tbuckley/cabot-search huggingface dataset:
Genomic Signatures of Recent Adaptation in a Wild Bumblebee
Authors: Thomas J Colgan, Andres N Arce, Richard J Gill, Ana Ramos Rodrigues, Abdoulie Kanteh, Elizabeth J Duncan, Li Li, Lars Chittka, Yannick Wurm
Journal: Molecular Biology and Evolution (2022)

Environmental changes threaten insect pollinators, creating risks for agriculture and ecosystem stability. Despite their importance, we know little about how wild insects respond to environmental pressures. To understand the genomic bases of adaptation in an ecologically important pollinator, we analyzed genomes of Bombus terrestris bumblebees collected across Great Britain. We reveal extensive genetic diversity within this population, and strong signatures of recent adaptation throughout the genome affecting key processes including neurobiology and wing development. We also discover unusual features of the genome, including a region containing 53 genes that lacks genetic diversity in many bee species, and a horizontal gene transfer from a Wolbachia bacteria. Overall, the genetic diversity we observe and how it is distributed throughout the genome and the population should support the resilience of this important pollinator species to ongoing and future selective pressures. Applying our approach to more species should help understand how they can differ in their adaptive potential, and to develop conservation strategies for those most at risk.
Special Communication
Journal: JAMA (1962)

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
Rapid idiosyncratic mechanisms of clinical resistance to KRAS G12C inhibition
Authors: Yihsuan S. Tsai, Mark G. Woodcock, Salma H. Azam, Leigh B. Thorne, Krishna L. Kanchi, Joel S. Parker, Benjamin G. Vincent, Chad V. Pecot
Journal: Journal of Clinical Investigation (2022)

BACKGROUND. The KRAS proto-oncogene is among the most frequently mutated genes in cancer, yet for 40 years it remained an elusive therapeutic target. Recently, allosteric inhibitors that covalently bind to KRAS G12C mutations have been approved for use in lung adenocarcinomas. Although responses are observed, they are often short-lived, thus making in-depth characterization of the mechanisms of resistance of paramount importance.
A subset of follicular helper-like MAIT cells can provide B cell help and support antibody production in the mucosa
Authors: Owen Jensen, Shubhanshi Trivedi, Jeremy D. Meier, Keke C. Fairfax, J. Scott Hale, Daniel T. Leung
Journal: Science Immunology (2022)

Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that aid in protection against bacterial pathogens at mucosal surfaces through the release of inflammatory cytokines and cytotoxic molecules. Recent evidence suggests that MAIT cells can also provide B cell help. In this study, we describe a population of CXCR5+ T follicular helper (Tfh)–like MAIT cells (MAITfh) that have the capacity to provide B cell help within mucosal lymphoid organs. MAITfh cells are preferentially located near germinal centers in human tonsils and express the classical Tfh-associated transcription factor, B cell lymphoma 6 (BCL-6), the costimulatory markers inducible T cell costimulatory (ICOS) and programmed death receptor 1 (PD-1), and interleukin-21 (IL-21). We demonstrate the ability of MAIT cells to provide B cell help in vivo after mucosal challenge with Vibrio cholerae. Specifically, we show that adoptive transfer of MAIT cells into αβ T cell–deficient mice promoted B cell differentiation and increased serum V. cholerae–specific IgA responses. Our data demonstrate the capacity of MAIT cells to participate in adaptive immune responses and suggest that MAIT cells may be potential targets for mucosal vaccines.
Translational advances in hepatology
Authors: Camilla Pilati, Jean-Charles Nault, Eric Letouzé, Sandrine Imbeaud, Maxime Mallet, Anaïs Boulai, Julien Calderaro, Charles Balabaud, Benoit Terris, Valerie Paradis, Jean Scoazec, Anne De Muret, Catherine Guettier, Paulette Bioulac- Sage, Fabien Calvo, Jessica Zucman-Rossi, Paulette Bioulac-Sage, R Todd, William Lee, Caitlyn Ellerbe, Valerie Durkalski, Adrian Reuben
Journal: Hepatology (2013)

