tbuckley/cabot-search huggingface dataset:
A Comprehensive Evolutionary Scenario of Cell Division and Associated Processes in the Firmicutes
Authors: Pierre S Garcia, Wandrille Duchemin, Jean-Pierre Flandrois, Simonetta Gribaldo, Christophe Grangeasse, Céline Brochier-Armanet
Journal: Molecular Biology and Evolution (2021)

Abstract The cell cycle is a fundamental process that has been extensively studied in bacteria. However, many of its components and their interactions with machineries involved in other cellular processes are poorly understood. Furthermore, most knowledge relies on the study of a few models, but the real diversity of the cell division apparatus and its evolution are largely unknown. Here, we present a massive in-silico analysis of cell division and associated processes in around 1,000 genomes of the Firmicutes, a major bacterial phylum encompassing models (i.e. Bacillus subtilis, Streptococcus pneumoniae, and Staphylococcus aureus), as well as many important pathogens. We analyzed over 160 proteins by using an original approach combining phylogenetic reconciliation, phylogenetic profiles, and gene cluster survey. Our results reveal the presence of substantial differences among clades and pinpoints a number of evolutionary hotspots. In particular, the emergence of Bacilli coincides with an expansion of the gene repertoires involved in cell wall synthesis and remodeling. We also highlight major genomic rearrangements at the emergence of Streptococcaceae. We establish a functional network in Firmicutes that allows identifying new functional links inside one same process such as between FtsW (peptidoglycan polymerase) and a previously undescribed Penicilin-Binding Protein or between different processes, such as replication and cell wall synthesis. Finally, we identify new candidates involved in sporulation and cell wall synthesis. Our results provide a previously undescribed view on the diversity of the bacterial cell cycle, testable hypotheses for further experimental studies, and a methodological framework for the analysis of any other biological system.
Inhibition of FAO in AML Co-Cultured with BM Adipocytes: Mechanisms of Survival and Chemosensitization to Cytarabine
Authors: Yoko Tabe, Kazumasa Sekihara, Haeun Yang, Kaori Saito, Vivian Ruvolo, Hikari Taka, Naoko Kaga, Takashi Miida, Michael Andreeff, Paul A. Spagnuolo, Marina Konopleva
Journal: Blood (2017)
Trends in opioid prescribing at outpatient visits for psoriasis and psoriatic arthritis
Authors: M.T. Taylor, M.H. Noe, D.B. Horton, J.S. Barbieri
Journal: British Journal of Dermatology (2021)

Funding sources: this study was funded in part through National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) award 1P30AR069589‐01. J.S.B. is supported by the NIAMS of the National Institutes of Health (NIH) under award number T32‐AR‐007465 and receives partial salary support through a Pfizer Fellowship grant to the trustees of the University of Pennsylvania. D.B.H. is supported by the NIAMS of the NIH under award number K23AR070286. M.H.N. is supported by NIAMS award K23‐AR073932 and has received a research grant from Boehringer Ingelheim, unrelated to this work. The funders had no role in the design and conduct of the study; collection, management, analysis or interpretation of the data; preparation, review or approval of the manuscript; or decision to submit the manuscript for publication. Conflicts of interest: The authors declare they have no conflicts of interest. Dear Editor, Recent studies have demonstrated high rates of opioid prescribing among patients with psoriasis and psoriatic arthritis (PsA).1, 2 However, it is uncertain whether opioid prescribing patterns are changing over time. The objective of this study was to examine trends in opioid prescribing at outpatient visits for psoriasis and PsA in the USA.
Corrigendum re “Fibroblast Growth Factor Receptor 3 Alteration Status is Associated with Differential Sensitivity to Platinum-based Chemotherapy in Locally Advanced and Metastatic Urothelial Carcinoma” [Eur Urol 2020;78:907–15]
Authors: Min Yuen Teo, Jose Mauricio Mota, Karissa A. Whiting, Han A. Li, Samuel A. Funt, Chung-Han Lee, David B. Solit, Hikmat Al-Ahmadie, Matthew I. Milowsky, Arjun V. Balar, Eugene Pietzak, Guido Dalbagni, Bernard H. Bochner, Irina Ostrovnaya, Dean F. Bajorin, Jonathan E. Rosenberg, Gopa Iyer
Journal: European Urology (2021)
Evolving Status of Clinical Immunotherapy with Oncolytic Adenovirus
Authors: Martí Farrera-Sal, Laura Moya-Borrego, Miriam Bazan-Peregrino, Ramon Alemany
Journal: Clinical Cancer Research (2021)

