tbuckley/cabot-search huggingface dataset:
RO7049389, a core protein allosteric modulator, demonstrates robust anti-HBV activity in chronic hepatitis B patients and is safe and well tolerated
Authors: E. Gane, A. Liu, M.-F. Yuen, C. Schwabe, Q. Bo, S. Das, L. Gao, X. Zhou, Y. Wang, E. Coakley, Y. Jin
Journal: Journal of Hepatology (2018)
When Physicians Turn Into Patients—Becoming Kafka’s Cockroach
Authors: Shaurya Taran, Allan S. Detsky
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
Achieving Gender Equity in Physician Compensation and Career Advancement: A Position Paper of the American College of Physicians
Authors: Renee Butkus, Joshua Serchen, Darilyn V. Moyer, Sue S. Bornstein, Susan Thompson Hingle
Journal: Annals of Internal Medicine (2018)

Women comprise more than one third of the active physician workforce, an estimated 46% of all physicians-in-training, and more than half of all medical students in the United States. Although progress has been made toward gender diversity in the physician workforce, disparities in compensation exist and inequities have contributed to a disproportionately low number of female physicians achieving academic advancement and serving in leadership positions. Women in medicine face other challenges, including a lack of mentors, discrimination, gender bias, cultural environment of the workplace, imposter syndrome, and the need for better work-life integration. In this position paper, the American College of Physicians summarizes the unique challenges female physicians face over the course of their careers and provides recommendations to improve gender equity and ensure that the full potential of female physicians is realized.
Epigenetic modification of urea cycle enzymes in NAFLD animal models and patients: Implications for novel therapeutic approaches
Authors: F. De Chiara, R. Jalan, G. Marrone, S. Heeboll, C. Montoliu, S. Hamilton-Dutoit, M. García-Torres, F. Andreola, K. Rombouts, H. Grønbæk, V. Felipo, R. Mookerjee, K. Louise Thomsen
Journal: Journal of Hepatology (2018)
Additional Risk Factors for Breast Implant–Associated Anaplastic Large Cell Lymphoma
Authors: Eduardo de Faria Castro Fleury
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
MGL-3196, a selective thyroid hormone receptor-beta agonist significantly decreases hepatic fat in NASH patients at 12 weeks, the primary endpoint in a 36 week serial liver biopsy study
Authors: S. Harrison, S. Moussa, M. Bashir, N. Alkhouri, J. Frias, S. Baum, B. Tetri, M. Bansal, R. Taub
Journal: Journal of Hepatology (2018)
Sudden Death in Patients With Coronary Heart Disease Without Severe Systolic Dysfunction
Authors: Neal A. Chatterjee, M. Vinayaga Moorthy, Julie Pester, Andi Schaecter, Gopi K. Panicker, Dhiraj Narula, Daniel C. Lee, Jeffrey J. Goldberger, Alan Kadish, Nancy R. Cook, Christine M. Albert
Journal: JAMA Cardiology (2018)

