tbuckley/cabot-search huggingface dataset:
The mitochondrial protein Opa1 promotes adipocyte browning that is dependent on urea cycle metabolites
Authors: Camilla Bean, Matteo Audano, Tatiana Varanita, Francesca Favaretto, Marta Medaglia, Marco Gerdol, Lena Pernas, Fabio Stasi, Marta Giacomello, Stèphanie Herkenne, Maheswary Muniandy, Sini Heinonen, Emma Cazaly, Miina Ollikainen, Gabriella Milan, Alberto Pallavicini, Kirsi H. Pietiläinen, Roberto Vettor, Nico Mitro, Luca Scorrano
Journal: Nature Metabolism (2021)
RSV Vaccines, Finally Within Reach, Could Prevent Tens of Thousands of Yearly Deaths
Authors: Jennifer Abbasi
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
High Sensitivity Detection of <i>FLT3</i>-ITD Measurable Residual Disease By Deep Sequencing Prior to Hematopoietic Cell Transplant Is Highly Prognostic for Outcome in Acute Myeloid Leukemia
Authors: Sun Loo, Richard Dillon, Natasha S Anstee, Ing S Tiong, Adam Ivey, Nicola Potter, Jad Othman, Manohursingh Runglall, Jelena Jovanovic, Amanda Gilkes, Ian Thomas, Sean Johnson, Nigel H. Russell, Andrew H. Wei
Journal: Blood (2021)
Endoscopic submucosal resection: a technique using novel devices for incision and resection of neoplastic lesions
Authors: Klaus Metter, Patrick Aepli, Franz Ludwig Dumoulin, Bu'Hussain Hayee, Karl-Ernst Grund, Günter Farin, Remus Frei
Journal: Endoscopy (2021)

Background Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are established techniques for treatment of superficial gastrointestinal neoplasia. Limitations of EMR are low en bloc resection rates for larger lesions, resulting in frequent recurrences. Major disadvantages of ESD are technical difficulty and long procedure times. We evaluated technical feasibility and safety of newly designed devices for en bloc resection of lesions measuring 20–40 mm in a technique called endoscopic submucosal resection (ESR). Methods This case series included 93 lesions from different locations (11 stomach, 25 colon, 57 rectum) with a median size of 29 mm (range 10–70). ESR was performed using two novel instruments for circumferential mucosal incision and deep submucosal resection, respectively. Results Resection by ESR was feasible in all cases. En bloc and R0 rates were insufficient when ESR was attempted without prior circumferential mucosal incision, but were 70 % and 63 %, respectively, when mucosal incision was done before application of the submucosal resection device. We observed three complications (two delayed bleedings, one microperforation) but no cases of emergency surgery or 30-day mortality. Conclusions Results demonstrated feasibility and excellent safety of ESR using two novel devices for en bloc resection of early gastrointestinal neoplasia. The technique offered relative technical ease and high efficacy.
Peroxisomal β-oxidation acts as a sensor for intracellular fatty acids and regulates lipolysis
Authors: Lianggong Ding, Wenfei Sun, Miroslav Balaz, Anyuan He, Manuel Klug, Stefan Wieland, Robert Caiazzo, Violeta Raverdy, Francois Pattou, Philippe Lefebvre, Irfan J. Lodhi, Bart Staels, Markus Heim, Christian Wolfrum
Journal: Nature Metabolism (2021)