Abstract Cancer immunotherapy targeting immune checkpoint inhibitors shows efficacy in several human cancers, but “cold tumors” that lack immune cells are typically unresponsive. Among the potential therapeutic approaches that could “heat” or promote lymphocyte infiltration of cold tumors, oncolytic viruses have attracted interest for their lytic and immunogenic mechanisms of action. In this article, we review the use of oncolytic adenoviruses in cancer immunotherapy, with a particular focus on preclinical and clinical data of oncolytic adenovirus-triggered immune responses against tumor antigens. We also discuss parameters to consider in clinical trial design and the combination of oncolytic adenoviruses with conventional treatments or other immunotherapies.
Age- and Sex-Associated Variations in the Sensitivity of Serological Tests Among Individuals Infected With SARS-CoV-2
Authors: Rohit Vashisht, Ayan Patel, Bridgit O. Crews, Omai B. Garner, Lisa Dahm, Charles Wilson, Atul J. Butte
Journal: JAMA Network Open (2021)

ResultsAcross the UC Health system, 277 567 patients were tested via RT-PCR for SARS-CoV-2 infection (mean [SD] age 47.0 [21.0] years; 150 133 [54.1%] women), and 14 290 were tested for SARS-CoV-2 IgG antibodies (Table).Of 10 065 patients with RT-PCR results positive for SARS-CoV-2 infection (mean [SD] age 41.4 [19.9] years; 5165 [51.3%] women), 486 patients (4.8%) underwent subsequent SARS-CoV-2 antibody testing a median (interquartile range) of 34 [3-64] days later (Figure, A).Of these, 365 patients (75.1%) had test results positive for antibodies.Antibody response significantly varied based on when the measurement was made.Patients whose serological tests were conducted closer to their positive RT-PCR results were more likely to have negative serological results than those tested later (Figure, A).The likelihood of positive SARS-CoV-2 antibody test results increased with time between the positive RT-PCR result and the antibody test, with sensitivity reaching 0.75 (95% CI, 0.71-0.79)at 112 days after the positive RT-PCR result (Figure, B)
Clinical and Treatment History of Patients with Partial DiGeorge Syndrome and Autoimmune Cytopenia
Authors: Priya Patel, Emma Westermann-Clark, Sonia Joychan, Ahmad Shaker, Boglarka Ujhazi, Cristina Meehan, Maryssa Ellison, Krisztian Csomos, Sumai Gordon, Daime Nieves, Jaz Mateus, Irmel Ayala, Jolan Walter, Panida Sriaroon
Journal: Journal of Allergy and Clinical Immunology (2021)
Human Immunodeficiency Virus (HIV) Status Drives Diffuse Large B Cell Lymphoma through Oncogenic Signaling Pathways
Authors: Alanna Maguire, Gary B Fogel, Samantha L. Kendrick, Enoch S Liu, Lee Wisner, Colleen Ramsower, Betty Glinsmann-Gibson, Susanna L Lamers, Michael S. McGrath, Lisa M. Rimsza
Journal: Blood (2017)
Association of Beta-Lactam Allergy Documentation and Antibiotic Use in Patients with Febrile Neutropenia
Authors: Caitlin Li, Xioqing Fu, Christian Mancini, Yuqing Zhang, Michael Postelnick, Lucas Schultz, Tanaya Bhowmick, Francesca Lee, Kimberly Blumenthal
Journal: Journal of Allergy and Clinical Immunology (2021)
COVID-19 database launched in the USA
Authors: Ian Fyfe
Journal: Nature Reviews Neurology (2021)

