tbuckley/cabot-search huggingface dataset:
Population impact of direct-acting antiviral treatment on new presentations of hepatitis C-related decompensated cirrhosis: a national record-linkage study
Authors: Sharon J Hutchinson, Heather Valerio, Scott A McDonald, Alan Yeung, Kevin Pollock, Shanley Smith, Stephen Barclay, John F Dillon, Raymond Fox, Peter Bramley, Andrew Fraser, Nicholas Kennedy, Rory N Gunson, Kate Templeton, Hamish Innes, Allan McLeod, Amanda Weir, Peter C Hayes, David Goldberg
Journal: Gut (2020)

Objective Population-based studies demonstrating the clinical impact of interferon-free direct-acting antiviral (DAA) therapies are lacking. We examined the impact of the introduction of DAAs on HCV-related decompensated cirrhosis (DC) through analysis of population-based data from Scotland. Design Through analysis of national surveillance data (involving linkage of HCV diagnosis and clinical databases to hospital and deaths registers), we determined i) the scale-up in the number of patients treated and achieving a sustained viral response (SVR), and ii) the change in the trend of new presentations with HCV-related DC, with the introduction of DAAs. Results Approximately 11 000 patients had been treated in Scotland over the 8-year period 2010/11 to 2017/18. The scale-up in the number of patients achieving SVR between the pre-DAA and DAA eras was 2.3-fold overall and 5.9-fold among those with compensated cirrhosis (the group at immediate risk of developing DC). In the pre-DAA era, the annual number of HCV-related DC presentations increased 4.6-fold between 2000 (30) and 2014 (142). In the DAA era, presentations decreased by 51% to 69 in 2018 (and by 67% among those with chronic infection at presentation), representing a significant change in trend (rate ratio 0.88, 95% CI 0.85 to 0.90). With the introduction of DAAs, an estimated 330 DC cases had been averted during 2015–18. Conclusions National scale-up in interferon-free DAA treatment is associated with the rapid downturn in presentations of HCV-related DC at the population-level. Major progress in averting HCV-related DC in the short-term is feasible, and thus other countries should strive to achieve the same.
Additional Considerations for Screening and Treatment of Depression in Patients With Acute Coronary Syndrome—Reply
Authors: Ian M. Kronish, Nathalie Moise, Karina W. Davidson
Journal: JAMA Internal Medicine (2020)

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
Feasibility of a trial to evaluate nicotinamide for chemoprevention of skin cancers in organ transplant recipients in the <scp>UK</scp>
Authors: C.E. Gollins, A. Shah, K. Sinha, S. Khan, N. Paul, B. Meeajun, R.A. Abbott, C. Blasdale, H. Cooper, C.A. Harwood, F. Ismail, J.T. Lear, L. Mackintosh, S. McCormack, C.M. Perrett, C.M. Proby, A. Durack, R. Patalay, R.N. Matin
Journal: British Journal of Dermatology (2020)
Matrix decoded – A pancreatic extracellular matrix with organ specific cues guiding human iPSC differentiation
Authors: Constantin Berger, Yngvild Bjørlykke, Lukas Hahn, Markus Mühlemann, Sebastian Kress, Heike Walles, Robert Luxenhofer, Helge Ræder, Marco Metzger, Daniela Zdzieblo
Journal: Biomaterials (2020)

The extracellular matrix represents a dynamic microenvironment regulating essential cell functions in vivo. Tissue engineering approaches aim to recreate the native niche in vitro using biological scaffolds generated by organ decellularization. So far, the organ specific origin of such scaffolds was less considered and potential consequences for in vitro cell culture remain largely elusive. Here, we show that organ specific cues of biological scaffolds affect cellular behavior. In detail, we report on the generation of a well-preserved pancreatic bioscaffold and introduce a scoring system allowing standardized inter-study quality assessment. Using multiple analysis tools for in-depth-characterization of the biological scaffold, we reveal unique compositional, physico-structural, and biophysical properties. Finally, we prove the functional relevance of the biological origin by demonstrating a regulatory effect of the matrix on multi-lineage differentiation of human induced pluripotent stem cells emphasizing the significance of matrix specificity for cellular behavior in artificial microenvironments.
Ancient Coretention of Paralogs of Cid Centromeric Histones and Cal1 Chaperones in Mosquito Species
Authors: Lisa E Kursel, Frances C Welsh, Harmit S Malik
Journal: Molecular Biology and Evolution (2020)

