tbuckley/cabot-search huggingface dataset:
Phase 1b Results for Subcutaneous Talquetamab Plus Daratumumab in Patients with Relapsed/Refractory Multiple Myeloma
Authors: Ajai Chari, Parameswaran Hari, Nizar J. Bahlis, Maria-Victoria Mateos, Niels W.C.J. van de Donk, Bhagirathbhai Dholaria, Alfred L. Garfall, Hartmut Goldschmidt, K. Martin Kortuem, Amrita Y. Krishnan, Thomas Martin, Daniel Morillo Giles, Albert Oriol, Donna E. Reece, Cesar Rodriguez, Paula Rodriguez-Otero, Jesús F. San-Miguel, Saad Z. Usmani, Raluca I. Verona, Shun Xin Wang Lin, Thomas J. Prior, Mark Wade, Brendan M. Weiss, Jenna D. Goldberg, Elham Askari
Journal: Blood (2021)
대한간학회지 제2차 춘계학술대회 초록집 : 식도정맥류 출혈시 내시경적 경화요법과 고무밴드 결찰요법의 치료 효과
Authors: 김영탁 ( Kim Yeong Tag ), 금민수 ( Geum Min Su ), 이양일 ( Lee Yang Il ), 최성곤 ( Choe Seong Gon ), 이창형 ( Lee Chang Hyeong ), 권영오 ( Kwon Yeong O ), 김성국 ( Kim Seong Gug ), 최용환 ( Choe Yong Hwan ), 정준모 ( Jeong Jun Mo )
Journal: Clinical and Molecular Hepatology (1996)
An expansion of the non-coding genome and its regulatory potential underlies vertebrate neuronal diversity
Authors: Michael Closser, Yuchun Guo, Ping Wang, Tulsi Patel, Sumin Jang, Jennifer Hammelman, Joriene C. De Nooij, Rachel Kopunova, Esteban O. Mazzoni, Yijun Ruan, David K. Gifford, Hynek Wichterle
Journal: Neuron (2021)
Distinct structural and dynamic components of portal hypertension in different animal models and human liver disease etiologies
Authors: Philipp Königshofer, Benedikt Silvester Hofer, Ksenia Brusilovskaya, Benedikt Simbrunner, Oleksandr Petrenko, Katharina Wöran, Merima Herac, Judith Stift, Katharina Lampichler, Gerald Timelthaler, David Bauer, Lukas Hartl, Bernhard Robl, Maria Sibila, Bruno K. Podesser, Georg Oberhuber, Philipp Schwabl, Mattias Mandorfer, Michael Trauner, Thomas Reiberger
Journal: Hepatology (2021)

Liver fibrosis is the static and main (70%-80%) component of portal hypertension (PH). We investigated dynamic components of PH by a three-dimensional analysis based on correlation of hepatic collagen proportionate area (CPA) with portal pressure (PP) in animals or HVPG in patients.Different animal models (bile duct ligation: n = 31, carbon tetrachloride: n = 12, thioacetamide: n = 12, choline-deficient high-fat diet: n = 12) and patients with a confirmed single etiology of cholestatic (primary biliary cholangitis/primary sclerosing cholangitis: n = 16), alcohol-associated (n = 22), and metabolic (NASH: n = 19) liver disease underwent CPA quantification on liver specimens/biopsies. Based on CPA-to-PP/HVPG correlation, potential dynamic components were identified in subgroups of animals/patients with lower-than-expected and higher-than-expected PP/HVPG. Dynamic PH components were validated in a patient cohort (n = 245) using liver stiffness measurement (LSM) instead of CPA. CPA significantly correlated with PP in animal models (Rho = 0.531; p < 0.001) and HVPG in patients (Rho = 0.439; p < 0.001). Correlation of CPA with PP/HVPG varied across different animal models and etiologies in patients. In models, severity of hyperdynamic circulation and specific fibrosis pattern (portal fibrosis: p = 0.02; septa width: p = 0.03) were associated with PH severity. In patients, hyperdynamic circulation (p = 0.04), vascular dysfunction/angiogenesis (VWF-Ag: p = 0.03; soluble vascular endothelial growth factor receptor 1: p = 0.03), and bile acids (p = 0.04) were dynamic modulators of PH. The LSM-HVPG validation cohort confirmed these and also indicated IL-6 (p = 0.008) and hyaluronic acid (HA: p < 0.001) as dynamic PH components.The relative contribution of "static" fibrosis on PH severity varies by type of liver injury. Next to hyperdynamic circulation, increased bile acids, VWF-Ag, IL-6, and HA seem to indicate a pronounced dynamic component of PH in patients.
