tbuckley/cabot-search huggingface dataset:
Childhood asthma outcomes during the COVID‐19 pandemic: Findings from the PeARL multi‐national cohort
Authors: Nikolaos G. Papadopoulos, Alexander G. Mathioudakis, Adnan Custovic, Antoine Deschildre, Wanda Phipatanakul, Gary Wong, Paraskevi Xepapadaki, Rola Abou‐Taam, Ioana Agache, Jose A. Castro‐Rodriguez, Zhimin Chen, Pierrick Cros, Jean‐Christophe Dubus, Zeinab Awad El‐Sayed, Rasha El‐Owaidy, Wojciech Feleszko, Vincenzo Fierro, Alessandro Fiocchi, Luis Garcia‐Marcos, Anne Goh, Elham M. Hossny, Yunuen R. Huerta Villalobos, Tuomas Jartti, Pascal Le Roux, Julia Levina, Aida Inés López García, Ángel Mazón Ramos, Mário Morais‐Almeida, Clare Murray, Karthik Nagaraju, Major K. Nagaraju, Elsy Maureen Navarrete Rodriguez, Leyla Namazova‐Baranova, Antonio Nieto Garcia, Cesar Fireth Pozo Beltrán, Thanaporn Ratchataswan, Daniela Rivero Yeverino, Eréndira Rodríguez Zagal, Cyril E. Schweitzer, Marleena Tulkki, Katarzyna Wasilczuk, Dan Xu
Journal: Allergy (2021)

Abstract Background The interplay between COVID‐19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID‐19 pandemic on childhood asthma outcomes. Methods The PeARL multinational cohort included 1,054 children with asthma and 505 non‐asthmatic children aged between 4 and 18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID‐19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control. Results During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks, and hospitalizations due to asthma, in comparison with the preceding year. Sixty‐six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre‐bronchodilatation FEV 1 and peak expiratory flow rate were improved during the pandemic. When compared to non‐asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits, or hospitalizations during the pandemic. However, an increased risk of URTIs emerged. Conclusion Childhood asthma outcomes, including control, were improved during the first wave of the COVID‐19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID‐19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent.
TRANSFORMER: A Randomized Phase II Study Comparing Bipolar Androgen Therapy Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Metastatic Prostate Cancer
Authors: Samuel R. Denmeade, Hao Wang, Neeraj Agarwal, David C. Smith, Michael T. Schweizer, Mark N. Stein, Vasileios Assikis, Przemyslaw W. Twardowski, Thomas W. Flaig, Russell Z. Szmulewitz, Jeffrey M. Holzbeierlein, Ralph J. Hauke, Guru Sonpavde, Jorge A. Garcia, Arif Hussain, Oliver Sartor, Shifeng Mao, Harry Cao, Wei Fu, Ting Wang, Rehab Abdallah, Su Jin Lim, Vanessa Bolejack, Channing J. Paller, Michael A. Carducci, Mark C. Markowski, Mario A. Eisenberger, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2021)

Prostate cancer (PCa) becomes resistant to androgen ablation through adaptive upregulation of the androgen receptor in response to the low-testosterone microenvironment. Bipolar androgen therapy (BAT), defined as rapid cycling between high and low serum testosterone, disrupts this adaptive regulation in castration-resistant PCa (CRPC).
Differential sensitivity to 2-deoxy-D-glucose between two pancreatic cell lines correlates with GLUT 1 expression
Authors: Johnathon C. Maher, Waldemar Priebe, Niramol Savaraj, Elena Paley, Huaping Liu, Subbarayan R. Pochi, Theodore J. Lampidis
Journal: Cancer Research (2004)

