tbuckley/cabot-search huggingface dataset:
Medical Assistance in Dying—Unanswered Questions
Authors: Annmarie Hosie
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Integrin a6 loss promotes colitis-associated colorectal cancer. Response to: “Integrin a6 variants and colorectal cancer” by Beaulieu JF
Authors: Adèle De Arcangelis, Mathias Chamaillard, Patricia Simon-Assmann, Michel Labouesse
Journal: Gut (2018)

In a recently published letter,1 Dr Beaulieu questions our recent publication suggesting that α6 integrin acts as a tumour suppressor gene in colorectal cancer (CRC),2 given the apparent antagonistic role of α6A and α6B integrin isoforms in the intestine. We thank him for raising this important issue and welcome the opportunity of clarifying the topic. We showed that mice failing to express the α6 integrin (both α6A and α6B isoforms) specifically in intestinal epithelial cells (α6ΔIEC) spontaneously develop fully penetrant colitis and adenocarcinoma afterwards.2 These mice display epithelium detachment from the basement membrane, followed …
Infographic: Physical activity, sitting time and mortality
Authors: Ulf Ekelund
Journal: British Journal of Sports Medicine (2018)

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Physical inactivity, defined as not meeting the current public health guidelines for physical activity, is a major risk factor for non-communicable diseases and premature mortality. Recent estimates suggest that about 9% of all deaths annually, which corresponds to more than 5 million deaths globally, can be attributed to physical inactivity.1 

Sitting time constitutes the majority of awake time in the adult population. Sedentary behaviours have been proposed to be associated with many chronic conditions independent of physical activity,2 and many national health and scientific authorities have introduced guidelines on sitting.3 4 

In one of the papers published as part of The Lancet 2016 series of physical activity,5 we sought to examine how much physical …
Gene Therapy for Adenosine Deaminase Deficiency: A Comprehensive Evaluation of Short- and Medium-Term Safety
Authors: Maria Pia Cicalese, Francesca Ferrua, Laura Castagnaro, Katie Rolfe, Erika De Boever, Rickey R. Reinhardt, Jonathan Appleby, Maria Grazia Roncarolo, Alessandro Aiuti
Journal: Molecular Therapy (2018)

Loss of adenosine deaminase activity leads to severe combined immunodeficiency (ADA-SCID); production and function of T, B, and natural killer (NK) cells are impaired. Gene therapy (GT) with an autologous CD34+-enriched cell fraction that contains CD34+ cells transduced with a retroviral vector encoding the human ADA cDNA sequence leads to immune reconstitution in most patients. Here, we report short- and medium-term safety analyses from 18 patients enrolled as part of single-arm, open-label studies or compassionate use programs. Survival was 100% with a median of 6.9 years follow-up (range, 2.3 to 13.4 years). Adverse events were mostly grade 1 or grade 2 and were reported by all 18 patients following GT. Thirty-nine serious adverse events (SAEs) were reported by 15 of 18 patients; no SAEs were considered related to GT. The most common adverse events reported post-GT include upper respiratory tract infection, gastroenteritis, rhinitis, bronchitis, oral candidiasis, cough, neutropenia, diarrhea, and pyrexia. Incidence rates for all of these events were highest during pre-treatment, treatment, and/or 3-month follow-up and then declined over medium-term follow-up. GT did not impact the incidence of neurologic/hearing impairments. No event indicative of leukemic transformation was reported.
Opioid Withdrawal Symptoms Subside With Cranial Nerve Stimulation
Authors: Rebecca Voelker
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 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
Clinical significance of serum tumor marker for advanced gastric cancer with palliative chemotherapy: A retrospective study.
Authors: Yahui Zhu, Baorui Liu, Jia Wei, Juan Du, Ju Yang, Yan Yang, Kangxin Wang, Yang Yang, Zhengyun Zou
Journal: Journal of Clinical Oncology (2017)

