tbuckley/cabot-search huggingface dataset:
Cost-Effectiveness of Durvalumab After Chemoradiotherapy in Unresectable Stage III NSCLC: A US Healthcare Perspective
Authors: Ranee Mehra, Candice Yong, Brian Seal, Marjolijn van Keep, Angie Raad, Yiduo Zhang
Journal: Journal of the National Comprehensive Cancer Network (2021)

Durvalumab was approved by the FDA in February 2018 for patients with unresectable stage III NSCLC that has not progressed after platinum-based concurrent chemoradiotherapy (cCRT), and this regimen is the current standard of care. The objective of this study was to examine the cost-effectiveness of durvalumab following cCRT versus cCRT alone in patients with locally advanced, unresectable stage III NSCLC.A 3-state semi-Markov model was used. Modeling was performed in a US healthcare setting from Medicare and commercial payer perspectives over a 30-year time horizon. Clinical efficacy (progression-free and post progression survival) and utility inputs were based on PACIFIC study data (ClinicalTrials.gov identifier: NCT02125461; data cutoff March 22, 2018). Overall survival extrapolation was validated using overall survival data from a later data cutoff (January 31, 2019). The main outcome was the incremental cost-effectiveness ratio (ICER) of durvalumab following cCRT versus cCRT alone, calculated as the difference in total costs between treatment strategies per quality-adjusted life-year (QALY) gained.In the base-case analysis, durvalumab following cCRT was cost-effective versus cCRT alone from Medicare and commercial insurance perspectives, with ICERs of $55,285 and $61,111, respectively, per QALY gained. Durvalumab was thus considered cost-effective at the $100,000 willingness-to-pay (WTP) threshold. Sensitivity analyses revealed the model was particularly affected by variables associated with subsequent treatment, although no tested variable increased the ICER above the WTP threshold. Scenario analyses showed the model was most sensitive to assumptions regarding time horizon, treatment effect duration, choice of fitted progression-free survival curve, subsequent immunotherapy treatment duration, and use of a partitioned survival model structure.In a US healthcare setting, durvalumab was cost-effective compared with cCRT alone, further supporting the adoption of durvalumab following cCRT as the new standard of care in patients with unresectable stage III NSCLC.
Sex differences in cardiorespiratory fitness are explained by blood volume and oxygen carrying capacity
Authors: Candela Diaz-Canestro, Brandon Pentz, Arshia Sehgal, David Montero
Journal: Cardiovascular Research (2021)

