tbuckley/cabot-search huggingface dataset:
Prevalence and Outcomes of SARS-CoV-2 Infection Among Migrant Workers in Singapore
Authors: Iain Beehuat Tan, Clive Tan, Li Yang Hsu, Yock Young Dan, Andrew Aw, Alex R. Cook, Vernon J. Lee
Journal: JAMA (2021)

Prevalence and Outcomes of SARS-CoV-2 Infection Among Migrant Workers in SingaporeHigh-density communal residences are at elevated risk of large outbreaks of respiratory disease. 1,2 After an initial nationwide outbreak of 231 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Singapore, which was contained as of March 24, 2020, a surge of 244 cases among migrant workers residing in dormitories, largely from Bangladesh and India, occurred from March 25 to April 7.A national task force was formed to coordinate Singapore's outbreak response.A national lockdown from April 7 to June 1 enforced movement restriction and confined workers to their dormitories.Medical posts were deployed on-site in all dormitories, and testing capacity for testing and screening residents increased.All workers with a positive polymerase chain reaction (PCR) test result were admitted to health care facilities for isolation and treatment.We examined the prevalence and outcomes of SARS-CoV-2 infection among migrant workers in Singapore.
Nondrug Treatments for Idiopathic Pulmonary Fibrosis: IPF Part 3
Authors: Sabina A. Guler, Kathleen O. Lindell, Jeff Swigris, Christopher J. Ryerson
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Nondrug Treatments for Idiopathic Pulmonary Fibrosis: IPF Part 3." American Journal of Respiratory and Critical Care Medicine, 203(4), pp. P10–P11
Emergence of Enzalutamide Resistance in Prostate Cancer is Associated with BCL-2 and IKKB Dependencies
Authors: Yi Liang, Sujeeve Jeganathan, Stefano Marastoni, Adam Sharp, Ines Figueiredo, Richard Marcellus, Amanda Mawson, Zvi Shalev, Aleksandra Pesic, Joan Sweet, Haiyang Guo, David Uehling, Bora Gurel, Antje Neeb, Housheng Hansen He, Bruce Montgomery, Marianne Koritzinsky, Samantha Oakes, Johann S. de Bono, Martin Gleave, Amina Zoubeidi, Bradly G. Wouters, Anthony M. Joshua
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Although enzalutamide (ENZ) has been widely used to treat de novo or castration-resistant metastatic prostate cancer, resistance develops and disease progression is ultimately inevitable. There are currently no approved targeted drugs to specifically delay or overcome ENZ resistance. Experimental Design: We selected several ENZ-resistant cell lines that replicated clinical characteristics of the majority of patients with ENZ-resistant disease. A high-throughput pharmacologic screen was utilized to identify compounds with greater cytotoxic effect for ENZ-resistant cell lines, compared with parental ENZ-sensitive cells. We validated the potential hits in vitro and in vivo, and used knockdown and overexpression assays to study the dependencies in ENZ-resistant prostate cancer. Results: ABT199 (BCL-2 inhibitor) and IMD0354 (IKKB inhibitor) were identified as potent and selective inhibitors of cell viability in ENZ-resistant cell lines in vitro and in vivo which were further validated using loss-of-function assays of BCL-2 and IKKB. Notably, we observed that overexpression of BCL-2 and IKKB in ENZ-sensitive cell lines was sufficient for the emergence of ENZ resistance. In addition, we confirmed that BCL-2 or IKKB inhibitors suppressed the development of ENZ resistance in xenografts. However, validation of both BCL-2 and IKKB in matched castration-sensitive/resistant clinical samples showed that, concurrent with the development of ENZ/abiraterone resistance in patients, only the protein levels of IKKB were increased. Conclusions: Our findings identify BCL-2 and IKKB dependencies in clinically relevant ENZ-resistant prostate cancer cells in vitro and in vivo, but indicate that IKKB upregulation appears to have greater relevance to the progression of human castrate-resistant prostate cancer.
Gaining a Better Sense for ASXL1 Mutations in Myelofibrosis: Assessing the Variable Impact of Frameshift, Nonsense, and Missense Mutations
Authors: Andrew Kuykendall, Jori L Kaplan, Chetasi Talati, Najla Al Ali, Kendra L. Sweet, David A Sallman, Eric Padron, Jeffrey E. Lancet, Alan F. List, Kenneth S. Zuckerman, Rami S. Komrokji
Journal: Blood (2017)
Fossil fuel air pollution blamed for 1 in 5 deaths worldwide
Authors: Ingrid Torjesen
Journal: BMJ (2021)