5302  Increased glucose uptake and metabolism is a well-characterized trait in many malignant tumors. Among the various known glucose transporters expressed in tumors, GLUT 1 is the most commonly found. Previously, we showed that, due to their dependence on glycolysis for energy, osteosarcoma cells under distinct conditions of hypoxia were hypersensitive to the glycolytic inhibitors, 2-deoxy-D-glucose (2-DG) and oxamate. Here, under normal oxygen tension we find that the pancreatic cell line MIA PaCa2 is 7X more sensitive to 2-DG, and equally sensitive to oxamate, as compared to Panc-1. Lactate levels in both cell types were similarly low, indicating that mitochondria were functioning normally in these cells and that they were not solely dependent on glycolysis for survival under an aerobic microenvironment. Additionally, the equal sensitivity to oxamate, which does not use glucose transporters for entry into the cell, suggested that the sensitivity differences to 2-DG in these two cell types might be reflective of differential 2-DG uptake. Indeed, it was found that 2-DG accumulates 2X greater in MIA PaCa2 than Panc-1, which correlates with higher GLUT 1 expression in the former cell line. Overall, our results suggest that certain pancreatic tumors may be inherently sensitive to 2-DG, even under normal oxygen tension, due to greater intracellular accumulation of this inhibitor. Moreover, if 2-DG shows clinical efficacy it may be possible to predict which pancreatic tumors would be sensitive to this agent based on their GLUT 1 expression profile and their increased uptake of 2-fluoro-deoxy-D-glucose currently used to localize tumors via PET scanning.
Polydopamine-modified collagen sponge scaffold as a novel dermal regeneration template with sustained release of platelet-rich plasma to accelerate skin repair: A one-step strategy
Authors: Zijun Zheng, Minxiong Li, Pengwei Shi, Yanbin Gao, Jun Ma, Yuchen Li, Lei Huang, Zhangfeifan Yang, Lei Yang
Journal: Bioactive Materials (2021)

Although employed to release growth factors (GFs) for regenerative medicine, platelet-rich plasma (PRP) has been hindered by issues like burst effect. Based on collagen sponge scaffolds (CSSs) modified with polydopamine (pDA), a novel dermal regeneration template (DRT) was designed. However, whether it could efficiently deliver PRP and even foster wound healing remained unclear. In this work, after PRP was prepared and pDA-modified CSSs (pDA-CSSs) were fabricated, microscopic observation, GFs release assay and in-vitro biological evaluations of pDA-CSSs with PRP ([email protected]) were performed, followed by BALA-C/nu mice full-thickness skin defects implanted with [email protected] covered by grafted skins (termed as a One-step strategy). As a result, scanning electron microscope demonstrated more immobilized platelets on pDA-CSS′ surface with GFs' controlled release via enzyme-linked immunosorbent assay, compared with CSSs. In line with enhanced in-vitro proliferation, adhesion and migration of keratinocytes & endothelial cells, [email protected] were histologically revealed to accelerate wound healing with less scar via rapid angiogenesis, arrangement of more mature collagen, guiding cells to spread, etc. In conclusion, pDA-CSSs have potential to serve as a novel DRT capable of delivering PRP, which may foster full-thickness skin defect healing by means of a One-step strategy.
In- and out-of-hospital mortality for myocardial infarction during the first wave of the COVID-19 pandemic in Emilia-Romagna, Italy: A population-based observational study
Authors: Gianluca Campo, Daniela Fortuna, Elena Berti, Rossana De Palma, Giuseppe Di Pasquale, Marcello Galvani, Alessandro Navazio, Giancarlo Piovaccari, Andrea Rubboli, Gabriele Guardigli, Nazzareno Galiè, Giuseppe Boriani, Stefano Tondi, Diego Ardissino, Massimo Piepoli, Federico Banchelli, Andrea Santarelli, Gianni Casella
Journal: The Lancet Regional Health - Europe (2021)

