tbuckley/cabot-search huggingface dataset:
A new year, but familiar challenges from COVID-19 in the USA
Authors: Talha Khan Burki
Journal: The Lancet Respiratory Medicine (2021)

On Jan 2, 2021, the USA registered 297 491 new cases of COVID-19. Three days earlier, the country saw 3750 deaths from the disease. Both figures represented record highs, though with cases trending upwards, and the effect of the holiday season yet to be fully quantified, further spikes are expected. "The pandemic is at its worst moment in the USA", said Ashish Jha, dean of Brown University School of Public Health (Providence, RI, USA). "We are unlikely to see any improvement at least until the end of January, and even then it is going to take a while before the virus is brought under control."
Evaluation of Etanercept for Treatment of Reactive Infectious Mucocutaneous Eruption
Authors: Melanie M. Miller, Sonia Kamath, Meagan Hughes, Nicole Harter, Minnelly Luu
Journal: JAMA Dermatology (2021)

This cohort study evaluates the association of etanercept treatment with outcomes of reactive infectious mucocutaneous eruption in hospitalized children and adolescents.
Breast tumor-on-chip models: From disease modeling to personalized drug screening
Authors: Bano Subia, Ujjwal Ranjan Dahiya, Sarita Mishra, Jessica Ayache, Guilhem Velve Casquillas, David Caballero, Rui L. Reis, Subhas C. Kundu
Journal: Journal of Controlled Release (2021)

Breast cancer is one of the leading causes of mortality worldwide being the most common cancer among women. Despite the significant progress obtained during the past years in the understanding of breast cancer pathophysiology, women continue to die from it. Novel tools and technologies are needed to develop better diagnostic and therapeutic approaches, and to better understand the molecular and cellular players involved in the progression of this disease. Typical methods employed by the pharmaceutical industry and laboratories to investigate breast cancer etiology and evaluate the efficiency of new therapeutic compounds are still based on traditional tissue culture flasks and animal models, which have certain limitations. Recently, tumor-on-chip technology emerged as a new generation of in vitro disease model to investigate the physiopathology of tumors and predict the efficiency of drugs in a native-like microenvironment. These microfluidic systems reproduce the functional units and composition of human organs and tissues, and importantly, the rheological properties of the native scenario, enabling precise control over fluid flow or local gradients. Herein, we review the most recent works related to breast tumor-on-chip for disease modeling and drug screening applications. Finally, we critically discuss the future applications of this emerging technology in breast cancer therapeutics and drug development.
Effect of Simulated Obstructive Apnea on Thoracic Fluid Volume and Airway Narrowing in Asthma
Authors: Xiaoshu Cao, T. Douglas Bradley, Swati A. Bhatawadekar, Shumit Saha, Susan M. Tarlo, Matthew B. Stanbrook, Mark D. Inman, Khadija Rana, Ronald J. Dandurand, Azadeh Yadollahi
Journal: American Journal of Respiratory and Critical Care Medicine (2021)
QcrB in <i>Mycobacterium tuberculosis</i>: The new drug target of antitubercular agents
Authors: Aparna Bahuguna, Srishti Rawat, Diwan S. Rawat
Journal: Medicinal Research Reviews (2021)

Abstract Drug‐resistance in mycobacterial infections is a major global health problem that leads to high mortality and socioeconomic pressure in developing countries around the world. From finding new targets to discovering novel chemical scaffolds, there is an urgent need for the development of better approaches for the cure of tuberculosis. Recently, energy metabolism in mycobacteria, particularly the oxidative phosphorylation pathway of cellular respiration, has emerged as a novel target pathway in drug discovery. New classes of antibacterials which target oxidative phosphorylation pathway either by interacting with a protein or any step in the pathway of oxidative phosphorylation can combat dormant mycobacterial infections leading to shortening of tuberculosis chemotherapy. Adenosine triphosphate synthase is one such recently discovered target of the newly approved antitubercular drug bedaquiline. Cytochrome bcc is another new target of the antitubercular drug candidate Q203, currently in phase II clinical trial. Research suggests that b subunit of cytochrome bcc , QcrB, is the target of Q203. The review article describes the structure, function, and importance of targeting QcrB throwing light on all chemical classes of QcrB inhibitors discovered to date. An understanding of the structure and function of validated targets and their inhibitors would enable the development of new chemical entities.
Healthy ageing for a healthy planet: do sustainable solutions exist?
Authors: Angelique Mavrodaris, Calum Mattocks, Carol E Brayne
Journal: The Lancet Healthy Longevity (2021)