Abstract Aims Intrinsic sex differences in fundamental blood attributes have long been hypothesized to contribute to the gap in cardiorespiratory fitness between men and women. This study experimentally assessed the role of blood volume and oxygen (O2) carrying capacity on sex differences in cardiac function and aerobic power. Methods and results Healthy women and men (n = 60) throughout the mature adult lifespan (42–88 yr) were matched by age and physical activity levels. Transthoracic echocardiography, central blood pressure, and O2 uptake were assessed throughout incremental exercise (cycle ergometry). Main outcomes such as left ventricular end-diastolic volume (LVEDV), stroke volume (SV), cardiac output (Q), and peak O2 uptake (VO2peak), as well as blood volume (BV) were determined with established methods. Measurements were repeated in men following blood withdrawal and O2 carrying capacity reduction matching women’s levels. Prior to blood normalization, BV and O2 carrying capacity were markedly reduced in women compared with men (P &amp;lt; 0.001). Blood normalization resulted in a precise match of BV (82.36 ± 9.83 vs. 82.34 ± 7.70 ml·kg−1, P = 0.993) and O2 carrying capacity (12.0 ± 0.6 vs. 12.0 ± 0.7 g·dl−1, P = 0.562) between women and men. Body size-adjusted cardiac filling and output (LVEDV, SV, Q) during exercise as well as VO2peak (30.8 ± 7.5 vs. 35.6 ± 8.7 ml·min−1·kg−1, P &amp;lt; 0.001) were lower in women compared with men prior to blood normalization. VO2peak did not differ between women and men after blood normalization (30.8 ± 7.5 vs. 29.7 ± 7.4 ml·min−1·kg−1, P = 0.551). Conclusions Sex differences in cardiorespiratory fitness are abolished when blood attributes determining O2 delivery are experimentally matched between adult women and men.
Difference in clinical characteristics of patients with common variable immunodeficiency (CVID) according to pulmonary alterations - A cohort of 182 patients from a Brazilian tertiary hospital
Authors: Priscila Franco, Rosana Agondi, Grazielly Pereira, Pereira GF, Octavio Grecco, Ana Karolina Marinho, Myrthes Toledo Barros, Myrthes T. Barros, Jorge Kalil, Cristina Kokron
Journal: Journal of Allergy and Clinical Immunology (2021)
Baseline Asthma Impairment and Risk Questionnaire (AIRQ™) Control Level is Associated with Future Risk of Exacerbations
Authors: David Beuther, Kevin Murphy, Robert Zeiger, Robert Wise, William McCann, Joan Reibman, Maureen George, Ileen Gilbert, James Eudicone, Hitesh Ghandi, Karin Coyne, Melissa Ross, Bradley Chipps
Journal: Journal of Allergy and Clinical Immunology (2021)
Risk Factors for Early-Onset Colorectal Cancer: A Systematic Review and Meta-analysis
Authors: Dylan E. O’Sullivan, R. Liam Sutherland, Susanna Town, Kristian Chow, Jeremy Fan, Nauzer Forbes, Steven J. Heitman, Robert J. Hilsden, Darren R. Brenner
Journal: Clinical Gastroenterology and Hepatology (2021)
Sputum TNF markers are increased in neutrophilic and severe asthma and are reduced by azithromycin treatment
Authors: Natalie M. Niessen, Peter G. Gibson, Katherine J. Baines, Daniel Barker, Ian A. Yang, John W. Upham, Paul N. Reynolds, Sandra Hodge, Alan L. James, Christine Jenkins, Matthew J. Peters, Guy B. Marks, Melissa Baraket, Jodie L. Simpson, Michael Fricker
Journal: Allergy (2021)

Abstract Background The AMAZES randomized controlled trial demonstrated that long‐term low‐dose azithromycin treatment reduces exacerbations of poorly controlled asthma, but the therapeutic mechanisms remain unclear. Dysregulation of the inflammatory tumour necrosis factor (TNF) pathway is implicated in asthma and could be suppressed by azithromycin. We aimed to determine the inflammatory and clinical associations of soluble TNF signalling proteins (TNF receptors [TNFR] 1 and 2, TNF) in sputum and serum, and to test the effect of 48 weeks of azithromycin vs placebo on TNF markers. Methods Sputum supernatant and serum TNFR1, TNFR2 (n = 142; 75 azithromycin‐treated, 67 placebo‐treated) and TNF (n = 48; 22 azithromycin‐treated, 26 placebo‐treated) were measured by ELISA in an AMAZES trial sub‐population at baseline and end of treatment. Baseline levels were compared between sputum inflammatory phenotypes, severe/non‐severe asthma and frequent/non‐frequent exacerbators. Effect of azithromycin on markers was tested using linear mixed models. Results Baseline sputum TNFR1 and TNFR2 were significantly increased in neutrophilic vs non‐neutrophilic asthma phenotypes, while serum markers did not differ. Sputum TNFR1 and TNFR2 were increased in severe asthma and correlated with poorer lung function, worse asthma control and increasing age. Serum TNFR1 was also increased in severe asthma. Sputum and serum TNFR2 were increased in frequent exacerbators. Azithromycin treatment significantly reduced sputum TNFR2 and TNF relative to placebo, specifically in non‐eosinophilic participants. Conclusions We demonstrate dysregulation of TNF markers, particularly in the airways, that relates to clinically important phenotypes of asthma including neutrophilic and severe asthma. Suppression of dysregulated TNF signalling by azithromycin could contribute to its therapeutic mechanism.
SARS-CoV-2 vaccination and phase 1 cancer clinical trials
Authors: Timothy A Yap, Lillian L Siu, Emiliano Calvo, Martijn P Lolkema, Patricia M LoRusso, Jean-Charles Soria, Ruth Plummer, Johann S de Bono, Josep Tabernero, Udai Banerji
Journal: The Lancet Oncology (2021)
Microneedle-based devices for point-of-care infectious disease diagnostics
Authors: Rachael V. Dixon, Eldhose Skaria, Wing Man Lau, Philip Manning, Mark A. Birch-Machin, S. Moein Moghimi, Keng Wooi Ng
Journal: Acta Pharmaceutica Sinica B (2021)