Virulence-related O islands in enterohemorrhagic Escherichia coli O157:H7
Authors: Lingyan Jiang, Wen Yang, Xinlei Jiang, Ting Yao, Lu Wang, Bin Yang
Journal: Gut Microbes (2021)

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a principally foodborne pathogen linked to serious diseases, including bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome. Comparative genomics analysis revealed that EHEC O157 contains 177 unique genomic islands, termed O islands, compared with the nonpathogenic E. coli K-12 laboratory strain. These O islands contribute largely to the pathogenicity of EHEC O157:H7 by providing numerous virulence factors, effectors, virulence regulatory proteins, and virulence regulatory sRNAs. The present review aimed to provide a comprehensive understanding of the research progress on the function of O islands, especially focusing on virulence-related O islands.
Baseline IL-6 is a biomarker for unfavourable tuberculosis treatment outcomes: a multisite discovery and validation study
Authors: Akshay N. Gupte, Pavan Kumar, Mariana Araújo-Pereira, Vandana Kulkarni, Mandar Paradkar, Neeta Pradhan, Pradeep Menon, Chandrasekaran Padmapriyadarsini, Luke-Elizabeth Hanna, Shri Vijay Bala Yogendra Shivakumar, Neesha Rockwood, Elsa Du Bruyn, Rajesh Karyakarte, Sanjay Gaikwad, Robert Bollinger, Jonathan Golub, Nikhil Gupte, Vijay Viswanathan, Robert J. Wilkinson, Vidya Mave, Subash Babu, Hardy Kornfeld, Bruno B. Andrade, Amita Gupta
Journal: European Respiratory Journal (2021)

Background Biomarkers of unfavourable tuberculosis (TB) treatment outcomes are needed to accelerate new drug and regimen development. Whether plasma cytokine levels can predict unfavourable TB treatment outcomes is unclear. Methods We identified and internally validated the association between 20 a priori selected plasma inflammatory markers and unfavourable treatment outcomes of failure, recurrence and all-cause mortality among adults with drug-sensitive pulmonary TB in India. We externally validated these findings in two independent cohorts of predominantly diabetic and HIV co-infected TB patients in India and South Africa, respectively. Results Pre-treatment interferon-γ, interleukin (IL)-13 and IL-6 were associated with treatment failure in the discovery analysis. Internal validation confirmed higher pre-treatment IL-6 concentrations among failure cases compared with controls. External validation among predominantly diabetic TB patients found an association between pre-treatment IL-6 concentrations and subsequent recurrence and death. Similarly, external validation among predominantly HIV co-infected TB patients found an association between pre-treatment IL-6 concentrations and subsequent treatment failure and death. In a pooled analysis of 363 TB cases from the Indian and South African validation cohorts, high pre-treatment IL-6 concentrations were associated with higher risk of failure (adjusted OR (aOR) 2.16, 95% CI 1.08–4.33; p=0.02), recurrence (aOR 5.36, 95% CI 2.48–11.57; p&lt;0.001) and death (aOR 4.62, 95% CI 1.95–10.95; p&lt;0.001). Adding baseline IL-6 to a risk prediction model comprised of low body mass index, high smear grade and cavitation improved model performance by 15% (C-statistic 0.66 versus 0.76; p=0.02). Conclusions Pre-treatment IL-6 is a biomarker for unfavourable TB treatment outcomes. Future studies should identify optimal IL-6 concentrations for point-of-care risk prediction.