The COVID-19 pandemic has put several healthcare systems under severe pressure. The present analysis investigates how the first wave of the COVID-19 pandemic affected the myocardial infarction (MI) network of Emilia-Romagna (Italy).Based on Emilia-Romagna mortality registry and administrative data from all the hospitals from January 2017 to June 2020, we analysed: i) temporal trend in MI hospital admissions; ii) characteristics, management, and 30-day mortality of MI patients; iii) out-of-hospital mortality for cardiac cause.Admissions for MI declined on February 22, 2020 (IRR -19.5%, 95%CI from -8.4% to -29.3%, p = 0.001), and further on March 5, 2020 (IRR -21.6%, 95%CI from -9.0% to -32.5%, p = 0.001). The return to pre-COVID-19 MI-related admission levels was observed from May 13, 2020 (IRR 34.3%, 95%CI 20.0%-50.2%, p<0.001). As compared to those before the pandemic, MI patients admitted during and after the first wave were younger and with fewer risk factors. The 30-day mortality remained in line with that expected based on previous years (ratio observed/expected was 0.96, 95%CI 0.84-1.08). MI patients positive for SARS-CoV-2 were few (1.5%) but showed poor prognosis (around 5-fold increase in 30-day mortality). In 2020, the number of out-of-hospital cardiac deaths was significantly higher (ratio observed/expected 1.17, 95%CI 1.08-1.27). The peak was reached in April.In Emilia-Romagna, MI hospitalizations significantly decreased during the first wave of the COVID-19 pandemic. Management and outcomes of hospitalized MI patients remained unchanged, except for those with SARS-CoV-2 infection. A concomitant increase in the out-of-hospital cardiac mortality was observed.None.
Pan-cancer Transcriptomic Predictors of Perineural Invasion Improve Occult Histopathologic Detection
Authors: Jimmy A. Guo, Hannah I. Hoffman, Stuti G. Shroff, Peter Chen, Peter G. Hwang, Daniel Y. Kim, Daniel W. Kim, Stephanie W. Cheng, Daniel Zhao, Brandon A. Mahal, Mohammed Alshalalfa, Andrzej Niemierko, Jennifer Y. Wo, Jay S. Loeffler, Carlos Fernandez-del Castillo, Tyler Jacks, Andrew J. Aguirre, Theodore S. Hong, Mari Mino-Kenudson, William L. Hwang
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Perineural invasion (PNI) is associated with aggressive tumor behavior, recurrence, and metastasis, and can influence the administration of adjuvant treatment. However, standard histopathologic examination has limited sensitivity in detecting PNI and does not provide insights into its mechanistic underpinnings. Experimental Design: A multivariate Cox regression was performed to validate associations between PNI and survival in 2,029 patients across 12 cancer types. Differential expression and gene set enrichment analysis were used to learn PNI-associated programs. Machine learning models were applied to build a PNI gene expression classifier. A blinded re-review of hematoxylin and eosin (H&amp;E) slides by a board-certified pathologist helped determine whether the classifier could improve occult histopathologic detection of PNI. Results: PNI associated with both poor overall survival [HR, 1.73; 95% confidence interval (CI), 1.27–2.36; P &amp;lt; 0.001] and disease-free survival (HR, 1.79; 95% CI, 1.38–2.32; P &amp;lt; 0.001). Neural-like, prosurvival, and invasive programs were enriched in PNI-positive tumors (Padj &amp;lt; 0.001). Although PNI-associated features likely reflect in part the increased presence of nerves, many differentially expressed genes mapped specifically to malignant cells from single-cell atlases. A PNI gene expression classifier was derived using random forest and evaluated as a tool for occult histopathologic detection. On a blinded H&amp;E re-review of sections initially described as PNI negative, more specimens were reannotated as PNI positive in the high classifier score cohort compared with the low-scoring cohort (P = 0.03, Fisher exact test). Conclusions: This study provides salient biological insights regarding PNI and demonstrates a role for gene expression classifiers to augment detection of histopathologic features.
DeepHCS<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si1.svg"><mml:msup><mml:mrow/><mml:mrow><mml:mo>+</mml:mo><mml:mo>+</mml:mo></mml:mrow></mml:msup></mml:math>: Bright-field to fluorescence microscopy image conversion using multi-task learning with adversarial losses for label-free high-content screening
Authors: Gyuhyun Lee, Jeong-Woo Oh, Nam-Gu Her, Won-Ki Jeong
Journal: Medical Image Analysis (2021)
Nasal high flow oxygen in acute respiratory failure
Authors: M.L. Vega, L. Pisani
Journal: Pulmonology (2021)