The majority of sudden and/or arrhythmic deaths (SAD) in patients with coronary heart disease occur in those without severe systolic dysfunction, for whom strategies for sudden death prevention are lacking.To provide contemporary estimates of SAD vs other competing causes of death in patients with coronary heart disease without severe systolic dysfunction to search for high-risk subgroups that might be targeted in future trials of SAD prevention.This prospective observational cohort study included 135 clinical sites in the United States and Canada. A total of 5761 participants with coronary heart disease who did not qualify for primary prevention implantable cardioverter defibrillator therapy based on left ventricular ejection fraction (LVEF) of more than 35% or New York Heart Association (NYHA) heart failure class (LVEF >30%, NYHA I).Clinical risk factors measured at baseline including age, LVEF, and NYHA heart failure class.Primary outcome of SAD, which is a composite of SAD and resuscitated ventricular fibrillation arrest.The mean (SD) age of the cohort was 64 (11) years. During a median of 3.9 years, the cumulative incidence of SAD and non-SAD was 2.1% and 7.7%, respectively. Sudden and/or arrhythmic death was the most common mode of cardiovascular death accounting for 114 of 202 cardiac deaths (56%), although noncardiac death was the primary mode of death in this population. The 4-year cumulative incidence of SAD was lowest in those with an LVEF of more than 60% (1.0%) and highest among those with LVEF of 30% to 40% (4.9%) and class III/IV heart failure (5.1%); however, the cumulative incidence of non-SAD was similarly elevated in these latter high-risk subgroups. Patients with a moderately reduced LVEF (40%-49%) were more likely to die of SAD, whereas those with class II heart failure and advancing age were more likely to die of non-SAD. The proportion of deaths due to SAD varied widely, from 14% (18 of 131 deaths) in patients with NYHA II to 49% (37 of 76 deaths) in those younger than 60 years.In a contemporary population of patients with coronary heart disease without severe systolic dysfunction, SAD accounts for a significant proportion of overall mortality. Moderately reduced LVEF, age, and NYHA class distinguished SAD and non-SAD, whereas other markers were equally associated with both modes of death. Absolute and proportional risk of SAD varied significantly across clinical subgroups, and both will need to be maximized in future risk stratification efforts.
AT-527, a pan-genotypic purine nucleotideprodrug, exhibits potent antiviral activity in subjects with chronic hepatitis C
Authors: X.-J. Zhou, E. Berliba, F. Vanhoutte, M. Bogus, P.-J. Berghmans, K. Pietropaolo, S. Good, A. Moussa, R. Murphy, J.-P. Sommadossi
Journal: Journal of Hepatology (2018)
MRI Visualization of Injectable Ureidopyrimidinone Hydrogelators by Supramolecular Contrast Agent Labeling
Authors: Maarten H. Bakker, Cheyenne C. S. Tseng, Henk M. Keizer, Peter R. Seevinck, Henk M. Janssen, Frebus J. Van Slochteren, Steven A. J. Chamuleau, Patricia Y. W. Dankers
Journal: Advanced Healthcare Materials (2018)

Abstract Information about the in vivo location, shape, degradation, or erosion rate of injected in situ gelating hydrogels can be obtained with magnetic resonance imaging (MRI). Herein, an injectable supramolecular ureidopyrimidinone‐based hydrogel (UPy‐PEG) is functionalized with a modified Gadolinium(III)‐DOTA complex (UPy‐Gd) for contrast enhanced MRI. The contrast agent is designed to supramolecularly interact with the hydrogel network to enable high‐quality imaging of this hydrogel. The applicability of the approach is demonstrated with successful visualization of the Gd‐labeled UPy‐PEG hydrogel after targeted intramyocardial catheter injection in a pig heart.
Frequencyand outcomes of liver transplantation for nonalcoholic steatohepatitis in Europe
Authors: D. Haldar, B. Kern, J. Hodson, V. Karam, J. Fritz, R. Adam, B. Feurstein, W. Popp, H. Tilg, H. Zoller, P. Muiesan, S. Schneeberger, P. Newsome
Journal: Journal of Hepatology (2018)
Defective NKp30-mediated function in hepatocellular carcinoma-infiltrating NK cells
Authors: S. Mantovani, B. Oliviero, D. Mele, A. Sangiovanni, M. Donadon, G. Torzilli, C. Soldani, C. Porta, S. Chiellino, R. Santambrogio, E. Opocher, M.U. Mondelli
Journal: Journal of Hepatology (2018)
Multidomain Control Over TEC Kinase Activation State Tunes the T Cell Response
Authors: Amy H. Andreotti, Raji E. Joseph, James M. Conley, Janet Iwasa, Leslie J. Berg
Journal: Annual Review of Immunology (2018)

Signaling through the T cell antigen receptor (TCR) activates a series of tyrosine kinases. Directly associated with the TCR, the SRC family kinase LCK and the SYK family kinase ZAP-70 are essential for all downstream responses to TCR stimulation. In contrast, the TEC family kinase ITK is not an obligate component of the TCR cascade. Instead, ITK functions as a tuning dial, to translate variations in TCR signal strength into differential programs of gene expression. Recent insights into TEC kinase structure have provided a view into the molecular mechanisms that generate different states of kinase activation. In resting lymphocytes, TEC kinases are autoinhibited, and multiple interactions between the regulatory and kinase domains maintain low activity. Following TCR stimulation, newly generated signaling modules compete with the autoinhibited core and shift the conformational ensemble to the fully active kinase. This multidomain control over kinase activation state provides a structural mechanism to account for ITK's ability to tune the TCR signal.
The end of US hospitals as we know them?
Authors: Douglas Kamerow
Journal: BMJ (2018)