Abstract To liberate fatty acids (FAs) from intracellular stores, lipolysis is regulated by the activity of the lipases adipose triglyceride lipase (ATGL), hormone-sensitive lipase and monoacylglycerol lipase. Excessive FA release as a result of uncontrolled lipolysis results in lipotoxicity, which can in turn promote the progression of metabolic disorders. However, whether cells can directly sense FAs to maintain cellular lipid homeostasis is unknown. Here we report a sensing mechanism for cellular FAs based on peroxisomal degradation of FAs and coupled with reactive oxygen species (ROS) production, which in turn regulates FA release by modulating lipolysis. Changes in ROS levels are sensed by PEX2, which modulates ATGL levels through post-translational ubiquitination. We demonstrate the importance of this pathway for non-alcoholic fatty liver disease progression using genetic and pharmacological approaches to alter ROS levels in vivo, which can be utilized to increase hepatic ATGL levels and ameliorate hepatic steatosis. The discovery of this peroxisomal β-oxidation-mediated feedback mechanism, which is conserved in multiple organs, couples the functions of peroxisomes and lipid droplets and might serve as a new way to manipulate lipolysis to treat metabolic disorders.
177P TP53 and PRBM1 mutations predict “hot” tumor microenvironment in intrahepatic cholangiocarcinoima
Authors: I. Lozzi Da Costa, B. Sinn, A. Arnold, A. Andreou, M. Felsenstein, A. Schirmeier, A. Reutzel-Selke, J. Pratschke, I.M. Sauer, M. Feist
Journal: Annals of Oncology (2021)
Correction: Blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia: results of the RIALTO trial, an expanded access study
Authors: Franco Locatelli, Gerhard Zugmaier, Noemi Mergen, Peter Bader, Sima Jeha, Paul-Gerhardt Schlegel, Jean-Pierre Bourquin, Rupert Handgretinger, Benoit Brethon, Claudia Rossig, Christiane Chen-Santel
Journal: Blood Cancer Journal (2021)
Abstract 10874: Evaluation of Intensive Care Unit and Ventilator-free Days as Alternative Outcomes in Out-of-Hospital Cardiac Arrest Trials
Authors: Henry E Wang, Ashish R Panchal, Michelle Nassal, Terry Vanden hoek, Jing Li, Clifton W CALLAWAY, Graham Nichol, Mohamud R Daya, Robert Schmicker, Ahamed Idris, Tom P Aufderheide, Matthew L Hansen, Madison Hyer, Lai Wei
Journal: Circulation (2021)

Objective: Compared with traditional out-of-hospital cardiac arrest (OHCA) trial outcomes such as hospital survival, alternative outcomes such as intensive care unit-free (IFD) and ventilator-free days (VFD) have potential advantages including requiring smaller sample sizes to detect significant differences. Few studies have evaluated these outcomes in OHCA. We sought to evaluate the utility and validity of IFD and VFD as candidate outcomes for OHCA trials. Methods: We analyzed data from the Pragmatic Airway Resuscitation Trial (PART), which tested laryngeal tube (LT) vs. endotracheal intubation (ETI) airway strategies in adult OHCA. We defined IFD as the number of days alive and permanently out of ICU during the first 30 days after the OHCA event. We examined IFD distribution and correlation with Modified Rankin Scale (MRS). To test associations with trial interventions, we applied a range of analytic strategies, including modeling IFD as continuous (Generalized Estimating Equations - GEE), non-parametric (Wilcoxon Rank-Sum test - WRS) and count (zero-inflated negative binomial regression - ZINB) data. We also modeled time-to-ICU discharge using a survival model with death as a competing risk. We repeated the analysis assessing VFD. Results: IFD was available for 2,898 of 3,004 patients. IFD was skewed and J-shaped; 91% IFD=0 and 5.3% IFD≥22. Mean (±SD) IFD was 2.0±6.6 days; 21.2±7.5 days for survivors. IFD varied by intervention (LT 2.4±7.2, ETI 1.6±5.8 days). IFD and VFD strongly correlated with MRS (ρ= -0.88, -0.89). LT was associated with increased IFD using GEE, WRS, and ZINB, but not competing risks model. (Table) LT was associated with increased VFD using GEE and WRS, but not ZINB or competing risks models. Conclusion: IFD and VFD differentiated OHCA interventions, suggesting their utility. IFD and VFD were highly correlated with MRS, suggesting validity. IFD and VFD have important features that may influence OHCA trial design.
Abstract 12464: Signs of Life as a Predictor of Survival in Patients With Out-of-Hospital Cardiac Arrest and Long Low-Flow Times
Authors: Sivagowry Moerk, Carsten Stengaard, Morten Thingemann Boetker, steffen christensen, Mariann Tang, Christian J Terkelsen
Journal: Circulation (2021)