Introduction: Hepatocellular adenomas (HCA) are rare benign tumors developed in normal liver predominantly in young women using oral contraception.HCA lead to diagnostic pitfalls and several difficulties to assess the risk of malignant transformation in these young patients.Specific HCA subgroups are define by either (1) inactivation of the HNF1A transcription factor, (2) activation of the WNT/β-catenin or (3) activation of the IL6/STAT3 pathway by somatic mutation of IL6ST, GNAS or STAT3.Here we performed whole exome sequencing analysis in classical HCA and in 5 malignant transformation of HCA in hepatocellular carcinoma (HCC).Methods: 223 classical HCA, 18 borderline lesions between HCA and HCC and 9 HCC developed on HCA were collected, pathologically reviewed and classified according to the molecular classification.We performed whole exome sequencing, CGH-SNP analyses and methylome analyses in 46, 126 and 50 of the cases respectively and the results were validated in the whole series of tumors.Results: Chromosome instability increased progressively and significantly in borderline HCA/HCC lesions and in HCC derived from malignant transformation (P = 0.05) compared to classical HCA.In methylome analysis, the level of hypomethylation increased during malignant transformation (P = 0.002).Exome sequencing identified a progressive accumulation of somatic damaging mutation from classical HCA (mean 7.5 events per tumor), to HCA that transformed in HCC (mean of 24.4 events per tumors, P < 0.0001) to the highest number in HCC resulting from a HCA transformation (mean of 39 events per tumor) that is similar to that observed in classical HCC (41 events per tumor).Two genes with somatic mutations were found associated with malignant transformation of HCA: (1) CTNNB1 mutations activating β-catenin occurred early in the process (13% of classical HCC to 66% of transformed HCA) and (2) mutations in TERT promoter that increase the expression of TERT was identified exclusively in borderline (17%) and transformed HCA (56%).In contrast, we showed that HCA with mutation activating gp130 without CTNNB1 mutation were not at higher risk of malignant transformation.Conclusion: In conclusion, this work provided new insights about the major genetic determinants of malignant transformation and their timeframe accumulation during the adenoma-carcinoma sequence.This approach enlightened β-catenin activation as an early alteration in malignant transformation process and TERT promoter mutations as associated with the late step of carcinoma transition.
What Is Polycystic Ovary Syndrome?
Authors: Kristin Walter
Journal: JAMA (2022)

What Is Polycystic Ovary Syndrome?Polycystic ovary syndrome (PCOS) is a disorder of hormonal imbalance.Polycystic ovary syndrome includes elevated male sex hormones (hyperandrogenism), failure of the ovaries to release eggs (ovulatory dysfunction), and ovaries that are enlarged, have fluid-filled sacs (polycystic ovaries), or both.The cause of PCOS is unknown and treatment is primarily based on management of symptoms.
Prolonged L-arginine administration but not inducible nitric oxide synthase gene transfer reduces neointima formation after stent injury in rats Pieter Vermeersch, Zengxuan Nong, Hilde Gillijns, Natasha Van Pelt, Olivier Varenne, Eugenio Stabile, Ivan De Scheerder, Desire Collen, Stefan Janssens. Cardiac Unit, University Hospital Gasthuisberg, Leuven, Belgium, Center for Transgene Technology and Gene Therapy, University of Leuven, Leuven, Belgium
Journal: Journal of the American College of Cardiology (2001)
Diagnosis of pancreatic carcinoma by photoscanning
Authors: J. A. Burdine
Journal: JAMA (1965)

