tbuckley/cabot-search huggingface dataset:
Detection of somatic variants in peripheral blood lymphocytes using a 25-gene hereditary cancer panel.
Authors: Bradford Coffee, Hannah Cox, Scott Sizemore, Susan Manley, Debora Mancini-Dinardo
Journal: Journal of Clinical Oncology (2016)

1580 Background: Next Generation Sequencing (NGS) can determine the relative proportion of normal and variant DNA in a sample by quantifying the read frequency for each variant. The vast majority of variants identified by our 25-gene cancer panel have read frequencies that are approximately 50:50 and follow a normal distribution, consistent with these variants being present in the germ-line. However, a small proportion of samples have variants with NGS read frequencies that fall outside of this range, consistent with these variants being somatic in origin. Here we report on the detection of these potentially somatic variants. Methods: A commercial testing cohort (N = 203,621) was queried to identify all variants classified as pathogenic or likely pathogenic with NGS read frequencies between 10%-30%, indicating that they may be somatic. Clinical parameters, such as personal cancer history and age at testing, were assessed. Results: 133 (0.065%) individuals were identified with a putative somatic variant based on NGS read frequencies outside of the heterozygous range. Among these individuals, 88% (117/133) were affected with cancer at the time of testing, compared to about 47% in our general testing population. Putative somatic mutations were detected in 12 of the 25 genes included in the panel, with the majority occurring inTP53 (77),ATM (18), and CHEK2 (20). Somatic variants in these three genes had an increased probability of being identified in older individuals, relative to somatic variants identified in the other panel genes. Eighteen of the 133 individuals (13.5%) also had a second pathogenic or likely pathogenic variant identified that is likely heterozygous based on NGS read frequency. This is similar to the positive rate for affected individuals in the overall testing cohort. Conclusions: The increased probability of observing a putative somatic variant in older individuals is consistent with previous studies demonstrating that variants are acquired in peripheral blood as people age. Together, these observations suggest that somatic variants are detectable by the more sensitive technique of NGS and are present in a proportion of the general population, specifically in older individuals.
Quantitative MRI Brain Studies in Mild Cognitive Impairment and Alzheimer's Disease: A Methodological Review
Authors: Stephanos Leandrou, Styliani Petroudi, Panayiotis A. Kyriacou, Constantino Carlos Reyes-Aldasoro, Constantinos S. Pattichis
Journal: IEEE Reviews in Biomedical Engineering (2018)

Classifying and predicting Alzheimer's disease (AD) in individuals with memory disorders through clinical and psychometric assessment is challenging, especially in mild cognitive impairment (MCI) subjects. Quantitative structural magnetic resonance imaging acquisition methods in combination with computer-aided diagnosis are currently being used for the assessment of AD. These acquisitions methods include voxel-based morphometry, volumetric measurements in specific regions of interest (ROIs), cortical thickness measurements, shape analysis, and texture analysis. This review evaluates the aforementioned methods in the classification of cases into one of the following three groups: normal controls, MCI, and AD subjects. Furthermore, the performance of the methods is assessed on the prediction of conversion from MCI to AD. In parallel, it is also assessed which ROIs are preferred in both classification and prognosis through the different states of the disease. Structural changes in the early stages of the disease are more pronounced in the medial temporal lobe, especially in the entorhinal cortex, whereas with disease progression, both entorhinal cortex and hippocampus offer similar discriminative power. However, for the conversion from MCI subjects to AD, entorhinal cortex provides better predictive accuracies rather than other structures, such as the hippocampus.
Decreased susceptibility to chlorhexidine affects a quarter of Escherichia coli isolates responsible for pneumonia in ICU patients
Authors: Béatrice La Combe, Alexandre Bleibtreu, Jonathan Messika, Romain Fernandes, Olivier Clermont, Catherine Branger, Typhaine Billard-Pomares, Guilène Barnaud, Fatma Magdoud, Matthieu Eveillard, Achille Kouatchet, Sigismond Lasocki, Pierre Asfar, Stéphane Corvec, Karim Lakhal, Laurence Armand-Lefevre, Michel Wolff, Jean-François Timsit, Sandrine Bourdon, Jean Reignier, Stéphanie Martin, Vincent Fihman, Nicolas de Prost, Julien Bador, Pierre-Emmanuel Charles, Julien Goret, Alexandre Boyer, Frederic Wallet, Emmanuelle Jaillette, Saad Nseir, Luce Landraud, Raymond Ruimy, Pierre-Eric Danin, Jean Dellamonica, Julie Cremniter, Jean-Pierre Frat, Françoise Jauréguy, Christophe Clec’h, Dominique Decré, Eric Maury, Didier Dreyfuss, Erick Denamur, Jean-Damien Ricard
Journal: Intensive Care Medicine (2018)
Therapeutic synergy between tigecycline and venetoclax in a preclinical model of <i>MYC</i> / <i>BCL2</i> double-hit B cell lymphoma
Authors: Micol Ravà, Aleco D’Andrea, Paola Nicoli, Ilaria Gritti, Giulio Donati, Mirko Doni, Marco Giorgio, Daniela Olivero, Bruno Amati
Journal: Science Translational Medicine (2018)

