tbuckley/cabot-search huggingface dataset:
The Human Islet: Mini-Organ With Mega-Impact
Authors: John T Walker, Diane C Saunders, Marcela Brissova, Alvin C Powers
Journal: Endocrine Reviews (2021)

This review focuses on the human pancreatic islet-including its structure, cell composition, development, function, and dysfunction. After providing a historical timeline of key discoveries about human islets over the past century, we describe new research approaches and technologies that are being used to study human islets and how these are providing insight into human islet physiology and pathophysiology. We also describe changes or adaptations in human islets in response to physiologic challenges such as pregnancy, aging, and insulin resistance and discuss islet changes in human diabetes of many forms. We outline current and future interventions being developed to protect, restore, or replace human islets. The review also highlights unresolved questions about human islets and proposes areas where additional research on human islets is needed.
CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope cross-react with selective seasonal coronaviruses
Authors: Katie E. Lineburg, Emma J. Grant, Srividhya Swaminathan, Demetra S.M. Chatzileontiadou, Christopher Szeto, Hannah Sloane, Archana Panikkar, Jyothy Raju, Pauline Crooks, Sweera Rehan, Andrea T. Nguyen, Lea Lekieffre, Michelle A. Neller, Zhen Wei Marcus Tong, Dhilshan Jayasinghe, Keng Yih Chew, Christian A. Lobos, Hanim Halim, Jacqueline M. Burrows, Alan Riboldi-Tunnicliffe, Weisan Chen, Lloyd D’Orsogna, Rajiv Khanna, Kirsty R. Short, Corey Smith, Stephanie Gras
Journal: Immunity (2021)
The Hurricane Katrina Aftermath and Its Impact on Diabetes Care
Authors: William T. Cefalu, Steven R. Smith, Lawrence Blonde, Vivian Fonseca
Journal: Diabetes Care (2006)

Hurricane Katrina was one of the most powerful storms to ever hit the coastal U.S. and one of the most destructive natural disasters to hit the country. As brutal and destructive as the winds and storm surge were, it was the aftermath of this storm that wreaked the greatest havoc. Katrina will continue to have an impact on our daily lives, particularly for those of us who lived and continue to live in the area affected. Clearly the greatest destruction of property from this storm occurred in the New Orleans area, surrounding parishes, and the Mississippi Gulf Coast. However, in the aftermath of Katrina, Baton Rouge, the closest major city to the massive destruction and a major route for evacuation, served as the staging area for disaster relief for a number of agencies. In the days immediately after the hurricane, hundreds of thousands of evacuees flooded Baton Rouge, and in this sense, Baton Rouge became “ground zero” for the medical disaster relief effort and nongovernmental organizations. We summarize below our observations on this disaster and suggest that guidelines are needed for health care organizations, health care professionals, and people with chronic diseases like diabetes to have a “plan of action” for major disasters, natural and man made (including terrorist attacks and industrial accidents). Table 1 outlines a potential list of items needed by a person with diabetes for disaster preparedness.

The disruption of a normal routine was particularly difficult for those who had to deal with chronic diseases. Caring for a chronic disease, particularly one such as diabetes, demands significant attention on a daily basis. An individual with diabetes must be certain that supplies of insulin and/or other medications are up to date and available. Individuals must find time to monitor their glucose and, once the value is obtained, make …
Venetoclax with azacitidine or decitabine in blast‐phase myeloproliferative neoplasm: A multicenter series of 32 consecutive cases
Authors: Naseema Gangat, Paola Guglielmelli, Natasha Szuber, Kebede H. Begna, Mrinal M. Patnaik, Mark R. Litzow, Aref Al‐Kali, James M. Foran, Jeanne M. Palmer, Hassan Alkhateeb, Michelle A. Elliott, Curtis A. Hanson, Animesh Pardanani, Francesco Mannelli, Alessandro M. Vannucchi, Ayalew Tefferi
Journal: American Journal of Hematology (2021)