e15524 Background:The predictive value of tumor markers has been previously reported a lot. However, the studies focused on advanced gastric cancer are few. In this study, we tried to investigate the relationship between the tumor markers of advanced gastric cancer and clinical characteristics, therapeutic effect of chemotherapy, and prognosis. Methods:A retrospective study including 146 advanced gastric cancer who had not received any previous anticancer therapy was performed. Blood samples for CEA, AFP, CA125, CA72-4, CA242 and CA19-9 were taken from patients before chemotherapy and monthly during their treatments. Statistical analysis was performed to predict the clinical value of these tumor markers. Results:CEA yielded an ROC value of 0.621 in predicting lymph node metastasis in gastric cancer, which was significantly higher than any of other markers. CA125 had the highest sensitivity, specificity and accuracy in gastric cancer patients with peritoneal metastasis. AFP and CEA were more frequently positive in patients with hepatic metastases. The response rate of Decreasing group, Stable group and Increasing group based on CA19-9, CEA, CA72-4, CA125 and CA242 levels achieved statistical significance. Positive cases of CA125, CA242, CA19-9 and CA72-4 showed poor prognosis, and significant differences in 3 year-survival rates were observed for CA125 and CA242. Conclusions:We found that different tumor markers in gastric cancer indicated different metastasis sits. CEA, CA242, CA19-9, CA125 and CA72-4 are predictive biomarkers in evaluating the effectiveness of chemotherapy. The elevated CA125, CA242, CA19-9 and CA72-4 levels at diagnosed had association with shorter overall survivals, especially CA125 and CA242.
Smart Artificial Beta Cells May Help Treat Diabetes
Authors: Tracy Hampton
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 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
Abstract 104: Defective Branched-chain Amino Acid Catabolism Impairs Glucose Metabolism and Sensitizes the Heart to Ischemia/Reperfusion Injury
Authors: TAO LI, Zhen Zhang, Stephen C Kolwicz, Haipeng Sun, Rong Tian
Journal: Circulation Research (2016)

The branched-chain amino acids (BCAA) are essential amino acids required for protein homeostasis, energy balance, and nutrient signaling. It has been shown recently that elevations in the circulating BCAAs and related metabolites are associated with insulin resistance and ischemic heart disease, suggesting an important link between BCAA metabolism and cardiac pathology. BCAA catabolism in mitochondria is regulated by the branched-chain keto acid dehydrogenase complex (BCKDC). A mitochondria localized phosphatase 2C (PP2Cm) has been identified to activate BCKDC, serving as a key regulator of BCAA catabolism. Deletion of PP2Cm (KO) increased blood BCAA levels but did not alter cardiac function in unstressed mice. Using 13 C- and 31 P-NMR spectroscopy, we found a significant reduction in the contribution of glucose to oxidative metabolism in KO hearts (16±3 vs. 26±2% for KO and wild-type (WT), respectively, P &lt;0.05), which was accompanied by an ~25% reduction in glucose uptake rate ( P &lt;0.05). Cardiac glycogen content was also reduced (4.4±0.5 vs. 10.9±1.8 μmol glucose/g, P &lt;0.05). In isolated mitochondria from KO or WT hearts treated with BCAAs, significant reductions in pyruvate supported respiration were observed. In enzyme kinetics experiment, acute exposure to BCAAs inhibited pyruvate dehydrogenase complex (PDH) activity in a dose-dependent manner. In isolated perfused hearts subjected to ischemia/reperfusion (I/R), KO hearts showed a greater increase of diastolic pressure during ischemia ( P &lt;0.05), which persisted throughout the reperfusion ( P &lt;0.05). The contractile function in KO barely recovered while it recovered to ~40% of baseline in WT at the end of reperfusion. Increasing glucose supply via overexpression of GLUT1, an insulin-independent glucose transporter, fully restored the impaired recovery to I/R in KO mice. These results show that BCAA catabolism deficiency, as a result of PP2Cm deletion, disrupts normal glucose metabolism and renders the heart highly sensitive to acute ischemia/reperfusion (I/R) injury. These findings reveal an important role of BCAA catabolism in regulating glucose metabolism and cardiac stress response.
BRD7 Regulates XBP1s’ Activity and Glucose Homeostasis through Its Interaction with the Regulatory Subunits of PI3K
Authors: Sang Won Park, Hilde Herrema, Mario Salazar, Isin Cakir, Serkan Cabi, Fatma Basibuyuk Sahin, Yu-Hsin Chiu, Lewis C. Cantley, Umut Ozcan
Journal: Cell Metabolism (2014)
Abstract 12559: Chronic GPER Activation Attenuates Cardiac Dysfunction in a Male Mouse Model of Progressive Heart Failure: Insights Into Cellular Mechanisms
Authors: Xiaowei Zhang, Tiankai Li, Hao Wang, Heng-Jie Cheng, Weimin Li, Carlos M Ferrario, Leanne Groban, Che Ping Cheng
Journal: Circulation (2016)