Recent infectious disease outbreaks, such as COVID-19 and Ebola, have highlighted the need for rapid and accurate diagnosis to initiate treatment and curb transmission. Successful diagnostic strategies critically depend on the efficiency of biological sampling and timely analysis. However, current diagnostic techniques are invasive/intrusive and present a severe bottleneck by requiring specialist equipment and trained personnel. Moreover, centralised test facilities are poorly accessible and the requirement to travel may increase disease transmission. Self-administrable, point-of-care (PoC) microneedle diagnostic devices could provide a viable solution to these problems. These miniature needle arrays can detect biomarkers in/from the skin in a minimally invasive manner to provide (near-) real-time diagnosis. Few microneedle devices have been developed specifically for infectious disease diagnosis, though similar technologies are well established in other fields and generally adaptable for infectious disease diagnosis. These include microneedles for biofluid extraction, microneedle sensors and analyte-capturing microneedles, or combinations thereof. Analyte sampling/detection from both blood and dermal interstitial fluid is possible. These technologies are in their early stages of development for infectious disease diagnostics, and there is a vast scope for further development. In this review, we discuss the utility and future outlook of these microneedle technologies in infectious disease diagnosis.
Frequency of Follicular T cells in a cohort of Brazilian Common Variable Immunodeficiency (CVID) patients
Authors: Cristina Kokron, Fernando Zilinski, Bianca Santos, Erica Coutinho, Juliana Apostolico, Milena Andrade, Ana Karolina Marinho, Myrthes Barros, Octavio Grecco, Jorge Kalil
Journal: Journal of Allergy and Clinical Immunology (2021)
Ronald West Strachan
Authors: David Strachan, Sue Robertson, Chris Isles
Journal: BMJ (2021)

Ronald West Strachan (“Ronnie”) was born in Aberdeen, attended Aberdeen Grammar School, and in 1947 started studying medicine at Aberdeen University. He spent two years of national service in the Royal Air Force and then married his childhood sweetheart, Helen, in 1959.

He trained as a physician …
Spider silk nerve graft promotes axonal regeneration on long distance nerve defect in a sheep model
Authors: T. Kornfeld, J. Nessler, C. Helmer, R. Hannemann, K.H. Waldmann, C.T. Peck, P. Hoffmann, G. Brandes, P.M. Vogt, C. Radtke
Journal: Biomaterials (2021)
Mepolizumab reduces disease symptoms for Patients with Chronic Rhinosinusitis with Nasal Polyps: Data from the SYNAPSE study
Authors: Maggie Tabberer, Andrew Trigg, William Busse, Valerie Lund, Jason Lee, Claus Bachert, Brent Senior, Kathleen Buchheit, Zuzana Diamant, Ana Sousa, Steven Smith, Bhabita Mayer, Steven Yancey, Robert Chan
Journal: Journal of Allergy and Clinical Immunology (2021)
Quality and Safety in Healthcare, Part LXXXV
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2021)

A high-reliability organization must have high-performing teams. Core teams in healthcare should include the patient and, where possible, the patient's family. Everyone on the team should understand what is expected of them in terms of expertise, leadership, communication, mutual support, and awareness of the situation. One test of the excellence of a clinical team is having high-quality handoffs of patients.
PM2.5 Concentration and Composition in Subway Systems in the Northeastern United States
Authors: David G. Luglio, Maria Katsigeorgis, Jade Hess, Rebecca Kim, John Adragna, Amna Raja, Colin Gordon, Jonathan Fine, George Thurston, Terry Gordon, M.J. Ruzmyn Vilcassim
Journal: Environmental Health Perspectives (2021)