Despite their essential role in chromosome segregation in most eukaryotes, centromeric histones (CenH3s) evolve rapidly and are subject to gene turnover. We previously identified four instances of gene duplication and specialization of Cid, which encodes for the CenH3 in Drosophila. We hypothesized that retention of specialized Cid paralogs could be selectively advantageous to resolve the intralocus conflict that occurs on essential genes like Cid, which are subject to divergent selective pressures to perform multiple functions. We proposed that intralocus conflict could be a widespread phenomenon that drives evolutionary innovation in centromeric proteins. If this were the case, we might expect to find other instances of coretention and specialization of centromeric proteins during animal evolution. Consistent with this hypothesis, we find that most mosquito species encode two CenH3 (mosqCid) genes, mosqCid1 and mosqCid2, which have been coretained for over 150 My. In addition, Aedes species encode a third mosqCid3 gene, which arose from an independent gene duplication of mosqCid1. Like Drosophila Cid paralogs, mosqCid paralogs evolve under different selective constraints and show tissue-specific expression patterns. Analysis of mosqCid N-terminal protein motifs further supports the model that mosqCid paralogs have functionally diverged. Extending our survey to other centromeric proteins, we find that all Anopheles mosquitoes encode two CAL1 paralogs, which are the chaperones that deposit CenH3 proteins at centromeres in Diptera, but a single CENP-C paralog. The ancient coretention of paralogs of centromeric proteins adds further support to the hypothesis that intralocus conflict can drive their coretention and functional specialization.
A cross-sectional report on melasma among Hispanic patients: Evaluating the role of oral tranexamic acid versus oral tranexamic acid plus hydroquinone
Authors: Ileana E. Arreola Jauregui, Gabriel Huerta Rivera, Manuel Soria Orozco, Silvia Meyer-Nava, Juan E. Paniagua Santos, Juan B. López Zaldo, Ilse Meyer-Nava, Clara Madrid Carrillo, Iara E. Zaldo Rolón, Aline E. Baeza Echeverría, Minerva Vázquez Huerta
Journal: Journal of the American Academy of Dermatology (2020)
Cardiovascular Mortality After Type 1 and Type 2 Myocardial Infarction in Young Adults
Authors: Avinainder Singh, Ankur Gupta, Ersilia M. DeFilippis, Arman Qamar, David W. Biery, Zaid Almarzooq, Bradley Collins, Amber Fatima, Candace Jackson, Patrycja Galazka, Mattheus Ramsis, Daniel C. Pipilas, Sanjay Divakaran, Mary Cawley, Jon Hainer, Josh Klein, Petr Jarolim, Khurram Nasir, James L. Januzzi, Marcelo F. Di Carli, Deepak L. Bhatt, Ron Blankstein
Journal: Journal of the American College of Cardiology (2020)
Abstract P400: The Association Between Cross-sex Hormone Therapy and Cardiovascular Disease Risk Factors Among Male-to-female Transgender Persons in Chiang Mai, Thailand
Authors: Rebecca L Molinsky, Kanokwan Kulprachakarn, Sakaewan Ounjaijean, Ryan Demmer, Kittipan Rerkasem
Journal: Circulation (2020)

