tbuckley/cabot-search huggingface dataset:
FDA Approval Summary: Oral Azacitidine for Continued Treatment of Adults with Acute Myeloid Leukemia Unable to Complete Intensive Curative Therapy
Authors: Emily Y. Jen, Xin Wang, Meng Li, Hongshan Li, Shwu-Luan Lee, Nina Ni, Donna Przepiorka, Jonathon Vallejo, Ruby Leong, Lian Ma, Brenda J. Gehrke, Sherita McLamore, Marc R. Theoret, R. Angelo de Claro
Journal: Clinical Cancer Research (2022)

Abstract On September 1, 2020, the FDA granted approval for oral azacitidine (Onureg, CC-486) for continued treatment of adult patients with acute myeloid leukemia (AML) who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy and who are not able to complete intensive curative therapy. Approval was based on improvement in overall survival using CC-486 300 mg daily in a 2 weeks on/2 weeks off schedule in comparison with placebo (HR, 0.69; 95% confidence interval, 0.55–0.86; P = 0.0009) in the randomized trial CC-486-AML-001 (QUAZAR) in adults ≥ 55 years old with AML in CR/CRi who did not complete standard intensive induction and postremission therapy. Of note, the study was not designed to test CC-486 as maintenance after standard postremission therapy or as an alternative to standard postremission therapy. Gastrointestinal toxicities, fatigue, and pneumonia were more common in patients treated with CC-486 compared with placebo. Additional studies are needed to establish safe dosing for patients with hepatic impairment. The pharmacokinetic parameters, recommended dose, and recommended schedule of CC-486 differ substantially from those of other azacitidine formulations; therefore, inappropriate substitutions between formulations pose a considerable risk for harm.
SEX DIFFERENCES IN MORTALITY AFTER MYOCARDIAL INFARCTION IN HIGH-INCOME AND MIDDLE-INCOME EUROPEAN COUNTRIES.
Authors: Edina Cenko, Jinsung Yoon, van der Schaar Mihaela, Maria Bergami, Olivia Manfrini, Chris Gale, Zorana Vasiljevic, Goran Stankovic, Marija Vavlukis, Sasko Kedev, Davor Milicic, Maria Dorobantu, Lina Badimon, Raffaele Bugiardini
Journal: Journal of the American College of Cardiology (2022)
Accessible Hepatitis C Care for People Who Inject Drugs
Authors: Benjamin Eckhardt, Pedro Mateu-Gelabert, Yesenia Aponte-Melendez, Chunki Fong, Shashi Kapadia, Melinda Smith, Brian R. Edlin, Kristen M. Marks
Journal: JAMA Internal Medicine (2022)

To achieve hepatitis C elimination, treatment programs need to engage, treat, and cure people who inject drugs.
Differences in healthy longevity by HIV status and viral load among older South African adults: an observational cohort modelling study
Authors: Collin F Payne, Brian Houle, Chido Chinogurei, Carlos Riumallo Herl, Chodziwadziwa Whiteson Kabudula, Lindsay C Kobayashi, Joshua Salomon, Jennifer Manne-Goehler
Journal: The Lancet Healthy Longevity (2022)