The goals of this study were to assess the air quality in subway systems in the northeastern United States and estimate the health risks for transit workers and commuters.We report real-time and gravimetric PM2.5 concentrations and particle composition from area samples collected in the subways of Philadelphia, Pennsylvania; Boston, Massachusetts; New York City, New York/New Jersey (NYC/NJ); and Washington, District of Columbia. A total of 71 stations across 12 transit lines were monitored during morning and evening rush hours.We observed variable and high PM2.5 concentrations for on-train and on-platform measurements during morning (from 0600 hours to 1000 hours) and evening (from 1500 hours to 1900 hours) rush hour across cities. Mean real-time PM2.5 concentrations in underground stations were 779±249, 548±207, 341±147, 327±136, and 112±46.7 μg/m3 for the PATH-NYC/NJ; MTA-NYC; Washington, DC; Boston; and Philadelphia transit systems, respectively. In contrast, the mean real-time ambient PM2.5 concentration taken above ground outside the subway stations of PATH-NYC/NJ; MTA-NYC; Washington, DC; Boston; and Philadelphia were 20.8±9.3, 24.1±9.3, 12.01±7.8, 10.0±2.7, and 12.6±12.6 μg/m3, respectively. Stations serviced by the PATH-NYC/NJ system had the highest mean gravimetric PM2.5 concentration, 1,020 μg/m3, ever reported for a subway system, including two 1-h gravimetric PM2.5 values of approximately 1,700 μg/m3 during rush hour at one PATH-NYC/NJ subway station. Iron and total carbon accounted for approximately 80% of the PM2.5 mass in a targeted subset of systems and stations.Our results document that there is an elevation in the PM2.5 concentrations across subway systems in the major urban centers of Northeastern United States during rush hours. Concentrations in some subway stations suggest that transit workers and commuters may be at increased risk according to U.S. federal environmental and occupational guidelines, depending on duration of exposure. This concern is highest for the PM2.5 concentrations encountered in the PATH-NYC/NJ transit system. Further research is urgently needed to identify the sources of PM2.5 and factors that contribute to high levels in individual stations and lines and to assess their potential health impacts on workers and/or commuters. https://doi.org/10.1289/EHP7202.
Pregnancy Outcomes in Women With Moderate-to-Severe Psoriasis From the Psoriasis Longitudinal Assessment and Registry (PSOLAR)
Authors: Alexa B. Kimball, Lyn Guenther, Sunil Kalia, Elke M. G. J. de Jong, Kimberly Parnell Lafferty, Dan Y. Chen, Wayne Langholff, Neil H. Shear
Journal: JAMA Dermatology (2021)