Pancreas scintiscanning with selenomethionine Se 75 and the photoscanner was employed in the study of 29 patients suspected of having pancreatic disease. In six of these patients, abnormalities ranging from localized defects to nonvisualization were encountered and subsequently proved to be caused by pancreatic adenocarcinoma. In four of these six cases, the pancreas scan was the only diagnostic test clearly implicating the pancreas as the source of difficulty. Due to the somewhat limited experience with this technique, pancreas scanning would be performed and the scintiscans interpreted with caution. These cases do demonstrate that the procedure can be a useful adjunct in the diagnosis of pancreatic carcinoma.
Comparison of percutaneous intervention with surgery in the treatment of total occlusion of abdominal aorta Won-Heum Shim, Seung-Hyuk Choi, Byoung-Kwon Lee, Donghoon Choi, Yangsoo Jang, Byung-Chul Chang, Seung-Yun Cho. Yonsei University, Seoul, South Korea
Journal: Journal of the American College of Cardiology (2001)
Eligibility for new therapies in elderly heart failure patients: Results from the National Heart Failure project Edward P. Havranek, Frederick A. Masoudi, Pam Wolfe, Kelly A. Westfall, Richard J. Delaney, Christine L. Mulgrew, Harlan M. Krumholz, Diana L. Ordin. Colorado Foundation for Medical Care, Aurora, CO, Health Care Financing Adminstration, Boston, MA
Journal: Journal of the American College of Cardiology (2001)
A phase 1b multicenter study of trifluridine/tipiracil (FTD/TPI) in combination with irinotecan (IRI) in patients (pts) with metastatic or unresectable gastric and gastroesophageal adenocarcinoma (mGEC) after at least one line of treatment with a fluoropyrimidine and platinum (FP) containing regimen.
Authors: Farshid Dayyani, Kit Wah Tam, Edward Jae-Hoon Kim, Samuel Ejadi, Fa Chyi Lee, Jennifer B. Valerin, Thomas H. Taylor, May Thet Cho
Journal: Journal of Clinical Oncology (2021)

e16006 Background: FTD/TPI, an antimetabolite, is approved for treatment of refractory mGEC. This study sought to determine whether the combination of FTD/TPI with IRI (“TASIRI”) was safe and effective in mGEC previously treated with FP. Methods: This investigator‐initiated, multicenter, open‐label, single-dose level, single‐arm phase 1b study enrolled pts with mGEC previously treated with at least one line of FP containing regimen. FTD/TPI was given at 25 mg/m 2 twice daily on days 1 to 5 with 180 mg/m 2 IRI on day 1 of a 14‐day cycle. The primary endpoint was progression-free survival at six months (mo) (PFS-6). The aim was to show an improvement of PFS-6 from 15% to at least 30% based on historical controls. Results: At the time of data-cutoff (03Feb2021), 23 pts were screened and ultimately 20 pts were treated. The study met its primary endpoint. With a median follow-up of 9.8 mo (range 0.7 – 17), 8 pts are still on treatment and 4 pts have died. PFS-6 is 53.9% (lower limit of 95% CI: 28%). Median PFS and overall survival are 6.9 mo and not reached, respectively. At the time of data-cutoff, data were available for 13 pts with measurable disease by RECIST criteria and at least 1 on-treatment scan. Of those, 11 had stable disease and 2 had progressive disease as best response (5 pts had tumor shrinkage &lt; 30%), therefore the disease control rate was 84.6%. The most common any grade (G) treatment related adverse events (TRAE) were nausea (n = 14, 70%), diarrhea (n = 9, 45%), and fatigue (n = 8, 40%). G3-4 TRAE in &gt; 5% of pts were anemia (17%) and neutropenia (9%). 2 serious TRAE were reported: G4 febrile neutropenia (n = 1) and G3 hypotension (n = 1). There was no G5 TRAE. Conclusions: The combination of TASIRI showed encouraging clinical activity with a meaningful improvement in PFS-6 compared to historic controls. TASIRI was well tolerated and no new safety signals were seen. TASIRI warrants further investigation for patients with refractory mGEC and limited treatment options. Updated results with longer follow-up will be presented at the meeting. Clinical trial information: NCT04074343.
Exercise and high-density lipoproteins
Authors: W. P. Castelli
Journal: JAMA (1979)