COVID-19 database launched in the USAThe US National Institutes of Health has created the COVID-19 Neuro Databank/Biobank (NeuroCOVID), a database to enable recording and tracking of neurological involvement in COVID-19.Health-care providers in the USA can submit anonymized information online about neurological symptoms, comorbidities, disease course, complications, sequelae and outcomes of patients with COVID-19.Biospecimens collected for research or clinical management can also be provided to the biobank.
Trends in geographic and home program preferences in the dermatology residency match: A retrospective cohort analysis
Authors: Jatin Narang, Frederick Morgan, Anna Eversman, Mehak Kalra, Wilhemina Osei-Koomson, Elizabeth Obi, Emma R. Russell, Angela H. Wei, David X. Zheng, Bryan T. Carroll, Timmie R. Sharma
Journal: Journal of the American Academy of Dermatology (2021)
Time Trends in Receipt of Germline Genetic Testing and Results for Women Diagnosed With Breast Cancer or Ovarian Cancer, 2012-2019
Authors: Allison W. Kurian, Kevin C. Ward, Paul Abrahamse, Irina Bondarenko, Ann S. Hamilton, Dennis Deapen, Monica Morrow, Jonathan S. Berek, Timothy P. Hofer, Steven J. Katz
Journal: Journal of Clinical Oncology (2021)

Genetic testing is important for breast and ovarian cancer risk reduction and treatment, yet little is known about its evolving use.
Coroners’ concerns to prevent harms: a series of coroners’ case reports to serve patient safety and educate the public, clinicians and policy-makers
Authors: Georgia C. Richards, Jeffrey K. Aronson, Carl Heneghan
Journal: BMJ (2020)

Understanding the causes of deaths and how they can be prevented is critical for improving healthcare outcomes. At a population level, over-reporting or under-reporting of deaths can have a profound impact on policy decisions, which in turn affect global economies and the day-to-day lives of citizens. At the individual level, understanding how and why deaths occur may prevent similar deaths or serious harms from occurring in the future. One in 20 people are exposed to preventable harms in medical settings globally, and 12% of preventable harms result in disability or death.1

Coroners’ reports hold a wealth of information on the circumstances of individual deaths. In England and Wales, the law requires coroners to report and communicate a death when the coroner believes that action should be taken to prevent deaths.2 These reports, named Prevent Future Deaths (PFDs), are mandated under paragraph 7 of schedule 5 of the Coroners and Justice Act 2009, and regulations 28 and 29 of the Coroners (Investigations) Regulations 2013.3 4 Under these regulations, individuals or organisations that receive a PFD report are required under statue to respond to the coroner within 56 days of receiving the report, to outline actions proposed or taken to address the coroner’s concerns. The Courts and Tribunals Judiciary website hosts the PFD reports and responses to the reports.5

As these reports contain valuable lessons, concerns have been raised regarding …
Analysis of classical neutrophils and polymorphonuclear myeloid-derived suppressor cells in cancer patients and tumor-bearing mice
Authors: Filippo Veglia, Ayumi Hashimoto, Harsh Dweep, Emilio Sanseviero, Alessandra De Leo, Evgenii Tcyganov, Andrew Kossenkov, Charles Mulligan, Brian Nam, Gregory Masters, Jaymala Patel, Vipul Bhargava, Patrick Wilkinson, Denis Smirnov, Manuel A. Sepulveda, Sunil Singhal, Evgeniy B. Eruslanov, Razvan Cristescu, Andrey Loboda, Yulia Nefedova, Dmitry I. Gabrilovich
Journal: The Journal of Experimental Medicine (2021)