Prospective data are limited on pregnancy outcomes among women with psoriasis who may be receiving biologic or conventional systemic therapy.To report pregnancy outcomes observed in the Psoriasis Longitudinal Assessment and Registry (PSOLAR).This cohort study used data from PSOLAR, a multicenter, disease-based, observational registry evaluating long-term safety and clinical outcomes for patients receiving or eligible to receive treatment for psoriasis with biologics and/or conventional systemic therapies. Of 12 090 enrollees, 5456 were women (45.1%), and 2224 women were of childbearing age (18-45 years). Participants had a total of 12 929 patient-years of follow-up (median, 7.2 [range, 3.3-8.0] years per patient). Data were collected from June 20, 2007, to August 23, 2019, and analyzed from April 23 to June 23, 2020.Exposure to biologics within the prenatal period (≤1 year before birth or ≤6 months before spontaneous abortion) or at any other time.Descriptive summaries of pregnancies and pregnancy-related outcomes were self-reported in PSOLAR, including births, stillbirths, spontaneous abortions, and elective terminations. Live birth characteristics collected in PSOLAR include whether a birth was full-term (≥37 weeks) or premature (<37 weeks) and whether neonatal adverse events or congenital anomalies occurred.A total of 298 pregnancies occurred among 220 women (mean [SD] age, 27.8 [5.2] years), and the general fertility rate was 18.9 per 1000 women aged 18 to 45 years. Of the 298 pregnancies, 244 (81.9%) resulted in birth, 41 (13.8%) ended in spontaneous abortion, and 13 (4.4%) were electively terminated. Gestational age was available for 243 births; 221 infants (90.9%) were full-term, and 22 (9.1%) were born prematurely. Birth outcomes included 231 healthy newborns, 10 infants with a neonatal problem, 2 infants with a congenital anomaly, and 1 stillbirth. Of the 298 pregnancies, 252 were associated with biologic exposure before or during pregnancy. Pregnancy outcomes for women exposed to biologics were similar to those for women exposed to nonbiologics. Among women who became pregnant, mean (SD) age at the time of pregnancy outcome was 30.9 (4.8) years; at enrollment into the registry, 74 of 219 (33.8%) had obesity, and 121 of 220 (55.0%) were past or current smokers.The findings of this cohort study suggest that pregnancy outcomes in PSOLAR have remained consistent with previous reports. Overall and live birth outcomes were similar to those for the general population.
Evaluation of the polyp-based resect and discard strategy: a retrospective study
Authors: Antoine Duong, Heiko Pohl, Roupen Djinbachian, Annie Deshêtres, Alan N. Barkun, Paola N. Marques, Mickael Bouin, Eric Deslandres, Andres Aguilera-Fish, Raymond Leduc, Daniel von Renteln
Journal: Endoscopy (2021)

Abstract Background Standard colonoscopy practice requires removal and histological characterization of almost all detected small (&lt; 10 mm) and diminutive (≤ 5 mm) colorectal polyps. This study aimed to test a simplified polyp-based resect and discard (PBRD) strategy that assigns surveillance intervals based only on size and number of small/diminutive polyps, without the need for pathology examination. Methods A post hoc analysis was performed on patients enrolled in a prospective study. The primary outcome was surveillance interval agreement of the PBRD strategy with pathology-based management according to 2020 US Multi-Society Task Force guidelines. Chart analysis also evaluated clinician adherence to pathology-based recommendations. One-sided testing was performed with a null-hypothesis of 90 % agreement with pathology-based surveillance intervals and a two-sided 96.7 % confidence interval (CI) using correction for multiple testing. Results 452 patients were included in the study. Surveillance intervals assigned using the PBRD strategy were correct in 97.8 % (96.7 %CI 96.3–99.3 %) of patients compared with pathology-based management. The PBRD strategy reduced pathology examinations by 58.7 % while providing 87.8 % of patients with immediate surveillance interval recommendations on the day of colonoscopy, compared with 47.1 % when using pathology-based management. Chart analysis of surveillance interval assignments showed 63.3 % adherence to pathology-based guidelines. Conclusion The PBRD strategy surpassed the 90 % agreement with the pathology-based standard for determining surveillance interval, reduced the need for pathology examinations, and increased the proportion of patients receiving immediate surveillance interval recommendations. The PBRD strategy does not require expertise in optical diagnosis and may replace histological characterization of small and diminutive colorectal polyps.
Covid-19: No convincing evidence for increasing the vaccine dosing interval
Authors: Milan Dagli
Journal: BMJ (2021)