Association of Sodium-Glucose Cotransporter–2 Inhibitors With Fracture Risk in Older Adults With Type 2 Diabetes
Authors: Min Zhuo, Chelsea E. Hawley, Julie M. Paik, Lily G. Bessette, Deborah J. Wexler, Dae H. Kim, Angela Y. Tong, Seoyoung C. Kim, Elisabetta Patorno
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Whether sodium-glucose cotransporter–2 inhibitors (SGLT-2i) are associated with an increased risk of fractures in older adults with type 2 diabetes (T2D) outside of clinical trials remains unknown. <h3>Objective</h3> To examine the association of incident fracture among older adults with T2D with initiating an SGLT-2i compared with initiating a dipeptidyl peptidase 4 inhibitor (DPP-4i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA). <h3>Design, Setting, and Participants</h3> This is a population-based, new-user cohort study including older adults (aged ≥65 years) with T2D enrolled in Medicare fee-for-service from April 2013 to December 2017. Data analysis was performed from October 2020 to April 2021. <h3>Exposures</h3> New users of an SGLT-2i, DPP-4i, or GLP-1RA without a previous fracture were matched in a 1:1:1 ratio using 3-way propensity score matching. <h3>Main Outcomes and Measures</h3> The primary outcome was a composite end point of nontraumatic pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention within 30 days. After 3-way 1:1:1 propensity score matching, multivariable Cox proportional hazards regression models were used to generate hazard ratios (HRs) for SGLT-2i compared with DPP-4i and GLP-1RA and Kaplan-Meier curves to visualize fracture risk over time across groups. <h3>Results</h3> Of 466 933 new initiators of study drugs, 62 454 patients were new SGLT-2i users. After 3-way matching, 45 889 (73%) new SGLT-2i users were matched to new users of DPP-4i and GLP-1RA, yielding a cohort of 137 667 patients (mean [SD] age, 72 [5] years; 64 126 men [47%]) matched 1:1:1 for analyses. There was no difference in the risk of fracture in SGLT-2i users compared with DPP-4i users (HR, 0.90; 95% CI, 0.73-1.11) or GLP-1RA users (HR, 1.00; 95% CI, 0.80-1.25). Results were consistent across categories of sex, frailty (nonfrail, prefrail, and frail), age (&lt;75 and ≥75 years), and insulin use (baseline users and nonusers). <h3>Conclusions and Relevance</h3> In this nationwide Medicare cohort, initiating an SGLT-2i was not associated with an increased risk of fracture in older adults with T2D compared with initiating a DPP-4i or GLP-1RA, with consistent results across categories of frailty, age, and insulin use. These findings add to the evidence base evaluating the potential risks associated with SGLT-2i use for older adults outside of randomized clinical trials.
Author Correction: 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy
Authors: Andrew H. Wei, Panayiotis Panayiotidis, Pau Montesinos, Kamel Laribi, Vladimir Ivanov, Inho Kim, Jan Novak, Don A. Stevens, Walter Fiedler, Maria Pagoni, Julie Bergeron, Stephen B. Ting, Jing-Zhou Hou, Achilles Anagnostopoulos, Andrew McDonald, Vidhya Murthy, Takahiro Yamauchi, Jianxiang Wang, Brenda Chyla, Yan Sun, Qi Jiang, Wellington Mendes, John Hayslip, Courtney D. DiNardo
Journal: Blood Cancer Journal (2021)
DNA methylation signatures reveal that distinct combinations of transcription factors specify human immune cell epigenetic identity
Authors: Roshni Roy, Senthilkumar Ramamoorthy, Benjamin D Shapiro, Mary Kaileh, Dena Hernandez, Dimitra Sarantopoulou, Sampath Arepalli, Sören Boller, Amit Singh, Arsun Bektas, Jaekwan Kim, Ann Zenobia Moore, Toshiko Tanaka, Julia McKelvey, Linda Zukley, Cuong Nguyen, Tonya Wallace, Christopher Dunn, Robert Wersto, William Wood, Yulan Piao, Kevin G Becker, Christopher Coletta, Supriyo De, Jyoti Misra Sen, Alexis Battle, Nan-Ping Weng, Rudolf Grosschedl, Luigi Ferrucci, Ranjan Sen
Journal: Immunity (2021)
Even low doses of steroids increase the risk of cardiovascular disease in people with inflammatory diseases
Authors: Helen Saul, Deniz Gursul
Journal: BMJ (2021)

The studyPujades-Rodríguez M, Morgan AW, Cubbon RM, Wu J. Dose-dependent oral glucocorticoid cardiovascular risks in people with immune-mediated inflammatory diseases: a population-based cohort study. PLoS Med 2020;17:e1003432.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/low-doses-steroids-increase-cardiovascular-risks-in-inflammatory-diseases/.