In terms of both scale and impact, population ageing has far-reaching implications for our planet, not least as a major driver of population growth and consequent ever-increasing human demands on natural resources and ecosystems. Worldwide in 2018, for the first time in history, people aged 65 years and older outnumbered children younger than 5 years,1 with two-thirds of the world's older population now living in low-income and middle-income countries. Increases in life expectancy and subsequent population growth will fundamentally affect sustainable development efforts to eradicate poverty, achieve food security, ensure sustainable water supplies, build inclusive and resilient communities, and ensure sustainable consumption.
MO01.29 Randomized, Open-Label Study of Bintrafusp Alfa vs. Pembrolizumab as First-Line (1L) Treatment in Patients with PD-L1–Expressing Advanced Non-Small Cell Lung Cancer (NSCLC)
Authors: M.-J. Ahn, F. Barlesi, E. Felip, E. Garon, C.M. Martin, E. Vokes, A. Koenig, I. Dussault, L.S. Ojalvo, L. Paz-Ares
Journal: Journal of Thoracic Oncology (2021)
Toward a Framework for Assessing Privacy Risks in Multi-Omic Research and Databases
Authors: Charles Dupras, Eline M. Bunnik
Journal: The American Journal of Bioethics (2021)

While the accumulation and increased circulation of genomic data have captured much attention over the past decade, privacy risks raised by the diversification and integration of omics have been largely overlooked. In this paper, we propose the outline of a framework for assessing privacy risks in multi-omic research and databases. Following a comparison of privacy risks associated with genomic and epigenomic data, we dissect ten privacy risk-impacting omic data properties that affect either the risk of re-identification of research participants, or the sensitivity of the information potentially conveyed by biological data. We then propose a three-step approach for the assessment of privacy risks in the multi-omic era. Thus, we lay grounds for a data property-based, 'pan-omic' approach that moves away from genetic exceptionalism. We conclude by inviting our peers to refine these theoretical foundations, put them to the test in their respective fields, and translate our approach into practical guidance.
Tetracyclines improve experimental lymphatic filariasis pathology by disrupting interleukin-4 receptor–mediated lymphangiogenesis
Authors: Julio Furlong-Silva, Stephen D. Cross, Amy E. Marriott, Nicolas Pionnier, John Archer, Andrew Steven, Stefan Schulte Merker, Matthias Mack, Young-Kwon Hong, Mark J. Taylor, Joseph D. Turner
Journal: Journal of Clinical Investigation (2021)