BackgroundThe population of people living with HIV in South Africa is rapidly ageing. The co-incidence of demographic ageing and a high HIV burden means that understanding the combined impacts of HIV and antiretroviral therapy (ART) on healthy longevity is of key importance in South Africa.MethodsWe use longitudinal data from the 2015 and 2018 waves of the population-based study, Health and aging in Africa: a longitudinal study of an INDEPTH community in South Africa, to explore life expectancy and disability-free life expectancy of adults aged 45 years and older in rural South Africa. Individuals were classified into one of three health states: disability-free (defined as no reported activities of daily living [ADL] limitations), ADL disabled individuals (defined as difficulty with ≥1 ADL activities), and dead. Annual transition probabilities were modelled using multinomial logistic regression, stratified by initial disability state. We used these estimated transition probabilities as the input for a microsimulation model generating 100 000 simulated life courses, which were used to estimate life expectancy and disability-free life expectancy. CIs, which reflect both the uncertainty of the estimated parameters and the uncertainty from the microsimulation, were created by re-estimating the above analysis sequence using 499 bootstrap re-samples for each age group under study. We took the central 95% of the distribution of these bootstrapped parameters as the 95% CI.FindingsWe found a gradient in remaining life expectancy based on HIV serostatus and viral suppression. At age 45 years, an HIV-negative man could expect to live an additional 27·2 years (95% CI 25·8–29·1), compared with 24·1 years (20·9–27·2) for an HIV-positive, virally suppressed man (defined as <200 copies/mL) and 17·4 years (15·0–20·3) for an HIV-positive, unsuppressed man. Patterns were similar among women. Individuals achieving viral control could expect to live nearly as many disability-free years as HIV-negative individuals at age 45 years. By age 65 years, the healthy longevity of these two groups was indistinguishable.InterpretationThese findings highlight the major population health and longevity gains that are possible when the 90–90–90 goals are realised. We found that viral suppression of HIV-positive individuals through ART has increased lifespan and healthspan to similar levels as observed among HIV-negative individuals. Achievement of viral suppression for millions of people with HIV, especially in high prevalence contexts such as South Africa, is critical for ensuring healthy population ageing.FundingNational Institutes of Health.
Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues
Authors: Zijie Feng, Xin He, Xuyao Zhang, Yuan Wu, Bowen Xing, Alison Knowles, Qiaonan Shan, Samuel Miller, Taylor Hojnacki, Jian Ma, Bryson W. Katona, Terence P. F. Gade, Don L. Siegel, Jörg Schrader, David C. Metz, Carl H. June, Xianxin Hua
Journal: Nature Cancer (2022)
PNEUMOPERICARDIUM FOLLOWING LAPAROSCOPIC HIATAL HERNIA REPAIR - A CASE REPORT
Authors: Antonio Lewis, Jenakan Dev, Alejandro Sanchez, Dipan Uppal, Eduardo Javier Perez, Diana Miranda, Abdullah Sarkar, Manojna Nimmagadda, Jose Sleiman, Craig R. Asher
Journal: Journal of the American College of Cardiology (2022)
Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor–Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies
Authors: Leo Luznik, Marcelo C. Pasquini, Brent Logan, Robert J. Soiffer, Juan Wu, Steven M. Devine, Nancy Geller, Sergio Giralt, Helen E. Heslop, Mary M. Horowitz, Richard J. Jones, Mark R. Litzow, Adam Mendizabal, Lori Muffly, Eneida R. Nemecek, Lynn O'Donnell, Richard J. O'Reilly, Raquel Palencia, Johannes Schetelig, Leyla Shune, Scott R. Solomon, Sumithira Vasu, Vincent T. Ho, Miguel-Angel Perales
Journal: Journal of Clinical Oncology (2021)

Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD).
Hospitalization of Infants and Children Aged 0–4 Years with Laboratory-Confirmed COVID-19 — COVID-NET, 14 States, March 2020–February 2022
Authors: Kristin J. Marks, Michael Whitaker, Nickolas T. Agathis, Onika Anglin, Jennifer Milucky, Kadam Patel, Huong Pham, Pam Daily Kirley, Breanna Kawasaki, James Meek, Evan J. Anderson, Andy Weigel, Sue Kim, Ruth Lynfield, Susan L. Ropp, Nancy L. Spina, Nancy M. Bennett, Eli Shiltz, Melissa Sutton, H. Keipp Talbot, Andrea Price, Christopher A. Taylor, Fiona P. Havers, Jeremy Roland, Jordan Surgnier, Carol Lyons, Kyle Openo, Kenzie Teno, Alexander Kohrman, Erica Bye, Cory Cline, Alison Muse, Virginia Cafferky, Laurie Billing, Nasreen Abdullah, William Schaffner, Keegan McCaffrey
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