Fossil fuel air pollution is responsible for around one in five deaths, which is more than double the number previously thought, a study has found.

The researchers estimated that 8.7 million people worldwide died in 2018 as a result of breathing in air containing particles from burning fuels like coal, petrol, and diesel, which aggravate respiratory conditions like asthma and can lead to lung cancer, coronary heart disease, strokes, and early death. The highest rates of death linked to fossil fuel related air pollution were found in South East Asia, Europe, and eastern North America. The study was published online in the journal Environmental Research .1

Previous estimates from the Global Burden of Disease Study put the total number of deaths each year from all outdoor airborne particulate matter (not just fossil fuel emissions, but including dust …
Observed Face Mask Use at Six Universities — United States, September–November 2020
Authors: Lisa C. Barrios, Margaret A. Riggs, Ridgely Fisk Green, Michaila Czarnik, Randall J. Nett, J. Erin Staples, Michael David Welton, Jessica Legge Muilenburg, Keith J. Zullig, Linda Gibson-Young, Andrea V. Perkins, Cindy Prins, Michael Lauzardo, Jerne Shapiro, George Asimellis, Genesia Kilgore-Bowling, Kenny Ortiz-Jurado, Margaret J. Gutilla
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Approximately 41% of adults aged 18-24 years in the United States are enrolled in a college or university (1). Wearing a face mask can reduce transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (2), and many colleges and universities mandate mask use in public locations and outdoors when within six feet of others. Studies based on self-report have described mask use ranging from 69.1% to 86.1% among adults aged 18-29 years (3); however, more objective measures are needed. Direct observation by trained observers is the accepted standard for monitoring behaviors such as hand hygiene (4). In this investigation, direct observation was used to estimate the proportion of persons wearing masks and the proportion of persons wearing masks correctly (i.e., covering the nose and mouth and secured under the chin*) on campus and at nearby off-campus locations at six rural and suburban universities with mask mandates in the southern and western United States. Trained student observers recorded mask use for up to 8 weeks from fixed sites on campus and nearby. Among 17,200 observed persons, 85.5% wore masks, with 89.7% of those persons wearing the mask correctly (overall correct mask use: 76.7%). Among persons observed indoors, 91.7% wore masks correctly. The proportion correctly wearing masks indoors varied by mask type, from 96.8% for N95-type masks and 92.2% for cloth masks to 78.9% for bandanas, scarves, and similar face coverings. Observed indoor mask use was high at these six universities with mask mandates. Colleges and universities can use direct observation findings to tailor training and messaging toward increasing correct mask use.
The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling
Authors: Qian Zhang, Challa Tenagne Delessa, Robert Augustin, Mostafa Bakhti, Gustav Colldén, Daniel J. Drucker, Annette Feuchtinger, Cristina Garcia Caceres, Gerald Grandl, Alexandra Harger, Stephan Herzig, Susanna Hofmann, Cassie Lynn Holleman, Martin Jastroch, Susanne Keipert, Maximilian Kleinert, Patrick J. Knerr, Konxhe Kulaj, Beata Legutko, Heiko Lickert, Xue Liu, Gerd Luippold, Dominik Lutter, Emilija Malogajski, Marta Tarquis Medina, Stephanie A. Mowery, Andreas Blutke, Diego Perez-Tilve, Ciro Salinno, Laura Sehrer, Richard D. DiMarchi, Matthias H. Tschöp, Kerstin Stemmer, Brian Finan, Christian Wolfrum, Timo D. Müller
Journal: Cell Metabolism (2021)