Lymphatic filariasis is the major global cause of nonhereditary lymphedema. We demonstrate that the filarial nematode Brugia malayi induced lymphatic remodeling and impaired lymphatic drainage following parasitism of limb lymphatics in a mouse model. Lymphatic insufficiency was associated with elevated circulating lymphangiogenic mediators, including vascular endothelial growth factor C. Lymphatic insufficiency was dependent on type 2 adaptive immunity, the interleukin-4 receptor, and recruitment of C-C chemokine receptor-2-positive monocytes and alternatively activated macrophages with a prolymphangiogenic phenotype. Oral treatments with second-generation tetracyclines improved lymphatic function, while other classes of antibiotic had no significant effect. Second-generation tetracyclines directly targeted lymphatic endothelial cell proliferation and modified type 2 prolymphangiogenic macrophage development. Doxycycline treatment impeded monocyte recruitment, inhibited polarization of alternatively activated macrophages, and suppressed T cell adaptive immune responses following infection. Our results determine a mechanism of action for the antimorbidity effects of doxycycline in filariasis and support clinical evaluation of second-generation tetracyclines as affordable, safe therapeutics for lymphedemas of chronic inflammatory origin.
Exploration of Individual and System-Level Well-being Initiatives at an Academic Surgical Residency Program
Authors: Carter C. Lebares, Anya L. Greenberg, Nancy L. Ascher, Kevin L. Delucchi, Linda M. Reilly, Marieke van der Schaaf, Fredrik Baathe, Patricia O’Sullivan, Karin Isaksson Rø
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Physician well-being is a critical component of sustainable health care. There are few data on the effects of multilevel well-being programs nor a clear understanding of where and how to target resources. <h3>Objective</h3> To inform the design of future well-being interventions by exploring individual and workplace factors associated with surgical trainees' well-being, differences by gender identity, and end-user perceptions of these initiatives. <h3>Design, Setting, and Participants</h3> This mixed-methods study among surgical trainees within a single US academic surgical department included a questionnaire in January 2019 (98 participants, including general surgery residents and clinical fellows) and a focus group (9 participants, all clinical residents who recently completed their third postgraduate year [PGY 3]) in July 2019. Participants self-reported gender (man, woman, nonbinary). <h3>Exposures</h3> Individual and organizational-level initiatives, including mindfulness-based affective regulation training (via Enhanced Stress Resilience Training), advanced scheduling of time off, wellness half-days, and the creation of a resident-driven well-being committee. <h3>Main Outcomes and Measures</h3> Well-being was explored using validated measures of psychosocial risk (emotional exhaustion, depersonalization, perceived stress, depressive symptoms, alcohol use, languishing, anxiety, high psychological demand) and resilience (mindfulness, social support, flourishing) factors. End-user perceptions were assessed through open-ended responses and a formal focus group. <h3>Results</h3> Of 98 participants surveyed, 64 responded (response rate, 65%), of whom 35 (55%) were women. Women vs men trainees were significantly more likely to report high depersonalization (odds ratio [OR], 5.50; 95% CI, 1.38-21.85) and less likely to report high mindfulness tendencies (OR, 0.17; 95% CI, 0.05-0.53). Open-ended responses highlighted time and priorities as the greatest barriers to using well-being resources. Focus group findings reflected Job Demand–Resource theory tenets, revealing the value of individual-level interventions to provide coping skills, the benefit of advance scheduling of time off for maintaining personal support resources, the importance of work quality rather than quantity, and the demoralizing effect of inefficient or nonresponsive systems. <h3>Conclusions and Relevance</h3> In this study, surgical trainees indicated that multilevel well-being programs would benefit them, but tailoring these initiatives to individual needs and specific workplace elements is critical to maximizing intervention effects.
Injury prevention knowledge, beliefs and strategies in elite female footballers at the FIFA Women’s World Cup France 2019
Authors: Celeste Geertsema, Liesel Geertsema, Abdulaziz Farooq, Joar Harøy, Chelsea Oester, Alexis Weber, Roald Bahr
Journal: British Journal of Sports Medicine (2021)

Objectives This study assessed knowledge, beliefs and practices of elite female footballers regarding injury prevention. Methods A survey was sent to players participating in the FIFA Women’s World Cup France 2019. Questions covered three injury prevention domains: (1) knowledge; (2) attitudes and beliefs; (3) prevention practices in domestic clubs. Additionally, ACL injury history was assessed. Results Out of 552 players, 196 women responded (35.5%). More than 80% of these considered injury risk to be moderate or high. Players listed knee, ankle, thigh, head and groin as the most important injuries in women’s football. The most important risk factors identified were low muscle strength, followed by poor pitch quality, playing on artificial turf, too much training, reduced recovery and hard tackles. In these elite players, 15% did not have any permanent medical staff in their domestic clubs, yet more than 75% had received injury prevention advice and more than 80% performed injury prevention exercises in their clubs. Players identified the two most important implementation barriers as player motivation and coach attitude. Two-thirds of players used the FIFA 11+ programme in their clubs. Conclusions This diverse group of elite players demonstrated good knowledge of risk level and injury types in women’s football. Of the risk factors emphasised by players, there was only one intrinsic risk factor (strength), but several factors out of their control (pitch quality and type, training volume and hard tackles). Still players had positive attitudes and beliefs regarding injury prevention exercises and indicated a high level of implementation, despite a lack of medical support.
Reforming medical education: student experience during the covid-19 pandemic
Journal: BMJ (2021)