Thermo-humidified nasal high flow (NHF) oxygen therapy is increasingly used in the management of respiratory failure. This therapy has recently gained attention as an alternative non-invasive respiratory support in several clinical scenarios, including acute and chronic settings. NHF enhances the patient’s comfort and tolerance when compared with standard oxygen by supplying a heated and humidified mixture of air and oxygen at flows up to 60 L/min. It can be delivered through different devices. Although few studies have compared the clinical effects of different NHF systems, the purpose of this paper is to describe the major benefits of NHF and to provide a quick guide on how to implement this therapy in daily practice. We have also included a brief description of the most frequently used NHF systems.
QT effects of bedaquiline, delamanid, or both in patients with rifampicin-resistant tuberculosis: a phase 2, open-label, randomised, controlled trial
Authors: Kelly E Dooley, Susan L Rosenkranz, Francesca Conradie, Laura Moran, Richard Hafner, Florian von Groote-Bidlingmaier, Javier R. Lama, Justin Shenje, Jorge De Los Rios, Kyla Comins, Joel Morganroth, Andreas H Diacon, Yoninah S Cramer, Kathleen Donahue, Gary Maartens, Oladapo Alli, Joan Gottesman, Maria Guevara, Chris Hikuam, Laura Hovind, Mats Karlsson, Jennifer McClaren, Helen McIlleron, William Murtaugh, Barbara Rolls, Akbar Shahkolahi, Lynnett Stone, Gerald Tegha, Jacob Tenai, Caryn Upton, Chanelle Wimbish
Journal: The Lancet Infectious Diseases (2021)
A heterozygous germline CD100 mutation in a family with primary sclerosing cholangitis
Authors: Xiaojun Jiang, Annika Bergquist, Britt-Sabina Löscher, Geetha Venkatesh, Jeff E. Mold, Kristian Holm, Jon K. Laerdahl, Sigrid S. Skånland, Kimia T. Maleki, Martin Cornillet, Kjetil Taskén, Andre Franke, Tom H. Karlsen, Niklas K. Björkström, Espen Melum
Journal: Science Translational Medicine (2021)

A mutation in CD100, identified in a family with inherited primary sclerosing cholangitis, leads to dysfunctional T cells and cholangitis development.
Engineered prime editors with PAM flexibility
Authors: Jiyeon Kweon, Jung-Ki Yoon, An-Hee Jang, Ha Rim Shin, Ji-Eun See, Gayoung Jang, Jong-Il Kim, Yongsub Kim
Journal: Molecular Therapy (2021)

Although prime editors are a powerful tool for genome editing, which can generate various types of mutations such as nucleotide substitutions, insertions, and deletions in the genome without double-strand breaks or donor DNA, the conventional prime editors are still limited to their target scopes because of the PAM preference of the Streptococcus pyogenes Cas9 (spCas9) protein. Here, we describe the engineered prime editors to expand the range of their target sites using various PAM-flexible Cas9 variants. Using the engineered prime editors, we could successfully generate more than 50 types of mutations with up to 51.7% prime-editing activity in HEK293T cells. In addition, we successfully introduced the BRAF V600E mutation, which could not be induced by conventional prime editors. These variants of prime editors will broaden the applicability of CRISPR-based prime editing technologies in biological research. Although prime editors are a powerful tool for genome editing, which can generate various types of mutations such as nucleotide substitutions, insertions, and deletions in the genome without double-strand breaks or donor DNA, the conventional prime editors are still limited to their target scopes because of the PAM preference of the Streptococcus pyogenes Cas9 (spCas9) protein. Here, we describe the engineered prime editors to expand the range of their target sites using various PAM-flexible Cas9 variants. Using the engineered prime editors, we could successfully generate more than 50 types of mutations with up to 51.7% prime-editing activity in HEK293T cells. In addition, we successfully introduced the BRAF V600E mutation, which could not be induced by conventional prime editors. These variants of prime editors will broaden the applicability of CRISPR-based prime editing technologies in biological research.
Utility of a safety switch to abrogate CD19.CAR T-cell–associated neurotoxicity
Authors: Matthew C. Foster, Barbara Savoldo, Winnie Lau, Clio Rubinos, Natalie Grover, Paul Armistead, James Coghill, Robert S. Hagan, Kaitlin Morrison, Faith Brianne Buchanan, Catherine Cheng, Spencer Laing, Anastasia Ivanova, John West, Aaron Foster, Jonathan Serody, Gianpietro Dotti
Journal: Blood (2021)
Primary Neuroendocrine Neoplasia of the Liver
Authors: Daniel Kaemmerer, Almut Kunze, Franz C. Robiller, Merten Hommann, Martin Anlauf
Journal: Clinical Nuclear Medicine (2021)