Introduction: Long low-flow times in patients with out-of-hospital cardiac arrest (OHCA) are associated with poor outcome. Signs of life during cardiopulmonary resuscitation (CPR) is a simple method to evaluate in the field, but little is known about its impact on survival in patients with long low-flow times. Hypothesis: Thirty-day survival in OHCA patients with long prehospital low-flow times is higher in patients with signs of life during CPR than in patients with no signs of life during CPR. Methods: Observational, retrospective, single center study of OHCA patients referred to a tertiary cardiac arrest center in the Central Demark Region from 2015-2018. Risk factors were assessed by univariate logistic regression. Comparisons were made by Kaplan-Meier survival curves and log-rank test. Results: In a cohort of 807 patients with OHCA, 30-day survival was seen in 364 (45%). Among patients discharged from hospital, favorable neurological outcome with CPC 1-2 was observed in 93%. Signs of life during CPR was present in 315 (39%) patients. Risk of 30-day mortality was significantly reduced in patients presenting signs of life during CPR (RR 0.25, 95% CI [0.20-0.30]). Poor survival was seen in patients with low-flow times exceeding 30 minutes compared to patients with shorter low-flow times, (11% versus 66%, p &lt; 0.001). In patients with low-flow times &gt; 30 min, the survival rate increased to 33 % in the presence of signs of life during CPR compared to only 3% in patients without signs of life during CPR, p &lt; 0.001. Conclusions: In OHCA patients, low-flow times &gt; 30 minutes were highly associated with poor survival, however signs of life during CPR predicts higher survival both in the overall population and in patients with long low-flow times. Thus, resuscitation efforts may not be futile in patients with long low-flow times presenting signs of life during CPR.
Patients who misuse alcohol have poorer responses to systemic treatments for psoriasis
Journal: British Journal of Dermatology (2021)

This UK‐based study was set up to understand what factors can influence the results of treatment among patients with psoriasis. Previous work has indicated that there is a link between bad psoriasis and alcohol consumption, and this study was designed to identify any connection between alcohol consumption and the response to treatment. The group studied were patients attending clinics in England. All had moderate to severe psoriasis and were treated with the topical or oral therapies in common use (conventional therapies) but some had received the newer biologic treatments. All patients completed a questionnaire that included questions on the patients’ self‐estimate of misuse of alcohol as well as the severity of their psoriasis, which was recorded at various timepoints during treatment. Their information was recorded in a national database. Alcohol misuse and obesity were both associated with poorer responses to treatment with the conventional therapies. In addition, failure to stick to treatment schedules was also associated with poor results. At least 40% of those in this study reported psychological distress.
Sulforaphane elicts dual therapeutic effects on Renal Inflammatory Injury and crystal deposition in Calcium Oxalate Nephrocalcinosis: Erratum
Authors: Haoran Liu, Xiaoqi Yang, Kun Tang, Tao Ye, Chen Duan, Peng Lv, Libin Yan, Xiaoliang Wu, Zhiqiang Chen, Jianhe Liu, Yaoliang Deng, Guohua Zeng, Jinchun Xing, Zhangqun Ye, Hua Xu
Journal: Theranostics (2021)

