Tom G. Moreels, Tarik Aouattah, Hubert Piessevaux, Enrique Pérez-Cuadrado-Robles
Journal: Endoscopy (2020)

Background Self-expanding metal stents (SEMSs) are recommended in unresectable distal malignant biliary obstruction. However, problems with dysfunction and migration of these stents are not negligible. We aimed to investigate the effectiveness and safety of a new 12-Fr plastic stent. Methods In an observational, prospective study, all consecutive patients who underwent biliary stenting with the 12-Fr stent were considered (index group). Referent groups were a historical cohort, matched by sex, etiology, and metastatic status, including patients with 10-Fr plastic stents and with fully covered and uncovered SEMSs (FCSEMSs and UCSEMSs). Outcomes were stent patency, recurrent biliary obstruction (RBO), technical success, 30-day mortality and adverse events. A post-procedure examination of removed stents was done. Results 72 patients (median age 66, range 32 – 94 years, 50 % men) were included (24 index, 48 referents). There were no differences in median stent patency time (P = 0.684). RBO was significantly lower with the 12-Fr compared with the 10-Fr profile stent (50 % vs. 81.3 %, P = 0.04), but no difference was found compared with the FCSEMSs (50 % vs. 43.8 %, P = 0.698). Technical success was 100 %, with no differences in 30-day mortality P = 0.105). The adverse events rate was 4.2 % for both groups (index n = 1, referents n = 2). Of 11 removed 12-Fr plastic stents suspected to be dysfunctional, 7 (64 %) were still patent. Conclusions This new 12-Fr plastic stent could be an effective and cheaper alternative to SEMSs in distal malignant biliary obstruction.
Fertility clinic must release records of dead man’s sperm to his brother, judge rules
Authors: Clare Dyer
Journal: BMJ (2020)

The top family court judge in England and Wales has ordered a fertility clinic to hand over medical records about its use of a dead patient’s sperm to the man’s brother.1

Andrew McFarlane, president of the High Court’s family division, ruled that the unnamed clinic must release records relating to the storage and use of the patient’s sperm and any embryos created using his sperm.

The highly unusual case was heard partly in private, and a reporting restriction order bans publication of the names of the parties and other individuals involved in the case.

The application …
Erratum: Corrigendum: Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis
Authors: Adriano G Rossi, Deborah A Sawatzky, Annemieke Walker, Carol Ward, Tara A Sheldrake, Nicola A Riley, Alison Caldicott, Magdalena Martinez-Losa, Trevor R Walker, Rodger Duffin, Mohini Gray, Elvira Crescenzi, Morag C Martin, Hugh J Brady, John S Savill, Ian Dransfield, Christopher Haslett
Journal: Nature Medicine (2006)
Percutaneous Left Axillary Artery Placement of Intra-Aortic Balloon Pump in Advanced Heart Failure Patients
Authors: Arvind Bhimaraj, Tanushree Agrawal, Antonio Duran, Omar Tamimi, Javier Amione-Guerra, Barry Trachtenberg, Ashrith Guha, Imad Hussain, Ju Kim, Mahwash Kassi, Jiaqiong Xu, Erik Suarez, Uy Q. Ngo, Guillermo Torre-Amione, Jerry D. Estep
Journal: JACC Heart Failure (2020)
Terminology and definition of ‘antinuclear antibodies’: history and current debate
Authors: Robert Daniel Heinrich Markewitz, Klaus-Peter Wandinger
Journal: Annals of the Rheumatic Diseases (2020)

Recently, a series of letters has been published in the Annals of the Rheumatic Diseases 1–10 in response to an article by Pisetsky et al on the variability of indirect immunofluorescence (IIF) assays for testing for antinuclear antibodies (ANAs) in systemic lupus erythematodes (SLE).11 This discussion has focused on the merits and shortcomings of different assays used in the detection of ANA. Only one of the contributions briefly addresses one of the key questions: ‘What is an ANA?’.3 Because the term ANA itself has been judged anachronistic and misleading by many,12 with efforts to replace it under way,13 14 this is not a trivial question to answer. Since the terminology around ANA has developed historically, it is useful to explore the contexts in which these terms originated in order to understand their original definition and the changes therein over time.