The presence of primary neuroendocrine tumors in the liver is still a matter of controversy. We present a case of a somatostatin-receptor-positive mass of the liver in the 68Ga-DOTATOC PET/CT. No other primary tumor was found after conventional imaging, endoscopically, and after liver-segment resection. Immunohistochemically, a constellation of findings was found to be compatible with a primary neuroendocrine neoplasm of the liver.
Neutralizing Activity of BNT162b2-Elicited Serum
Authors: Yang Liu, Jianying Liu, Hongjie Xia, Xianwen Zhang, Camila R Fontes-Garfias, Kena A Swanson, Hui Cai, Ritu Sarkar, Wei Chen, Mark Cutler, David Cooper, Scott C Weaver, Alexander Muik, Ugur Sahin, Kathrin U Jansen, Xuping Xie, Philip R Dormitzer, Pei-Yong Shi
Journal: New England Journal of Medicine (2021)

Variant SARS-CoV-2 and BNT162b2 Vaccine How well do serum samples obtained from persons injected with the BNT162b2 vaccine neutralize the P.1, B.1.1.7, and B.1.135 lineages of SARS-CoV-2, first ide...
Assessment of Clinical Benefit of Integrative Genomic Profiling in Advanced Solid Tumors
Authors: Erin F. Cobain, Yi-Mi Wu, Pankaj Vats, Rashmi Chugh, Francis Worden, David C. Smith, Scott M. Schuetze, Mark M. Zalupski, Vaibhav Sahai, Ajjai Alva, Anne F. Schott, Megan E. V. Caram, Daniel F. Hayes, Elena M. Stoffel, Michelle F. Jacobs, Chandan Kumar-Sinha, Xuhong Cao, Rui Wang, David Lucas, Yu Ning, Erica Rabban, Janice Bell, Sandra Camelo-Piragua, Aaron M. Udager, Marcin Cieslik, Robert J. Lonigro, Lakshmi P. Kunju, Dan R. Robinson, Moshe Talpaz, Arul M. Chinnaiyan
Journal: JAMA Oncology (2021)

