tbuckley/cabot-search huggingface dataset:
Rilpivirine attenuates liver fibrosis through selective STAT1-mediated apoptosis in hepatic stellate cells
Authors: Alberto Martí-Rodrigo, Fernando Alegre, Ángela B Moragrega, Francisco García-García, Pablo Martí-Rodrigo, Anabel Fernández-Iglesias, Jordi Gracia-Sancho, Nadezda Apostolova, Juan V Esplugues, Ana Blas-García
Journal: Gut (2019)

Liver fibrosis constitutes a major health problem worldwide due to its rapidly increasing prevalence and the lack of specific and effective treatments. Growing evidence suggests that signalling through cytokine-activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways regulates liver fibrosis and regeneration. Rilpivirine (RPV) is a widely used anti-HIV drug not reported to produce hepatotoxicity. We aimed to describe the potential hepatoprotective effects of RPV in different models of chronic liver injury, focusing on JAK-STAT signalling regulation.The effects of RPV on hepatic steatosis, inflammation and fibrogenesis were studied in a nutritional mouse model of non-alcoholic fatty liver disease, carbon tetrachloride-induced fibrosis and bile duct ligation-induced fibrosis. Primary human hepatic stellate cells (hHSC) and human cell lines LX-2 and Hep3B were used to investigate the underlying molecular mechanisms.RPV exerted a clear anti-inflammatory and antifibrotic effect in all the in vivo models of liver injury employed, and enhanced STAT3-dependent proliferation in hepatocytes and apoptosis in HSC through selective STAT1 activation. These results were reproduced in vitro; RPV undermined STAT3 activation and triggered STAT1-mediated pathways and apoptosis in HSC. Interestingly, this selective pro-apoptotic effect completely disappeared when STAT1 was silenced. Conditioned medium experiments showed that HSC apoptosis activated STAT3 in hepatocytes in an interleukin-6-dependent mechanism.RPV ameliorates liver fibrosis through selective STAT1-dependent induction of apoptosis in HSC, which exert paracrinal effects in hepatocytes, thus promoting liver regeneration. RPV's actions may represent an effective strategy to treat chronic liver diseases of different aetiologies and help identify novel therapeutic targets.
Malaria in travellers to Gambia
Authors: Z Bisoffi
Journal: Eurosurveillance (2008)

Malaria incidence is reportedly declining steadily in many parts of the world, including in at least several African countries. The incidence of imported malaria is also declining in a number of European countries. However, incidence rates in travellers, both European tourists and the so called VFR (visiting friends and relatives) are difficult to estimate, due to problems with the numerator (many cases are not reported) and more importantly with the denominator, for which the information is generally lacking. An exception in the European Union is the United Kingdom (UK), where the International Passenger Survey provides a reliable denominator on the number of travellers to the different countries, duration of stay and reason for travel.
Radiation Dose and Volume to the Pancreas and Subsequent Risk of Diabetes Mellitus: A Report from the Childhood Cancer Survivor Study
Authors: Danielle Novetsky Friedman, Chaya S Moskowitz, Patrick Hilden, Rebecca M Howell, Rita E Weathers, Susan A Smith, Suzanne L Wolden, Emily S Tonorezos, Sogol Mostoufi-Moab, Eric J Chow, Lillian R Meacham, Joanne F Chou, John A Whitton, Wendy M Leisenring, Leslie L Robison, Gregory T Armstrong, Kevin C Oeffinger, Charles A Sklar
Journal: JNCI Journal of the National Cancer Institute (2019)

Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for diabetes mellitus, but the association between risk and radiation dose and volume is unclear.Participants included 20 762 5-year survivors of childhood cancer (4568 exposed to abdRT) and 4853 siblings. For abdRT, we estimated maximum dose to abdomen; mean doses for whole pancreas, pancreatic head, body, tail; and percent pancreas volume receiving no less than 10, 20, and 30 Gy. Relative risks (RRs) were estimated with a Poisson model using generalized estimating equations, adjusted for attained age. All statistical tests were two-sided.Survivors exposed to abdRT (median age = 31.6 years, range = 10.2-58.3 years) were 2.92-fold more likely than siblings (95% confidence interval [CI] = 2.02 to 4.23) and 1.60-times more likely than survivors not exposed to abdRT (95%CI = 1.24 to 2.05) to develop diabetes. Among survivors treated with abdRT, greater attained age (RRper 10 years = 2.11, 95% CI = 1.70 to 2.62), higher body mass index (RRBMI 30+ = 5.00, 95% CI = 3.19 to 7.83 with referenceBMI 18.5-24.9), and increasing pancreatic tail dose were associated with increased diabetes risk in a multivariable model; an interaction was identified between younger age at cancer diagnosis and pancreatic tail dose with much higher diabetes risk associated with increasing pancreatic tail dose among those diagnosed at the youngest ages (P < .001). Radiation dose and volume to other regions of the pancreas were not statistically significantly associated with risk.Among survivors treated with abdRT, diabetes risk was associated with higher pancreatic tail dose, especially at younger ages. Targeted interventions are needed to improve cardiometabolic health among those at highest risk.