From the late 1940s onwards research into the serology of SLE gradually led to the discovery that autoantibodies against components of the cells’ nucleus could be found in sera of SLE patients.13–21 Because the exact target antigens remained largely unknown at first (except for dsDNA and histone) Holman et al coined the term ‘antinuclear antibody’ or ANA for them.22 23 With the advent of IIF testing on HEp-2-cells as standard method for the detection of ANA, it …
Geographic Distribution of Racial Differences in Prostate Cancer Mortality
Authors: Sean A. Fletcher, Maya Marchese, Alexander P. Cole, Brandon A. Mahal, David F. Friedlander, Marieke Krimphove, Kerry L. Kilbridge, Stuart R. Lipsitz, Paul L. Nguyen, Toni K. Choueiri, Adam S. Kibel, Quoc-Dien Trinh
Journal: JAMA Network Open (2020)

<h3>Importance</h3> While racial disparities in prostate cancer mortality are well documented, it is not well known how these disparities vary geographically within the US. <h3>Objective</h3> To characterize geographic variation in prostate cancer–specific mortality differences between black and white men. <h3>Design, Setting, and Participants</h3> This cohort study included data from 17 geographic registries within the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2007, to December 31, 2014. Inclusion criteria were men 18 years and older with biopsy-confirmed prostate cancer. Men missing data on key variables (ie, cancer stage, Gleason grade group, prostate-specific antigen level, and survival follow-up data) were excluded. Analysis was performed from September 5 to December 25, 2018. <h3>Exposure</h3> Patient SEER-designated race (ie, black, white, or other). <h3>Main Outcomes and Measures</h3> Fine and Gray competing-risks regression analyses were used to evaluate the difference in prostate-cancer specific mortality between black and white men. A stratified analysis by Gleason grade group was performed stratified as grade group 1 and grade groups 2 through 5. <h3>Results</h3> The final cohort consisted of 229 771 men, including 178 204 white men (77.6%), 35 006 black men (15.2%), and 16 561 men of other or unknown race (7.2%). Mean (SD) age at diagnosis was 64.9 (8.8) years. There were 4773 prostate cancer deaths among white men and 1250 prostate cancer deaths among black men. Compared with white men, black men had a higher risk of mortality overall (adjusted hazard ratio [AHR], 1.39 [95% CI, 1.30-1.48]). In the stratified analysis, there were 4 registries in which black men had worse prostate cancer-specific survival in both Gleason grade group 1 (Atlanta, Georgia: AHR, 5.49 [95% CI, 2.03-14.87]; Greater Georgia: AHR, 1.88 [95% CI, 1.10-3.22]; Louisiana: AHR, 1.80 [95% CI, 1.06-3.07]; New Jersey: AHR, 2.60 [95% CI, 1.53-4.40]) and Gleason grade groups 2 through 5 (Atlanta: AHR, 1.88 [95% CI, 1.46-2.45]; Greater Georgia: AHR, 1.29 [95% CI, 1.07-1.56]; Louisiana: AHR, 1.28 [95% CI, 1.07-1.54]; New Jersey: AHR, 1.52 [95% CI, 1.24-1.87]), although the magnitude of survival difference was lower than for Gleason grade group 1 in each of these registries. The greatest race-based survival difference for men with Gleason grade group 1 disease was in the Atlanta registry. <h3>Conclusions and Relevance</h3> These findings suggest that population-level differences in prostate cancer survival among black and white men were associated with a small set of geographic areas and with low-risk prostate cancer. Targeted interventions in these areas may help to mitigate prostate cancer care disparities at the national level.
Abstract 320: Selective Estrogen Receptor Modulator Retards Arterial Senescence and Atherosclerosis via Upregulation of Sirt-1 and Autophagy in Post-menopause Model Mouse
Authors: Yoshiyuki Ikeda, Takahiro Miyauchi, Masaaki Iwabayashi, Yuichi Akasaki, Yuichi Sasaki, Masaaki Miyata, Mitsuru Ohishi
Journal: Circulation Research (2015)