The B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, has been the predominant circulating variant in the United States since late December 2021.* Coinciding with increased Omicron circulation, COVID-19-associated hospitalization rates increased rapidly among infants and children aged 0-4 years, a group not yet eligible for vaccination (1). Coronavirus Disease 19-Associated Hospitalization Surveillance Network (COVID-NET)† data were analyzed to describe COVID-19-associated hospitalizations among U.S. infants and children aged 0-4 years since March 2020. During the period of Omicron predominance (December 19, 2021-February 19, 2022), weekly COVID-19-associated hospitalization rates per 100,000 infants and children aged 0-4 years peaked at 14.5 (week ending January 8, 2022); this Omicron-predominant period peak was approximately five times that during the period of SARS-CoV-2 B.1.617.2 (Delta) predominance (June 27-December 18, 2021, which peaked the week ending September 11, 2021).§ During Omicron predominance, 63% of hospitalized infants and children had no underlying medical conditions; infants aged <6 months accounted for 44% of hospitalizations, although no differences were observed in indicators of severity by age. Strategies to prevent COVID-19 among infants and young children are important and include vaccination among currently eligible populations (2) such as pregnant women (3), family members, and caregivers of infants and young children (4).
EXERCISE CAPACITY AND ATRIAL FIBRILLATION RISK IN 459,592 HYPERTENSIVE US VETERANS: A COHORT STUDY
Authors: Andreas E. Pittaras, Charles Faselis, Immanuel Babu Henry Samuel, Michael Doumas, Haralampos Grassos, Rayelyn Murphy, Jonathan N. Myers, Peter Kokkinos
Journal: Journal of the American College of Cardiology (2022)
Association between dosing and combination use of medications and outcomes in heart failure with reduced ejection fraction: data from the <scp>S</scp>wedish Heart Failure Registry
Authors: Domenico D'Amario, Daniele Rodolico, Giuseppe M.C. Rosano, Ulf Dahlström, Filippo Crea, Lars H. Lund, Gianluigi Savarese
Journal: European Journal of Heart Failure (2022)

To assess the association between combination, dose and use of current guideline-recommended target doses (TD) of renin-angiotensin system inhibitors (RASi), angiotensin receptor-neprilysin inhibitors (ARNi) and β-blockers, and outcomes in a large and unselected contemporary cohort of patients with heart failure (HF) and reduced ejection fraction.Overall, 17 809 outpatients registered in the Swedish Heart Failure Registry (SwedeHF) from May 2000 to December 2018, with ejection fraction <40% and duration of HF ≥90 days were selected. Primary outcome was a composite of time to cardiovascular death and first HF hospitalization. Compared with no use of RASi or ARNi, the adjusted hazard ratio (HR) (95% confidence interval [CI]) was 0.83 (0.76-0.91) with <50% of TD, 0.78 (0.71-0.86) with 50%-99%, and 0.73 (0.67-0.80) with ≥100% of TD. Compared with no use of β-blockers, the adjusted HR (95% CI) was 0.86 (0.76-0.91), 0.81 (0.74-0.89) and 0.74 (0.68-0.82) with <50%, 50%-99% and ≥100% of TD, respectively. Patients receiving both an angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/ARNi and a β-blocker at 50%-99% of TD had a lower adjusted risk of the primary outcome compared with patients only receiving one drug, i.e. ACEi/ARB/ARNi or β-blocker, even if this was at ≥100% of TD.Heart failure with reduced ejection fraction patients using higher doses of RASi or ARNi and β-blockers had lower risk of cardiovascular death or HF hospitalization. Use of two drug classes at 50%-99% of TD dose was associated with lower risk than one drug class at 100% of TD.
Soluble ECM promotes organotypic formation in lung alveolar model
Authors: Jonard C. Valdoz, Nicholas A. Franks, Collin G. Cribbs, Dallin J. Jacobs, Ethan L. Dodson, Connor J. Knight, P. Daniel Poulson, Seth R. Garfield, Benjamin C. Johnson, Brandon M. Hemeyer, Miranda T. Sudo, Jordan A. Saunooke, Braden C. Kartchner, Aubrianna Saxton, Mary L. Vallecillo-Zuniga, Matheus Santos, Brandon Chamberlain, Kenneth A. Christensen, Greg P. Nordin, A. Sampath Narayanan, Ganesh Raghu, Pam M. Van Ry
Journal: Biomaterials (2022)