Abstract Venetoclax (Ven) combined with a hypomethylating agent (HMA) has now emerged as an effective treatment regimen for acute myeloid leukemia, in both de novo and relapsed/refractory setting. The current multicenter study retrospectively examined Ven + HMA treatment outcome among 32 patients (median age 69 years; 59% males) with blast‐phase myeloproliferative neoplasm (MPN‐BP). Pre‐leukemic phenotype included essential thrombocythemia (ET)/post‐ET myelofibrosis (34%), polycythemia vera (PV)/post‐PV myelofibrosis (38%) and primary myelofibrosis (28%). Twenty‐nine study patients were fully annotated cytogenetically and molecularly (NGS): 69% harbored complex karyotype and/or mutations, including TP53 (41%), IDH1/2 (21%), ASXL1 (21%), N/KRAS (14%), SRSF2 (10%), EZH2 (10%) and U2AF1 (7%). All patients received Ven combined with either azacitidine ( n = 12) or decitabine ( n = 20); either up front ( n = 23) or after failing another induction therapy ( n = 9). Complete remission with (CR) or without (CRi) count recovery was achieved in 14 (44%) patients and was more likely to occur in the absence of pre‐leukemic PV/post‐PV myelofibrosis phenotype ( p &lt; .01), complex karyotype ( p &lt; .01) or K/NRAS ( p = .03) mutations; seven of eight patients (88%) without vs four of 21 (19%) with complex karyotype or K/NRAS mutation achieved CR/CRi ( p &lt; .01); all 11 informative patients with pre‐leukemic PV/post‐PV myelofibrosis phenotype displayed complex karyotype ( p &lt; .01). In contrast, neither TP53 ( p = .45) nor IDH1/2 ( p = .63) mutations affected response. Compared to historical controls treated with HMA alone ( n = 26), the CR/CRi rate (44% vs 4%) and median survival (8 vs 5.5 months) were more favorable with Ven + HMA, but without significant difference in overall survival. Importantly, six patients with CR/CRi subsequently received allogeneic hematopoietic stem cell transplant (AHSCT). Note, Ven + HMA produces robust CR/CRi rates in MPN‐BP, especially in the absence of RAS mutations and complex karyotype, thus enabling AHSCT, in some patients.
Management of Acute Coronary Syndromes in Patients Without Persistent ST-Segment Elevation
Authors: Rajeev Anchan, Adam S. Cifu, Jonathan Paul
Journal: JAMA (2021)

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
Extracellular Vesicles from 3D Engineered Microtissues Harbor Disease‐Related Cargo Absent in EVs from 2D Cultures
Authors: Christopher Millan, Lukas Prause, Queralt Vallmajo‐Martin, Natalie Hensky, Daniel Eberli
Journal: Advanced Healthcare Materials (2021)

Abstract Engineered microtissues that recapitulate key properties of the tumor microenvironment can induce clinically relevant cancer phenotypes in vitro. However, their effect on molecular cargo of secreted extracellular vesicles (EVs) has not yet been investigated. Here, the impact of hydrogel‐based 3D engineered microtissues on EVs secreted by benign and malignant prostate cells is assessed. Compared to 2D cultures, yield of EVs per cell is significantly increased for cancer cells cultured in 3D. Whole transcriptome sequencing and proteomics of 2D‐EV and 3D‐EV samples reveal stark contrasts in molecular cargo. For one cell type in particular, LNCaP, enrichment is observed exclusively in 3D‐EVs of GDF15, FASN, and TOP1, known drivers of prostate cancer progression. Using imaging flow cytometry in a novel approach to validate a putative EV biomarker, colocalization in single EVs of GDF15 with CD9, a universal EV marker, is demonstrated. Finally, in functional assays it is observed that only 3D‐EVs, unlike 2D‐EVs, confer increased invasiveness and chemoresistance to cells in 2D. Collectively, this study highlights the value of engineered 3D microtissue cultures for the study of bona fide EV cargoes and their potential to identify biomarkers that are not detectable in EVs secreted by cells cultured in standard 2D conditions.
Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses
Authors: Lisa C. Zaba, Irma Cardinale, Patricia Gilleaudeau, Mary Sullivan-Whalen, Mayte Suárez-Fariñas, Judilyn Fuentes-Duculan, Inna Novitskaya, Artemis Khatcherian, Mark J. Bluth, Michelle A. Lowes, James G. Krueger
Journal: The Journal of Experimental Medicine (2008)
Characteristics of SARS-CoV-2 variants of concern B.1.1.7, B.1.351 or P.1: data from seven EU/EEA countries, weeks 38/2020 to 10/2021
Authors: Tjede Funk, Anastasia Pharris, Gianfranco Spiteri, Nick Bundle, Angeliki Melidou, Michael Carr, Gabriel Gonzalez, Alejandro Garcia-Leon, Fiona Crispie, Lois O’Connor, Niamh Murphy, Joël Mossong, Anne Vergison, Anke K. Wienecke-Baldacchino, Tamir Abdelrahman, Flavia Riccardo, Paola Stefanelli, Angela Di Martino, Antonino Bella, Alessandra Lo Presti, Pedro Casaca, Joana Moreno, Vítor Borges, Joana Isidro, Rita Ferreira, João Paulo Gomes, Liidia Dotsenko, Heleene Suija, Jevgenia Epstein, Olga Sadikova, Hanna Sepp, Niina Ikonen, Carita Savolainen-Kopra, Soile Blomqvist, Teemu Möttönen, Otto Helve, Joana Gomes-Dias, Cornelia Adlhoch
Journal: Eurosurveillance (2021)