Dornan and colleagues suggest the importance of experience over competence and the risks that can arise if this is forgotten.1 This year, thousands of final year medical students graduated early to act as interim foundation year 1 doctors, and students in other years had their studies disrupted by covid-19.2 This has affected their experience and in turn their transition from medical school to clinical practice …
Robot-assisted Radical Cystectomy Versus Open Radical Cystectomy in Bladder Cancer Patients: A Multicentre Comparative Effectiveness Study
Authors: Carl J. Wijburg, Charlotte T.J. Michels, Gerjon Hannink, Janneke P.C. Grutters, Maroeska M. Rovers, J. Alfred Witjes, Carl J. Wijburg, J. Alfred Witjes, Ilze E.W. van Onna, Evert J. Barten, Evert L. Koldewijn, Joost L. Boormans, Bart P. Wijsman, Ronald I. Nooter, Peter J. Zwaan, Ed te Slaa, Saskia van der Meer, Sjoerd O. Klaver, Laurent M.C.L. Fossion, Siebe D. Bos, Harm H.E.van Melick, Anna M. Leliveld, Richard P. Meijer, André N. Vis, Gerard J. Molijn, Chris L. Berendsen, Jorg R. Oddens
Journal: European Urology (2021)
Plasma-activated interfaces for biomedical engineering
Authors: Pei Liu, Guomin Wang, Qingdong Ruan, Kaiwei Tang, Paul K. Chu
Journal: Bioactive Materials (2021)

As an important phenomenon to monitor disease development, cell signaling usually takes place at the interface between organisms/cells or between organisms/cells and abiotic materials. Therefore, finding a strategy to build the specific biomedical interfaces will help regulate information transmission and produce better therapeutic results to benefit patients. In the past decades, plasmas containing energetic and active species have been employed to construct various interfaces to meet biomedical demands such as bacteria inactivation, tissue regeneration, cancer therapy, and so on. Based on the potent functions of plasma modified surfaces, this mini-review is aimed to summarize the state-of-art plasma-activated interfaces and provide guidance to researchers to select the proper plasma and processing conditions to design and prepare interfaces with the optimal biological and related functions. After a brief introduction, plasma-activated interfaces are described and categorized according to different criteria including direct plasma-cells interfaces and indirect plasma-material-cells interfaces and recent research activities on the application of plasma-activated interfaces are described. The authors hope that this mini-review will spur interdisciplinary research efforts in this important area and expedite associated clinical applications.
Predicted Heart Age Among Cancer Survivors — United States, 2013–2017
Authors: Lia C. Scott, Quanhe Yang, Nicole F. Dowling, Lisa C. Richardson
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Abbreviation: HS = high school.* Difference was calculated as excess heart age among noncancer participants subtracted from excess heart age among cancer survivors.† Adjusted for age, education, and annual household income.§ Adjusted for age, education, and annual household income, with an interaction term of age-by-cancer status to estimate cancer status difference in excess heart age by age group.¶ P-value based on t-tests across the age group.** Adjusted for age, education, and annual household income, with an interaction term of education-by-cancer status to estimate cancer status difference in excess heart age by education group.† † Based on pairwise t-tests, the following comparisons were significantly different: less than high school versus high school (p = 0.25 for men; p = 0.04 for women); less than high school versus more than high school (p = 0.07 for men; p = 0.06 for women).§ § Adjusted for age, education, and annual household income, with an interaction term of annual household income-by-cancer status to estimate cancer status difference in excess heart age by household income level.¶ ¶ P-value based on pairwise t-tests.*** Adjusted for age, education, and annual household income, with an interaction term of race/ethnicity-by-cancer status to estimate cancer status difference in excess heart age by race/ethnicity.† † † Based on pairwise t-tests, statistical significance was established as p<0.05.The p-values for each comparison were as follows: White, non-Hispanic versus Black, non-Hispanic (p = 0 for men; p = <0.001for women); White, non-Hispanic versus Hispanic (p = 0.53 for men; p = 0.08 for women); White, non-Hispanic versus other (p = 0.03 for men and p = 0.02 for women); Black, non-Hispanic versus Hispanic: (p = 0.24 for men; p = 0.14 for women); Black, non-Hispanic versus other (p = 0.76 for men; p = 0.70 for women); Hispanic versus other: (p = 0.23 for men; p = 0.43 for women).
Effects of Dietary and Exercise Intervention on Progression of Carotid Intima-Media Thickness
Authors: Kim Sutton-Tyrrell, Anne B. Newman, Richard Holubkov, Laura Liebenauer, Laurey Simkin-Silverman, Lewis H Kuller
Journal: Circulation (2001)

