tbuckley/cabot-search huggingface dataset:
Extracellular vesicle activities regulating macrophage- and tissue-mediated injury and repair responses
Authors: Qian Hu, Christopher J. Lyon, Jesse K. Fletcher, Wenfu Tang, Meihua Wan, Tony Y. Hu
Journal: Acta Pharmaceutica Sinica B (2020)

Macrophages are typically identified as classically activated (M1) macrophages and alternatively activated (M2) macrophages, which respectively exhibit pro- and anti-inflammatory phenotypes, and the balance between these two subtypes plays a critical role in the regulation of tissue inflammation, injury, and repair processes. Recent studies indicate that tissue cells and macrophages interact via the release of small extracellular vesicles (EVs) in processes where EVs released by stressed tissue cells can promote the activation and polarization of adjacent macrophages which can in turn release EVs and factors that can promote cell stress and tissue inflammation and injury, and vice versa. This review discusses the roles of such EVs in regulating such interactions to influence tissue inflammation and injury in a number of acute and chronic inflammatory disease conditions, and the potential applications, advantage and concerns for using EV-based therapeutic approaches to treat such conditions, including their potential role of drug carriers for the treatment of infectious diseases.
Aortic Stenosis: It Is a Hot Topic: The Link to Coronary Artery Disease⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Blase A. Carabello
Journal: Journal of the American College of Cardiology (2008)
Modulating the quantity of HIV Env-specific CD4 T cell help promotes rare B cell responses in germinal centers
Authors: Jeong Hyun Lee, Joyce K. Hu, Erik Georgeson, Catherine Nakao, Bettina Groschel, Thamotharampillai Dileepan, Marc K. Jenkins, Gregory Seumois, Pandurangan Vijayanand, William R. Schief, Shane Crotty
Journal: The Journal of Experimental Medicine (2020)

Immunodominance to nonneutralizing epitopes is a roadblock in designing vaccines against several diseases of high interest. One hypothetical possibility is that limited CD4 T cell help to B cells in a normal germinal center (GC) response results in selective recruitment of abundant, immunodominant B cells. This is a central issue in HIV envelope glycoprotein (Env) vaccine designs, because precursors to broadly neutralizing epitopes are rare. Here, we sought to elucidate whether modulating the quantity of T cell help can influence recruitment and competition of broadly neutralizing antibody precursor B cells at a physiological precursor frequency in response to Env trimer immunization. To do so, two new Env-specific CD4 transgenic (Tg) T cell receptor (TCR) mouse lines were generated, carrying TCR pairs derived from Env-protein immunization. Our results suggest that CD4 T cell help quantitatively regulates early recruitment of rare B cells to GCs.
Abstract P266: Prevalence and Risk Factors of Thyroid Dysfunction in Older Adults in the Community
Authors: Nermin Diab, Natalie Daya, Stephen P Juraschek, Seth Martin, John W McEvoy, Ulla T Schultheiß, Anna Köttgen, Elizabeth Selvin
Journal: Circulation (2018)

Context: Prevalence estimates and evidence informing treatment targets for thyroid dysfunction largely come from studies of middle-aged adults. There are limited data on the prevalence of thyroid dysfunction in older populations. Objective: To determine the prevalence of thyroid dysfunction and risk factors for abnormal thyroid tests in older adults. Methods: We conducted a cross-sectional analysis of data from participants aged 65 or older in the Atherosclerosis Risk in Communities (ARIC) study who attended visit 5 in 2011-2013. We measured serum concentrations of triiodothyronine (T3), free thyroxine (FT4), thyroid peroxidase antibody (Anti-TPO), and thyroid stimulating hormone (TSH) in 5,392 participants. We used multivariable linear and logistic regression to assess associations of demographic and clinical risk factors with thyroid hormone levels. Results: In this population of older adults (mean age 76; 56% women and 22% black), the prevalence of thyroid dysfunction was up to 25% when accounting for treated and untreated thyroid dysfunction categories. 15.6% reported use of medication for thyroid dysfunction. Among those not being treated, the prevalence of overt chemical hypothyroidism was 6.0% and subclinical hypothyroidism was 0.82%. Overt chemical hyperthyroidism and subclinical hyperthyroidism affected 0.26% and 0.78% of the population, respectively. Multivariable adjusted cardiovascular risk factor associations for TSH, FT4 and T3 levels are presented in Table . Men were less likely to be anti-TPO positive compared to women (OR=0.59, CI: 0.47,0.75, P&lt;0.001). Conclusions: There is a high prevalence of thyroid dysfunction in this older, community-based population. Prevalence of thyroid dysfunction and thyroid hormone levels vary with sex, race, age group and multiple cardiovascular risk factors. Accounting for these associations in the clinical setting might prove useful in improving thyroid function assessment in this age group.
Association of Burnout With Depression and Anxiety in Critical Care Clinicians in Brazil
Authors: Ronald Fischer, Paulo Mattos, Cassiano Teixeira, Daniel S. Ganzerla, Regis Goulart Rosa, Fernando A. Bozza
Journal: JAMA Network Open (2020)