Background: Cross-sex hormone therapy (CSHT) is prescribed to transition secondary sexual characteristics among individuals undergoing male-to-female (MtF) transitions (age range 18-41, mean age=24). Limited data exist to inform the cardiovascular disease (CVD) risk factor profile associated with CSHT. We investigated the relationship between CSHT and cardiovascular risk factors in MtF transgender persons and hypothesize that CSHT will be associated with adverse CVD risk factor profiles. Methods: A cross-sectional study was conducted from October 1 st , 2018 to November 30 th , 2018 in 100 MtF transgender people not receiving CSHT vs. 100 receiving CSHT. CSHT use was defined by self-report use of up to 23 medications. Serum testosterone and 17-beta estradiol were assessed to validate CSHT use. Systolic and diastolic blood pressure was measured. Lipid profiles, fasting plasma glucose (FPG), C-reactive protein, cardiac troponin I and pro b-type natriuretic peptide (proBNP) were assessed from fasting blood. Non-invasive arterial examinations included: carotid intima-media thickness (CIMT), ankle-brachial index (ABI), cardio-ankle vascular index (CAVI), and pulse wave velocity (PWV). Multivariable linear regression models, regressed CVD risk factors on CSHT status. Among the subgroup of CSHT users, we assessed the relationship between duration of use and CVD risk factors. Multivariable models included age, gender, education, income, drinking, smoking, exercise, and BMI. Results: Participant mean age was 24±0.38 years and did not differ by CSHT use. Mean±SE values of testosterone were in the CSHT vs. control group were 4.8±0.3 vs. 5.8±0.3 ng/ml, p=0.06 and 17-beta estradiol levels were 45.6±14.9 vs. 34.7±14.8, p=0.7). CIMT was modestly lower among CSHT vs. controls (0.35±0.01 vs. 0.38±0.01, p=0.09). The average duration of CSHT use was 6.65±0.522 years. Among CSHT users, for every 1-year increase in duration of CSHT use total cholesterol decreased by -2.360 ± 1.096, p=0.0341 mg/dL, LDL-cholesterol decreased by -3.076 ± 1.182, p=0.0109 mg/dL, ABI decreased by -0.006 ± 0.002, p=0.0087 while FPG increased by 2.558 ± 0.899 mg/dL, p=0.0055. Conclusion: Among MtF transgender persons, using CSHT was not associated with increased CVD risk factors levels.
Active Monitoring of Persons Exposed to Patients with Confirmed COVID-19 — United States, January–February 2020
Authors: Rachel M. Burke, Claire M. Midgley, Alissa Dratch, Marty Fenstersheib, Thomas Haupt, Michelle Holshue, Isaac Ghinai, M. Claire Jarashow, Jennifer Lo, Tristan D. McPherson, Sara Rudman, Sarah Scott, Aron J. Hall, Alicia M. Fry, Melissa A. Rolfes
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, began in Wuhan, China (1). The disease spread widely in China, and, as of February 26, 2020, COVID-19 cases had been identified in 36 other countries and territories, including the United States. Person-to-person transmission has been widely documented, and a limited number of countries have reported sustained person-to-person spread.* On January 20, state and local health departments in the United States, in collaboration with teams deployed from CDC, began identifying and monitoring all persons considered to have had close contact† with patients with confirmed COVID-19 (2). The aims of these efforts were to ensure rapid evaluation and care of patients, limit further transmission, and better understand risk factors for transmission.
Abstract 18939: Trends in Antithrombotic Therapy for Atrial Fibrillation in the Veterans Affairs
Authors: Mary Vaughan Sarrazin, Pete Cram, Peter Kaboli
Journal: Circulation (2013)

INTRODUCTION: The CHADS2 is a stroke risk score developed in 2001 to guide the selection of antithrombotic therapy for patients with atrial fibrillation (AF). Since 2001 the CHADS2 has been adopted into multiple practice guidelines. Anticoagulation by warfarin or newer anticoagulants is recommended for patients with CHADS2 of 2 or higher, with aspirin or clopidogrel recommended for lower CHADS2 scores. We evaluated trends during 2002-2011 in antithrombotic therapy by CHADS2 score for patients with new AF episodes in the Veterans Affairs (VA). METHODS: New AF episodes were defined by at least two encounters for AF (ICD-9-CM 427.31) and no previous AF episodes based on national VA data (n=297,611). Patient age and diagnoses for hypertension, diabetes, heart failure, and stroke during the 12 months preceding AF were used to calculate CHADS2 scores. Receipt of warfarin, dabigatran, or clopidogrel within 90 days of the AF episode was identified in VA national pharmacy data. Trends in antithrombotic therapy by CHADS2 score were examined in unadjusted analyses and in analyses that controlled for bleeding risk. RESULTS: Overall, 54% of patients received antithrombotics within 90 days of AF. Among those, 88% received warfarin and 18% received clopidogrel. Dabigatran (available in the VA in 2011) accounted for 0.4% of patients in 2010-2011. From 2002 through 2011, the proportion of patients prescribed warfarin within 90 days of AF decreased by 26%, 23%, 15%, 13%, 8%, and 10%, for patients with CHADS2 score of 0, 1, 2, 3, 4, and 5-6, respectively (p&lt;.0010). Clopidogrel use decreased by 17% and 20% over the 10-year period for patients with CHADS2 of 1 or 5 or more, respectively, but increased for patients with CHADS2 of 1, 2, or 3. Results were similar controlling for bleeding risk factors. LIMITATIONS: We were unable to assess the use of aspirin due to its availability without a prescription. CONCLUSIONS: Widespread adoption of the CHADS2 stroke risk score in practice guidelines appears to have impacted anticoagulation prescribing patterns for warfarin. Results for clopidogrel were mixed, likely due to the use of clopidogrel for other cardiac conditions. The overall decline in antithrombotic agents in our study, even among patients with high CHADS, warrants investigation.
Abstract P465: Standardizing Hypertension Management In A Primary Care Setting In India Through A Protocol Based Model
Authors: Priyanka Satish, Aditya Khetan, Shyamsundar Raithatha, Richard A Josephson
Journal: Circulation (2020)