We compared 19,207 cases of SARS-CoV-2 variant B.1.1.7/S gene target failure (SGTF), 436 B.1.351 and 352 P.1 to non-variant cases reported by seven European countries. COVID-19 cases with these variants had significantly higher adjusted odds ratios for hospitalisation (B.1.1.7/SGTF: 1.7, 95% confidence interval (CI): 1.0–2.9; B.1.351: 3.6, 95% CI: 2.1–6.2; P.1: 2.6, 95% CI: 1.4–4.8) and B.1.1.7/SGTF and P.1 cases also for intensive care admission (B.1.1.7/SGTF: 2.3, 95% CI: 1.4–3.5; P.1: 2.2, 95% CI: 1.7–2.8).
Abstract PO-024: Paclitaxel induced apoptosis through ROS production and eliminated cellular senescence in PC9-MET cells
Authors: Md Mohiuddin, Kazuo Kasahara
Journal: Clinical Cancer Research (2021)

Abstract Background: Paclitaxel is used as first-line and subsequent therapy for the treatment of various cancers. However, the mechanisms by which paclitaxel exerts its anticancer activity against non-small cell lung cancer (NSCLC) are not well understood. This study aimed to investigate paclitaxel's role in cell proliferation, apoptosis, and cellular senescence of PC9-MET (gefitinib-resistant) cells and reveal the underlying mechanisms. Methods: PC9-MET cells were treated with paclitaxel for 72 h and then evaluated by cell viability assay, Giemsa staining, DAPI staining, apoptosis assay, SA-β-Gal staining, ROS assay, TUNEL assay and western blotting. Results: Our results revealed that paclitaxel significantly reduced the viability of PC9-MET cells and induced morphological signs of apoptosis. The apoptotic effects of paclitaxel were observed by increased levels of cleaved caspase-3, cleaved caspase-9 and cleaved PARP. Additionally, paclitaxel increased ROS production, leading to DNA damage. Importantly, paclitaxel eliminated cellular senescence, which was observed by SA-β-Gal staining. Conclusion: In light of these findings, paclitaxel could be a promising agent for cancer treatment against human PC9-MET (gefitinib-resistant) cells. Citation Format: Md Mohiuddin, Kazuo Kasahara. Paclitaxel induced apoptosis through ROS production and eliminated cellular senescence in PC9-MET cells [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-024.
Changes to the Standards for Integrity and Independence in Continuing Medical Education
Authors: Graham T. McMahon
Journal: JAMA (2021)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2022 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
Reducing road traffic
Authors: G E Gamble, S Basu, A Porter
Journal: BMJ (1998)

Editor—The media devote much attention to proposed changes in transport policy, and Roberts has written an editorial on reducing road traffic.1 A poll of medical staff in our hospital showed that virtually all of them drive unaccompanied to work. The usual reasons for this were cited, and they were well aware of individual and communal health benefits from possible alternatives. There was a strong desire, especially among juniors, to combine exercise with commuting, but lack of workplace resources, including poor showering facilities and safe bicycle parks, led to staff continuing to drive. 