In this study, using single-cell RNA-seq, cell mass spectrometry, flow cytometry, and functional analysis, we characterized the heterogeneity of polymorphonuclear neutrophils (PMNs) in cancer. We describe three populations of PMNs in tumor-bearing mice: classical PMNs, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), and activated PMN-MDSCs with potent immune suppressive activity. In spleens of mice, PMN-MDSCs gradually replaced PMNs during tumor progression. Activated PMN-MDSCs were found only in tumors, where they were present at the very early stages of the disease. These populations of PMNs in mice could be separated based on the expression of CD14. In peripheral blood of cancer patients, we identified two distinct populations of PMNs with characteristics of classical PMNs and PMN-MDSCs. The gene signature of tumor PMN-MDSCs was similar to that in mouse activated PMN-MDSCs and was closely associated with negative clinical outcome in cancer patients. Thus, we provide evidence that PMN-MDSCs are a distinct population of PMNs with unique features and potential for selective targeting opportunities.
The case of methotrexate and the lung: Dr Jekyll and Mr Hyde
Authors: Vincent Cottin, Elisabeth Bendstrup, Philippe Bonniaud, Mouhamad Nasser, Paolo Spagnolo, Claudia Valenzuela, Martin Kolb
Journal: European Respiratory Journal (2021)

<b>Methotrexate can induce subacute hypersensitivity pneumonitis, a potentially lethal condition that should lead to drug discontinuation; however, its use does not seem to be associated with increased risk of chronic fibrosing ILD in rheumatoid arthritis</b>https://bit.ly/3sCyjji
Dupilumab Improves Signs And Symptoms Of Severe Atopic Dermatitis In Children Aged 6–11 Years With And Without Comorbid Asthma
Authors: Mark Boguniewicz, Lawrence Sher, Amy Paller, Elaine Siegfried, Zhen Chen, Randy Prescilla, Brad Shumel
Journal: Journal of Allergy and Clinical Immunology (2021)
Why it might be bad for brain cells to eat malaria parasites
Authors: Matthew K. Higgins
Journal: The Journal of Experimental Medicine (2021)

In this issue, Adams et al. (2021. J. Exp. Med. https://doi.org/10.1084/jem.20201266) show that red blood cells infected with strains of Plasmodium falciparum, which are commonly found in cerebral malaria patients, are specifically internalized by brain endothelial cells, perhaps contributing to the symptoms of the disease.
Neighbours in time of COVID-19
Authors: Rebecca Barksby
Journal: The Lancet Infectious Diseases (2021)

Los Angeles, the largest city in the state of California, USA, has a bustling reputation that is characterised by traffic queues, Hollywood, and the constant footfall of a diverse population. However, on March 19, 2020, Mayor of Los Angeles Eric Garcetti issued an emergency order in response to the emerging COVID-19 pandemic, instructing all residents to stay at home and to only leave for essential needs. Since then, COVID-19 trends in Los Angeles have followed the same pattern as many other major cities around the world but the storylines behind each closed door are as varied as the residents themselves, a concept explored in the new romantic comedy entitled #MyCorona—the first known feature-length film to be directed remotely.
Early-tips should be performed in high-risk cirrhotic patients despite the presence of hepatic encephalopathy at admission
Authors: Marika Rudler, Virginia Hernandez-Gea, Bogdan Procopet, Alvaro Giraldez-Gallego, Lucio Amitrano, Candid Villanueva, Luis Ibañez, Gilberto Silva-Junior, Javier Martinez, Joan Genesca, Christophe Bureau, Trebicka Jonel, Elba Llop, Wim Laleman, Jose María Palazon, José Castellote Alonso, Susana G. Rodrigues, Lise Lotte Gluud, Carlos Noronha Ferreira, Nuria Cañete, Prof. Dr. Arnulf Ferlitsch, Jose Luis Mundi, Henning Grønbæk, Manuel Hernandez-Guerra, Romanno Sassatelli, Alessandra Dell’Era, Juan G. Abraldes, Rafael Barcelo, Marco Senzolo, Manuel Romero Gomez, Alexander Zipprich, Helena Masnou, Massimo Primignani, Aleksander Krag, Ferran Torres, Frederik Nevens, José Luis Calleja Panero, Georgina Casanovas, Christian Jansen, Agustin Albillos, Guardascione Maria, Edilmar Alvarado, Meritxell Casas, Marie-Angèle Robic, María-Vega Catalina, Irene Conejo Sosa, Mallet Maxime, Tripon Simona, Jaime Bosch, Juan Carlos Garcia Pagan, Dominique Thabut
Journal: Journal of Hepatology (2020)
A Machine Learning Approach Enables Quantitative Measurement of Liver Histology and Disease Monitoring in NASH
Authors: Amaro Taylor‐Weiner, Harsha Pokkalla, Ling Han, Catherine Jia, Ryan Huss, Chuhan Chung, Hunter Elliott, Benjamin Glass, Kishalve Pethia, Oscar Carrasco‐Zevallos, Chinmay Shukla, Urmila Khettry, Robert Najarian, Ross Taliano, G. Mani Subramanian, Robert P. Myers, Ilan Wapinski, Aditya Khosla, Murray Resnick, Michael C. Montalto, Quentin M. Anstee, Vincent Wai‐Sun Wong, Michael Trauner, Eric J. Lawitz, Stephen A. Harrison, Takeshi Okanoue, Manuel Romero‐Gomez, Zachary Goodman, Rohit Loomba, Andrew H. Beck, Zobair M. Younossi
Journal: Hepatology (2021)

