tbuckley/cabot-search huggingface dataset:
Myocardial localization of coronavirus in COVID‐19 cardiogenic shock
Authors: Guido Tavazzi, Carlo Pellegrini, Marco Maurelli, Mirko Belliato, Fabio Sciutti, Andrea Bottazzi, Paola Alessandra Sepe, Tullia Resasco, Rita Camporotondo, Raffaele Bruno, Fausto Baldanti, Stefania Paolucci, Stefano Pelenghi, Giorgio Antonio Iotti, Francesco Mojoli, Eloisa Arbustini
Journal: European Journal of Heart Failure (2020)
The prognostic impact of the extent of ulceration in patients with clinical stage I– <scp>II</scp> melanoma: a multicentre study of the Italian Melanoma Intergroup ( <scp>IMI</scp> )
Authors: F. Portelli, F. Galli, L. Cattaneo, M. Cossa, V. De Giorgi, G. Forte, G. Fraternali Orcioni, A. Gianatti, A. Indini, A. Labianca, A. Maurichi, B. Merelli, M.C. Montesco, M. Occelli, R. Patuzzo, D. Piazzalunga, J. Pigozzo, P. Quaglino, S. Ribero, R. Salvatori, D. Saraggi, P. Sena, R. Senetta, B. Valeri, M. Tanaka, M. Fukayama, G. Palmieri, M. Mandalà, D. Massi
Journal: British Journal of Dermatology (2020)

Background The presence of ulceration has been recognized as an adverse prognostic factor in primary cutaneous melanoma (PCM). Objectives To investigate whether the extent of ulceration (EoU) predicts relapse-free survival (RFS) and overall survival (OS) in PCM. Materials and methods We retrieved data for 477 patients with ulcerated PCM from databases of the Italian Melanoma Intergroup. Univariate and multivariable Cox proportional hazard models were used to assess the independent prognostic impact of EoU. Results A significant interaction emerged between Breslow thickness (BT) and EoU, considering both RFS (P < 0·0001) and OS (P = 0·0006). At multivariable analysis, a significant negative impact of EoU on RFS [hazard ratio (HR) (1-mm increase) 1·26, 95% confidence interval (CI) 1·08–1·48, P = 0·0047] and OS [HR (1-mm increase) 1·25, 95% CI 1·05–1·48, P = 0·0120] was found in patients with BT ≤ 2 mm, after adjusting for BT, age, tumour-infiltrating lymphocytes, sentinel lymph node status and mitotic rate. No impact of EoU was found in patients with 2·01–4 mm and > 4 mm BT. Conclusions This study demonstrates that EoU has an independent prognostic impact in PCM and should be recorded as a required element in pathology reports.
1-[(4-Nitrophenyl)sulfonyl]-4-phenylpiperazine treatment after brain irradiation preserves cognitive function in mice
Authors: Kruttika Bhat, Paul Medina, Ling He, Le Zhang, Mohammad Saki, Angeliki Ioannidis, Nhan T Nguyen, Sirajbir S Sodhi, David Sung, Clara E Magyar, Linda M Liau, Harley I Kornblum, Frank Pajonk
Journal: Neuro-Oncology (2020)

Normal tissue toxicity is an inevitable consequence of primary or secondary brain tumor radiotherapy. Cranial irradiation commonly leads to neurocognitive deficits that manifest months or years after treatment. Mechanistically, radiation-induced loss of neural stem/progenitor cells, neuroinflammation, and demyelination are contributing factors that lead to progressive cognitive decline.The effects of 1-[(4-nitrophenyl)sulfonyl]-4-phenylpiperazine (NSPP) on irradiated murine neurospheres, microglia cells, and patient-derived gliomaspheres were assessed by sphere-formation assays, flow cytometry, and interleukin (IL)-6 enzyme-linked immunosorbent assay. Activation of the hedgehog pathway was studied by quantitative reverse transcription PCR. The in vivo effects of NSPP were analyzed using flow cytometry, sphere-formation assays, immunohistochemistry, behavioral testing, and an intracranial mouse model of glioblastoma.We report that NSPP mitigates radiation-induced normal tissue toxicity in the brains of mice. NSPP treatment significantly increased the number of neural stem/progenitor cells after brain irradiation in female animals, and inhibited radiation-induced microglia activation and expression of the pro-inflammatory cytokine IL-6. Behavioral testing revealed that treatment with NSPP after radiotherapy was able to successfully mitigate radiation-induced decline in memory function of the brain. In mouse models of glioblastoma, NSPP showed no toxicity and did not interfere with the growth-delaying effects of radiation.We conclude that NSPP has the potential to mitigate cognitive decline in patients undergoing partial or whole brain irradiation without promoting tumor growth and that the use of this compound as a radiation mitigator of radiation late effects on the central nervous system warrants further investigation.
Effects of Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide on Biomarkers of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes
Authors: Mark L. Hartman, Arun J. Sanyal, Rohit Loomba, Jonathan M. Wilson, Amir Nikooienejad, Ross Bray, Chrisanthi A. Karanikas, Kevin L. Duffin, Deborah A. Robins, Axel Haupt
Journal: Diabetes Care (2020)