Background: Incidence of cardiovascular disease (CVD) increases with development of arterial senescence and atherosclerosis, which are accelerated after menopause in women. This study aims 1) to clarify the mechanism of which post-menopose facilitates arterial senescence and atherosclerosis, and 2) to develop optical treatment. Methods and results: Female Apolipoprotein E deficient (ApoE KO) mice underwent ovariectomy at 8 weeks old were used as post-menopausal model mice (PM). Age-matched female mice with sham operation were used as control (Ctr). We confirmed that serum estrogen concentration was significantly lower in PM than in Ctr. Twelve weeks after surgery, aortas were harvested to examine molecular biological analysis. Sirt-1 and the ratio of LC3II/LC3I protein expressions were significantly lower in PM than in Ctr. Ratio of senescence associated β galactosidase (SA-β Gal) positive cells and expressions of acetyl (Ac)-p53, p21, and PAI-1 were significantly higher in PM than in Ctr. Aortic atherosclerotic lesions assessed by Oil Red O staining was significantly greater in PM than in Ctr. Overexpression of either Sirt-1 or autophagy retarded arterial senescence in vitro. These results suggest that ovariectomy accelerates arterial senescence and atherosclerotic development through downregulation of Sirt-1 and autophagy. Next, we administrated selective estrogen receptor modulator (SERM) to PM mice. Sirt-1 and the ratio of LC3II/LC3I protein expression were significantly higher in SERM-treated PM mice than in untreated mice. Ratio of SA-β Gal positive cells, protein expressions of Ac-p53, p21, and PAI-1, and aortic atherosclerotic lesions were significantly lower in SERM-treated PM mice than in untreated mice. The effect of SERM on augmentation of autophagy and inhibition of arterial senescence and atherosclerotic development was attenuated by administration of sirtinol, Sirt-1 inhibitor. Conclusion: SERM retards development of arterial senescence and atherosclerosis by activation of Sirt-1 and autophagy in postmenopause mice.
Hemodynamics of Cerebral Aneurysms: Connecting Medical Imaging and Biomechanical Analysis
Authors: Vitaliy L. Rayz, Aaron A. Cohen-Gadol
Journal: Annual Review of Biomedical Engineering (2020)

In the last two decades, numerous studies have conducted patient-specific computations of blood flow dynamics in cerebral aneurysms and reported correlations between various hemodynamic metrics and aneurysmal disease progression or treatment outcomes. Nevertheless, intra-aneurysmal flow analysis has not been adopted in current clinical practice, and hemodynamic factors usually are not considered in clinical decision making. This review presents the state of the art in cerebral aneurysm imaging and image-based modeling, discussing the advantages and limitations of each approach and focusing on the translational value of hemodynamic analysis. Combining imaging and modeling data obtained from different flow modalities can improve the accuracy and fidelity of resulting velocity fields and flow-derived factors that are thought to affect aneurysmal disease progression. It is expected that predictive models utilizing hemodynamic factors in combination with patient medical history and morphological data will outperform current risk scores and treatment guidelines. Possible future directions include novel approaches enabling data assimilation and multimodality analysis of cerebral aneurysm hemodynamics.
Case 10-2020: An 83-Year-Old Man with Pancytopenia and Acute Renal Failure
Authors: David B. Sykes, Eric W. Zhang, Rebecca S. Karp Leaf, Valentina Nardi, Sarah E. Turbett
Journal: New England Journal of Medicine (2020)

An 83-year-old man presented with pancytopenia and acute renal failure. The haptoglobin level was normal, but levels of d-dimer and lactate dehydrogenase were markedly elevated. Tretinoin was administered, and diagnostic test results were received.
Older Clinicians and the Surge in Novel Coronavirus Disease 2019 (COVID-19)
Authors: Peter I. Buerhaus, David I. Auerbach, Douglas O. Staiger
Journal: JAMA (2020)

This Viewpoint summarizes the distribution of physicians and registered nurses aged 55 years and older in US cities caring for COVID-19 patients and proposes roles they can play in health systems that preserve their ability to apply their experience over the long-term course of the pandemic.