The antibiotic tigecycline and the BCL2 inhibitor venetoclax cooperate to treat MYC/BCL2 double-hit lymphomas in xenografted mice.
Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial
Authors: Mats Jerkeman, Christian Winther Eskelund, Martin Hutchings, Riikka Räty, Karin Fahl Wader, Anna Laurell, Helle Toldbod, Lone Bredo Pedersen, Carsten Utoft Niemann, Christina Dahl, Hanne Kuitunen, Christian H Geisler, Kirsten Grønbæk, Arne Kolstad
Journal: The Lancet Haematology (2018)
Label-Free Analyses of Minimal Residual Disease in ALL Using Deep Learning and Imaging Flow Cytometry
Authors: Minh Doan, Marian Case, Dino Mašić, Holger Hennig, Claire McQuin, Allen Goodman, Juan Caicedo, Olaf Wolkenhauer, Huw Summers, Anne E Carpenter, Andy Filby, Paul Rees, Julie Irving
Journal: Blood (2017)
Letter to the GMC chair regarding Hadiza Bawa-Garba
Authors: Nick Ross
Journal: BMJ (2018)

The following is a letter to the chair of the General Medical Council.

Dear Professor Stephenson,

I write to you about what seems to be a serious misjudgment by the GMC regarding Hadiza Bawa-Garba.1

To set the context for my concerns, I am, among other things, a non-executive director of a major acute hospital trust, president of the charity Healthwatch, which promotes evidence based medicine, and the longest serving member of the Royal College of Physicians’ committee on ethics in medicine.

On all three criteria—management, evidence, and ethics—I fear the GMC has misjudged this case. As a journalist and broadcaster I suspect that one of the factors might have been pressure from the media, and I remind you that newspaper reporters are out to make a story, not nuanced judgments, and their printed …
Among Patients With Nonalcoholic Fatty Liver Disease, Modest Alcohol Use Is Associated With Less Improvement in Histologic Steatosis and Steatohepatitis
Authors: Veeral Ajmera, Patricia Belt, Laura A. Wilson, Ryan M. Gill, Rohit Loomba, David E. Kleiner, Brent A. Neuschwander-Tetri, Norah Terrault
Journal: Clinical Gastroenterology and Hepatology (2018)
Rhinovirus respiratory tract infection in hospitalized adult patients is associated with T H 2 response irrespective of asthma
Authors: Kelvin K.W. To, Lu Lu, Carol H.Y. Fong, Alan K.L. Wu, Ka-Yi Mok, Cyril C.Y. Yip, Yi-Hong Ke, Kong-Hung Sze, Susanna K.P. Lau, Ivan F.N. Hung, Kwok-Yung Yuen
Journal: Journal of Infection (2018)
Abstract 11390: The Personal and Family History Questions in the AHA Cardiovascular Screen for Athletes and the Screening ECG
Authors: Tim Dunn, Sonya Aggarwal, David Pickham, Divya Sani, Nikhil Kumar, Victor Froelicher
Journal: Circulation (2014)

Background: The American Heart Association (AHA) guidelines regarding the preparticipation evaluation (PPE) of competitive athletes recommend screening with 12-elements which consists of 8 question...
Treatment of rheumatoid arthritis with biologic agents lowers the risk of incident chronic kidney disease
Authors: Keiichi Sumida, Miklos Z. Molnar, Praveen K. Potukuchi, Fatima Hassan, Fridtjof Thomas, Kunihiro Yamagata, Kamyar Kalantar-Zadeh, Csaba P. Kovesdy
Journal: Kidney International (2018)
PTH-054B The clinical applications of the pillcam colon capsule endoscopy: a single centre experience
Authors: S Thayalasekaran, P Bhandari, A Quine, G Longcroft-Wheaton
Journal: Gut (2017)