Value-Based Purchasing and Physician Professionalism
Authors: Lawrence P. Casalino, Dhruv Khullar
Journal: JAMA (2019)

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
Tertiary lymphoid organs in the inflammatory myopathy associated with PD-1 inhibitors
Authors: Shiro Matsubara, Morinobu Seki, Shigeaki Suzuki, Takashi Komori, Mikio Takamori
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Programmed cell death 1 inhibitors have revolutionized therapy for cancer by their outstanding effectiveness. However, they may cause adverse effects, among which inflammatory myopathy is one of the most disabling. To elucidate its mechanism, we analysed muscle biopsies and compared them with other inflammatory myopathies. <h3>Methods</h3> Muscle biopsies from three patients with inflammatory myopathy after treatment with PD-1 inhibitors for cancer were subjected to immunohistochemical and ultrastructural analyses to localize CD8+ cytotoxic cells and markers of lymphoid follicles. For comparison, two cases of polymyositis and one of juvenile dermatomyositis were examined. <h3>Results</h3> Nearly identical pathological features were observed in the three cases. In the island-like foci of inflammation, muscle fibers were undergoing degeneration. CD8+ cytotoxic T cells, macrophages, CD4+ cells, and B cells were observed in the foci. CD8+ cells were seen outside and inside the basal lamina of non-necrotic muscle fibers. Lymphoid follicle-like structures with CD21+ follicular dendritic cells were present. The blood vessels in the foci showed features consistent with the high endothelial venules, on which their markers, PNAd and CCL21, were expressed. In polymyositis, blood vessels stained only faintly for PNAd and CCL21, while in juvenile dermatomyositis, in which tertiary lymphoid follicle-like structure was reported in the past, they stained positively. <h3>Conclusions</h3> In inflammatory myopathy associated with PD-1 inhibitors, CD8+ cells appear to predominantly destruct muscle fibers. The presence of lymphoid follicle-like structures and expression of PNAd and CCL21 on the endothelial cells suggest the tertiary lymphoid organs are formed, and involved in the leakage of lymphocytes. Thus, in the three cases examined, formation of the tertiary lymphoid organs is likely to play an important role in genesis of the PD-1 myopathy.
A framework for the investigation of rare genetic disorders in neuropsychiatry
Authors: Stephan J. Sanders, Mustafa Sahin, Joseph Hostyk, Audrey Thurm, Sebastien Jacquemont, Paul Avillach, Elise Douard, Christa L. Martin, Meera E. Modi, Andres Moreno-De-Luca, Armin Raznahan, Alan Anticevic, Ricardo Dolmetsch, Guoping Feng, Daniel H. Geschwind, David C. Glahn, David B. Goldstein, David H. Ledbetter, Jennifer G. Mulle, Sergiu P. Pasca, Rodney Samaco, Jonathan Sebat, Anne Pariser, Thomas Lehner, Raquel E. Gur, Carrie E. Bearden
Journal: Nature Medicine (2019)
Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial
Authors: Sabine Kahl, Sofiya Gancheva, Klaus Straßburger, Christian Herder, Jürgen Machann, Hisayuki Katsuyama, Stefan Kabisch, Elena Henkel, Stefan Kopf, Merit Lagerpusch, Konstantinos Kantartzis, Yuliya Kupriyanova, Daniel Markgraf, Theresa van Gemert, Birgit Knebel, Martin F. Wolkersdorfer, Oliver Kuss, Jong-Hee Hwang, Stefan R. Bornstein, Christian Kasperk, Norbert Stefan, Andreas Pfeiffer, Andreas L. Birkenfeld, Michael Roden
Journal: Diabetes Care (2019)

OBJECTIVE To evaluate whether the sodium–glucose cotransporter 2 inhibitor empagliflozin (EMPA) reduces liver fat content (LFC) in recent-onset and metabolically well-controlled type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Patients with T2D (n = 84) (HbA1c 6.6 ± 0.5% [49 ± 10 mmol/mol], known disease duration 39 ± 27 months) were randomly assigned to 24 weeks of treatment with 25 mg daily EMPA or placebo. The primary end point was the difference of the change in LFC as measured with magnetic resonance methods from 0 (baseline) to 24 weeks between groups. Tissue-specific insulin sensitivity (secondary outcome) was assessed by two-step clamps using an isotope dilution technique. Exploratory analysis comprised circulating