[This corrects the article DOI: 10.7150/thno.44054.].
Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas
Authors: Hirokazu Ogino, Jennie W. Taylor, Takahide Nejo, David Gibson, Payal B. Watchmaker, Kaori Okada, Atsuro Saijo, Meghan R. Tedesco, Anny Shai, Cynthia M. Wong, Jane E. Rabbitt, Michael R. Olin, Christopher L. Moertel, Yasuhiko Nishioka, Andres M. Salazar, Annette M. Molinaro, Joanna J. Phillips, Nicholas A. Butowski, Jennifer L. Clarke, Nancy Ann Oberheim Bush, Shawn L. Hervey-Jumper, Philip Theodosopoulos, Susan M. Chang, Mitchel S. Berger, Hideho Okada
Journal: Journal of Clinical Investigation (2021)

BACKGROUNDLong-term prognosis of WHO grade II low-grade gliomas (LGGs) is poor, with a high risk of recurrence and malignant transformation into high-grade gliomas. Given the relatively intact immune system of patients with LGGs and the slow tumor growth rate, vaccines are an attractive treatment strategy.METHODSWe conducted a pilot study to evaluate the safety and immunological effects of vaccination with GBM6-AD, lysate of an allogeneic glioblastoma stem cell line, with poly-ICLC in patients with LGGs. Patients were randomized to receive the vaccines before surgery (arm 1) or not (arm 2) and all patients received adjuvant vaccines. Coprimary outcomes were to evaluate safety and immune response in the tumor.RESULTSA total of 17 eligible patients were enrolled - 9 in arm 1 and 8 in arm 2. This regimen was well tolerated with no regimen-limiting toxicity. Neoadjuvant vaccination induced upregulation of type-1 cytokines and chemokines and increased activated CD8+ T cells in peripheral blood. Single-cell RNA/T cell receptor sequencing detected CD8+ T cell clones that expanded with effector phenotype and migrated into the tumor microenvironment (TME) in response to neoadjuvant vaccination. Mass cytometric analyses detected increased tissue resident-like CD8+ T cells with effector memory phenotype in the TME after the neoadjuvant vaccination.CONCLUSIONThe regimen induced effector CD8+ T cell response in peripheral blood and enabled vaccine-reactive CD8+ T cells to migrate into the TME. Further refinements of the regimen may have to be integrated into future strategies.TRIAL REGISTRATIONClinicalTrials.gov NCT02549833.FUNDINGNIH (1R35NS105068, 1R21CA233856), Dabbiere Foundation, Parker Institute for Cancer Immunotherapy, and Daiichi Sankyo Foundation of Life Science.
Erratum: Childhood Obesity and Asthma Control in the GALA II and SAGE II Studies
Authors: Jurjan Aman, J Mike, Carla Weenink, Geerten Van Nieuw Amerongen, Vonk Anton
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

employed on our patient may have important implications for conditions that share endothelial barrier dysfunction as a common pathophysiological mechanism.The application of imatinib for reversal of endothelial barrier dysfunction may therefore include various conditions like systemic capillary leak, sepsis, and acute respiratory distress syndrome, which currently lack specific therapy (1-3).Causal treatment for vascular leak is currently lacking.Although phase I/II trials are required to assess safety of imatinib in vascular leak-associated conditions, the current case suggests that imatinib may seal the gap.
139P First-in-human (FIH), pharmacokinetic (PK) and pharmacodynamic (PD) study of IOA-244, a phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, in patients with advanced metastatic mesothelioma, uveal and cutaneous melanoma
Authors: A.M. Di Giacomo, F. Santangelo, G. Amato, E. Simonetti, J. Graham, M. Lahn, R. Zorilla, L. van der Veen, Z. Johnson, C. Pickering, E. Maréchal, J. Blanco, M. Durini, B. Gufford, T. Lakshmikanth, P. Brodin, P. Spiliopoulou, T.R.J. Evans, M. Maio
Journal: Annals of Oncology (2021)
Mapping low-resource contexts to prepare for lung health interventions in four countries (FRESH AIR): a mixed-method study
Authors: Evelyn A Brakema, Rianne M J J van der Kleij, Charlotte C Poot, Pham Le An, Marilena Anastasaki, Matty R Crone, Le Huynh Thi Cam Hong, Bruce Kirenga, Christos Lionis, Maamed Mademilov, Mattijs E Numans, Lê Thi Tu Oanh, Ioanna Tsiligianni, Talant Sooronbaev, Simon Walusimbi, Siân Williams, Niels H Chavannes, Ria Reis
Journal: The Lancet Global Health (2021)