MicroRNA-206 promotes the recruitment of CD8<sup>+</sup> T cells by driving M1 polarisation of Kupffer cells
Authors: Ningning Liu, Xiaomei Wang, Clifford John Steer, Guisheng Song
Journal: Gut (2021)

Objective Kupffer cells (KCs) protect against hepatocellular carcinoma (HCC) by communicating with other immune cells. However, the underlying mechanism(s) of this process is incompletely understood. Design FVB/NJ mice were hydrodynamically injected with AKT/Ras and Sleeping Beauty transposon to induce HCC. Mini-circle and Sleeping Beauty were used to overexpress microRNA-206 in KCs of mice. Flow cytometry and immunostaining were used to evaluate the change in the immune system. Results Hydrodynamic injection of AKT/Ras into mice drove M2 polarisation of KCs and depletion of cytotoxic T cells (CTLs) and promoted HCC development. M1-to-M2 transition of KCs impaired microRNA-206 biogenesis. By targeting Klf4 (kruppel like factor 4) and, thereby, enhancing the production of M1 markers including C-C motif chemokine ligand 2 (CCL2), microRNA-206 promoted M1 polarisation of macrophages. Indeed, microRNA-206-mediated increase of CCL2 facilitated hepatic recruitment of CTLs via CCR2. Disrupting each component of the KLF4/CCL2/CCR2 axis impaired the ability of microRNA-206 to drive M1 polarisation of macrophages and recruit CTLs. In AKT/Ras mice, KC-specific expression of microRNA-206 drove M1 polarisation of KCs and hepatic recruitment of CTLs and fully prevented HCC, while 100% of control mice died from HCC. Disrupting the interaction between microRNA-206 and Klf4 in KCs and depletion of CD8 + T cells impaired the ability of miR-206 to prevent HCC. Conclusions M2 polarisation of KCs is a major contributor of HCC in AKT/Ras mice. MicroRNA-206, by driving M1 polarisation of KCs, promoted the recruitment of CD8 + T cells and prevented HCC, suggesting its potential use as an immunotherapeutic approach.
Early Minimal Residual Disease Assessment after Acute Myeloid Leukemia Induction with Fludarabine Cytarabine and Idarubicin (FLAI) Provides the Most Useful Prognostic Information
Authors: Paola Minetto, Fabio Guolo, Marino Clavio, Annalisa Kunkl, Nicoletta Colombo, Enrico Carminati, Giuseppina Fugazza, Simona Matarese, Daniela Guardo, Filippo Ballerini, Carmen Di Grazia, Anna Maria Raiola, Antonia Cagnetta, Michele Cea, Maurizio Miglino, Roberto Massimo Lemoli, Marco Gobbi
Journal: Blood (2017)
Covid-19: Trump’s “distraction” by the 2020 election led to thousands of deaths, says pandemic response adviser
Authors: Owen Dyer
Journal: BMJ (2021)

Community-acquired pneumonia (CAP) represents a major life threatening infection, but disease course and outcome is highly variable. Major drivers of prognosis are respiratory failure, sepsis related organ dysfunction and unstable comorbidities. Current risk stratification tools primarily have been designed to predict mortality and identify low risk patients potentially suitable for ambulatory management. Detection of patients at high risk for clinical deterioration by current scores remains suboptimal. Therefore management related risk stratification tools designed to predict benefit from early intensified monitoring and treatment strategies in hospitalised CAP are advocated. An approach including early and repeatedly evaluated clinical markers of respiratory failure, sepsis related organ dysfunction or decompensating comorbidity combined with individual definition of treatment goals is suggested. Inflammatory biomarkers can add prognostic information. New cardiovascular or stress-related biomarkers like copeptin, MR-proadrenomedullin and cortisol have been repeatedly linked with outcome and disease course in CAP and improved clinical scoring in observational studies. Thus they represent promising tools for individualized risk stratification. A major task in future CAP research will be the evaluation of their additional value in large interventional trials with control groups incorporating strict management guidance by clinical criteria.