To determine the effect of tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptors, on biomarkers of nonalcoholic steatohepatitis (NASH) and fibrosis in patients with type 2 diabetes mellitus (T2DM).Patients with T2DM received either once weekly tirzepatide (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks. Changes from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), keratin-18 (K-18), procollagen III (Pro-C3), and adiponectin were analyzed in a modified intention-to-treat population.Significant (P < 0.05) reductions from baseline in ALT (all groups), AST (all groups except tirzepatide 10 mg), K-18 (tirzepatide 5, 10, 15 mg), and Pro-C3 (tirzepatide 15 mg) were observed at 26 weeks. Decreases with tirzepatide were significant compared with placebo for K-18 (10 mg) and Pro-C3 (15 mg) and with dulaglutide for ALT (10, 15 mg). Adiponectin significantly increased from baseline with tirzepatide compared with placebo (10, 15 mg).In post hoc analyses, higher tirzepatide doses significantly decreased NASH-related biomarkers and increased adiponectin in patients with T2DM.
Circulating MicroRNAs and Treatment Response in Childhood Asthma
Authors: Jiang Li, Ronald Panganiban, Alvin T. Kho, Michael J. McGeachie, Leanna Farnam, Robert P. Chase, Scott T. Weiss, Quan Lu, Kelan G. Tantisira
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Inhaled corticosteroids (ICS) are key treatments for controlling asthma and preventing asthma attacks. However, the responsiveness to ICS varies among individuals. MicroRNAs (miRNAs) have been lauded for their prognostic utility.
COVID-19 and emerging viral infections: The case for interferon lambda
Authors: Ludmila Prokunina-Olsson, Noémie Alphonse, Ruth E. Dickenson, Joan E. Durbin, Jeffrey S. Glenn, Rune Hartmann, Sergei V. Kotenko, Helen M. Lazear, Thomas R. O’Brien, Charlotte Odendall, Olusegun O. Onabajo, Helen Piontkivska, Deanna M. Santer, Nancy C. Reich, Andreas Wack, Ivan Zanoni
Journal: The Journal of Experimental Medicine (2020)