<h3>Importance</h3> It is unclear whether burnout, anxiety, and depression constitute the same or different constructs. Better understanding of these constructs is important for diagnosis and treatment for intensive care unit (ICU) clinicians. <h3>Objective</h3> To determine the associations and distinctiveness of burnout, depression, and anxiety in a sample of ICU clinicians. <h3>Design, Setting, and Participants</h3> This cross-sectional study used baseline data from the ICU Visits Study, a cluster-randomized crossover clinical trial conducted from April 2017 to July 2018 in 36 mixed public and private nonprofit ICUs in Brazil. ICU clinicians, including day-shift physicians, nurses, nurse technicians, and physiotherapists working in an ICU at least 20 hours per week, were enrolled. Data were analyzed from December 27, 2019, to October 10, 2020. <h3>Main Outcomes and Measures</h3> The main outcome measures were burnout, depression, and anxiety measured with the Maslach Burnout Inventory (MBI; range, 0-6, with high scores indicating more burnout) and the Hospital Depression and Anxiety Scale (HADS; range, 0-3, with higher scores indicating more depression or anxiety). Internal consistencies were satisfactory. <h3>Results</h3> The total sample included 715 ICU clinicians (median [interquartile range] age, 34.8 [30.2-39.3] years; 520 [72.7%] women), including 96 physicians (13.4%), 159 nurses (22.2%), 358 nurse technicians (50.1%), and 102 physiotherapists (14.3%). Clinicians reported low levels of emotional exhaustion (mean [SD] score, 1.84 [1.18]), depersonalization (mean [SD] score, 0.98 [1.03]), and personal accomplishment (mean [SD] score, 5.05 [0.87]) on the MBI, and similarly low levels of depression (mean [SD] score, 0.54 [0.40]) and anxiety (mean [SD] score, 0.70 [0.45]) on the HADS. Confirmatory factor analyses consistently showed improved fit separating latent burnout dimensions from depression and anxiety. An exploratory graph analysis combining gaussian graphical model with clustering algorithms for weighted networks suggested 3 clusters, with distinct burnout, anxiety, and depression clusters. This structure was confirmed using a bootstrap with 1000 random samples, in which the 3-cluster solution emerged in 625 samples (62.5%). Both latent variable loadings and network statistics suggested 3 key indicators (ie, feeling burned out from work, worrying thoughts, and reverse-scored reporting feeling cheerful) that can be used for short screening instruments. <h3>Conclusions and Relevance</h3> These findings suggest that burnout and clinical symptoms of depression and anxiety were empirically distinct in a large sample of ICU clinicians, highlighting the importance of screening for burnout and clinical symptoms to allow fast access to adequate support and treatment in health professionals at high risk of burnout.
An integrated multiomic and quantitative label-free microscopy-based approach to study pro-fibrotic signalling in<i>ex vivo</i>human precision-cut lung slices
Authors: Muzamil Majid Khan, Daniel Poeckel, Aliaksandr Halavatyi, Joanna Zukowska-Kasprzyk, Frank Stein, Johanna Vappiani, Daniel C. Sevin, Christian Tischer, Nico Zinn, Jessica D. Eley, Natasja Stæhr Gudmann, Thomas Muley, Hauke Winter, Andrew J. Fisher, Carmel B. Nanthakumar, Giovanna Bergamini, Rainer Pepperkok
Journal: European Respiratory Journal (2020)