Background and Aims Manual histological assessment is currently the accepted standard for diagnosing and monitoring disease progression in NASH, but is limited by variability in interpretation and insensitivity to change. Thus, there is a critical need for improved tools to assess liver pathology in order to risk stratify NASH patients and monitor treatment response. Approach and Results Here, we describe a machine learning (ML)‐based approach to liver histology assessment, which accurately characterizes disease severity and heterogeneity, and sensitively quantifies treatment response in NASH. We use samples from three randomized controlled trials to build and then validate deep convolutional neural networks to measure key histological features in NASH, including steatosis, inflammation, hepatocellular ballooning, and fibrosis. The ML‐based predictions showed strong correlations with expert pathologists and were prognostic of progression to cirrhosis and liver‐related clinical events. We developed a heterogeneity‐sensitive metric of fibrosis response, the Deep Learning Treatment Assessment Liver Fibrosis score, which measured antifibrotic treatment effects that went undetected by manual pathological staging and was concordant with histological disease progression. Conclusions Our ML method has shown reproducibility and sensitivity and was prognostic for disease progression, demonstrating the power of ML to advance our understanding of disease heterogeneity in NASH, risk stratify affected patients, and facilitate the development of therapies.
Alterations in <i>BAP1</i> Are Associated with Cisplatin Resistance through Inhibition of Apoptosis in Malignant Pleural Mesothelioma
Authors: Kathrin Oehl, Bart Vrugt, Ulrich Wagner, Michaela B. Kirschner, Mayura Meerang, Walter Weder, Emanuela Felley-Bosco, Bernd Wollscheid, Katrin Bankov, Melanie C. Demes, Isabelle Opitz, Peter J. Wild
Journal: Clinical Cancer Research (2021)