With the first reports on coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the scientific community working in the field of type III IFNs (IFN-λ) realized that this class of IFNs could play an important role in this and other emerging viral infections. In this Viewpoint, we present our opinion on the benefits and potential limitations of using IFN-λ to prevent, limit, and treat these dangerous viral infections.
Letter to the Editor: Glucocorticosteroids for Alcohol‐Associated Hepatitis
Authors: Daria L. Varganova, Chavdar S. Pavlov, Giovanni Casazza, Dimitrinka Nikolova, Christian Gluud
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To the Editor: Szabo et al. summarized the goals and aims of the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases at a joint 2017 London meeting on alcohol‐associated liver disease.1 They state that glucocorticosteroids are the current treatment for severe alcohol‐associated hepatitis, if contraindications are absent.1 Severe is defined as Maddrey discriminant function >32.1 Our Cochrane systematic review on glucocorticosteroids versus placebo or no intervention for people with alcohol‐associated hepatitis found no evidence of a difference in clinically important outcomes at either of the three timepoints of follow‐up.4 Our review (last search January 18, 2019) was based on a prepublished, peer‐reviewed protocol. In a subgroup meta‐analysis of 14 trials with 1,679 participants with severe alcoholic hepatitis, we found no evidence of the effect of glucocorticosteroids on mortality.4 We observed the same result in our overall meta‐analysis, including people with nonsevere alcohol‐associated hepatitis. All trials, except for the STOPAH (Steroids or Pentoxifylline for Alcoholic Hepatitis) trial, are overall at a high risk of bias.2 The GRADE (Grading of Recommendations Assessment, Development and Evaluation) certainty of evidence is very low for all outcomes.4 The Louvet et al. meta‐analysis included only six trials with 956 participants.3 Their control intervention was placebo in four trials, and enteral nutrition and antioxidants in one trial each (the latter excluded from our review). Their meta‐analysis showed that glucocorticosteroids appeared to reduce mortality within 28 days, but not at 6 months. However, they selected only those participants with severe alcohol‐associated hepatitis who would benefit from the intervention (i.e., excluding those with severe complications who would require immediate help). Their decision may have led to a misleading estimate for the subpopulation of patients and the intervention. They did not grade the evidence for certainty. Both the Louvet et al. meta‐analysis and our own lack precision and power (mostly due to small trial sample sizes, few events, and wide confidence intervals).3 There is limited confidence in the effect estimate of the Louvet et al. meta‐analysis, which is why the current clinical practice is questioned. Further evidence from randomized clinical trials is needed for certainty whether glucocorticosteroids influence mortality.
The use of noninvasive imaging techniques in the diagnosis of melanoma: a prospective diagnostic accuracy study
Authors: A. Nikolas MacLellan, Emma L. Price, Pamela Publicover-Brouwer, Kara Matheson, Thai Yen Ly, Sylvia Pasternak, Noreen M. Walsh, Christopher J. Gallant, Amanda Oakley, Peter R. Hull, Richard G. Langley
Journal: Journal of the American Academy of Dermatology (2020)
Factors Associated With Increased Collection of Patient-Reported Outcomes Within a Large Health Care System
Authors: Rachel C. Sisodia, Christian Dankers, John Orav, Bernard Joseph, Peter Meyers, Patrick Wright, David St. Amand, Marcela del Carmen, Tim Ferris, Marilyn Heng, Adam Licurse, Gregg Meyer, Thomas D. Sequist
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The collection of patient-reported outcomes (PROs) has garnered intense interest, but dissemination of PRO programs has been limited, as have analyses of the factors associated with successful programs. <h3>Objective</h3> To identify factors associated with improving PRO collection rates within a large health care system using a centralized PRO infrastructure. <h3>Design, Setting, and Participants</h3> This cohort study included 205 medical and surgical clinics in the Partners Healthcare system in Massachusetts that implemented a PRO program between March 15, 2014, and December 31, 2018, using a standardized centralized infrastructure. Data were analyzed from March to April 2019. <h3>Exposures</h3> Relevant clinical characteristics were recorded for each clinic launching a PRO program. <h3>Main Outcomes and Measures</h3> The primary outcome was the mean PRO collection rate during each clinic's most recent 6 months of collection prior to January 2019. Data were analyzed using a linear regression model with the 6-month PRO collection rate as the dependent variable and clinic characteristics as independent variables. Secondary analysis used a logistic regression model to assess clinical factors associated with successful clinics, defined as those that collected PROs at a rate greater than 50%. <h3>Results</h3> Between March 2014 and December 2018, 205 Partners Healthcare clinics were available for analysis, and 4 061 205 PRO measures from 745 028 encounters were collected. Among these, 103 clinics (50.2%) collected at a rate greater than 50%. Increased collection rates were associated with more than 50% of physicians in a clinic trained on PROs (change, 19.6% [95% CI, 9.9%-29.4%];<i>P</i> &lt; .001), routine administrative oversight of collection rates (change, 16.0% [95% CI, 6.6%-25.5%];<i>P</i> = .001), previous collection of PROs on paper (change, 12.5% [95% CI, 4.7%-20.3%];<i>P</i> = .002), presence of a clinical champion (change, 11.2% [95% CI, 2.5%-20.0%];<i>P</i> = .01) and payer incentive (change, 10.5% [95% CI, 2.0%-18.9%];<i>P</i> = .02). <h3>Conclusions and Relevance</h3> These findings suggest that training physicians on the use of PROs, administrative surveillance of collection rates, and the presence of a local clinical champion may be promising interventions for increasing PRO collection. Clinics that have previously collected PROs may have greater success in increasing collections. Payer incentive for collection was associated with improved collections, but not associated with successful programs.
Emerging role of deep learning‐based artificial intelligence in tumor pathology
Authors: Yahui Jiang, Meng Yang, Shuhao Wang, Xiangchun Li, Yan Sun
Journal: Cancer Communications (2020)