The global NAFLD policy review and preparedness index: are countries ready to address this silent public health challenge?
Authors: JV Lazarus, HE Mark, M Villota-Rivas, A Palayew, P Carrieri, M Colombo, M Ekstedt, G Esmat, J George, G Marchesini, K Novak, P Ocama, Ratziu, H Razavi, M Romero-Gómez, M Silva, CW Spearman, F Tacke, EA Tsochatzis, Y Yilmaz, ZM Younossi, VW Wong, S Zelber-Sagi, H Cortez-Pinto, QM Anstee
Journal: Journal of Hepatology (2021)
Vaccination uptake amongst older adults from minority ethnic backgrounds: A systematic review
Authors: Cini Bhanu, Dipesh P. Gopal, Kate Walters, Umar A. R. Chaudhry
Journal: PLoS Medicine (2021)

Background Older adults from minority ethnic backgrounds are at increased risk of contracting COVID-19 and developing severe infection and have increased risk of mortality. Whilst an age-based vaccination approach prioritising older groups is being implemented worldwide, vaccine hesitancy is high amongst minority ethnic groups. Methods and findings We conducted a systematic review and convergent synthesis to systematically examine perceptions of vaccinations amongst older adults from minority ethnic backgrounds. We included studies that reported on perceptions, beliefs, and attitudes towards vaccinations in older adults aged ≥65 years from a minority ethnic background. We excluded studies of vaccinations in investigation or development, studies focused on specific medical conditions, studies where ethnic background or age group was unidentifiable, systematic reviews, editorials, and conference abstracts. We searched MEDLINE, Embase, Virtual Health Library, Web of Science, Cochrane Library, medRxiv, and PROSPERO databases from inception to 15 July 2021. Risk of bias for studies was assessed using the Mixed Methods Appraisal Tool. The quality of evidence of collective outcomes was estimated using the Grading of Recommendations Assessment, Development and Evaluation–Confidence in the Evidence from Reviews of Qualitative research (GRADE–CERQual) framework. A total of 28 eligible studies conducted between 1997 and 2020 were included in the final analysis (17 quantitative surveys, 8 focus group or interview studies, 2 mixed methods studies, and 1 case–control study). The majority were US studies in English or Spanish, except for 6 studies set in Hong Kong, 2 studies in Japan, 1 study in Brazil, and 1 multi-centre study (including China, Indonesia, Turkey, South Korea, Greece, UK, Brazil, and Nigeria). In total, 28,262 individuals with an estimated mean age of 69.8 years were included, 63.2% of whom were female. We summarised the common concepts and themes across studies and populations using a convergent synthesis analysis. Thirteen themes categorised as barriers or facilitators were identified and grouped into structural factors—healthcare provider and system related, patient related, and policy and operational—and were analysed by minority ethnic group. The main limitation of the study was the predominance of studies from the US and East Asia. Conclusions In this systematic review, we found that factors influencing vaccination uptake involve healthcare provider and system, patient-related, and governance-level factors that are specific to the older ethnic minority community being served. The evidence included in this review is supported by high or moderate certainty and can be translated to practice and policy. A tailored, multi-level approach combining increased education, access, and culturally competent discussions with trusted healthcare professionals to address health beliefs can maximise the potential impact of widespread vaccination policies.