Hypertension is a leading cause of death in India. There are numerous barriers to adequate management of hypertension in Indian healthcare settings, including therapeutic inertia and the lack of a systematic approach. Standardizing hypertension management through an evidence based model that sets thresholds for diagnosis, treatment goals, follow up intervals and choice of drugs can lead to improved management of hypertension in an individual hospital or health system. We describe the design of a model that focuses on efficacy, safety and ease of use by healthcare providers with different levels of training. The algorithm endorses a urine albumin first approach in deciding the course of antihypertensive therapy. Providers undergo training in the implementation of this model using a training guide and handout developed for this purpose. The algorithm itself can be utilized as a point of care reference by individual practitioners, hospitals, primary health centers (PHCs) and the Health and Wellness Centers (HWCs) under the Ayushman Bharat initiative. We plan to evaluate the effectiveness of our model at Shree Krishna Hospital, Gujarat, India through a quality improvement framework. The algorithm is designed to allow adaptability to individual institutional requirements in India (and similar low and middle income countries) while standardizing the basic elements of hypertension management.
IRF4 instructs effector Treg differentiation and immune suppression in human cancer
Authors: Giorgia Alvisi, Jolanda Brummelman, Simone Puccio, Emilia M.C. Mazza, Elisa Paoluzzi Tomada, Agnese Losurdo, Veronica Zanon, Clelia Peano, Federico S. Colombo, Alice Scarpa, Marco Alloisio, Ajithkumar Vasanthakumar, Rahul Roychoudhuri, Marinos Kallikourdis, Massimiliano Pagani, Egesta Lopci, Pierluigi Novellis, Jonas Blume, Axel Kallies, Giulia Veronesi, Enrico Lugli
Journal: Journal of Clinical Investigation (2020)

The molecular mechanisms responsible for the high immunosuppressive capacity of CD4+ Tregs in tumors are not well known. High-dimensional single-cell profiling of T cells from chemotherapy-naive individuals with non–small-cell lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral CD4+ effector Tregs with superior suppressive activity. In contrast to the IRF4– counterparts, IRF4+ Tregs expressed a vast array of suppressive molecules, and their presence correlated with multiple exhausted subpopulations of T cells. Integration of transcriptomic and epigenomic data revealed that IRF4, either alone or in combination with its partner BATF, directly controlled a molecular program responsible for immunosuppression in tumors. Accordingly, deletion of Irf4 exclusively in Tregs resulted in delayed tumor growth in mice while the abundance of IRF4+ Tregs correlated with poor prognosis in patients with multiple human cancers. Thus, a common mechanism underlies immunosuppression in the tumor microenvironment irrespective of the tumor type.
Long-term toxicity of high-dose sequential chemotherapy with autologous hematopoietic stem cells support in very high-risk early breast cancer patients (pts)
Authors: A. Bernardi, C. Zamagni, S. Quercia, F. Massari, N. Cacciari, A. A. Martoni
Journal: Journal of Clinical Oncology (2007)