<h3>Importance</h3> Use of next-generation sequencing (NGS) to identify clinically actionable genomic targets has been incorporated into routine clinical practice in the management of advanced solid tumors; however, the clinical utility of this testing remains uncertain. <h3>Objective</h3> To determine which patients derived the greatest degree of clinical benefit from NGS profiling. <h3>Design, Setting, and Participants</h3> Patients in this cohort study underwent fresh tumor biopsy and blood sample collection for genomic profiling of paired tumor and normal DNA (whole-exome or targeted-exome capture with analysis of 1700 genes) and tumor transcriptome (RNA) sequencing. Somatic and germline genomic alterations were annotated and classified according to degree of clinical actionability. Results were returned to treating oncologists. Data were collected from May 1, 2011, to February 28, 2018, and analyzed from May 1, 2011, to April 30, 2020. <h3>Main Outcomes and Measures</h3> Patients’ subsequent therapy and treatment response were extracted from the medical record to determine clinical benefit rate from NGS-directed therapy at 6 months and exceptional responses lasting 12 months or longer. <h3>Results</h3> During the study period, NGS was attempted on tumors from 1138 patients and was successful in 1015 (89.2%) (MET1000 cohort) (538 men [53.0%]; mean [SD] age, 57.7 [13.3] years). Potentially clinically actionable genomic alterations were discovered in 817 patients (80.5%). Of these, 132 patients (16.2%) received sequencing-directed therapy, and 49 had clinical benefit (37.1%). Exceptional responses were observed in 26 patients (19.7% of treated patients). Pathogenic germline variants (PGVs) were identified in 160 patients (15.8% of cohort), including 49 PGVs (4.8% of cohort) with therapeutic relevance. For 55 patients with carcinoma of unknown primary origin, NGS identified the primary site in 28 (50.9%), and sequencing-directed therapy in 13 patients resulted in clinical benefit in 7 instances (53.8%), including 5 exceptional responses. <h3>Conclusions and Relevance</h3> The high rate of therapeutically relevant PGVs identified across diverse cancer types supports a recommendation for directed germline testing in all patients with advanced cancer. The high frequency of therapeutically relevant somatic and germline findings in patients with carcinoma of unknown primary origin and other rare cancers supports the use of comprehensive NGS profiling as a component of standard of care for these disease entities.
The Differential Diagnosis of Depression
Authors: Jeffrey M. Schwartz
Journal: JAMA (1987)

DEPRESSIVE disorders are conditions whose high prevalence<sup>1,2</sup>and frequent need for medical intervention<sup>3</sup>require increased understanding in the general medical community. Antidepressants are prescribed with increasing frequency by a wide range of medical practitioners and a recent listing of the most prescribed drugs included seven antidepressants.<sup>4</sup>Data from an ongoing National Institute of Mental Health epidemiologic study,<sup>2</sup>using diagnostic criteria from<i>DSM-III</i>,<sup>5</sup>indicate that in the general population there is a six-month prevalence of depressive disorders (bipolar and unipolar) of about 5%. Furthermore, over 75% of persons with recent depressive disorders have sought medical treatment of some type in the last six months and nearly half of all mental health—related visits made by depressed individuals are to general medical practitioners.<sup>3</sup>These figures constitute a compelling reason for all physicians to be familiar with the typology of depressive disorders. In psychiatry, as in all fields
SARS-CoV-2 infection and COVID-19 in asthmatics: a complex relationship
Authors: Chrysanthi Skevaki, Antonina Karsonova, Alexander Karaulov, Daria Fomina, Min Xie, Sharon Chinthrajah, Kari C. Nadeau, Harald Renz
Journal: Nature reviews. Immunology (2021)

Risk of severe coronavirus disease 2019 (COVID-19) after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is increased in patients with certain comorbidities, including chronic obstructive pulmonary disease (COPD). By contrast, epidemiological data from many (but not all) countries indicate a low prevalence of asthma among patients with severe COVID-19. This reduced risk of severe COVID-19 may apply specifically to patients with the type 2 asthma endotype, which is most common in childhood asthma. Somewhat surprisingly, individuals with asthma do not seem to have a greater risk of developing severe COVID-19. Here, the authors offer mechanistic insights to explain the epidemiological data.
Abstract 16213: The Trajectory of Left Ventricular Remodeling in Children With Valvar Aortic Stenosis After Balloon Aortic Valvuloplasty
Authors: Koyelle Papneja, Zachary Blatman, Ian D Kawpeng, Jacqueline Wheatley, Hanne Oscé, Boning Li, Myriam Lafreniere-Roula, Chun Po S fan, Cedric Manlhiot, Lee Benson, Luc Mertens
Journal: Circulation (2019)

Introduction: The long term trajectory of LV remodelling following balloon aortic valvuloplasty (BAV) in children has not been described. Objectives: Our aim was to assess the trajectory of LV remo...