BackgroundEffectiveness of health programmes can be undermined when the implementation misaligns with local beliefs and behaviours. To design context-driven implementation strategies, we explored beliefs and behaviours regarding chronic respiratory disease (CRD) in diverse low-resource settings.MethodsThis observational mixed-method study was conducted in Africa (Uganda), Asia (Kyrgyzstan and Vietnam) and Europe (rural Greece and a Roma camp). We systematically mapped beliefs and behaviours using the SETTING-tool. Multiple qualitative methods among purposively selected community members, health-care professionals, and key informants were triangulated with a quantitative survey among a representative group of community members and health-care professionals. We used thematic analysis and descriptive statistics.FindingsWe included qualitative data from 340 informants (77 interviews, 45 focus group discussions, 83 observations of community members' households and health-care professionals' consultations) and quantitative data from 1037 community members and 204 health-care professionals. We identified three key themes across the settings; namely, (1) perceived CRD identity (community members in all settings except the rural Greek strongly attributed long-lasting respiratory symptoms to infection, predominantly tuberculosis); (2) beliefs about causes (682 [65·8%] of 1037 community members strongly agreed that tobacco smoking causes symptoms, this number was 198 [19·1%] for household air pollution; typical perceived causes ranged from witchcraft [Uganda] to a hot–cold disbalance [Vietnam]); and (3) norms and social structures (eg, real men smoke [Kyrgyzstan and Vietnam]).InterpretationWhen designing context-driven implementation strategies for CRD-related interventions across these global settings, three consistent themes should be addressed, each with common and context-specific beliefs and behaviours. Context-driven strategies can reduce the risk of implementation failure, thereby optimising resource use to benefit health outcomes.FundingEuropean Commission Horizon 2020.TranslationsFor the Greek, Russian and Vietnamese translations of the abstract see Supplementary Materials section.
Not so rational: A more natural way to understand the ANS
Authors: Eli Hecht, Tracey Mills, Steven Shin, Jonathan Phillips
Journal: Behavioral and Brain Sciences (2021)

Abstract In contrast to Clarke and Beck's claim that that the approximate number system (ANS) represents rational numbers, we argue for a more modest alternative: The ANS represents natural numbers, and there are separate, non-numeric processes that can be used to represent ratios across a wide range of domains, including natural numbers.
Abstract 16851: Simultaneous Mitral Valve Replacement, Aortic Valve Replacement, Tricuspid Valve Repair, Left Atrial Appendage Ligation, Maze Procedure And Cabg In A 57-year Old Female With History Of Tavr And Severe Mitral Annular Calcification
Authors: Hassan Mehmood Lak, Joshua Cohen, Jean Pierre Iskandar, Mohamed Gad, Sanchit Chawla, Farah Yasmin, Ahmad Mustafa, Shinya Unai, Leslie Cho
Journal: Circulation (2021)