Ever since high-density lipoprotein (HDL)-cholesterol, as a measure of the HDLs, was found to be elevated in crosscountry skiers<sup>1</sup>and marathon runners,<sup>2</sup>investigators have debated whether this is a self-selection phenomenon, ie, skinny athletic persons naturally have higher HDL levels and are attracted to long-distance competitive sports because they are easy for them to do or that somehow increased physical activity changes body metabolism producing a rise in the HDL level. A series of reports has begun to appear where a group of persons (sometimes patients, sometimes volunteer medical students)<sup>3,4</sup>have had their HDL levels characterized before entering into an exercise program that demonstrated the eventual rise in their HDL level during exercise. Two articles in this issue ofThe Journalextend these observations to patients with coronary heart disease. Both focus on the now well-known fact that subjects who experience coronary heart disease have low HDL
Cholera
Journal: JAMA (1998)

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
Liver Transplant for Alcohol-Associated Liver Disease—Reply
Authors: Kayleigh M. Herrick-Reynolds, Andrew M. Cameron
Journal: JAMA Surgery (2022)

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
A multicenter phase II trial to assess the efficacy and safety of bevacizumab plus mFOLFOX6 as induction chemotherapy toward R0 surgical resection in advanced colorectal liver metastases with mutant-type KRAS: NEXTO-mt trial.
Authors: Genki Watanabe, Yoshihiro Mise, Masaru Oba, Akio Saiura, Yosuke Inoue, Yu Takahashi, Yoji Kishi, Koichi Suyama, Tadatoshi Takayama, Tamaki Noie, Yujiro Nishioka, Nobuhisa Akamatsu, Junichi Arita, Norihiro Kokudo, Kiyoshi Hasegawa
Journal: Journal of Clinical Oncology (2022)

450 Background: The oncological benefit of bevacizumab plus mFOLFOX6 in advanced colorectal liver metastases (CRLMs) in terms of conversion to curative resection remains unknown. This multicenter phase II trial aimed to evaluate the efficacy and safety of bevacizumab plus mFOLFOX6 as induction chemotherapy for advanced CRLMs harboring mutant-type KRAS. Methods: Patients who had advanced CRLMs (tumor number of ≥5 and/or technically unresectable) harboring mutant-type KRAS were included in this study. The induction chemotherapy of bevacizumab plus mFOLFOX6 was administered and assessed for resectability every 4 cycles. If the unresectable CRLMs were converted to be resectable, liver resection was planned after a waiting period of 4–6 weeks and followed by postoperative chemotherapy up to 12 cycles. The primary endpoint was R0 resection rate. The secondary endpoints were safety, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). The trial was conducted following approval from the Institutional Ethics Review Board of all institutions and registered in the University Hospital Medical Information Network Clinical Trials Registry (registration number: UMIN000009530). Results: Between February 2013 and December 2017, 29 patients from six centers were enrolled in this trial. The rates of complete and partial responses were 0% and 62.1%, respectively. R0 and R1 resections were performed in 19 and 1 patient, respectively (R0 resection rate: 65.5%). No mortality after liver resection occurred. During the median follow-up of 30.7 months (range, 7.2–82.6 months), the median OS for the 29 patients was 49.1 months. The 3-year PFS and OS rates were 7.4%, and 64.4%, respectively. The 3-year RFS rate was 10.0% in 20 patients who achieved R0 or R1 resections. Conclusions: Bevacizumab plus mFOLFOX6 achieved a high R0 resection rate with a favorable survival for patients with advanced CRLMs harboring mutant-type KRAS. Clinical trial information: UMIN000009530.
CircNFIB inhibits tumor growth and metastasis through suppressing MEK1/ERK signaling in intrahepatic cholangiocarcinoma
Authors: Jinpeng Du, Tian Lan, Haotian Liao, Xuping Feng, Xing Chen, Wenwei Liao, Guimin Hou, Lin Xu, Qingbo Feng, Kunlin Xie, Mingheng Liao, Xiangzheng Chen, Jiwei Huang, Kefei Yuan, Yong Zeng
Journal: Molecular Cancer (2022)