Micropatterned suspension culture creates consistently sized and shaped cell aggregates but has not produced organotypic structures from stable cells, thus restricting its use in accurate disease modeling. Here, we show that organotypic structure is achieved in hybrid suspension culture via supplementation of soluble extracellular matrix (ECM). We created a viable lung organoid from epithelial, endothelial, and fibroblast human stable cell lines in suspension culture. We demonstrate the importance of soluble ECM in organotypic patterning with the emergence of lumen-like structures with airspace showing feasible gas exchange units, formation of branching, perfusable vasculature, and long-term 70-day maintenance of lumen structure. Our results show a dependent relationship between enhanced fibronectin fibril assembly and the incorporation of ECM in the organoid. We successfully applied this technology in modeling lung fibrosis via bleomycin induction and test a potential antifibrotic drug in vitro while maintaining fundamental cell-cell interactions in lung tissue. Our human fluorescent lung organoid (hFLO) model represents features of pulmonary fibrosis which were ameliorated by fasudil treatment. We also demonstrate a 3D culture method with potential of creating organoids from mature cells, thus opening avenues for disease modeling and regenerative medicine, enhancing understanding of lung cell biology in health and lung disease.
Macrophage NOX2 NADPH oxidase maintains alveolar homeostasis in mice
Authors: Sourav Bhattacharya, Rachel A. Idol, Wei Yang, Jorge David Rojas Márquez, Yanan Li, Guangming Huang, Wandy L. Beatty, Jeffrey J. Atkinson, John H. Brumell, Juhi Bagaitkar, Jeffrey A. Magee, Mary C. Dinauer
Journal: Blood (2022)
Lymph node fibroblastic reticular cells regulate differentiation and function of CD4 T cells via CD25
Authors: Dongeon Kim, Mingyo Kim, Tae Woo Kim, Yong-ho Choe, Hae Sook Noh, Hyun Min Jeon, HyunSeok Kim, Youngeun Lee, Gayeong Hur, Kyung-Mi Lee, Kihyuk Shin, Sang-il Lee, Seung-Hyo Lee
Journal: The Journal of Experimental Medicine (2022)

Lymph node fibroblastic reticular cells (LN-FRCs) provide functional structure to LNs and play important roles in interactions between T cells and antigen-presenting cells. However, the direct impact of LN-FRCs on naive CD4+ T cell differentiation has not been explored. Here, we show that T cell zone FRCs of LNs (LN-TRCs) express CD25, the α chain of the IL-2 receptor heterotrimer. Moreover, LN-TRCs trans-present IL-2 to naive CD4+ T cells through CD25, thereby facilitating early IL-2-mediated signaling. CD25-deficient LN-TRCs exhibit attenuated STAT5 phosphorylation in naive CD4+ T cells during T cell differentiation, promoting T helper 17 (Th17) cell differentiation and Th17 response-related gene expression. In experimental autoimmune disease models, disease severity was elevated in mice lacking CD25 in LN-TRCs. Therefore, our results suggest that CD25 expression on LN-TRCs regulates CD4+ T cell differentiation by modulating early IL-2 signaling of neighboring, naive CD4+ T cells, influencing the overall properties of immune responses.
Cardiovascular outcomes in obstructive sleep apnoea and implications of clinical phenotyping on effect of CPAP treatment
Authors: Pei-Hang Xu, Daniel Y T Fong, Macy M S Lui, David C L Lam, Mary Sau Man Ip
Journal: Thorax (2022)