Uncertainty exists as to whether the glucose-dependent insulinotropic polypeptide receptor (GIPR) should be activated or inhibited for the treatment of obesity. Gipr was recently demonstrated in hypothalamic feeding centers, but the physiological relevance of CNS Gipr remains unknown. Here we show that HFD-fed CNS-Gipr KO mice and humanized (h)GIPR knockin mice with CNS-hGIPR deletion show decreased body weight and improved glucose metabolism. In DIO mice, acute central and peripheral administration of acyl-GIP increases cFos neuronal activity in hypothalamic feeding centers, and this coincides with decreased body weight and food intake and improved glucose handling. Chronic central and peripheral administration of acyl-GIP lowers body weight and food intake in wild-type mice, but shows blunted/absent efficacy in CNS-Gipr KO mice. Also, the superior metabolic effect of GLP-1/GIP co-agonism relative to GLP-1 is extinguished in CNS-Gipr KO mice. Our data hence establish a key role of CNS Gipr for control of energy metabolism.
Antibodies to SARS-CoV-2 protect against re-infection during outbreaks in care homes, September and October 2020
Authors: Anna Jeffery-Smith, Nalini Iyanger, Sarah V Williams, J Yimmy Chow, Felicity Aiano, Katja Hoschler, Angie Lackenby, Joanna Ellis, Steven Platt, Shahjahan Miah, Kevin Brown, Gayatri Amirthalingam, Monika Patel, Mary E Ramsay, Robin Gopal, Andre Charlett, Shamez N Ladhani, Maria Zambon
Journal: Eurosurveillance (2021)

Two London care homes experienced a second COVID-19 outbreak, with 29/209 (13.9%) SARS-CoV-2 RT-PCR-positive cases (16/103 residents, 13/106 staff). In those with prior SARS-CoV-2 exposure, 1/88 (1.1%) individuals (antibody positive: 87; RT-PCR-positive: 1) became PCR-positive compared with 22/73 (30.1%) with confirmed seronegative status. After four months protection offered by prior infection against re-infection was 96.2% (95% confidence interval (CI): 72.7-99.5%) using risk ratios from comparison of proportions and 96.1% (95% CI: 78.8-99.3%) using a penalised logistic regression model.
Improved hemostatic effects by Fe3+ modified biomimetic PLLA cotton-like mat via sodium alginate grafted with dopamine
Authors: Caili Lv, Linlong Li, Zixue Jiao, Huanhuan Yan, Zongliang Wang, Zhenxu Wu, Min Guo, Yu Wang, Peibiao Zhang
Journal: Bioactive Materials (2021)

The development of an excellent, bioabsorbable hemostatic material for deep wound remains a challenge. In this work, a biodegradable cotton-like biomimetic fibrous mat of poly (l-lactic acid) (PLLA) was made by melt spinning. Subsequently, SD composite was prepared by cross-linking sodium alginate (SA) with dopamine (DA). It was immobilized on the fibre surface, which inspired by mussel byssus. Finally, Fe
Abstract 14559: Venous Flow Dynamics Rather Than Venous Pressure is Important for the Development of Liver Fibrosis After Atriopulmonary Fontan Procedure
Authors: Gaku Izumi, Hideaki Senzaki, Atsuhito Takeda, Kei Inai, Tokuko Shinohara, Toshio Nakanishi
Journal: Circulation (2013)