Doctors are often asked to—and do—lead by example in health issues, so encouraging medical staff to give up their cars is an important early step. Trust boards should provide certain basic requirements as standard. All we want is a safe home for a bicycle and sweaty clothes.
Doing our best to do no harm
Authors: Uri Ladabaum
Journal: Endoscopy (2021)

First do no harm. Colorectal cancer (CRC) screening is an exemplary public health success – but the vast majority of people will never develop CRC, with or without screening. The great successes of CRC screening require exposing very large numbers of people to the potential risks of screening. The study by Benazzato et al. of adverse events post-colonoscopy in Veneto’s CRC screening program [1] makes a valuable contribution by focusing on a population undergoing colonoscopy primarily because of an abnormal fecal immunochemical test (FIT).
Genetic polymorphisms, vitamin D binding protein and vitamin D deficiency in COVID-19
Authors: Aduragbemi A. Faniyi, Sebastian T. Lugg, Sian E. Faustini, Craig Webster, Joanne E. Duffy, Martin Hewison, Adrian Shields, Peter Nightingale, Alex G. Richter, David R. Thickett
Journal: European Respiratory Journal (2021)

We thank M.M. Speeckaert and co-workers for their interest in our paper about vitamin D status and seroconversion for coronavirus disease 2019 (COVID-19) in UK healthcare workers [1]. We agree with the authors that vitamin D binding protein (DBP) is important in determining serum 25(OH)D3 levels. The majority of vitamin D in the circulation is bound to DBP, also known as gc-globulin, which has actin-binding and immunomodulatory functions independent of vitamin D carriage [2]. DBP levels may be particularly relevant to determining 25(OH)D3 levels in severely ill COVID-19 patients with acute respiratory distress syndrome (ARDS), as we have previously demonstrated that DBP is a negative acute phase protein with levels dropping by about a third in patients with ARDS [3]. This tends to lower circulating total vitamin D but releases free 25(OH)D that can be taken up by cells of the immune system and epithelial cells. The consequences of changes in serum 25(OH)D during illness are, therefore, complex and difficult to interpret [4]. Genome-wide association analyses have shown that single nucleotide polymorphisms (SNPs) in the gene for DBP ( GC ) are important contributors to the genetic component of circulating 25D concentrations, but this is still a relatively small proportion of overall serum 25D levels, and it is unclear how these SNPs impact DBP/25D homeostasis in the setting of disease. This work outlines the potential importance of vitamin D binding protein and vitamin D in immune function and COVID-19 infection <https://bit.ly/3byTaO5>
The emerging paradigm of calcium homeostasis as a new therapeutic target for protozoan parasites
Authors: Yash Gupta, Steven Goicoechea, Catherine M. Pearce, Raman Mathur, Jesus G. Romero, Samuel K. Kwofie, Matthew C. Weyenberg, Bharathi Daravath, Neha Sharma, None Poonam, Hoseah M. Akala, Stefan M. Kanzok, Ravi Durvasula, Brijesh Rathi, Prakasha Kempaiah
Journal: Medicinal Research Reviews (2021)

Abstract Calcium channels (CCs), a group of ubiquitously expressed membrane proteins, are involved in many pathophysiological processes of protozoan parasites. Our understanding of CCs in cell signaling, organelle function, cellular homeostasis, and cell cycle control has led to improved insights into their structure and functions. In this article, we discuss CCs characteristics of five major protozoan parasites Plasmodium , Leishmania , Toxoplasma , Trypanosoma , and Cryptosporidium . We provide a comprehensive review of current antiparasitic drugs and the potential of using CCs as new therapeutic targets. Interestingly, previous studies have demonstrated that human CC modulators can kill or sensitize parasites to antiparasitic drugs. Still, none of the parasite CCs, pumps, or transporters has been validated as drug targets. Information for this review draws from extensive data mining of genome sequences, chemical library screenings, and drug design studies. Parasitic resistance to currently approved therapeutics is a serious and emerging threat to both disease control and management efforts. In this article, we suggest that the disruption of calcium homeostasis may be an effective approach to develop new anti‐parasite drug candidates and reduce parasite resistance.
Towards Functional Immune Monitoring in Allogeneic Hematopoietic Stem Cell Transpant Recipients
Authors: Swati Naik, Paibel I. Aguayo-Hiraldo, Spyridoula Vasileiou, Shivani Mukhi, Aster Workineh, Robert A. Krance, Stephen Gottschalk, Ann M. Leen
Journal: Blood (2017)
Computational methods for chromosome-scale haplotype reconstruction
Authors: Shilpa Garg
Journal: Genome biology (2021)