Introduction  The PillCam Colon Capsule is a minimally invasive colonic imaging modality that is emerging as a safe and effective tool to visualise the colon. To date the majority of studies have focused on its use in research settings where it has been evaluated for colonic polyp and cancer detection.  Method  The aim of this study is to report on the current clinical use of colon capsule in a large teaching hospital in the South of  England. This was a single centre retrospective review of all the PillCam colon capsules performed from April 2015 to  November 2016.  Results  A total of 37 patients (27 females, 10 males), median age 43.5 (maximum age 82 years and minimum age 20 years) were evaluated. 22/37 (59.5%) had a previous attempt at colonoscopy. Reasons for colon capsule over colonoscopy were: 12/37 pain. 12/37 need for small bowel investigations, 4/37 anxiety, 2/37 patient choice, 2/37 reaction to IV contrast for CT, 1/37 learning difficulties, 1/37 Ehlers-Danlos, 1/37 tachycardia at flexible sigmoidoscopy and 1/37 agorophobia.  The colon capsule was completed in 23/37 (62%) of patients. In 4/14 cases the capsule did not exit the stomach, so a clinic appointment is scheduled to discuss positioning of the capsule with gastroscopy. In 10/14 patients the colon capsule was incomplete; 3 reached the left colon and 7 reached the rectum. In 2/14 incomplete colon capsules a flexible sigmoidoscopy completed investigations. 3/14 incomplete colon capsule patients were discharged as a functional disorder was diagnosed. 2/14 patients are awaiting colonoscopy under GA and 1/14 a flexible sigmoidoscopy for polyp removal. 1/14 had a colonoscopy and polypectomy under sedation. 1 patient subsequently died, but this was unrelated to the colon capsule. 87% of the cases avoided subsequent colonoscopy. There were no complications observed in the series.  16/23 (69.6%) completed colon capsules identified pathology. 7 had features of inflammatory bowel disease. 6 identified polyps; 2 proceeded to endoscopic resection and the remaining 4 diminutive polyps are scheduled a clinic appointment to discuss the relative merits of endoscopic resection. The remaining 3 colon capsules identified threadworms; diverticular disease and angioectasia respectively.  Conclusion  Colon capsule is safe and colonoscopy was avoided in 87% of patients. It is associated with a high pick up rate for pathology. The failure rate is high but usually in the left colon where a flexible sigmoidoscopy can complete examination easily. We believe that it is an effective approach for investigation of patients where tolerance to colonoscopy is likely to be poor, or where additional small bowel investigation is required, particularly in the evaluation of IBD or obscure bleeding where radiological imaging may be less effective or contraindicated.  Disclosure of Interest  None Declared
Trump administration halts “evidence based” treatment database
Authors: Owen Dyer
Journal: BMJ (2018)

The Trump administration has stopped all funding of the National Registry of Evidence Based Programs and Practices (NREPP), a searchable database that evaluates hundreds of treatments for addiction and mental ill health.

NREPP, which was formed in 1997, stopped adding new data to its website in September. The reason became clear four months later, when the contractor charged with compiling the database, Development Services Group, sent an email to registry participants to say that it could no longer collect data.

“It is with …
Brentuximab Vedotin in Combination with Bendamustine in Relapsed or Refractory Hodgkin Lymphoma: A Retrospective Analysis on 23 Paediatric Patients or Young Adults
Authors: Luciana Vinti, Franco Locatelli, Pietro Merli, Rosanna Parasole, Salvatore Buffardi, Marta Pillon, Luisa Strocchio, Katia Girardi
Journal: Blood (2017)
Comparison of different histological indexes in the assessment of UC activity and their accuracy regarding endoscopic outcomes and faecal calprotectin levels
Authors: Fernando Magro, Joanne Lopes, Paula Borralho, Susana Lopes, Rosa Coelho, José Cotter, Francisca Dias de Castro, Helena Tavares de Sousa, Marta Salgado, Patrícia Andrade, Ana Isabel Vieira, Pedro Figueiredo, Paulo Caldeira, A Sousa, Maria A Duarte, Filipa Ávila, João Silva, Joana Moleiro, Sofia Mendes, Sílvia Giestas, Paula Ministro, Paula Sousa, Raquel Gonçalves, Bruno Gonçalves, Ana Oliveira, Isadora Rosa, Marta Rodrigues, Cristina Chagas, Cláudia Camila Dias, Joana Afonso, Karel Geboes, Fátima Carneiro
Journal: Gut (2018)