Background: Elevated venous pressure is thought to play a pivotal role in the development of liver fibrosis/dysfunction, an important complication after Fontan surgery, particularly that for the at...
真性多血症に対するロペグインターフェロンα-2b対標準療法:無作為化,非劣性,第3相試験およびその拡張試験【JST・京大機械翻訳】
Authors: Gisslinger Heinz, Klade Christoph, Georgiev Pencho, Krochmalczyk Dorota, Gercheva-Kyuchukova Liana, Egyed Miklos, Rossiev Viktor, Dulicek Petr, Illes Arpad, Pylypenko Halyna, Sivcheva Lylia, Mayer Jiri, Yablokova Vera, Krejcy Kurt, Grohmann-Izay Barbara, Hasselbalch Hans C, Kralovics Robert, Kiladjian Jean-Jacques
Journal: The Lancet Haematology (2020)
Covid-19: Russian vaccine efficacy is 91.6%, show phase III trial results
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Covid-19: Russian vaccine efficacy is 91.6%, show phase III trial results Elisabeth MahaseThe covid-19 vaccine developed by the Gamaleya Research Institute, part of the Russian Ministry of Health, has an efficacy of 91.6%, according to interim results from a phase III trial. 1 The findings, published in the Lancet, showed that the two dose regime of the viral vector vaccine was generally well tolerated with no associated serious adverse events and similar efficacy in those aged over and under 60.
YAP and β-Catenin Cooperate to Drive Oncogenesis in Basal Breast Cancer
Authors: Hazel M. Quinn, Regina Vogel, Oliver Popp, Philipp Mertins, Linxiang Lan, Clemens Messerschmidt, Alexandro Landshammer, Kamil Lisek, Sophie Château-Joubert, Elisabetta Marangoni, Elle Koren, Yaron Fuchs, Walter Birchmeier
Journal: Cancer Research (2021)

Abstract Targeting cancer stem cells (CSC) can serve as an effective approach toward limiting resistance to therapies. While basal-like (triple-negative) breast cancers encompass cells with CSC features, rational therapies remain poorly established. We show here that the receptor tyrosine kinase Met promotes YAP activity in basal-like breast cancer and find enhanced YAP activity within the CSC population. Interfering with YAP activity delayed basal-like cancer formation, prevented luminal to basal transdifferentiation, and reduced CSC. YAP knockout mammary glands revealed a decrease in β-catenin target genes, suggesting that YAP is required for nuclear β-catenin activity. Mechanistically, nuclear YAP interacted with β-catenin and TEAD4 at gene regulatory elements. Proteomic patient data revealed an upregulation of the YAP signature in basal-like breast cancers. Our findings demonstrate that in basal-like breast cancers, β-catenin activity is dependent on YAP signaling and controls the CSC program. These findings suggest that targeting the YAP/TEAD4/β-catenin complex offers a potential therapeutic strategy for eradicating CSCs in basal-like breast cancers. Significance: These findings show that YAP cooperates with β-catenin in basal-like breast cancer to regulate CSCs and that targeting this interaction may be a novel CSC therapy for patients with basal-like breast cancer.
Skewed inflammation is associated with aberrant interleukin‐37 signaling pathway in atopic dermatitis
Authors: Tianheng Hou, Miranda Sin‐Man Tsang, Ida Miu‐Ting Chu, Lea Ling‐Yu Kan, Kam‐Lun Hon, Ting‐Fan Leung, Christopher Wai‐Kei Lam, Chun‐Kwok Wong
Journal: Allergy (2021)