Background: Activation of G protein-coupled estrogen receptor, GPER, has been shown to exhibit beneficial actions in several cardiovascular diseases, including heart failure (HF). While reports on GPER have highlighted mostly female sex-specific health issues, recent evidence indicates its cardiovascular benefits may include the opposite sex. However, the exact means by which GPER affords cardioprotection are unclear. Moreover whether and how GPER activation may limit HF progression and have a salutary role in males is unknown. We tested the hypothesis that chronic GPER activation by its specific agonist G 1 improves myocyte function and [Ca 2+ ] i regulation, thus limiting HF progression in male mice. Methods: We simultaneously examined LV and myocyte function and [Ca 2+ ] i transient ([Ca 2+ ] iT ) responses in 3 groups of male mice (11/group) over 4 weeks (W): HF receiving the initial injection of isoproterenol (ISO) (150 mg/kg sq for 2 days) over 2 W, then receiving placebo; HF/G 1 after ISO for 2W, then receiving G 1 (150 μg /kg/day sq via mini pump), given for 2W; and controls . Results: Compared with controls, both Echo and hemodynamic assessments revealed that ISO-treated mice had HFpEF onset at 2 W after ISO and progressed to mild HF at 4 W with LV dilatation, increased LV time constant of relaxation (τ) (5.4 vs 3.1 ms), and 52% reductions in peak rate of mitral flow (dV/dt max ); accompanied by significantly reduced myocyte contraction (dL/dt max , 102.7 vs 143.6 μm/s), relaxation (dR/dt max ,69.9 vs 107.9 μm/s) and [Ca 2+ ] iT (0.16 vs 0.21). Importantly, compared with normal myocytes, ISO (10 -8 M) caused significantly less increases in dL/dt max (24% vs 61%), dR/dt max (23% vs 57%), and [Ca 2+ ] iT (15% vs 30%) in HF myocytes. HF/G1 rats, compared to HF, showed significantly increased LV dV/dt max and decreased t (4.0 ms) accompanied by increased dL/dt max (142.6 μm/s), dR/dt max (107.9 μm/s) and [Ca 2+ ] iT (0.21). Moreover, ISO-induced increases in dL/dt max (61%), dR/dt max (56%), and [Ca 2+ ] iT (30%) in myocytes from HF/G 1 were significantly augmented, similar to controls. Conclusions: Chronic G 1 treatment restores normal myocyte basal and β-AR stimulated contraction, relaxation and [Ca 2+ ] i regulation, leading to regression of LV dysfunction in a male mouse model of HF.
Somatic Activating <i>KRAS</i> Mutations in Arteriovenous Malformations of the Brain
Authors: Sergey I. Nikolaev, Sandra Vetiska, Ximena Bonilla, Emilie Boudreau, Suvi Jauhiainen, Behnam Rezai Jahromi, Nadiya Khyzha, Peter V. DiStefano, Santeri Suutarinen, Tim-Rasmus Kiehl, Vitor Mendes Pereira, Alexander M. Herman, Timo Krings, Hugo Andrade-Barazarte, Takyee Tung, Taufik Valiante, Gelareh Zadeh, Mike Tymianski, Tuomas Rauramaa, Seppo Ylä-Herttuala, Joshua D. Wythe, Stylianos E. Antonarakis, Juhana Frösen, Jason E. Fish, Ivan Radovanovic
Journal: New England Journal of Medicine (2018)