Objective Histological remission is being increasingly acknowledged as a therapeutic endpoint in patients with UC. The work hereafter described aimed to evaluate the concordance between three histological classification systems—Geboes Score (GS), Nancy Index (NI) and RobartsHistopathologyIndex (RHI), as well as to evaluate their association with the endoscopic outcomes and the faecal calprotectin (FC) levels. Design Biopsy samples from 377 patients with UC were blindly evaluated using GS, NI and RHI. The results were compared with the patients’ Mayo Endoscopic Score and FC levels. Result GS, NI and RHI have a good concordance concerning the distinction between patients in histological remission or activity. RHI was particularly close to NI, with 100% of all patients classified as being in remission with NI being identified as such with RHI and 100% of all patients classified as having activity with RHI being identified as such with NI. These scores could also predict the Mayo Endoscopic Score and the FC levels, with their sensitivity and specificity levels depending on the chosen cut-offs. Moreover, higher FC levels were statistically associated with the presence of neutrophils in the epithelium, as well as with ulceration or erosion of the intestinal mucosa. Conclusions GS, NI and RHI histopathological scoring systems are comparable in what concerns patients’ stratification into histological remission/activity. Additionally, FC levels are increased when neutrophils are present in the epithelium and the intestinal mucosa has erosions or ulcers. The presence of neutrophils in the epithelium is, indeed, the main marker of histological activity.
Friend or foe? The dual role of neutrophils in lung injury and repair
Authors: Frances S Grudzinska, Elizabeth Sapey
Journal: Thorax (2018)

Studies describing the role of neutrophils in acute lung injury (ALI) show divergent results. Some support a pivotal role for neutrophils in the development of lung injury, with improvements in outcomes following inhibition of neutrophil recruitment or their granular contents. Others describe poorer outcomes in patients with neutropenia and no improvements in clinical outcomes or inflammatory biomarkers following interventions which target neutrophils. This has led to uncertainty about whether neutrophils are a therapeutic target in this condition. The recent publication by Blazquez-Prieto et al provides some insight into why different studies may vary in outcome. It describes increased inflammation and a poorer recovery in a murine model where neutrophils are depleted 24 hours after a ventilator-induced lung injury (VILI), and links tissue repair to the sustained activity of neutrophil-derived matrix metalloproteinase (MMP)-9 in cellular, animal and human studies. These data suggest the timing of targeting neutrophils may be critical for improving outcomes in ALI. This editorial explores the evidence for this finding and discusses heterogeneous neutrophil populations in disease and the role of MMP-9 in tissue repair. 

Our current understanding of the pathogenesis of ALI includes a paradox which incorporates the following four pieces of evidence.

First, in human and animal studies, neutrophil numbers in bronchoalveolar lavage fluid (BALF) correlate with ALI severity and are predictive of mortality.1 Furthermore, there is evidence of increased neutrophil proteinase (especially neutrophil elastase) and oxidant2 activity in ALI which correlate with the severity of the clinical syndrome. This suggests that neutrophils are centrally implicated in the onset and progression of ALI, where endothelial and epithelial injuries are associated with microvascular permeability, increased tissue oedema and an early accumulation of activated neutrophils to the lung.

Second, in animal models of ALI, reducing neutrophil accumulation to the lung (eg, by targeting CXCR2) or/and inhibiting the …
Scopolamine Poisoning Among Heroin Users— New York City, Newark, Philadelphia, and Baltimore, 1995 and 1996
Journal: JAMA (1996)

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
Renal Interstitial Platelet-Derived Growth Factor Receptor-β Cells Support Proximal Tubular Regeneration
Authors: Ina Maria Schiessl, Alexandra Grill, Katharina Fremter, Dominik Steppan, Maj-Kristina Hellmuth, Hayo Castrop
Journal: Journal of the American Society of Nephrology (2018)