Abstract  Epiretinal prostheses are designed to restore vision in people blinded by photoreceptor degenerative diseases, by directly activating retinal ganglion cells (RGCs) using an electrode array implanted on the retina. In present-day clinical devices, current spread from the stimulating electrode to a distant return electrode often results in the activation of many cells, limiting the quality of artificial vision. In the laboratory, epiretinal activation of RGCs with cellular resolution has been demonstrated with small electrodes, but distant returns may still cause more current spread than necessary. In this study, the ability of local return stimulation to improve the selective activation of RGCs at cellular scale was evaluated. A custom multi-electrode array (512 electrodes, 10 μm diameter, 60 μm pitch) was used to simultaneously stimulate and record from RGCs in isolated primate retina. Stimulation with a single electrode and a distant return was compared to stimulation in which the return was provided by six neighboring electrodes. Local return stimulation enhanced the capability to activate cells near the central electrode ( 30 μm). These results suggest that a device that restricts the electric field through local returns could optimize activation of neurons at cellular resolution, improving the quality of artificial vision.
Accelerated and enhanced osteointegration of MAO-treated implants: histological and histomorphometric evaluation in a rabbit model
Authors: Xin Li, Haiyang Xu, Baodong Zhao, Shuai Jiang
Journal: International Journal of Oral Science (2018)

Microarc oxidation (MAO) has become a promising technique for the surface modification of implants. Therefore, the aims of this study were to further quantitatively and qualitatively evaluate the osteointegration abilities of MAO-treated and smooth surface (SF) implants in vivo and to investigate the areas in which the superiority of MAO-treated implants are displayed. In a rabbit model, a comprehensive histomorphological, osteogenic, mineralizational, and integrative assessment was performed using light microscopy, fluorescence microscopy, confocal laser scanning microscopy, and radiographic analyses. Compared with the SF groups, the MAO-treated groups exhibited more active contact osteogenesis, as well as distant osteogenesis, under fluorescence examination, the mineral apposition rate was found to be greater for all of the MAO-treated implants, and the osteointegration index (OI) value was greater in the MAO-treated groups at different times. In conclusion, the calcium-rich amorphous layer created by MAO provided a better environment for osteointegration, with more active contact osteogenesis, a more rapid mineral apposition rate and greater OI values.
Development and Validation of a Calculator for Estimating the Probability of Urinary Tract Infection in Young Febrile Children
Authors: Nader Shaikh, Alejandro Hoberman, Stephanie W. Hum, Anastasia Alberty, Gysella Muniz, Marcia Kurs-Lasky, Douglas Landsittel, Timothy Shope
Journal: JAMA Pediatrics (2018)