11101 Background: High-dose chemotherapy with autologous haematopoietic stem cells support (HDCT) in the adjuvant treatment of breast cancer has been abandoned by many, but it remains unclear the real role of this treatment and a meta-analysis of high-dose chemotherapy adjuvant trials is ongoing. Methods: Twenty-five consecutive high risk early breast cancer pts with at least 40 months of follow-up treated at our institution with HDCT are included in the present analysis. Median age was 44 (range 24–59 years) and 15 pts were premenopausal. The median number of axillary lymph-nodes metastases was 13 (range 3–49) and the pathological stage was IIB in one pt, IIIA in 3 pts, IIIB in one pt and IIIC in 20 pts. Estrogen and/or progesterone receptors were positive in 15 pts and both negative in 10 pts. The 10- year risk of relapse of pts with disease characteristics similar to those included in our study population is 80–85%. The HDCT regimen used was cyclophosphamide 7g/m2 plus G-CSF (followed by apheresis of peripheral haematopoietic stem cells), methotrexate 8 g/m2 followed by thiotepa 600 mg/m2 and melphalan 160 mg/m2 or by mitozantrone 60 mg/m2 and melphalan 180 mg/m2 and stem cells reinfusion. Results: At a median follow-up of 7 years (range 3,5 - 8 years) 13 pts (52%) relapsed and 10 pts (40%) died. The most common sites of recurrence were lung, liver and bones; 6 pts developed brain metastases and in 2 cases a bone marrow infiltration was documented. No toxic deaths and no long term toxicities, except irreversible amenorrhoea in all the premenopausal pts, were observed. No secondary malignancies occurred.The median relapse-free survival is 65,1 months, while the median overall survival has not been reached yet. Conclusions: In our experience high-dose sequential chemotherapy with autologous stem cells support is a safe treatment with no toxic deaths and no long-term toxicities. This regimen should therefore be further investigated if translational research will be able to identify subgroups of pts with the highest probability to benefit from intensive chemotherapy. No significant financial relationships to disclose.
Use of Disposable Perioperative Jackets and Surgical Site Infections—Reply
Authors: Erik J. Stapleton, Nicholas Frane, Adam D. Bitterman
Journal: JAMA Surgery (2020)

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
Physiological predictors of survival in patients with sarcoidosis-associated pulmonary hypertension: results from an international registry
Authors: Oksana A. Shlobin, Vasilis Kouranos, Scott D. Barnett, Esam H. Alhamad, Daniel A. Culver, Joseph Barney, Francis C. Cordova, Eva M. Carmona, Mary Beth Scholand, Marlies Wijsenbeek, Sivagini Ganesh, Elyse E. Lower, Peter J. Engel, John Wort, Laura Price, Athol U. Wells, Steven D. Nathan, Robert P. Baughman
Journal: European Respiratory Journal (2020)

Introduction Sarcoidosis-associated pulmonary hypertension (SAPH) is associated with reduced survival in single-centre studies. The international Registry for SAPH (ReSAPH) with long-term follow-up was established to enrich our knowledge of this complication of sarcoidosis. This analysis aims to elucidate factors associated with reduced transplant-free survival in SAPH patients. Methods ReSAPH contains prospectively collected outcomes of SAPH patients since the time of registry enrolment. Information analysed includes right heart catheterisation data, pulmonary function testing, chest radiography, Scadding stage and 6-min walk distance (6MWD), among others. Cox regression models were used to identify independent predictors of transplant-free survival. Results Data from 215 patients followed for a mean± sd 2.5±1.9 years were available for analysis. In the 159 precapillary patients, the Kaplan–Meier-adjusted 1-, 3- and 5-year transplant-free survival was 89.2%, 71.7% and 62.0%, respectively. Kaplan–Meier-adjusted 1-, 3- and 5-year transplant-free survival in the incident group was 83.5%, 70.3% and 58.3%, respectively, and in the prevalent group was 94.7%, 72.2% and 66.3%, respectively. Patients with reduced diffusing capacity of the lung for carbon monoxide ( D LCO ) (&lt;35% predicted) and 6MWD &lt;300 m in the precapillary cohort had significantly worse transplant-free survival. Reduced 6MWD and preserved forced expiratory volume (FEV 1 )/forced vital capacity (FVC) ratio were identified as independent risk factors for reduced transplant-free survival in the precapillary cohort. Conclusion Reduced D LCO (&lt;35% pred) and 6MWD (&lt;300 m) at the time of registry enrolment were associated with reduced transplant-free survival in the overall precapillary cohort. Preserved FEV 1 /FVC ratio was identified as an independent risk factor for worsened outcomes.