Background: Open heart surgery is preferred for patients with multiple valvular issues with conflicting physiology. Case: A 57-year-old female with a past medical history of Type I Diabetes Mellitus complicated by kidney &amp; pancreatic transplant in 1999 s/p failed kidney transplant in 2016 subsequently back on dialysis, aortic stenosis leading to Transcatheter Aortic Valve Replacement (TAVR) in 2016 who presented to the hospital for profound cardiogenic shock and was found to have severe tricuspid regurgitation, severe mitral stenosis secondary to mitral annular calcification with severe concentric hypertrophy of left ventricle. Decision Making: Her conflicting right and left heart physiology due to Tricuspid Regurgitation and Mitral Stenosis was very difficult to manage medically. She was not deemed a candidate for a heart transplant due to a history of a failed kidney transplant. She underwent surgery which included Mitral Valve Replacement, explant TAVR and repeat aortic valve replacement, Tricuspid repair, Left atrial appendage ligation and maze procedure, and CABG x1 with saphenous vein graft to PDA. She stayed on V-V extracorporeal membrane oxygenation (ECMO) post-operatively and was discharged on post-operative Day # 14. Conclusion: Severe tricuspid Regurgitation &amp; coexisting mitral stenosis pose a dilemma for medical management and only feasible option is surgery which could be extremely challenging.
FDA Approval Summary: Margetuximab plus Chemotherapy for Advanced or Metastatic HER2-Positive Breast Cancer
Authors: Melanie Royce, Christy L. Osgood, Anup K. Amatya, Mallorie H. Fiero, C.J. George Chang, Tiffany K. Ricks, Krithika A. Shetty, Jeffrey Kraft, Junshan Qiu, Pengfei Song, Rosane Charlab, Jingyu Yu, Kathryn E. King, Anshu Rastogi, Brian Janelsins, Wendy C. Weinberg, Kathleen Clouse, Vicky Borders-Hemphill, Lindsey Brown, Candace Gomez-Broughton, Zhong Li, Thuy Thanh Nguyen, Zhihao Qiu, Anh-Thy Ly, Suyoung Chang, Tingting Gao, Chi-Ming Tu, Bellinda King-Kallimanis, William F. Pierce, Kelly Chiang, Clara Lee, Kirsten B. Goldberg, John K. Leighton, Shenghui Tang, Richard Pazdur, Julia A. Beaver, Laleh Amiri-Kordestani
Journal: Clinical Cancer Research (2021)

Abstract On December 16, 2020, the FDA granted regular approval to margetuximab-cmkb (MARGENZA), in combination with chemotherapy, for the treatment of adult patients with HER2-positive (HER2+) metastatic breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Approval was based on data from SOPHIA, a multicenter, randomized, open-label, active controlled study comparing margetuximab with trastuzumab, in combination with chemotherapy. The primary efficacy endpoint was progression-free survival (PFS) by blinded independent central review. SOPHIA demonstrated a 0.9-month difference in median PFS between the two treatment arms [5.8 vs. 4.9 months, respectively; stratified HR, 0.76 (95% confidence interval: 0.59–0.98; P = 0.0334)]. Overall survival (OS) was immature at the data cut-off date of September 10, 2019. Infusion-related reactions (IRR) are an important safety signal associated with margetuximab plus chemotherapy. In SOPHIA, 13% of patients treated with margetuximab plus chemotherapy reported IRRs, of which 1.5% were grade 3. The most commonly reported adverse drug reactions (&amp;gt;10%) with margetuximab in combination with chemotherapy were fatigue/asthenia, nausea, diarrhea, vomiting, constipation, headache, pyrexia, alopecia, abdominal pain, peripheral neuropathy, arthralgia/myalgia, cough, decreased appetite, dyspnea, IRR, palmar-plantar erythrodysesthesia, and extremity pain. Overall, the favorable risk-benefit profile for margetuximab when added to chemotherapy supported its approval for the intended indication.
Association of Gestational Age and Developmental Coordination Disorder
Authors: Jill G. Zwicker
Journal: JAMA Network Open (2021)

Jing Hua, MD, PhD; Anna L. Barnett, PhD; Gareth J. Williams, PhD; Xiaotian Dai, MD; Yuanjie Sun, MD; Haifeng Li, MD; Guixia Chen, MD; Lei Wang, MD; Junyan Feng, MD; Yingchun Liu, MD; Lan Zhang, MD; Ling Zhu, MD; Tingting Weng, MD; Hongyan Guan, MD; Yue Gu, BS; Yingchun Zhou, PhD; Andrew Butcher, MD; Wenchong Du, PhD