Abstract Purpose: The clinical standard treatment for patients with malignant pleural mesothelioma (MPM) includes a cisplatin-based chemotherapy, leading to reduction of tumor size in only a minority of patients. Predicting response to chemotherapy in patients with MPM by using a genetic marker would, therefore, enable patient stratification. Experimental Design: In this retrospective biomarker study, eligible patients had resectable MPM, measurable disease, and available primary MPM tissue. All patients underwent first-line treatment with cisplatin and pemetrexed, followed by surgery. Thorough molecular analysis was performed (whole-exome and targeted deep sequencing, and copy-number analyses), and also mechanistic in vitro data (viability assays, Western blots, and immunoprecipitation) using mesothelioma cell lines with and without siRNA-mediated BRCA1-associated protein 1 (BAP1) knockdown were provided. Results: In a training cohort of patients with MPM (n = 28), mutations or deletions of BAP1 each predicted resistance to chemotherapy in patients with primary MPM. The negative predictive value of BAP1 loss in patients with MPM was confirmed by amplicon sequencing and copy-number array technology in an independent test cohort (n = 39). Preliminary mechanistic studies using siRNA-based knockdown of BAP1 in MPM cell culture models along with immunoprecipitation assays confirmed chemoresistance in vitro, possibly through inhibition of apoptosis and transcriptional regulation of the BAP1/HCF1/E2F1 axis. Conclusions: Alterations in BAP1 in MPM were a negative predictor for response to chemotherapy and could possibly be used as a companion biomarker for treatment decision.
Corrigendum to ‘Fumaryl diketopiperazine based effervescent microparticles to escape macrophage phagocytosis for enhanced treatment of pneumonia via pulmonary delivery’ Biomaterials 228C (2019) 119575
Authors: Qiyue Wang, Yan Shen, Gujie Mi, Dongsheng He, Yue Zhang, Yerong Xiong, Thomas J. Webster, Jiasheng Tu
Journal: Biomaterials (2021)
Corrigendum to “Review of trials currently testing treatment and prevention of COVID-19” [Clin Microbiol Infect 26.8 (2020) 988–998]
Authors: Paraskevi C. Fragkou, Drifa Belhadi, Nathan Peiffer-Smadja, Charalampos D. Moschopoulos, François-Xavier Lescure, Hannah Janocha, Emmanouil Karofylakis, Yazdan Yazdanpanah, France Mentré, Chrysanthi Skevaki, Cédric Laouénan, Sotirios Tsiodras
Journal: Clinical Microbiology and Infection (2021)
STEP 1 for Effective Weight Control — Another First Step?
Authors: Julie R. Ingelfinger, Clifford J. Rosen
Journal: New England Journal of Medicine (2021)

Given the worldwide increase in obesity, with attendant coexisting conditions and increased risk of death, there is a pressing need to address weight loss and maintenance strategies.1-3 Behavioral methods of weight control fail more often than not, and bariatric surgery is invasive and, often, eventually followed by regain of weight.1-3 Medications approved for weight loss by the Food and Drug Administration, the European Medicines Agency, and other regulatory bodies have had a troubling history, with withdrawal of several approved drugs owing to serious adverse events; among these are various amphetamines (addiction), fenfluramine (cardiac toxicity), and, most recently, lorcaserin (cancer risk).4,5 . . .
Five-month Outcomes for Asthmatics with COVID-19 and Associations with Atopy and Inhaled Corticosteroids Use
Authors: Katharine Foster, Donyea Moore, Emilio Jauregui, Aame Andy-Nweye, Mahboobeh Mahdavinia
Journal: Journal of Allergy and Clinical Immunology (2021)

COVID-19 viral infection has been associated with respiratory tract inflammation. Asthma exacerbations are frequently triggered by viral respiratory infections, which subsequently cause poor asthma control. However, the effect of COVID-19 on asthma exacerbations and outcomes beyond the initial COVID-19 infection is not well studied. Adult COVID-19-positive patients with history of asthma evaluated at a university medical center between February and April,2020 were entered in the study at the time of COVID-19 infection and followed for 4-6 months. Seventy-six patients with asthma were followed for a 151-day-average after COVID-19 infection. At COVID-19 infection onset, 55.2% of subjects presented with symptoms suggestive of an asthma exacerbation. These patients experienced an average of 2.6-weeks of uncontrolled asthma and sought medical care for asthma symptoms at 1.9 mean provider visits. 9.2% of patients required step-up therapy; 23.6% received oral steroids post-COVID-19 infection. Stratified by asthma severity, 66.6% of subjects with intermittent, 50.0% with mild persistent and 68.4% with moderate/severe persistent asthma experienced exacerbations(p=0.78). The asthma exacerbation rate in patients who took inhaled corticosteroids (ICS+LABA) (n=25, 53.3%) or ICS alone(n=13, 55.2%) did not differ from those who were not taking ICS (n=38, 52.6%), (p=0.82). 42.3% of asthma patients with a history of allergic rhinitis versus 64.5% of nonallergic patients experienced an exacerbation(p=0.086). Our data showed no effect of asthma severity nor ICS+/-LABA therapy on the rate of asthma exacerbations after COVID-19 infection in five-month follow up. Atopic patients had a trend towards protection against COVID-19-associated asthma exacerbations, which needs confirmation in larger studies.