Atopic dermatitis (AD) is a severe global burden on physical, physiological, and mental health. The role of IL-37, a fundamental inhibitor of immunity, in AD was herein explored.Serum levels of IL-37 and T helper (Th) 2-related inflammatory mediators were quantified in subjects with or without AD. The expression of IL-37 receptors was determined by flow cytometry. Proteomics was employed to explore the serum protein profile and novel biomarkers. In vitro cell model, 3D-keratinocytes mimicking skin model, and the serum of subjects with or without AD were investigated to verify the proteomic results.AD patients were found to present with higher levels of total and specific IgE as well as Th2 inflammatory mediators compared with healthy controls (HC). IL-37 level and its receptor IL18Rɑ expression in AD patients were significantly decreased, together with increased population of eosinophils, indicating that the signaling of IL37/IL18Rɑ was dampened. In addition, proteomic analysis revealed a significantly differential protein profile of AD patients compared with HC. IL-37 showed the strongest negative correlation with involucrin, a keratinizing epithelia protein. IL-37 was verified to suppress induced involucrin expression in in vitro skin cell models. AD patients show a significantly higher serum concentration of involucrin compared with HC. Together, our results demonstrated that IL-37 plays a regulatory role in AD. Its deficiency may lead to the aberrant involucrin expression in AD.The dysregulation of serum protein and skin disruption in AD is related to the insufficiency of IL-37 and its attenuated anti-inflammatory signaling.
THE ROLE OF PIPERACILLIN AS A TRIGGER IN DRUG ALLERGY. A RETROSPECTIVE STUDY
Authors: Almudena Delgado González, Marta Isabel Rodriguez Cabreros, Iria Roibas Veiga, Miriam Barrios Albajar, Marta Gema López San Martin, Alfredo Iglesias Cadarso
Journal: Journal of Allergy and Clinical Immunology (2021)
Atezolizumab and <i>nab</i>-Paclitaxel in Advanced Triple-Negative Breast Cancer: Biomarker Evaluation of the IMpassion130 Study
Authors: Leisha A Emens, Luciana Molinero, Sherene Loi, Hope S Rugo, Andreas Schneeweiss, Véronique Diéras, Hiroji Iwata, Carlos H Barrios, Marina Nechaeva, Anh Nguyen-Duc, Stephen Y Chui, Amreen Husain, Eric P Winer, Sylvia Adams, Peter Schmid
Journal: JNCI Journal of the National Cancer Institute (2021)

Understanding the impact of the tumor immune microenvironment and BRCA1/2-related DNA repair deficiencies on the clinical activity of immune checkpoint inhibitors may help optimize both patient and treatment selection in metastatic triple-negative breast cancer. In this substudy from the phase 3 IMpassion130 trial, immune biomarkers and BRCA1/2 alterations were evaluated for association with clinical benefit with atezolizumab and nab-paclitaxel (A+nP) vs placebo and nP in unresectable (P+nP) locally advanced or metastatic triple-negative breast cancer.Patients were randomly assigned 1:1 to nab-paclitaxel 100 mg/m2 (days 1, 8, and 15 of a 28-day cycle) and atezolizumab 840 mg every 2 weeks or placebo until progression or toxicity. Progression-free survival and overall survival were evaluated based on programmed death-ligand 1 (PD-L1) expression on immune cells (IC) and tumor cells, intratumoral CD8, stromal tumor-infiltrating lymphocytes, and BRCA1/2 mutations.PD-L1 IC+ in either primary or metastatic tumor tissue was linked to progression-free survival and overall survival benefit with A+nP. PD-L1 IC+ low (26.9%; 243 of 902 patients) and high (13.9%; 125 of 902 patients) populations had improved outcomes that were comparable. Intratumoral CD8 and stromal tumor-infiltrating lymphocytes positivity (sTIL+) were associated with PD-L1 IC+ status; improved outcomes were observed with A+nP vs P+nP only in CD8+ and sTIL+ patients who were also PD-L1 IC+. BRCA1/2 mutations (occurring in 14.5% [89 of 612 patients]) were not associated with PD-L1 IC status, and PD-L1 IC+ patients benefited from A+nP regardless of BRCA1/2 mutation status.Although A+nP was more efficacious in patients with richer tumor immune microenvironment, clinical benefit was only observed in patients whose tumors were PD-L1 IC+.
Interim results on the validation of a novel method for measuring gastric residual volume and intra-abdominal pressure in mechanically ventilated critically ill patients
Authors: Manu Malbrain, P.J. Palmers, R. Tepaske, J. Valtysson, A. Van Ingelgem, N. Van Regenmortel, I. De Laet, K. Schoonheydt, H. Dits
Journal: Intensive Care Medicine (2010)
SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas
Authors: Janis A. Müller, Rüdiger Groß, Carina Conzelmann, Jana Krüger, Uta Merle, Johannes Steinhart, Tatjana Weil, Lennart Koepke, Caterina Prelli Bozzo, Clarissa Read, Giorgio Fois, Tim Eiseler, Julia Gehrmann, Joanne van Vuuren, Isabel M. Wessbecher, Manfred Frick, Ivan G. Costa, Markus Breunig, Beate Grüner, Lynn Peters, Michael Schuster, Stefan Liebau, Thomas Seufferlein, Steffen Stenger, Albrecht Stenzinger, Patrick E. MacDonald, Frank Kirchhoff, Konstantin M. J. Sparrer, Paul Walther, Heiko Lickert, Thomas F. E. Barth, Martin Wagner, Jan Münch, Sandra Heller, Alexander Kleger
Journal: Nature Metabolism (2021)