Abstract The development of digital pathology and progression of state‐of‐the‐art algorithms for computer vision have led to increasing interest in the use of artificial intelligence (AI), especially deep learning (DL)‐based AI, in tumor pathology. The DL‐based algorithms have been developed to conduct all kinds of work involved in tumor pathology, including tumor diagnosis, subtyping, grading, staging, and prognostic prediction, as well as the identification of pathological features, biomarkers and genetic changes. The applications of AI in pathology not only contribute to improve diagnostic accuracy and objectivity but also reduce the workload of pathologists and subsequently enable them to spend additional time on high‐level decision‐making tasks. In addition, AI is useful for pathologists to meet the requirements of precision oncology. However, there are still some challenges relating to the implementation of AI, including the issues of algorithm validation and interpretability, computing systems, the unbelieving attitude of pathologists, clinicians and patients, as well as regulators and reimbursements. Herein, we present an overview on how AI‐based approaches could be integrated into the workflow of pathologists and discuss the challenges and perspectives of the implementation of AI in tumor pathology.
Antecedent rationalization: Rationalization prior to action
Authors: Eric Thomas Sievers
Journal: Behavioral and Brain Sciences (2020)

Abstract Often times we find ourselves wrestling with the urge to commit a non-rational action. When this happens, we are quite good at adopting quasi-beliefs that, if true, would make the action rational. In other words, rationalization often occurs antecedent to a behavioral choice. A complete account of the evolutionary history of rationalization must include antecedent rationalization.
Extreme Genomic CpG Deficiency in SARS-CoV-2 and Evasion of Host Antiviral Defense
Authors: Xuhua Xia
Journal: Molecular Biology and Evolution (2020)

Wild mammalian species, including bats, constitute the natural reservoir of betacoronavirus (including SARS, MERS, and the deadly SARS-CoV-2). Different hosts or host tissues provide different cellular environments, especially different antiviral and RNA modification activities that can alter RNA modification signatures observed in the viral RNA genome. The zinc finger antiviral protein (ZAP) binds specifically to CpG dinucleotides and recruits other proteins to degrade a variety of viral RNA genomes. Many mammalian RNA viruses have evolved CpG deficiency. Increasing CpG dinucleotides in these low-CpG viral genomes in the presence of ZAP consistently leads to decreased viral replication and virulence. Because ZAP exhibits tissue-specific expression, viruses infecting different tissues are expected to have different CpG signatures, suggesting a means to identify viral tissue-switching events. The author shows that SARS-CoV-2 has the most extreme CpG deficiency in all known betacoronavirus genomes. This suggests that SARS-CoV-2 may have evolved in a new host (or new host tissue) with high ZAP expression. A survey of CpG deficiency in viral genomes identified a virulent canine coronavirus (alphacoronavirus) as possessing the most extreme CpG deficiency, comparable with that observed in SARS-CoV-2. This suggests that the canine tissue infected by the canine coronavirus may provide a cellular environment strongly selecting against CpG. Thus, viral surveys focused on decreasing CpG in viral RNA genomes may provide important clues about the selective environments and viral defenses in the original hosts.
A Highly Efficacious PS Gene Editing System Corrects Metabolic and Neurological Complications of Mucopolysaccharidosis Type I
Authors: Li Ou, Michael J. Przybilla, Ozan Ahlat, Sarah Kim, Paula Overn, Jeanine Jarnes, M. Gerard O’Sullivan, Chester B. Whitley
Journal: Molecular Therapy (2020)