Accurately estimating the probability of urinary tract infection (UTI) in febrile preverbal children is necessary to appropriately target testing and treatment.To develop and test a calculator (UTICalc) that can first estimate the probability of UTI based on clinical variables and then update that probability based on laboratory results.Review of electronic medical records of febrile children aged 2 to 23 months who were brought to the emergency department of Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania. An independent training database comprising 1686 patients brought to the emergency department between January 1, 2007, and April 30, 2013, and a validation database of 384 patients were created. Five multivariable logistic regression models for predicting risk of UTI were trained and tested. The clinical model included only clinical variables; the remaining models incorporated laboratory results. Data analysis was performed between June 18, 2013, and January 12, 2018.Documented temperature of 38°C or higher in children aged 2 months to less than 2 years.With the use of culture-confirmed UTI as the main outcome, cutoffs for high and low UTI risk were identified for each model. The resultant models were incorporated into a calculation tool, UTICalc, which was used to evaluate medical records.A total of 2070 children were included in the study. The training database comprised 1686 children, of whom 1216 (72.1%) were female and 1167 (69.2%) white. The validation database comprised 384 children, of whom 291 (75.8%) were female and 200 (52.1%) white. Compared with the American Academy of Pediatrics algorithm, the clinical model in UTICalc reduced testing by 8.1% (95% CI, 4.2%-12.0%) and decreased the number of UTIs that were missed from 3 cases to none. Compared with empirically treating all children with a leukocyte esterase test result of 1+ or higher, the dipstick model in UTICalc would have reduced the number of treatment delays by 10.6% (95% CI, 0.9%-20.4%).UTICalc estimates the probability of UTI by evaluating the risk factors present in the individual child. As a result, testing and treatment can be tailored, thereby improving outcomes for children with UTI.
The 10-year chronic liver disease spectrum evolution in China: experience from the largest tartiary special hospital with 21382 liver biopsy cases
Authors: D. Ji, G. Chen, Y. Fu, C. Wang, J. Chen, Q. Shao, B. Li, F. Li, Z.B. Li, V. Wu, T. Wu, Y. Wang, G. Lau
Journal: Journal of Hepatology (2018)
Dominant-Negative TGF-β Receptor Enhances PSMA-Targeted Human CAR T Cell Proliferation And Augments Prostate Cancer Eradication
Authors: Christopher C. Kloss, Jihyun Lee, Aaron Zhang, Fang Chen, Jan Joseph Melenhorst, Simon F. Lacey, Marcela V. Maus, Joseph A. Fraietta, Yangbing Zhao, Carl H. June
Journal: Molecular Therapy (2018)

Cancer has an impressive ability to evolve multiple processes to evade therapies. While immunotherapies and vaccines have shown great promise, particularly in certain solid tumors such as prostate cancer, they have been met with resistance from tumors that use a multitude of mechanisms of immunosuppression to limit effectiveness. Prostate cancer, in particular, secretes transforming growth factor β (TGF-β) as a means to inhibit immunity while allowing for cancer progression. Blocking TGF-β signaling in T cells increases their ability to infiltrate, proliferate, and mediate antitumor responses in prostate cancer models. We tested whether the potency of chimeric antigen receptor (CAR) T cells directed to prostate-specific membrane antigen (PSMA) could be enhanced by the co-expression of a dominant-negative TGF-βRII (dnTGF-βRII). Upon expression of the dominant-negative TGF-βRII in CAR T cells, we observed increased proliferation of these lymphocytes, enhanced cytokine secretion, resistance to exhaustion, long-term in vivo persistence, and the induction of tumor eradication in aggressive human prostate cancer mouse models. Based on our observations, we initiated a phase I clinical trial to assess these CAR T cells as a novel approach for patients with relapsed and refractory metastatic prostate cancer (ClinicalTrials.gov: NCT03089203). Cancer has an impressive ability to evolve multiple processes to evade therapies. While immunotherapies and vaccines have shown great promise, particularly in certain solid tumors such as prostate cancer, they have been met with resistance from tumors that use a multitude of mechanisms of immunosuppression to limit effectiveness. Prostate cancer, in particular, secretes transforming growth factor β (TGF-β) as a means to inhibit immunity while allowing for cancer progression. Blocking TGF-β signaling in T cells increases their ability to infiltrate, proliferate, and mediate antitumor responses in prostate cancer models. We tested whether the potency of chimeric antigen receptor (CAR) T cells directed to prostate-specific membrane antigen (PSMA) could be enhanced by the co-expression of a dominant-negative TGF-βRII (dnTGF-βRII). Upon expression of the dominant-negative TGF-βRII in CAR T cells, we observed increased proliferation of these lymphocytes, enhanced cytokine secretion, resistance to exhaustion, long-term in vivo persistence, and the induction of tumor eradication in aggressive human prostate cancer mouse models. Based on our observations, we initiated a phase I clinical trial to assess these CAR T cells as a novel approach for patients with relapsed and refractory metastatic prostate cancer (ClinicalTrials.gov: NCT03089203).
Guideline: In patients with mild cognitive impairment, the AAN recommends regular exercise and no drugs or supplements
Authors: Eric B. Larson
Journal: Annals of Internal Medicine (2018)