P96 The Women’s Healthy Lifestyle clinical trial has reported that a dietary and exercise intervention results in the prevention of weight gain and LDL cholesterol rise over a 54 month follow-up in pre-menopausal women approaching menopause (average age 47 at baseline and 52 at final follow-up). During this trial, serial carotid ultrasound was performed in 234 women with an average of 3.5 years between scans. Intima-Media Thickness (IMT) was the mean of measures taken in the right and left common, bulb and internal carotid arteries. The average change in carotid IMT over time was +0.033 mm. Change in IMT was higher among the control than the intervention group (.039 mm vs. .027 mm, p = .172). Among 109 women who had reached menopause by the end of the study, average IMT progression was .058 mm among controls vs. .017 mm among the intervention group (p=.003, a difference of .041 mm). Among HRT users, IMT progression was .037 mm greater among control vs intervention women (N= 60, p = .040) and this difference was .047 mm among HRT non-users (N= 46, p=.035). Linear regression was used to determine whether the treatment effect was independent of minor differences between treatment groups at baseline and changes in vessel diameter over follow-up. After controlling for age, baseline IMT, baseline adventitial diameter, change in adventitial diameter, hysterectomy status, smoking, baseline waist girth and baseline energy expenditure, the treatment effect remained significant (p=.005). Among these postmenopausal women, the control group had greater increases in weight, waist circumference and LDL, and a lower increase in Kilocalories of energy expenditure over follow-up in comparison to the intervention group (p &lt; .01 for all but LDL). When change in each risk factor was tested in the model above, only change in waist girth modified the treatment effect. Increase in waist girth was positively associated with IMT progression (p=.04) and the p-value associated with the treatment effect was reduced from .005 to .04. We conclude that among women entering menopause, a successful dietary and exercise intervention was associated with measurable slowing of atherosclerosis progression.
Identification of epigenome-wide DNA methylation differences between carriers of APOE ε4 and APOE ε2 alleles
Authors: Rosie M. Walker, Kadi Vaher, Mairead L. Bermingham, Stewart W. Morris, Andrew D. Bretherick, Yanni Zeng, Konrad Rawlik, Carmen Amador, Archie Campbell, Chris S. Haley, Caroline Hayward, David J. Porteous, Andrew M. McIntosh, Riccardo E. Marioni, Kathryn L. Evans
Journal: Genome Medicine (2021)

The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late onset Alzheimer's disease, whilst the ε2 allele confers protection. Previous studies report differential DNA methylation of APOE between ε4 and ε2 carriers, but associations with epigenome-wide methylation have not previously been characterised.Using the EPIC array, we investigated epigenome-wide differences in whole blood DNA methylation patterns between Alzheimer's disease-free APOE ε4 (n = 2469) and ε2 (n = 1118) carriers from the two largest single-cohort DNA methylation samples profiled to date. Using a discovery, replication and meta-analysis study design, methylation differences were identified using epigenome-wide association analysis and differentially methylated region (DMR) approaches. Results were explored using pathway and methylation quantitative trait loci (meQTL) analyses.We obtained replicated evidence for DNA methylation differences in a ~ 169 kb region, which encompasses part of APOE and several upstream genes. Meta-analytic approaches identified DNA methylation differences outside of APOE: differentially methylated positions were identified in DHCR24, LDLR and ABCG1 (2.59 × 10-100 ≤ P ≤ 2.44 × 10-8) and DMRs were identified in SREBF2 and LDLR (1.63 × 10-4 ≤ P ≤ 3.01 × 10-2). Pathway and meQTL analyses implicated lipid-related processes and high-density lipoprotein cholesterol was identified as a partial mediator of the methylation differences in ABCG1 and DHCR24.APOE ε4 vs. ε2 carrier status is associated with epigenome-wide methylation differences in the blood. The loci identified are located in trans as well as cis to APOE and implicate genes involved in lipid homeostasis.