Our previous study delivered zinc finger nucleases to treat mice with mucopolysaccharidosis type I (MPS I), resulting in a phase I/II clinical trial (ClinicalTrials.gov: NCT02702115). However, in the clinical trial, the efficacy needs to be improved due to the low transgene expression level. To this end, we designed a proprietary system (PS) gene editing approach with CRISPR to insert a promoterless α-l-iduronidase (IDUA) cDNA sequence into the albumin locus of hepatocytes. In this study, adeno-associated virus 8 (AAV8) vectors delivering the PS gene editing system were injected into neonatal and adult MPS I mice. IDUA enzyme activity in the brain significantly increased, while storage levels were normalized. Neurobehavioral tests showed that treated mice had better memory and learning ability. Also, histological analysis showed efficacy reflected by the absence of foam cells in the liver and vacuolation in neuronal cells. No vector-associated toxicity or increased tumorigenesis risk was observed. Moreover, no off-target effects were detected through the unbiased genome-wide unbiased identification of double-stranded breaks enabled by sequencing (GUIDE-seq) analysis. In summary, these results showed the safety and efficacy of the PS in treating MPS I and paved the way for clinical studies. Additionally, as a therapeutic platform, the PS has the potential to treat other lysosomal diseases. Our previous study delivered zinc finger nucleases to treat mice with mucopolysaccharidosis type I (MPS I), resulting in a phase I/II clinical trial (ClinicalTrials.gov: NCT02702115). However, in the clinical trial, the efficacy needs to be improved due to the low transgene expression level. To this end, we designed a proprietary system (PS) gene editing approach with CRISPR to insert a promoterless α-l-iduronidase (IDUA) cDNA sequence into the albumin locus of hepatocytes. In this study, adeno-associated virus 8 (AAV8) vectors delivering the PS gene editing system were injected into neonatal and adult MPS I mice. IDUA enzyme activity in the brain significantly increased, while storage levels were normalized. Neurobehavioral tests showed that treated mice had better memory and learning ability. Also, histological analysis showed efficacy reflected by the absence of foam cells in the liver and vacuolation in neuronal cells. No vector-associated toxicity or increased tumorigenesis risk was observed. Moreover, no off-target effects were detected through the unbiased genome-wide unbiased identification of double-stranded breaks enabled by sequencing (GUIDE-seq) analysis. In summary, these results showed the safety and efficacy of the PS in treating MPS I and paved the way for clinical studies. Additionally, as a therapeutic platform, the PS has the potential to treat other lysosomal diseases.
Kidney Function in Patients With Type 2 Diabetes After Vitamin D Supplementation
Authors: Alan N. Peiris
Journal: JAMA (2020)

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Interactions between neutrophils and NSCLC cells in vitro effects on neutrophil inflammatory mediator generation and tumour cell proliferation
Authors: K. Hattar, K. Franz, M. Ludwig, A. Banat, W. Seeger, F. Grimminger, U. Sibelius, U. Grandel
Journal: Journal of Clinical Oncology (2009)

e22148 Background: Growing evidence indicates that interactions between tumour cells and the inflammatory cellular microenvironment are crucial for tumour biology. In NSCLC, both bacterial infections and leukocytosis are associated with a poor prognosis. Against this background, we studied the effect of normal bronchial epithelial cells (B2B) and NSCLC cells (A549) on inflammatory neutrophil behaviour and quantified tumour cell proliferation in the presence of neutrophils. Methods: Isolated human neutrophils were co-cultured with B2B or A549 cells. Neutrophil respiratory burst was quantified by cytochrome C reduction and elastase activity was measured by the kinetics of substrate turnover. Proliferation of A549 cells was determined by MTS- assay. Results: Co-culturing human neutrophils with A549 cells stimulated neutrophil respiratory burst and degranulation in response to the bacterial tripeptide fMLP. In contrast, when co-cultured with B2B cells, these inflammatory neutrophil reactions were blunted. This could be attributed to release of NO and adenosine by the B2B cells. The increase of oxygen radical release and elastase degranulation in the presence of A549 cells was mediated by direct cell-to-cell contact. COX-2 dependent prostanoids were obviously involved in the activation of inflammatory neutrophil behaviour, as shown by the inhibitory capacity of the COX-2 specific inhibitor NS-398 in the co-culture system. Interestingly, activated neutrophils induced proliferation of NSCLC cells in a dose-dependent manner. Conclusions: The reciprocal interactions between neutrophils and NSCLC cells may enhance neutrophil-derived tissue destruction and tumour growth under inflammatory conditions. No significant financial relationships to disclose.
Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010 (vol 380, pg 2197, 2012)
Authors: C.J.L. Murray, T. Vos, R. Lozano, Mohammad A. AlMazroa, Ziad A. Memish
Journal: The Lancet (2013)