Background The kidney is considered to be a structurally stable organ with limited baseline cellular turnover. Nevertheless, single cells must be constantly replaced to conserve the functional integrity of the organ. PDGF chain B (PDGF-BB) signaling through fibroblast PDGF receptor- β (PDGFR β ) contributes to interstitial-epithelial cell communication and facilitates regenerative functions in several organs. However, the potential role of interstitial cells in renal tubular regeneration has not been examined. Methods In mice with fluorescent protein expression in renal tubular cells and PDGFR β -positive interstitial cells, we ablated single tubular cells by high laser exposure. We then used serial intravital multiphoton microscopy with subsequent three-dimensional reconstruction and ex vivo histology to evaluate the cellular and molecular processes involved in tubular regeneration. Results Single-tubular cell ablation caused the migration and division of dedifferentiated tubular epithelial cells that preceded tubular regeneration. Moreover, tubular cell ablation caused immediate calcium responses in adjacent PDGFR β -positive interstitial cells and the rapid migration thereof toward the injury. These PDGFR β -positive cells enclosed the injured epithelium before the onset of tubular cell dedifferentiation, and the later withdrawal of these PDGFR β -positive cells correlated with signs of tubular cell redifferentiation. Intraperitoneal administration of trapidil to block PDGFR β impeded PDGFR β -positive cell migration to the tubular injury site and compromised the recovery of tubular function. Conclusions Ablated tubular cells are exclusively replaced by resident tubular cell proliferation in a process dependent on PDGFR β -mediated communication between the renal interstitium and the tubular system.
Abstract 13973: Time Course of Reverse Remodeling Following Catheter Ablation of Persistent Atrial Fibrillation
Authors: Takashi Kanda, Masaharu Masuda, Masashi Fujita, Osamu Iida, Shin Okamoto, Takayuki Ishihara, Kiyonori Nanto, Akihiro Sunaga, Takuya Tsujimura, Shota Okuno, Yasuhiro Masuda, Koji Yanaka, Takuya Ohashi, Hiroyuki Kawai, Aki Tsuji, Yosuke Hata, Masaaki Uematsu
Journal: Circulation (2016)

Introduction: Preservation of sinus rhythm following catheter ablation (CA) for persistent atrial fibrillation (PeAF) brings about structural reverse remodeling and recovery of cardiac function. However, the time course of reverse remodeling has not been well defined. Purpose: This study aimed to evaluate the time course of echocardiographic parameters following CA of PeAF. Methods: We enrolled 89 consecutive patients with PeAF undergoing CA. Patients with AF recurrence during the follow-up were excluded. Echocardiography was performed to evaluate the cardiac function on day 1, and 1, 3, and 6 months after CA. Results: Forty-five patients who remained in sinus rhythm after ablation were included (69±6 years old, 40 (89%) males, AF duration 28.7±42.8 months, and CHADS2 score 1.8±1.1). The atrial filling velocity (A), peak mitral annular late diastolic velocity (a’) and deceleration time of the early diastolic filling velocity significantly increased for 1 month and then reached a plateau. Early diastolic filling velocity (E) and E/A ratio significantly decreased for 1 month and then reached a plateau. The left atrial volume index and left atrial dimension significantly decreased gradually until 3 months (Figure). The left ventricular end-diastolic and systolic dimensions, left ventricular ejection fraction, peak early diastolic velocity of the mitral annulus (e’), and raito of the E to e’ did not change significantly. Conclusions: Preservation of sinus rhythm following PeAF CA brought about the hemodynamic reverse remodeling first, followed by the structural reverse remodeling.
Rib Fracture Associated with <i>Bordetella pertussis</i> Infection
Authors: John A Zambrano, Talia N Herman
Journal: New England Journal of Medicine (2018)

A 66-year-old woman presented with a 2-week history of cough as well as bruising and pain across the right flank. Nasopharyngeal culture confirmed infection with Bordetella pertussis, and imaging revealed a rib with a displaced fracture that had resulted from coughing.
Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions
Authors: Chuang-Wei Wang, Lan-Yan Yang, Chun-Bing Chen, Hsin-Chun Ho, Shuen-Iu Hung, Chih-Hsun Yang, Chee-Jen Chang, Shih-Chi Su, Rosaline Chung-Yee Hui, See-Wen Chin, Li-Fang Huang, Yang Yu-Wei Lin, Wei-Yang Chang, Wen-Lang Fan, Chin-Yi Yang, Ji-Chen Ho, Ya-Ching Chang, Chun-Wei Lu, Wen-Hung Chung
Journal: Journal of Clinical Investigation (2018)

BACKGROUND. Cytotoxic T lymphocyte–mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs.