tbuckley/cabot-search huggingface dataset:
<i>BRCA1</i>and<i>BRCA2</i>Gene Mutations and Colorectal Cancer Risk: Systematic Review and Meta-analysis
Authors: Mok Oh, Ali McBride, Seongseok Yun, Sandipan Bhattacharjee, Marion Slack, Jennifer R Martin, Joanne Jeter, Ivo Abraham
Journal: JNCI Journal of the National Cancer Institute (2018)

Investigations of the associations with colorectal cancer have yielded conflicting results. The aim of our study was to synthesize the research on colorectal cancer risks in BRCA mutation carriers by means of a systematic review and quantitatively by means of meta-analyses overall and in subgroups of BRCA mutation carriers. We searched PubMed/MEDLINE, Embase, Cochrane, Scopus, and ProQuest Dissertation & Theses. Unadjusted odds ratios (ORs) were used to derive pooled estimates of colorectal cancer risk overall and in subgroups defined by mutation type (BRCA1 or BRCA2), cancer type (colorectal or colon cancer), study design (age–sex-adjusted or crude), and ascertainment method (ascertained or inferred genotyping). The associations were evaluated using random-effect models. All statistical tests were two-sided. Eighteen studies were included in the systematic review: five cohort studies with ascertained BRCA mutation, six cohort studies involving pedigree analysis, five case–control studies, and two kin–cohort studies. Of these, 14 were used in the meta-analysis, which revealed a statistically significant increased risk of colorectal cancer in overall BRCA mutation carriers (OR = 1.24, 95% confidence interval (CI) = 1.02 to 1.51, P = .03). In subgroup meta-analyses by BRCA type, BRCA1 mutation was associated with increased risk of colorectal cancer (OR = 1.49, 95% CI = 1.19 to 1.85, P < .001), but BRCA2 was not (OR = 1.10, 95% CI = 0.77 to 1.58, P = .61). In subgroup meta-analyses of studies reporting estimates adjusted for age and sex, an increased risk of colorectal cancer for BRCA1 (OR = 1.56, 95% CI = 1.23 to 1.98, P < .001), but not for BRCA2 (OR = 1.09, 95% CI = 0.75 to 1.58, P = .66) was observed. Analyses stratified by ascertainment method found no association between BRCA mutation and colorectal cancer risk. The meta-analysis results provide clinicians and health-care regulatory agencies with evidence of the increased risk of colorectal cancer in BRCA1 mutation carriers, but not in BRCA2.
A Biology-First Approach in Perinatal Pharmacoepidemiology of Autism
Authors: Diana Schendel, Jakob Christensen, Dheeraj Rai
Journal: JAMA Psychiatry (2018)

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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast 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 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 Psychiatry journal
Brain-Derived Neurotrophic Factor Improves Limited Exercise Capacity in Mice With Heart Failure
Authors: Junichi Matsumoto, Shingo Takada, Shintaro Kinugawa, Takaaki Furihata, Hideo Nambu, Naoya Kakutani, Masaya Tsuda, Arata Fukushima, Takashi Yokota, Shinya Tanaka, Hidehisa Takahashi, Masashi Watanabe, Shigetsugu Hatakeyama, Masaki Matsumoto, Keiichi I. Nakayama, Yutaro Otsuka, Hisataka Sabe, Hiroyuki Tsutsui, Toshihisa Anzai
Journal: Circulation (2018)
A Novel Engineered Small Protein for Positron Emission Tomography Imaging of Human Programmed Death Ligand-1: Validation in Mouse Models and Human Cancer Tissues
Authors: Arutselvan Natarajan, Chirag B. Patel, Sindhuja Ramakrishnan, Paramjyot S. Panesar, Steven R. Long, Sanjiv S. Gambhir
Journal: Clinical Cancer Research (2018)

Abstract Purpose: To design and evaluate a small engineered protein binder targeting human programmed death-1 ligand (hPD-L1) in vivo for PET imaging in four mouse tumor models, and in situ in human cancer specimens. Experimental Design: The hPD-L1 protein binder, FN3hPD-L1, was engineered using a 12-kDa human fibronectin type-3 domain (FN3) scaffold. The binder's affinity was assayed in CT26 mouse colon carcinoma cells stably expressing hPD-L1 (CT26/hPD-L1). 64Cu-FN3hPD-L1 was assayed for purity, specific activity, and immunoreactivity. Four groups of NSG mice (n = 3–5/group) were imaged with 64Cu-FN3hPD-L1 PET imaging (1–24 hours postinjection of 3.7 MBq/7 μg of Do-FN3 in 200 μL PBS): Nod SCID Gamma (NSG) mice bearing (i) syngeneic CT26/hPD-L1tumors, (ii) CT26/hPD-L1 tumors blocked (blk) by preinjected nonradioactive FN3hPD-L1 binder, (iii) hPD-L1-negative Raji xenografts, and (iv) MDA-MB-231 xenografts. The FN3hPD-L1 binder staining was evaluated against validated hPD-L1 antibodies by immunostaining in human cancer specimens. Results: FN3hPD-L1 bound hPD-L1 with 1.4 ± 0.3 nmol/L affinity in CT26/hPD-L1 cells. 64Cu-FN3hPD-L1 radiotracer showed &amp;gt;70% yield and &amp;gt;95% purity. 64Cu-FN3hPD-L1 PET imaging of mice bearing CT26/hPD-L1 tumors showed tumor-to-muscle ratios of 5.6 ± 0.9 and 13.1 ± 2.3 at 1 and 4 hours postinjection, respectively. The FN3hPD-L1 binder detected hPD-L1 expression in human tissues with known hPD-L1 expression status based on two validated antibodies. Conclusions: The 64Cu-FN3hPD-L1 radiotracer represents a novel, small, and high-affinity binder for imaging hPD-L1 in tumors. Our data support further exploration and clinical translation of this binder for noninvasive identification of cancer patients who may respond to immune checkpoint blockade therapies.
Abstract 15500: Comparisons of All-cause, Stroke- and Major Bleeding-related Medical Costs Among Non-valvular Atrial Fibrillation Patients Who Initiated Oral Anticoagulation Therapies in the US Department of Defense Military Health System
Authors: Kiran Gupta, Jack Mardekian, Tom Shank, Allison Keshishian, Qisu Zhang, Jeffrey Trocio
Journal: Circulation (2017)

Background: Few studies have compared the medical costs of oral anticoagulants (OACs) among non-valvular atrial fibrillation (NVAF) patients. The objective of the study was to compare the all-cause...
Addressing the Value of Gene Therapy and Enhancing Patient Access to Transformative Treatments
Authors: Rachel Salzman, Francesca Cook, Timothy Hunt, Harry L. Malech, Philip Reilly, Betsy Foss-Campbell, David Barrett
Journal: Molecular Therapy (2018)

Although high upfront costs for the high value of gene therapy have resulted in concerns about sufficient reimbursement to allow patient access to these therapies, the significant benefits of gene therapies will not be realized unless patients have access to them. Stakeholders are discussing these issues, and the payment models being developed for the newly approved gene therapies provide an early indication of the flexibility that will be needed from treatment manufacturers, payers, and policy makers to optimize patient access. Maximizing patient access to effective gene therapies is one integral part of the overall mission of the American Society of Gene and Cell Therapy, along with maximizing the quality of therapies and minimizing their costs.
Anthony Victor Hirsh
Authors: Malcolm Scott
Journal: BMJ (2018)

Anthony Victor Hirsh (“Tony”) was one of the leading andrologists in the UK and a general practitioner in central London. He did his preclinical training at King’s College London and his clinical training at Westminster Hospital Medical School, having gained an entrance scholarship to the latter. He went on to win a Nuffield travelling scholarship to Uganda, where he spent his elective in the year before he qualified.

After completing house jobs and a senior house officer post in obstetrics, Tony started training to become a surgeon, initially at Guy’s Hospital and then on the surgical registrar rotation programme at Whiston and St Helen’s hospitals in Liverpool. For family reasons, he returned to London and entered general practice in Wanstead, east London, in 1973.

He decided to restart his surgical training in 1976 and became a surgical registrar at Queen Mary’s Hospital in Roehampton and Putney Hospital. He was a clinical research fellow in andrology at the Institute of Urology, London, from 1979 to 1982, with honorary appointments …
Yemen: charities can’t agree on likelihood of famine
Authors: Sophie Arie
Journal: BMJ (2018)

A water delivery point in Yemen’s capital, Sanaa. Millions of children and adults across the war torn country rely on aid organisations to provide clean water

Mohammed Mohammed/Xinhua/PA

A lack of good data is making it difficult to assess whether Yemen faces an imminent threat of famine, after three years of civil war.

The United Nations, which is already coordinating food aid for eight million Yemenis, has been warning of a possible famine since early 2017. Most recently Mark Lowcock, head of the UN Office for the Coordination of Humanitarian Affairs, told the Security Council in New York, “There is now a clear …
CG0070, a conditionally replicating GM-CSF armed oncolytic adenovirus for the treatment of bladder cancer
Authors: Nagarajan Ramesh, Ying Ge, Shanti Ganesh, De-Chao Yu
Journal: Cancer Research (2005)

5019  In spite of early intervention with Bacillus Calmette-Guerin (BCG) and transurethral resection (TUR), high recurrence rates of bladder cancer has warranted the development of novel therapeutic modalities. Oncolytic viruses are currently being developed as biological therapeutic agent for the treatment of several cancers. CG0070 is a conditionally replicating oncolytic adenovirus designed to preferentially replicate in and kill retinoblastoma (Rb) pathway-defective cancer cells, which include the majority of bladder cancers. CG0070 has the potential for additional anti-tumor activity in that it carries the cDNA for human granulocyte macrophage colony stimulating factor (GM-CSF). In this communication, we report results of preclinical pharmacology studies of CG0070, including virus-mediated cytotoxicity, tumor specificity, GM-CSF expression in human bladder TCC cell lines and in vivo antitumor efficacy in two subcutaneous and one orthotopic xenograft bladder tumor models. CG0070 replicates in Rb-defective bladder TCC cell lines as efficiently as wild-type adenovirus, but produces 100-fold less virus in Rb-positive normal human cells. Additionally, CG0070 is up to 1000-fold more cytotoxic in Rb-defective bladder TCC cells in comparison to Rb-positive normal human cells. Infection of Rb pathway-defective bladder tumor cells with CG0070 (10 vp/cell) results in the production of 38-221 ng of GM-CSF/106 cells/24 hrs. The anti-tumor activity of CG0070 was evaluated in subcutaneously implanted 253J B-V and SW780 bladder TCC xenograft tumor models in NCR.nude mice. Significant anti-tumor activity was observed in the 253J B-V tumor model following five intratumoral injections of CG0070 at 3 different dose levels compared to saline-treated tumors (p
Practical Method for Calculation of Graft Index in Renal Transplant Scintigraphy
Authors: Bulent Yazici
Journal: Clinical Nuclear Medicine (2018)

Some quantitative indices have been described for renal transplant scintigraphy in evaluating graft dysfunction, some medical complications, and in predicting early and delayed graft function and long-term graft prognosis. Graft index is very useful and more accurate than many other indices in the prediction of delayed graft function and long-term prognosis. In this technical note, the method of calculation of graft index is shown in detail for the authors who want to use this index in further studies or in clinical practice.
Sialic acid is a critical fetal defense against maternal complement attack
Authors: Markus Abeln, Iris Albers, Ulrike Peters-Bernard, Kerstin Flächsig-Schulz, Elina Kats, Andreas Kispert, Stephen Tomlinson, Rita Gerardy-Schahn, Anja Münster-Kühnel, Birgit Weinhold
Journal: Journal of Clinical Investigation (2018)

The negatively charged sugar sialic acid (Sia) occupies the outermost position in the bulk of cell surface glycans. Lack of sialylated glycans due to genetic ablation of the Sia-activating enzyme CMP-sialic acid synthase (CMAS) resulted in embryonic lethality around day 9.5 post coitum (E9.5) in mice. Developmental failure was caused by complement activation on trophoblasts in Cmas-/- implants and was accompanied by infiltration of maternal neutrophils at the fetal-maternal interface, intrauterine growth restriction, impaired placental development, and a thickened Reichert's membrane. This phenotype, which shared features with complement receptor 1-related protein Y (Crry) depletion, was rescued in E8.5 Cmas-/- mice upon injection of cobra venom factor, resulting in exhaustion of the maternal complement component C3. Here we show that Sia is dispensable for early development of the embryo proper but pivotal for fetal-maternal immune homeostasis during pregnancy, i.e., for protecting the allograft implant against attack by the maternal innate immune system. Finally, embryos devoid of cell surface sialylation suffered from malnutrition due to inadequate placentation as a secondary effect.
Indoximod Combined with Standard Induction Chemotherapy Is Well Tolerated and Induces a High Rate of Complete Remission with MRD-Negativity in Patients with Newly Diagnosed AML: Results from a Phase 1 Trial
Authors: Ashkan Emadi, Vu H. Duong, Jeremy Pantin, Mohammad Imran, Rima Koka, Zeba Singh, Edward A. Sausville, Jennie Y. Law, Seung Tae Lee, Huidong Shi, Ravindra Kolhe, Maria R. Baer, Michael R. Loken, Eugene P. Kennedy, Charles Link, David H. Munn
Journal: Blood (2018)
Abstract 10368: Early Afterdepolarization Alternans Manifests T Wave Alternans in Left Ventricular Hypertrophy
Authors: Tengxian Liu, Chinmay Patel, Donglin Guo, Robert Ju, Peter Kowey, Gan-Xin Yan
Journal: Circulation (2013)