surrogate markers of insulin sensitivity and liver function. Statistical comparison was done by ANCOVA adjusted for respective baseline values, age, sex, and BMI. RESULTS EMPA treatment resulted in a placebo-corrected absolute change of −1.8% (95% CI −3.4, −0.2; P = 0.02) and relative change in LFC of −22% (−36, −7; P = 0.009) from baseline to end of treatment, corresponding to a 2.3-fold greater reduction. Weight loss occurred only with EMPA (placebo-corrected change −2.5 kg [−3.7, −1.4]; P &amp;lt; 0.001), while no placebo-corrected change in tissue-specific insulin sensitivity was observed. EMPA treatment also led to placebo-corrected changes in uric acid (−74 mol/L [−108, −42]; P &amp;lt; 0.001) and high-molecular-weight adiponectin (36% [16, 60]; P &amp;lt; 0.001) levels from 0 to 24 weeks. CONCLUSIONS EMPA effectively reduces hepatic fat in patients with T2D with excellent glycemic control and short known disease duration. Interestingly, EMPA also decreases circulating uric acid and raises adiponectin levels despite unchanged insulin sensitivity. EMPA could therefore contribute to the early treatment of nonalcoholic fatty liver disease in T2D.
Racial/Ethnic Disparities in HIV Preexposure Prophylaxis Among Men Who Have Sex with Men — 23 Urban Areas, 2017
Authors: Dafna Kanny, William L. Jeffries, Johanna Chapin-Bardales, Paul Denning, Susan Cha, Teresa Finlayson, Cyprian Wejnert, Meaghan Abrego, Alia Al-Tayyib, Bridget Anderson, Narquis Barak, Jeremy M. Beckford, Barbara Bolden, Kathleen A. Brady, Mary-Grace Brandt, Meredith Brantley, Sarah Braunstein, Celestine Buyu, Rosalinda Cano, Sidney Carrillo, Jie Deng, Karen Diepstra, Rose Doherty, Anna Flynn, Colin Flynn, David Forrest, Danielle German, Sara Glick, Henry Godette, Vivian Griffin, Emily Higgins, Theresa Ick, Tom Jaenicke, Antonio D. Jimenez, Salma Khuwaja, Monina Klevens, Irene Kuo, Zaida Lopez, Yingbo Ma, Stephanie Masiello Schuette, Melanie Mattson, Shanell L. McGoy, David Melton, Sandra Miranda De León, Willie Nixon, Chrysanthus Nnumolu, Conall O’Cleirigh, Jenevieve Opoku, E. Roberto Orellana, Paige Padgett, Jonathon Poe, H. Fisher Raymond, Toyah Reid, Alexis Rivera, William T. Robinson, Yadira Rolón-Colón, Randi Rosack, Sean Schafer, Ekow Kwa Sey, Jennifer Shinefeld, Emma Spencer, Ashley Tate, Jeff Todd, Margaret Vaaler, Afework Wogayehu, Pascale Wortley
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

In 2017, preliminary data show that gay, bisexual, and other men who have sex with men (MSM) accounted for 67% of new diagnoses of human immunodeficiency virus (HIV) infection, that MSM who inject drugs accounted for an additional 3%, and that African American/black (black) and Hispanic/Latino (Hispanic) MSM were disproportionately affected (1). During 2010-2015, racial/ethnic disparities in HIV incidence increased among MSM; in 2015, rates among black and Hispanic MSM were 10.5 and 4.9 times as high, respectively, as the rate among white MSM (compared with 9.2 and 3.8 times as high, respectively, in 2010) (2). Increased use of preexposure prophylaxis (PrEP), which reduces the risk for sexual acquisition of HIV infection by approximately 99% when taken daily as prescribed,* would help to reduce these disparities and support the Ending the HIV Epidemic: A Plan for America initiative† (3). Although PrEP use has increased among all MSM since 2014 (4), racial/ethnic disparities in PrEP use could increase existing disparities in HIV incidence among MSM (5). To understand racial/ethnic disparities in PrEP awareness, discussion with a health care provider, and use (steps in the HIV PrEP continuum of care) (6), CDC analyzed 2017 National HIV Behavioral Surveillance (NHBS) data. Black and Hispanic MSM were significantly less likely than were white MSM to be aware of PrEP, to have discussed PrEP with a health care provider, or to have used PrEP within the past year. Among those who had discussed PrEP with a health care provider within the past year, 68% of white MSM, 62% of Hispanic MSM, and 55% of black MSM, reported PrEP use. Prevention efforts need to increase PrEP use among all MSM and target eliminating racial/ethnic disparities in PrEP use.§.