Recent index literature is replete with innovations that are based on quantitative strategies and predicated on sensible investment beliefs. Empirical studies confirm that these strategies deliver economically large and statistically significant excess returns over cap-weighted market benchmarks in nearly all regions and countries, over long periods of time. In this article, the authors show that inverting these portfolio-construction algorithms does not reverse the out-performance. Indeed, the upside-down strategies often outperform the originals. This paradoxical result is driven by the phenomenon that seemingly unrelated, non-value-based strategies and their inverted counterparts often have unintended and almost unavoidable value and small-cap tilts. Even Burt Malkiel’s legendary blindfolded monkey, throwing darts at the <i>Wall Street Journal’s</i> stock page, would produce a portfolio with a substantial value- and small-cap bias that would have historically outperformed the S&amp;P 500. The value and small-cap tilts stem from the fact that non-price-based weighting schemes sever the link between a company’s share price and its weight in the portfolio. Clearly, the inverted strategy of a non-price-weighted strategy is still a non-price-weighted strategy, would con-sequently have a value and small-cap tilt, and would there-fore have outperformed historically. <b>TOPICS:</b>Portfolio construction, passive strategies, equity portfolio management
Abstract 15537: Can Pulmonary Embolism Severity Index (PESI) Score Predict Readmission Rates in Patients With Pulmonary Embolism?
Authors: Reshma R Golamari, Shambo Guha Roy, Shengnan Zheng, Melissa Alvarez, Karthik Ramireddy, Christian Pedersen
Journal: Circulation (2019)

Introduction: The Pulmonary Embolism Severity Index (PESI) score is widely used as a prognostic assessment tool for mortality in patients with pulmonary embolism (PE). This raises the question if t...
Airway Epithelial Gene Expression Differs Across Urban Childhood Asthma Phenotypes
Authors: Matthew Altman, Edward Zoratti, Andrew Liu, Jacqueline Pongracic, Jessica Gereige, Robert Wood, Gurjit Khurana Hershey, Carolyn Kercsmar, Rebecca Gruchalla, Meyer Kattan, Stephen Teach, Alyssa Ylescupidez, Steve Sigelman, Peter Gergen, Alkis Togias, Cynthia Visness, Scott Presnell, James Gern, William Busse, Dan Jackson
Journal: Journal of Allergy and Clinical Immunology (2021)
“3G” Trial: An RNA Editing Signature to Guide Gastric Cancer Chemotherapy
Authors: Omer An, Yangyang Song, Xinyu Ke, Jimmy Bok-Yan So, Raghav Sundar, Henry Yang, Sun Young Rha, Ming Hui Lee, Su Ting Tay, Xuewen Ong, Angie Lay Keng Tan, Matthew Chau Hsien Ng, Erwin Tantoso, Leilei Chen, Patrick Tan, Wei Peng Yong
Journal: Cancer Research (2021)

Abstract Gastric cancer cases are often diagnosed at an advanced stage with poor prognosis. Platinum-based chemotherapy has been internationally accepted as first-line therapy for inoperable or metastatic gastric cancer. To achieve greater benefits, selection of patients eligible for this treatment is critical. Although gene expression profiling has been widely used as a genomic classifier to identify molecular subtypes of gastric cancer and to stratify patients for different chemotherapy regimens, its prediction accuracy can be improved. Adenosine-to-inosine (A-to-I) RNA editing has emerged as a new player contributing to gastric cancer development and progression, offering potential clinical utility for diagnosis and treatment. Using a systematic computational approach followed by both in vitro validations and in silico validations in The Cancer Genome Atlas (TCGA), we conducted a transcriptome-wide RNA editing analysis of a cohort of 104 patients with advanced gastric cancer and identified an RNA editing (GCRE) signature to guide gastric cancer chemotherapy. RNA editing events stood as a prognostic and predictive biomarker in advanced gastric cancer. A GCRE score based on the GCRE signature consisted of 50 editing sites associated with 29 genes, predicting response to chemotherapy with a high accuracy (84%). Of note, patients demonstrating higher editing levels of this panel of sites presented a better overall response. Consistently, gastric cancer cell lines with higher editing levels showed higher chemosensitivity. Applying the GCRE score on TCGA dataset confirmed that responders had significantly higher levels of editing in advanced gastric cancer. Overall, this newly defined GCRE signature reliably stratifies patients with advanced gastric cancer and predicts response from chemotherapy. Significance: This study describes a novel A-to-I RNA editing signature as a prognostic and predictive biomarker in advanced gastric cancer, providing a new tool to improve patient stratification and response to therapy.