Background There is a growing awareness of the heterogeneity of obstructive sleep apnoea (OSA). Clinical trials of CPAP treatment on cardiovascular protection have been mostly negative. We aimed to assess the association between polysomnographic parameters and incident major adverse cardiovascular events (MACEs), and to investigate if the CPAP effect could be better delineated among clinical subgroups. Methods This sleep cohort study was conducted using a clinical database and territory-wide electronic health administration data in Hong Kong. Cox regressions were used to calculate HRs. Latent class analysis was used to cluster patients with OSA according to clinical and polysomnographic features. Results Of 1860 eligible Chinese subjects who underwent polysomnography (2006–2013), 1544 (83%) had OSA. Over median follow-up of 8.3 years, 278 (14.9%) experienced MACEs. Apnoea–hypopnoea index (AHI) did not predict MACEs (HR: 0.95; 95% CI 0.76 to 1.17), whereas sleep time with oxygen saturation &lt;90% (TST90) (HR: 1.41; 95% CI 1.10 to 1.81) was an independent predictor of MACEs, as were wake and nocturnal heart rate. In moderate–severe OSA (n=1108) who were indicated for CPAP treatment, regular CPAP was not associated with reduction of incident MACEs. Further cluster analysis identified a subgroup (n=333) who was younger, more obese, had more severe OSA (higher AHI and TST90) and more cardiovascular risks, in whom regular CPAP was associated with a lower risk of MACEs (HR:0.49, 95% CI 0.25 to 0.95). Conclusions OSA-related TST90 and mean heart rate, but not AHI, were robust predictors of MACEs. A clinical phenotype subgroup who demonstrated beneficial effect of CPAP treatment was identified.
Hepatic kinome atlas: An in‐depth identification of kinase pathways in liver fibrosis of humans and rodents
Authors: Justin F. Creeden, Zachary A. Kipp, Mei Xu, Robert M. Flight, Hunter N. B. Moseley, Genesee J. Martinez, Wang‐Hsin Lee, Khaled Alganem, Ali S. Imami, Megan R. McMullen, Sanjoy Roychowdhury, Atta M. Nawabi, Jennifer A. Hipp, Samir Softic, Steven A. Weinman, Robert McCullumsmith, Laura E. Nagy, Terry D. Hinds
Journal: Hepatology (2022)