SPECT-Guided LV Lead Placement for Incremental CRT Efficacy
Authors: Jiangang Zou, Wei Hua, Yangang Su, Geng Xu, Liangrong Zhen, Yanchun Liang, Ji Yan, Bo Yu, Xinbing Liu, Xiaolin Xue, Jiefu Yang, Ji Fan, Tao Guo, Lixia Yang, Yugang Dong, Lin Cai, Xiang Gu, Li Zhu, Zuoying Hu, Xiaohan Fan, Xiaofeng Hou, Qijun Shan, Bing Yang, Zhiyong Qian, Yao Wang, Kai Gu, Yuanhao Qiu, Hongping Wu, Lijun Tang, Zhongqiang Zhao, Yongyue Wei, Feng Chen, Ji Chen, Kejiang Cao
Journal: JACC. Cardiovascular imaging (2019)
Proximal Tubule Translational Profiling during Kidney Fibrosis Reveals Proinflammatory and Long Noncoding RNA Expression Patterns with Sexual Dimorphism
Authors: Haojia Wu, Chun-Fu Lai, Monica Chang-Panesso, Benjamin D. Humphreys
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Having a comprehensive transcriptional profile of the proximal tubule in health and fibrosis would likely enhance understanding of fibrosis and perhaps help explain why CKD progresses more quickly in males versus females. To obtain a more complete picture of gene expression in the proximal tubule, the authors performed deep translational profiling of this segment in a mouse model of kidney fibrosis. Their findings demonstrate substantial sex differences in transcripts expressed in proximal tubule cells of males versus females, and indicate that the proximal tubule drives fibrosis through inflammatory and profibrotic paracrine signaling. The study also identified 439 long noncoding RNAs expressed in the proximal tubule, 143 of which undergo differential regulation in fibrosis, suggesting that this type of RNA has unanticipated regulatory roles kidney fibrosis. Background Proximal tubule injury can initiate CKD, with progression rates that are approximately 50% faster in males versus females. The precise transcriptional changes in this nephron segment during fibrosis and potential differences between sexes remain undefined. Methods We generated mice with proximal tubule–specific expression of an L10a ribosomal subunit protein fused with enhanced green fluorescent protein. We performed unilateral ureteral obstruction surgery on four male and three female mice to induce inflammation and fibrosis, collected proximal tubule–specific and bulk cortex mRNA at day 5 or 10, and sequenced samples to a depth of 30 million reads. We applied computational methods to identify sex-biased and shared molecular responses to fibrotic injury, including up- and downregulated long noncoding RNAs (lncRNAs) and transcriptional regulators, and used in situ hybridization to validate critical genes and pathways. Results We identified &gt;17,000 genes in each proximal tubule group, including 145 G-protein–coupled receptors. More than 700 transcripts were differentially expressed in the proximal tubule of males versus females. The &gt;4000 genes displaying altered expression during fibrosis were enriched for proinflammatory and profibrotic pathways. Our identification of nearly 150 differentially expressed proximal tubule lncRNAs during fibrosis suggests they may have unanticipated regulatory roles. Network analysis prioritized proinflammatory and profibrotic transcription factors such as Irf1 , Nfkb1 , and Stat3 as drivers of fibrosis progression. Conclusions This comprehensive transcriptomic map of the proximal tubule revealed sexually dimorphic gene expression that may reflect sex-related disparities in CKD, proinflammatory gene modules, and previously unappreciated proximal tubule–specific bidirectional lncRNA regulation.
Role of clinical variables for predicting pathologic response to neoadjuvant chemoradiation in locally advanced rectal cancer.