TCT-100 Real-World Experience and Outcomes of Protected Versus Unprotected Left Main Percutaneous Coronary Intervention: Insights From the VA CART Program
Authors: Yasin Hussain, Pedro Engel Gonzalez, Rohan Khera, Subhash Banerjee, Annika Hebbe, Mary Plomondon, Stephen Waldo, Steven Pfau, Jeptha Curtis, Samit Shah
Journal: Journal of the American College of Cardiology (2021)
TCT-9 FANTOM II Trial: Safety and Performance Study of the Fantom Sirolimus-Eluting Bioresorbable Coronary Scaffold: First Report: Final 5-Year Clinical Outcomes
Authors: Matthias Lutz, Jeffrey Anderson, Bernard Chevalier, Didier Carrie, David Muller, Alexandre Abizaid
Journal: Journal of the American College of Cardiology (2021)
Dual role of allele-specific DNA hypermethylation within the TERT promoter in cancer
Authors: Donghyun D. Lee, Martin Komosa, Sumedha Sudhaman, Ricardo Leão, Cindy H. Zhang, Joana D. Apolonio, Thomas Hermanns, Peter J. Wild, Helmut Klocker, Farshad Nassiri, Gelareh Zadeh, Bill H. Diplas, Hai Yan, Steven Gallinger, Trevor J. Pugh, Vijay Ramaswamy, Michael D. Taylor, Pedro Castelo-Branco, Nuno Miguel Nunes, Uri Tabori
Journal: Journal of Clinical Investigation (2021)

Aberrant activation of telomerase in human cancer is achieved by various alterations within the TERT promoter, including cancer-specific DNA hypermethylation of the TERT hypermethylated oncological region (THOR). However, the impact of allele-specific DNA methylation within the TERT promoter on gene transcription remains incompletely understood. Using allele-specific next-generation sequencing, we screened a large cohort of normal and tumor tissues (n = 652) from 10 cancer types and identified that differential allelic methylation (DAM) of THOR is restricted to cancerous tissue and commonly observed in major cancer types. THOR-DAM was more common in adult cancers, which develop through multiple stages over time, than in childhood brain tumors. Furthermore, THOR-DAM was especially enriched in tumors harboring the activating TERT promoter mutations (TPMs). Functional studies revealed that allele-specific gene expression of TERT requires hypomethylation of the core promoter, both in TPM and TERT WT cancers. However, the expressing allele with hypomethylated core TERT promoter universally exhibits hypermethylation of THOR, while the nonexpressing alleles are either hypermethylated or hypomethylated throughout the promoter. Together, our findings suggest a dual role for allele-specific DNA methylation within the TERT promoter in the regulation of TERT expression in cancer.
Abstract 16614: Single-Cell RNA Sequencing Reveals ZEB2 as a Cardioprotective Factor After Ischemic Injury
Authors: Monika M Gladka, Arwa Kohela, Bas Molenaar, Danielle Versteeg, Lieneke Kooijman, Vincent Groenewold, Harmjan R Vos, Manon M Huibers, Danny Huylebroeck, Mauro Giacca, Eva van Rooij
Journal: Circulation (2018)

Heart failure is the leading cause of death worldwide. Identification of factors that promote cardiac repair is of major importance. Here we show that the transcription factor ZEB2 confers cardioprotective effects after ischemia. Exposure of cardiomyocyte-specific ZEB2 knock out mice to a myocardial infarction reduced survival and impaired cardiac contractility and infarct healing. Conversely, cardiomyocyte-specific ZEB2 overexpression improved survival, infarct healing and cardiac function. To unveil the molecular mechanisms behind the cardioprotective effects of ZEB2 we performed mass spectrometry on conditioned medium from cardiomyocytes overexpressing ZEB2. We identified TMSB4, PTMA, RACK1 and DYNLL1 as main circulating factors in response to ZEB2 overexpression, which were reported to be cardioprotective, pro-angiogenic or anti-apoptotic. In line with this observation, we could validate the regulation of those factors in our gain- and loss-of-function mouse models, suggesting a role of ZEB2 in regulating their expression and release from cardiomyocytes in vivo. To test for the therapeutic effect of increasing the level of ZEB2 specifically in cardiomyocytes after ischemic injury we made use of both AAV9-mediated ZEB2 delivery directly to the heart and systemic antimiR-208 delivery that causes Zeb2 de-repression specifically in heart muscle cells. Both approaches prevented cardiac dysfunction after ischemic damage and promoted the activation of a cardioprotective gene program. Our data suggest that the increase in ZEB2 in cardiomyocytes in response to stress protects the heart from ischemic damage via non cell autonomous effects of cardioprotective factors. These findings reveal ZEB2 as a cardioprotective factor during ischemic injury, which may hold great promise for future heart failure therapies.