Source Citation Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update summary: mild cognitive impairment: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018;90:126-35. 29282327
BRAF Mutant Lung Cancer: Programmed Death Ligand 1 Expression, Tumor Mutational Burden, Microsatellite Instability Status, and Response to Immune Check-Point Inhibitors
Authors: Elizabeth Dudnik, Nir Peled, Hovav Nechushtan, Mira Wollner, Amir Onn, Abed Agbarya, Mor Moskovitz, Shoshana Keren, Noa Popovits-Hadari, Damien Urban, Moshe Mishaeli, Alona Zer, Aaron M. Allen, Natalie Maimon Rabinovich, Ofer Rotem, Teodor Kuznetsov, Tzippy Shochat, Laila C. Roisman, Jair Bar
Journal: Journal of Thoracic Oncology (2018)
P553H2S donor (NaHS) restores endothelium-dependent relaxation of smooth muscles in old rats
Authors: K Drachuk, V F Sagach
Journal: Cardiovascular Research (2018)

in CON, reflected in an increased MO2ex (P<0.05), while it had no effect in DMþHFDþCKD, suggesting that loss of NO was principally responsible for the perturbation in myocardial oxygen delivery in DMþHFDþCKD (Figure).This was supported by lower myocardial levels of NO2-þNO3in DMþHFDþCKD compared to CON (0.2060.02 vs 0.3460.06mmol/mg protein, P<0.05).Isolated vessels of DMþHFDþCKD swine showed decreased endothelial dependent vasodilation to BK, mediated via a complete abolishment of the NO-dependent vasodilator pathway, consistent with the in vivo observations.Conclusion: Prolonged exposure to DM, HFD and CKD results in a pro-inflammatory state associated with impaired coronary microvascular NO production, thereby altering coronary microvascular dilation and hampering myocardial perfusion.
Preventing sepsis in healthcare – 200 years after the birth of Ignaz Semmelweis
Authors: Didier Pittet, Benedetta Allegranzi
Journal: Eurosurveillance (2018)

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对于患有光化性角化病的器官移植受者来说,光动力疗法比咪喹莫特更加有效:一项随机个体对照试验
Authors: K. Togsverd-Bo, C. Halldin, C. Sandberg, H. Gonzalez, A.M. Wennberg, S.S. Sørensen, H.C.O. Wulf, M. Hædersdal
Journal: British Journal of Dermatology (2018)

Summary 器官移植(例如肾脏)受者必须服用强效药物来防止器官排斥。而这些药物也会降低人体抵御癌症病发的能力。这对皮肤来说尤其重要,来自阳光紫外线的伤害会导致暴露部位发生癌前病变(日光性角化症)。这些病变相当广泛,并且比在正常的健康皮肤上更容易发展成侵袭性皮肤癌。这项斯堪的纳维亚的研究在一组35名器官移植患者中比较了日光性角化症的两种确定治疗的有效性和可接受性。光动力疗法(PDT)在就诊时即可使用。它需要在皮肤上涂抹感光的乳膏,该乳膏随后会被红光激活。这会在皮肤上引发严重的炎症,但只会破坏异常(而非正常)的组织。另一种治疗是采用咪喹莫特乳膏,患者需每周在家涂抹三次,连续涂抹四周。该乳膏会刺激人体自身的防御机制,来抵抗异常组织病变。每位患者均拥有两处受到相同影响的皮肤部位。这些患者将被随机分配接受PDT或咪喹莫特治疗。如有必要,PDT治疗患者需在三个月后重复治疗,咪喹莫特治疗患者需在两个月后重复治疗。研究人员在三个月和六个月时计算了反馈率。本研究表明,在这组高风险患者中,光动力疗法在减少日光性角化症数量方面比咪喹莫特更加有效。由于PDT比咪喹莫特更加疼痛,患者并没有因此而更加倾向于哪一种治疗。
Clinical effectiveness of enhanced surveillance in “super-high risk” cirrhotics as evaluated in the ITA.LI.CA. Study Group
Authors: F. Pelizzaro, M. D’elia, G. Peserico, A. Meneghetti, A. Imondi, E.G. Giannini, F. Trevisani, F. Farinati
Journal: Journal of Hepatology (2018)