Background and Aims Resolution of pathways that converge to induce deleterious effects in hepatic diseases, such as in the later stages, have potential antifibrotic effects that may improve outcomes. We aimed to explore whether humans and rodents display similar fibrotic signaling networks. Approach and Results We assiduously mapped kinase pathways using 340 substrate targets, upstream bioinformatic analysis of kinase pathways, and over 2000 random sampling iterations using the PamGene PamStation kinome microarray chip technology. Using this technology, we characterized a large number of kinases with altered activity in liver fibrosis of both species. Gene expression and immunostaining analyses validated many of these kinases as bona fide signaling events. Surprisingly, the insulin receptor emerged as a considerable protein tyrosine kinase that is hyperactive in fibrotic liver disease in humans and rodents. Discoidin domain receptor tyrosine kinase, activated by collagen that increases during fibrosis, was another hyperactive protein tyrosine kinase in humans and rodents with fibrosis. The serine/threonine kinases found to be the most active in fibrosis were dystrophy type 1 protein kinase and members of the protein kinase family of kinases. We compared the fibrotic events over four models: humans with cirrhosis and three murine models with differing levels of fibrosis, including two models of fatty liver disease with emerging fibrosis. The data demonstrate a high concordance between human and rodent hepatic kinome signaling that focalizes, as shown by our network analysis of detrimental pathways. Conclusions Our findings establish a comprehensive kinase atlas for liver fibrosis, which identifies analogous signaling events conserved among humans and rodents.
ASSOCIATION OF MATERNAL GLYCEMIA AND ADVERSE PREGNANCY OUTCOMES IN UNITED STATES URBAN, LOW-INCOME UNDERREPRESENTED WOMEN
Authors: Yaa Kwapong, Ellen Boakye, Guoying Wang, Xiumei Hong, Michael Blaha, Khurram Nasir, Allison G. Hays, Roger S. Blumenthal, Garima Sharma, Xiaobin Wang
Journal: Journal of the American College of Cardiology (2022)
PREVALENCE AND CHARACTERISTICS OF WOMEN WITH TAKOTSUBO SYNDROME AND PERSISTENT ANGINA: A REPORT FROM THE WOMEN’S ISCHEMIA SYNDROME EVALUATION - CORONARY VASCULAR DYSFUNCTION (WISE-CVD) PROJECT
Authors: Breanna Hansen, Galen Cook-Wiens, Chrisandra Shufelt, John W. Petersen, R. David Anderson, Eileen M. Handberg, Daniel S. Berman, Louise Thomson, Carl J. Pepine, C. Noel Bairey Merz, Janet Wei
Journal: Journal of the American College of Cardiology (2022)
The five major autoimmune diseases increase the risk of cancer: epidemiological data from a large‐scale cohort study in China
Authors: Ziyue Zhou, Huazhen Liu, Yiying Yang, Jingya Zhou, Lidan Zhao, Hua Chen, Yunyun Fei, Wen Zhang, Mengtao Li, Yan Zhao, Xiaofeng Zeng, Fengchun Zhang, Huaxia Yang, Xuan Zhang
Journal: Cancer Communications (2022)

Cancer incidence and mortality have received critical attention during the long-term management of morbidities in patients with autoimmune diseases (AIDs). This study aimed to investigate and compare the risk of cancer associated with five major AIDs in a large-scale Chinese cohort.
Endosperm Evolution by Duplicated and Neofunctionalized Type I MADS-Box Transcription Factors
Authors: Yichun Qiu, Claudia Köhler
Journal: Molecular Biology and Evolution (2021)

MADS-box transcription factors (TFs) are present in nearly all major eukaryotic groups. They are divided into Type I and Type II that differ in domain structure, functional roles, and rates of evolution. In flowering plants, major evolutionary innovations like flowers, ovules, and fruits have been closely connected to Type II MADS-box TFs. The role of Type I MADS-box TFs in angiosperm evolution remains to be identified. Here, we show that the formation of angiosperm-specific Type I MADS-box clades of Mγ and Mγ-interacting Mα genes (Mα*) can be tracked back to the ancestor of all angiosperms. Angiosperm-specific Mγ and Mα* genes were preferentially expressed in the endosperm, consistent with their proposed function as heterodimers in the angiosperm-specific embryo nourishing endosperm tissue. We propose that duplication and diversification of Type I MADS genes underpin the evolution of the endosperm, a developmental innovation closely connected to the origin and success of angiosperms.
Fever, Hypotension, and a Worsening Necrotic Wound
Authors: Danielle M. Peterson, William E. Damsky, Matthew D. Vesely
Journal: JAMA (2022)

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INITIAL RESULTS OF A NEW INDEPENDENT DIAGNOSTIC TESTING FACILITY DESIGN FOR PATIENT-GENERATED SMARTPHONE-ECG ARRHYTHMIA DETECTION. THE ALIVECOR-IDTF PROGRAM.
Authors: Sanjeev P. Bhavnani, Charles C. Te, Kathryn Kirk, Vivek N. Dhruva, Dipan A. Desai, Niteen Milak, Theodore S. Takata, Lindsey A. Reddersen, Patrick Hranitzky, Charles E. Bailey, Hanoch Patt, Daniel R. Frisch
Journal: Journal of the American College of Cardiology (2022)