Objectives: T wave alternans (TWA) in the setting of left ventricular hypertrophy (LVH) and failure often heralds the development of R-on-T ectopic beat and torsade de pointes. In humans with LVH, ...
Incarceration, drug use, and infectious diseases: a syndemic still not addressed
Authors: Nickolas Zaller, Lauren Brinkley-Rubinstein
Journal: The Lancet Infectious Diseases (2018)

Substantial progress has been made in reducing HIV and, to a lesser extent, hepatitis C virus (HCV) incidence among people who inject drugs (PWID) globally.1 However, specific populations of PWID, particularly those who are incarcerated, are often overlooked or left out of interventions designed to reduce HIV and HCV transmission. In particular, we know that the period immediately following release from incarceration is a time of very high risk for HIV and HCV transmission as well as opioid-related overdose, largely owing to relapse to drug use post-release.
Risk Calculators and Decision Aids Are Not Enough for Shared Decision Making
Authors: Kimberly E. Kopecky, David Urbach, Margaret L. Schwarze
Journal: JAMA Surgery (2018)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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 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 Surgery journal
Drug-Penetration Gradients Associated with Acquired Drug Resistance in Patients with Tuberculosis
Authors: Keertan Dheda, Laura Lenders, Gesham Magombedze, Shashikant Srivastava, Prithvi Raj, Erland Arning, Paula Ashcraft, Teodoro Bottiglieri, Helen Wainwright, Timothy Pennel, Anthony Linegar, Loven Moodley, Anil Pooran, Jotam G. Pasipanodya, Frederick A. Sirgel, Paul D. van Helden, Edward Wakeland, Robin M. Warren, Tawanda Gumbo
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Acquired resistance is an important driver of multidrug-resistant tuberculosis (TB), even with good treatment adherence. However, exactly what initiates the resistance and how it arises remain poorly understood.To identify the relationship between drug concentrations and drug susceptibility readouts (minimum inhibitory concentrations [MICs]) in the TB cavity.We recruited patients with medically incurable TB who were undergoing therapeutic lung resection while on treatment with a cocktail of second-line anti-TB drugs. On the day of surgery, antibiotic concentrations were measured in the blood and at seven prespecified biopsy sites within each cavity. Mycobacterium tuberculosis was grown from each biopsy site, MICs of each drug identified, and whole-genome sequencing performed. Spearman correlation coefficients between drug concentration and MIC were calculated.Fourteen patients treated for a median of 13 months (range, 5-31 mo) were recruited. MICs and drug resistance-associated single-nucleotide variants differed between the different geospatial locations within each cavity, and with pretreatment and serial sputum isolates, consistent with ongoing acquisition of resistance. However, pretreatment sputum MIC had an accuracy of only 49.48% in predicting cavitary MICs. There were large concentration-distance gradients for each antibiotic. The location-specific concentrations inversely correlated with MICs (P < 0.05) and therefore acquired resistance. Moreover, pharmacokinetic/pharmacodynamic exposures known to amplify drug-resistant subpopulations were encountered in all positions.These data inform interventional strategies relevant to drug delivery, dosing, and diagnostics to prevent the development of acquired resistance. The role of high intracavitary penetration as a biomarker of antibiotic efficacy, when assessing new regimens, requires clarification.
Abstract 19305: High In-Hospital Mortality Rate in Patients Undergoing Impella CP Insertion During Cardiopulmonary Resuscitation
Authors: Hayaan Kamran, Supria K Batra, Christopher T Pyne, Sachin P Shah
Journal: Circulation (2017)