Sporadic arteriovenous malformations of the brain, which are morphologically abnormal connections between arteries and veins in the brain vasculature, are a leading cause of hemorrhagic stroke in young adults and children. The genetic cause of this rare focal disorder is unknown.
Heterozygous Mutations in NFKB2 Exhibit a Broad Clinical Phenotype
Authors: Erik N. Newman, Julie Feusier, Shancy P. Jacob, Lynn B. Jorde, Harry R. Hill, Celine Hanson, Kazushi Izawa, T. Ronan Leahy, Masafumi Yamada, William Rae, Fabian Hauck, Hassan Abolhassani, Asghar Aghamohammadi, Lennart Hammarström, Hirokazu Kanegane, Charlotte Slade, Chaim M. Roifman, Bodo Grimbacher, Guy A. Zimmerman, John F. Bohnsack, Karin Chen
Journal: Journal of Allergy and Clinical Immunology (2018)
Erratum: Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes (Nature Genetics (2011) 43 (561-564))
Authors: K S Small, A K Hedman, E Grundberg, A C Nica, G Thorleifsson, A Kong, U Thorsteindottir, S Y Shin, H B Richards, N Soranzo, K R Ahmadi, C M Lindgren, K Stefansson, E T Dermitzakis, P Deloukas, T D Spector, M I McCarthy
Journal: Nature Genetics (2011)
Two-years Postradiotherapy Biopsies: Lessons from MRC RT01 Trial
Authors: Antoine Kass-Iliyya, Gordana Jovic, Claire Murphy, Cyril Fisher, Isabel Syndikus, Chakiath Jose, Christopher D. Scrase, John D. Graham, David Nicol, Matthew R. Sydes, David Dearnaley
Journal: European Urology (2018)

The importance of 2-yr postradiotherapy prostate biopsy status remains uncertain.
Abstract 17891: Impact of Physical Activity and Sedentary Time on Heart Failure Outcomes
Authors: Rami Doukky, Marie-France Poulin, Elizabeth Avery, Ashvarya Mangla, Zeina Ibrahim, Fareed Collado, DeJuran Richardson, Lynda H Powell
Journal: Circulation (2015)

Introduction: The impact of physical inactivity and sedentary time on heart failure (HF) outcomes in patients not participating in exercise program is unclear. Hypothesis: Physical inactivity and sedentary time are associated with worse HF outcomes. Methods: We analyzed data from the multicenter, HF Adherence and Retention Trial (HART) which enrolled 902 NYHA - II/III HF patients with preserved or reduced ejection fraction, followed for 36 months. Based on the mean weekly purposeful physical activity duration, patients were classified into inactive (0 min/wk), partially active (1-90 min/wk), and active (&gt;90min/wk) groups. Patients were also classified according to average daily sedentary television (TV) time into &lt;2 hrs/d, 2-4 hrs/d, and &gt;4 hrs/d groups. Study groups were propensity score matched according to 33 baseline covariates in 1:1:1 ratio. The primary outcome was all-cause death. Secondary outcomes were cardiac death and HF hospitalization. Results: There were 196 inactive, 341 partially active and 365 active patients, of whom 492 (164 in each group) were successfully propensity matched. Physical inactivity was associated with higher risk of death and cardiac death than any level of physical activity, Fig 1. There was no significant difference in HF hospitalization. Furthermore, 465 subjects were propensity matched into three sedentary TV time groups (155 in each group). Sedentary TV time &gt;4 hrs/d was independently and incrementally associated with all-cause death (Δ χ 2 = 6.05; P=0.049), beyond physical activity time, Fig 1. There was no significant difference in mortality between &lt;2 and 2-4 hrs/d sedentary TV time groups, after adjusting to physical activity time, Fig 2. Conclusions: In symptomatic chronic HF patients, physical inactivity is associated with higher all-cause and cardiac mortality. Modest purposeful physical activity was associated with survival benefit. Extended sedentary time was associated incremental increased mortality.
Abstract 14539: Adamts5 Deficiency in Human Aortic Valves Elevates the Pro-osteogenic Activity Through Matrilin2-mediated Cellular Phenotypic Transition
Authors: Fei Li, Rui Song, Lihua Ao, T. Brett Reece, Joseph C Cleveland, Nianguo Dong, David A. Fullerton, Xianzhong Meng
Journal: Circulation (2016)