Authors: Paula Mendonca Taglietti, Samuel Aguiar, Paulo Henrique Amor Divino, Maria D. Begnami, Ranyell Spencer Sobreira Batista, Celso Lopes Mello, Ademar Lopes
Journal: Journal of Clinical Oncology (2013)

e14691 Background: pathologic response to neoadjuvant chemoradiation is a strong prognostic factor for rectal cancer. Some studies have suggesting a wait and see approach for rectal cancer after clinical complete response to chemoradiation. In this study, we tried to identify clinical predictive factors of pathologic response to neoadjuvant chemoradiation. Methods: we retrospectively reviewed data of 129 patients from a prospective database, treated between January, 2008 and December, 2012. Patients with mid and low rectal adenocarcinoma, clinically staged (MRI) as T3,T4 any N or any T, N+, received pre-operative chemoradiation, which consists in 5040 cGy, concomitant to 5-FU-based chemotherapy. All patients were operated, by radical TME procedures. The clinical variables analyzed were: age, gender, distance from dentate line, cT stage, cN stage, pre-treatment CEA level, NIH toxicity during chemoradiation, endoscopic assessment of response, and interval between the end of radiation and surgery. We investigate associations between these variables with complete pathological response (cPR) and “good” pathological response (gPR), defined as ypT0orT1 N0. Results: the rate of cPR was 20.2%. The rate of gPR was 31.8%. For predicting cPR, only the endoscopic assessment of response showed significant association with cPR. Among 18 patients with complete endoscopic response, 8 (44.4%) confirmed cPR after resection. Among 93 patients with endoscopic findings suggesting residual disease, 14 (15.1%) presented cPR (p=0.008). 55.6% (10/18) of patients with complete endoscopic response still have microscopic residual disease in the resected specimen. For predicting gPR, only the cN staging was significantly associated with ypT0orT1 N0 (23.9% of gPR among cN+ patients against 41.3% among cN0 patients; p=0.038). Conclusions: clinical tools are very poor for predicting pathological response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal carcinomas. Despite endoscopic assessment of response by retoscopy have showed significant association with cPR, the predictive value was weak.
Germline SAMD9 and SAMD9L Alterations in Adult Myelodysplastic Syndromes
Authors: Yasunobu Nagata, Bartlomiej P. Przychodzen, Cassandra M. Hirsch, Hideki Makishima, Victor Pastor Loyola, Babal K Jha, Teodora Kuzmanovic, Tomas Radivoyevitch, Vera Adema, Kenichi Yoshida, Samuel Li, Francesc Sole, Thomas Laframboise, Rabi Hanna, Mikkael A. Sekeres, Seishi Ogawa, Marcin W. Wlodarski, Jorg Cammenga, Jaroslaw P. Maciejewski
Journal: Blood (2017)
Targeting TB or MRSA in Norwegian municipalities during ‘the refugee crisis’ of 2015: a framework for priority setting in screening
Authors: Anders Skyrud Danielsen, Petter Elstrøm, Trude Margrete Arnesen, Unni Gopinathan, Oliver Kacelnik
Journal: Eurosurveillance (2019)

Introduction In 2015, there was an increase in the number of asylum seekers arriving in Europe. Like in other countries, deciding screening priorities for tuberculosis (TB) and meticillin-resistant Staphylococcus aureus (MRSA) was a challenge. At least five of 428 municipalities chose to screen asylum seekers for MRSA before TB; the Norwegian Institute for Public Health advised against this. Aim To evaluate the MRSA/TB screening results from 2014 to 2016 and create a generalised framework for screening prioritisation in Norway through simulation modelling. Methods This is a register-based cohort study of asylum seekers using data from the Norwegian Surveillance System for Communicable Diseases from 2014 to 2016. We used survey data from municipalities that screened all asylum seekers for MRSA and denominator data from the Directorate of Immigration. A comparative risk assessment model was built to investigate the outcomes of prioritising between TB and MRSA in screening regimes. Results Of 46,090 asylum seekers, 137 (0.30%) were diagnosed with active TB (notification rate: 300/100,000 person-years). In the municipalities that screened all asylum seekers for MRSA, 13 of 1,768 (0.74%) were found to be infected with MRSA. The model estimated that screening for MRSA would prevent eight MRSA infections while prioritising TB screening would prevent 24 cases of active TB and one death. Conclusion Our findings support the decision to advise against screening for MRSA before TB among newly arrived asylum seekers. The model was an effective tool for comparing screening priorities and can be applied to other scenarios in other countries.
MHC Class II Antigen Presentation by the Intestinal Epithelium Initiates Graft-versus-Host Disease and Is Influenced by the Microbiota
Authors: Motoko Koyama, Pamela Mukhopadhyay, Iona S. Schuster, Andrea S. Henden, Jan Hülsdünker, Antiopi Varelias, Marie Vetizou, Rachel D. Kuns, Renee J. Robb, Ping Zhang, Bruce R. Blazar, Ranjeny Thomas, Jakob Begun, Nicola Waddell, Giorgio Trinchieri, Robert Zeiser, Andrew D. Clouston, Mariapia A. Degli-Esposti, Geoffrey R. Hill
Journal: Immunity (2019)