Introduction: The Impella CP (Abiomed, Danvers, MA) percutaneous mechanical circulatory support (MCS) device is indicated for left ventricular support in the setting of cardiogenic shock. Patients ...
ZD2‐Engineered Gold Nanostar@Metal‐Organic Framework Nanoprobes for T<sub>1</sub>‐Weighted Magnetic Resonance Imaging and Photothermal Therapy Specifically Toward Triple‐Negative Breast Cancer
Authors: Luyun Zhang, Chuang Liu, Yang Gao, Zihou Li, Jie Xing, Wenzhi Ren, Lili Zhang, Aiguo Li, Guangming Lu, Aiguo Wu, Leyong Zeng
Journal: Advanced Healthcare Materials (2018)

Abstract Compared with other subtypes of breast cancer, triple‐negative breast cancer (TNBC) is seriously threatening to human life. Therefore, it is a matter of urgency to develop multifunctional nanoprobes for visualized theranostics of TNBC, achieving specific targeting toward only TNBC, but not other subtypes. Nanoscale metal–organic frameworks (MOFs) show important potential in visualized theranostics of tumors, but it is critical to synthesize well‐defined core–shell MOF‐based nanocomposites by encapsulating a single nanoparticle within MOF. In this study, a TNBC‐targeted peptide (ZD2)‐engineered, and a single gold nanostar (AuNS) coated within MIL‐101‐NH 2 (Fe) by coating MOF with four cycles, obtain well‐defined core–shell AuNS@MOF‐ZD2 nanocomposites, which are expected to achieve T 1 ‐weighted magnetic resonance imaging and photothermal therapy (PTT) specifically targeting toward TNBC. The prepared AuNS@MOF‐ZD2 nanocomposites possess good biocompatibility, efficient T 1 ‐weighted magnetic resonance (MR) relaxivity and stable photothermal conversion ability with an efficiency of 40.5%. The in vitro and in vivo characterizations prove their performances of T 1 ‐weighted MR and PTT with a low power density of 808 nm laser, achieving excellent theranostic efficacy in TNBC. Importantly, it is demonstrated that the prepared AuNS@MOF‐ZD2 nanoprobes can specifically target TNBC cells (MDA‐MB‐231), but not other subtypes of breast cancer cells (MDA‐MB‐435, MDA‐MB‐468, and MCF‐7), indicating their promising application in visualized theranostics of breast cancers with molecular classification.
Abstract 16475: Pre-Operative 3D Posterior Leaflet Mitral Measurements Can Differentiate Patients Needing Leaflet Resection in Degenerative Mitral Valve Repair Suergery
Authors: Anna Calleja, Frédéric Poulin, Anna Woo, Tirone David, Sean Jedrzkiewicz, Harry Rakowski, Wendy Tsang, Paaladinesh Thavendiranathan
Journal: Circulation (2013)

Background: Although nonresectional techniques for mitral valve (MV) repair are increasing, leaflet resection is still needed for some patients with excessive posterior leaflet tissue. We hypothesi...
Abstract 19839: Risk of Gastrointestinal Bleeding following Myocardial Infarction in Patients Treated With Dual Antiplatelet Therapy: A Nationwide Cohort Study
Authors: Thomas S Sehested, Thomas A Gerds, Peter W Hansen, Mette G Charlot, Nicholas Carlson, Christian Torp-Pedersen, Lars V Køber, Mark A Hlatky, Gunnar H Gislason, Emil L Fosbøl
Journal: Circulation (2017)

Introduction: Treatment with dual antiplatelet therapy (DAPT) following myocardial infarction (MI) is associated with increased risk of gastrointestinal (GI) bleeding. Current guidelines predominan...
Non-superiority of lumen-apposing metal stents: Is the evidence conclusive?
Authors: Lotte Boxhoorn, Paul Fockens, Rogier P Voermans
Journal: Gut (2018)

With great interest we have read the work of Bang et al , comparing the efficacy of lumen-apposing metal stents (LAMS) and double-pigtail plastic stents (DPS) for endoscopic drainage of walled-off necrosis (WON).1 We congratulate the authors on completing the first randomised controlled trial comparing these two drainage strategies. They found no difference in the total number of procedures needed to achieve treatment success at 6-month follow-up. However, we feel that three important limitations have not been mentioned in the discussion.

First, we question whether the …