Infection-related diabetes can arise as a result of virus-associated β-cell destruction. Clinical data suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), impairs glucose homoeostasis, but experimental evidence that SARS-CoV-2 can infect pancreatic tissue has been lacking. In the present study, we show that SARS-CoV-2 infects cells of the human exocrine and endocrine pancreas ex vivo and in vivo. We demonstrate that human β-cells express viral entry proteins, and SARS-CoV-2 infects and replicates in cultured human islets. Infection is associated with morphological, transcriptional and functional changes, including reduced numbers of insulin-secretory granules in β-cells and impaired glucose-stimulated insulin secretion. In COVID-19 full-body postmortem examinations, we detected SARS-CoV-2 nucleocapsid protein in pancreatic exocrine cells, and in cells that stain positive for the β-cell marker NKX6.1 and are in close proximity to the islets of Langerhans in all four patients investigated. Our data identify the human pancreas as a target of SARS-CoV-2 infection and suggest that β-cell infection could contribute to the metabolic dysregulation observed in patients with COVID-19. SARS-CoV-2 is shown to infect and replicate in human pancreatic tissue, including in β-cells, which is associated with morphological, transcriptomic and functional changes.
US pathologist who deceived drug testers and misdiagnosed patients is sentenced to 20 years
Authors: Owen Dyer
Journal: BMJ (2021)

A pathologist who worked for the US Veterans Administration (VA) has been sentenced to 20 years imprisonment after he admitted to consuming an industrial chemical to avoid detection by drug testing, and then making dozens of life altering misdiagnoses.

Robert Morris Levy, 54, was charged with three counts of involuntary manslaughter. He pleaded guilty to one count in his agreement with prosecutors. But pathologists who reviewed his work since 2005 found 3029 errors in 33 902 cases he had worked on, an error rate more than 10 times the average for VA doctors. This included 30 serious cancer misdiagnoses. Levy is being sued by several families.

Levy was first reported drunk by a …
Stromal contribution to the colorectal cancer transcriptome (vol 47, pg 312, 2015)
Authors: Claudio Isella, Andrea Terrasi, Sara Erika Bellomo, Consalvo Petti, Giovanni Galatola, Andrea Muratore, Alfredo Mellano, Rebecca Senetta, Adele Cassenti, Cristina Sonetto, Giorgio Inghirami, Livio Trusolino, Zsolt Fekete, Mark De Ridder, Paola Cassoni, Guy Storme, Andrea Bertotti, Enzo Medico
Journal: Nature Genetics (2016)
Taking a Stand Against Air Pollution—The Impact on Cardiovascular Disease
Authors: Michael Brauer, Barbara Casadei, Robert A. Harrington, Richard Kovacs, Karen Sliwa
Journal: Circulation (2021)

Although the attention of the world and the global health community specifically is deservedly focused on the COVID-19 pandemic, other determinants of health continue to have large impacts and may also interact with COVID-19. Air pollution is one crucial example. Established evidence from other respiratory viruses and emerging evidence for COVID-19 specifically indicates that air pollution alters respiratory defense mechanisms leading to worsened infection severity. Air pollution also contributes to comorbidities that are known to worsen outcomes among those infected with COVID-19, and air pollution may also enhance infection transmission due to its impact on more frequent coughing. Yet despite the massive disruption of the COVID-19 pandemic, there are reasons for optimism: broad societal lockdowns have shown us a glimpse of what a future with strong air pollution measures could yield. Thus, the urgency to combat air pollution is not diminished, but instead heightened in the context of the pandemic.