Abstract Background Considerable evidence shows that circular RNAs (circRNAs) play an important role in tumor development. However, their function in intrahepatic cholangiocarcinoma (ICC) metastasis and the underlying mechanisms are incompletely understood. Methods circNFIB (hsa_circ_0086376, termed as cNFIB hereafter) was identified in human ICC tissues through circRNAs sequencing. The biological role of cNFIB was determined in vitro and in vivo by gain or loss of functional experiments. Fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted to analyze the interaction of cNFIB with dual specificity mitogen-activated protein kinase kinase1 (MEK1). Duolink in situ proximity ligation assay (PLA) and coimmunoprecipitation (co-IP) assay were used to investigate the effects of cNFIB on the interaction between MEK1 and mitogen-activated protein kinase 2 (ERK2). Finally, a series of in vitro and in vivo experiments were performed to explore the influences of cNFIB on the anti-tumor activity of trametinib (a MEK inhibitor). Results cNFIB was significantly down-regulated in human ICC tissues with postoperative metastases. The loss of cNFIB was highly associated with aggressive characteristics and predicted unfavorable prognosis in ICC patients. Functional studies revealed that cNFIB inhibited the proliferation and metastasis of ICC cells in vitro and in vivo. Mechanistically, cNFIB competitively interacted with MEK1, which induced the dissociation between MEK1 and ERK2, thereby resulting in the suppression of ERK signaling and tumor metastasis. Moreover, we found that ICC cells with high levels of cNFIB held the potential to delay the trametinib resistance. Consistently, in vivo and in vitro studies demonstrated that cotreatment with trametinib and lentivirus vector encoding cNFIB showed greater inhibitory effect than isolated trametinib treatment. Conclusions Our findings identified that cNFIB played a key role in ICC growth and metastasis by regulating MEK1/ERK signaling. Given the efficacy of cNFIB modulation on ICC suppression and trametinib sensitivity, cNFIB appears to be a potential therapeutic molecule for ICC treatment.
Suicide
Authors: Nichola Cooper, Waleed Ghanima
Journal: New England Journal of Medicine (2020)

corrections among those with preexisting hemolysis, renal impairment, or concurrent infection (especially Epstein-Barr virus infection); in these patients, anti-D immune globulin should be avoided. 1However, the occurrence of severe hemolysis is rare, and many trials have shown that anti-D immune globulin has an acceptable safety and efficacy profile, especially in the pediatric population.
Nonfatal, Unintentional, Non–Fire-Related Carbon Monoxide Exposures—United States, 2004-2006
Journal: JAMA (2008)

Carbon monoxide (CO) is a colorless, odorless, nonirritating gas that is produced through the incomplete combustion of hydrocarbons. Sources of CO include combustion devices (e.g., boilers and furnaces), motor-vehicle exhaust, generators and other gasoline or diesel-powered engines, gas space heaters, woodstoves, gas stoves, fireplaces, tobacco smoke, and various occupational sources. CO poisoning is a leading cause of unintentional poisoning deaths in the United States; it was responsible for approximately 450 deaths each year during 1999-2004 and an estimated 15,200 emergency department (ED) visits each year during 2001-2003. Health effects of CO exposure can range from viral-like symptoms (e.g., fatigue, dizziness, headache, confusion, and nausea) to more severe conditions (e.g., disorientation, unconsciousness, long-term neurologic disabilities, coma, cardiorespiratory failure, and death). CO poisoning often is misdiagnosed and underdetected because of the nonspecific nature of symptoms. To update a previously published report and provide national estimates of CO-related ED visits during 2004-2006, CDC analyzed data from the National Electronic Injury Surveillance System--All Injury Program (NEISS-AIP) database. During 2004-2006, an estimated average of 20,636 ED visits for nonfatal, unintentional, non-fire-related CO exposures occurred each year. Approximately 73% of these exposures occurred in homes, and 41% occurred during winter months (December-February). Prevention efforts targeting residential and seasonal CO exposures can substantially reduce CO-related morbidity.