The transition of aortic valvular interstitial cells (AVICs) to myofibroblastic and osteoblast-like phenotypes plays a critical role in the progression of calcific aortic valve disease (CAVD). Understanding of the mechanism underlying VIC phenotypic transition may lead to the development of therapeutic approaches for prevention of CAVD progression. Extracellular matrix proteinases are implicated in the pathogenesis of CAVD. The ADAMTS5 (A Disintegrin and Metalloproteinase with Thrombospondin motifs 5) is a secreted, matrix-associated metalloendopeptidase, capable of degrading extracellular matrix proteins, particularly matrilin2. The   Objective:  of this study was to determine the role of the ADAMTS5/matrilin2 axis in mediating the phenotype transitions of AVICs associated with CAVD.   Methods and Results:  Levels of ADAMTS5, matrilin2 and α-smooth muscle actin (α-SMA) were evaluated in calcified and normal human aortic valve tissues and cells. Calcified aortic valves have reduced levels of ADAMTS5 and higher levels of matrilin2 and α-SMA. Treatment of normal AVICs with soluble matrilin2 caused an increase in α-SMA level through Toll-like receptor (TLR) 2 and 4, which was accompanied by up-regulation of Runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP). In addition, ADAMTS5 knockdown in AVICs of normal valves enhanced the effect of matrilin2. Matrilin2 activated NF-κB and nuclear factor of activated T cells complex 1 (NFATc1), and induced the interaction of these two nuclear factors. Inhibition of either NF-κB or NFATc1 suppressed matrilin2’s effect on VIC phenotypic change. Knockdown of α-SMA reduced and over-expression of α-SMA enhanced the expression of pro-osteogenic factors and calcium deposition in human VICs.   Conclusions:  These novel findings demonstrate that matrilin2 induces myofibroblastic transition and elevates pro-osteogenic activity in human AVICs through TLRs and that myofibroblastic transition is an important mechanism of elevating AVIC pro-osteogenic activity. NF-κB and NFATc1 coordinately mediate the effect of matrilin2 in AVICs. Matrilin2 accumulation associated with ADAMTS5 deficiency may promote aortic valve calcification through inducing AVIC myofibroblastic transition.
Management of Functional Somatic Syndromes and Bodily Distress
Authors: Peter Henningsen, Stephan Zipfel, Heribert Sattel, Francis Creed
Journal: Psychotherapy and Psychosomatics (2018)

Functional somatic syndromes (FSS), like irritable bowel syndrome or fibromyalgia and other symptoms reflecting bodily distress, are common in practically all areas of medicine worldwide. Diagnostic and therapeutic approaches to these symptoms and syndromes vary substantially across and within medical specialties from biomedicine to psychiatry. Patients may become frustrated with the lack of effective treatment, doctors may experience these disorders as difficult to treat, and this type of health problem forms an important component of the global burden of disease. This review intends to develop a unifying perspective on the understanding and management of FSS and bodily distress. Firstly, we present the clinical problem and review current concepts for classification. Secondly, we propose an integrated etiological model which encompasses a wide range of biopsychosocial vulnerability and triggering factors and considers consecutive aggravating and maintaining factors. Thirdly, we systematically scrutinize the current evidence base in terms of an umbrella review of systematic reviews from 2007 to 2017 and give recommendations for treatment for all levels of care, concentrating on developments over the last 10 years. We conclude that activating, patient-involving, and centrally acting therapies appear to be more effective than passive ones that primarily act on peripheral physiology, and we recommend stepped care approaches that translate a truly biopsychosocial approach into actual management of the patient.