Abstract High-quality chromosome-scale haplotype sequences of diploid genomes, polyploid genomes, and metagenomes provide important insights into genetic variation associated with disease and biodiversity. However, whole-genome short read sequencing does not yield haplotype information spanning whole chromosomes directly. Computational assembly of shorter haplotype fragments is required for haplotype reconstruction, which can be challenging owing to limited fragment lengths and high haplotype and repeat variability across genomes. Recent advancements in long-read and chromosome-scale sequencing technologies, alongside computational innovations, are improving the reconstruction of haplotypes at the level of whole chromosomes. Here, we review recent and discuss methodological progress and perspectives in these areas.
Copanlisib plus rituximab versus placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma (CHRONOS-3): a double-blind, randomised, placebo-controlled, phase 3 trial
Authors: Matthew J Matasar, Marcelo Capra, Muhit Özcan, Fangfang Lv, Wei Li, Eduardo Yañez, Katya Sapunarova, Tongyu Lin, Jie Jin, Wojciech Jurczak, Aryan Hamed, Ming-Chung Wang, Ross Baker, Igor Bondarenko, Qingyuan Zhang, Jifeng Feng, Klaus Geissler, Mihaela Lazaroiu, Guray Saydam, Árpád Szomor, Krimo Bouabdallah, Rinat Galiulin, Toshiki Uchida, Lidia Mongay Soler, Anjun Cao, Florian Hiemeyer, Aruna Mehra, Barrett H Childs, Yuankai Shi, Pier Luigi Zinzani
Journal: The Lancet Oncology (2021)
Transcatheter Aortic Valve Replacement Versus Surgical Aortic Valve Replacement: How Would You Manage This Patient With Severe Aortic Stenosis?
Authors: Eileen E. Reynolds, Suzanne J. Baron, Tsuyoshi Kaneko, Howard Libman
Journal: Annals of Internal Medicine (2021)

Aortic stenosis (AS) is common, especially among the elderly. Left untreated, severe symptomatic AS is typically fatal. Surgical aortic valve replacement (SAVR) was the standard of care until transcatheter aortic valve replacement (TAVR) was shown to have lower mortality rates in patients at the highest surgical risk and was recommended for this group in the 2014 American Heart Association/American College of Cardiology (AHA/ACC) guidelines. In the 2017 AHA/ACC focused update, evidence of benefit and noninferiority extended the use of TAVR to intermediate-risk patients. More recent studies suggest potential benefit to low-risk patients, although no published guidelines yet recommend the use of TAVR for this population. An advantage of SAVR is a 30-year experience with valve durability, but SAVR may have higher rates of perioperative death and a slower return of quality of life. Although TAVR has less than 10-year experience with valve durability, it has lower or noninferior primary end points, such as mortality and stroke, and fewer periprocedural complications among anatomically permissive patients. Here, a cardiologist and a cardiothoracic surgeon debate the risks and benefits of TAVR versus SAVR for a patient with severe symptomatic AS who is at low risk for surgical death.
NAD <sup>+</sup> Repletion Reverses Heart Failure With Preserved Ejection Fraction
Authors: Dan Tong, Gabriele G. Schiattarella, Nan Jiang, Francisco Altamirano, Pamela A. Szweda, Abdallah Elnwasany, Dong I. Lee, Heesoo Yoo, David A. Kass, Luke I. Szweda, Sergio Lavandero, Eric Verdin, Thomas G. Gillette, Joseph A. Hill
Journal: Circulation Research (2021)

Rationale: Heart failure with preserved ejection fraction (HFpEF) is a mortal clinical syndrome without effective therapies. We recently demonstrated in mice that a combination of metabolic and hypertensive stress recapitulates key features of human HFpEF. Objective: Using this novel preclinical HFpEF model, we set out to define and manipulate metabolic dysregulations occurring in HFpEF myocardium. Methods and Results: We observed impairment in mitochondrial fatty acid oxidation associated with hyperacetylation of key enzymes in the pathway. Downregulation of sirtuin 3 and deficiency of NAD + secondary to an impaired NAD + salvage pathway contribute to this mitochondrial protein hyperacetylation. Impaired expression of genes involved in NAD + biosynthesis was confirmed in cardiac tissue from patients with HFpEF. Supplementing HFpEF mice with nicotinamide riboside or a direct activator of NAD + biosynthesis led to improvement in mitochondrial function and amelioration of the HFpEF phenotype. Conclusions: Collectively, these studies demonstrate that HFpEF is associated with myocardial mitochondrial dysfunction and unveil NAD + repletion as a promising therapeutic approach in the syndrome.