Fibrosis can affect any organ, resulting in the loss of tissue architecture and function with often life-threatening consequences. Pathologically, fibrosis is characterised by the expansion of connective tissue due to excessive deposition of extracellular matrix (ECM) proteins, including the fibrillar forms of collagen. A significant limitation for discovering cures for fibrosis is the availability of suitable human models and techniques to quantify mature fibrillar collagen deposition as close as possible to human physiological conditions.Here we have extensively characterised an
Might changes in diagnostic practice explain increasing incidence of brain and central nervous system tumors? A population-based study in Wales (United Kingdom) and the United States
Authors: Michael Tin Chung Poon, Paul M Brennan, Kai Jin, Cathie L M Sudlow, Jonine D Figueroa
Journal: Neuro-Oncology (2020)

Increasing incidence of central nervous system (CNS) tumors has been noted in some populations. However, the influence of changing surgical and imaging practices has not been consistently accounted for.
Clinical and Psychosocial Impact in Mexican Hemodiafiltration Population During the COVID-19 Pandemic, Twice Weekly Sessions: Is This Safe?
Authors: Jose S. Lopez Gil, Hector Alejandro P. Garza, Magdalena Madero, Daniela Xavier
Journal: Journal of the American Society of Nephrology (2020)

Lopez Gil, Jose S.; Garza, Hector Alejandro P.; Madero, Magdalena; Xavier, Daniela; Division of Nephrology Author Information
Effects of interleukin-3 and interleukin-4 on the development of "connective tissue-type" mast cells: interleukin-3 supports their survival and interleukin-4 triggers and supports their proliferation synergistically with interleukin-3
Authors: K Tsuji, T Nakahata, M Takagi, T Kobayashi, A Ishiguro, T Kikuchi, K Naganuma, K Koike, A Miyajima, K Arai
Journal: Blood (1990)
Argentina legalises abortion in historic vote
Authors: Owen Dyer
Journal: BMJ (2020)

Argentina’s senate has voted to legalise abortion, becoming the third and by far the most populous country to do so in South America, which has some of the world’s most restrictive abortion laws.

Pro-choice campaigners outside the congressional palace erupted in cheers at 4 am on 30 December as the law to legalise terminations at up to 14 weeks’ gestation passed by 38 votes to 29, with one abstention, after an all night debate. Many in the crowd wore green face masks, instead of the green scarves that have become a trademark of the women’s movement throughout South America in recent years.

Opponents of the new law, who gathered around a giant model fetus, dispersed soon after …
Recommendations for determining the validity of consumer wearable and smartphone step count: expert statement and checklist of the INTERLIVE network
Authors: William Johnston, Pedro B Judice, Pablo Molina García, Jan M Mühlen, Esben Lykke Skovgaard, Julie Stang, Moritz Schumann, Shulin Cheng, Wilhelm Bloch, Jan Christian Brønd, Ulf Ekelund, Anders Grøntved, Brian Caulfield, Francisco B Ortega, Luis B Sardinha
Journal: British Journal of Sports Medicine (2020)

Consumer wearable and smartphone devices provide an accessible means to objectively measure physical activity (PA) through step counts. With the increasing proliferation of this technology, consumers, practitioners and researchers are interested in leveraging these devices as a means to track and facilitate PA behavioural change. However, while the acceptance of these devices is increasing, the validity of many consumer devices have not been rigorously and transparently evaluated. The Towards Intelligent Health and Well-Being Network of Physical Activity Assessment (INTERLIVE) is a joint European initiative of six universities and one industrial partner. The consortium was founded in 2019 and strives to develop best-practice recommendations for evaluating the validity of consumer wearables and smartphones. This expert statement presents a best-practice consumer wearable and smartphone step counter validation protocol. A two-step process was used to aggregate data and form a scientific foundation for the development of an optimal and feasible validation protocol: (1) a systematic literature review and (2) additional searches of the wider literature pertaining to factors that may introduce bias during the validation of these devices. The systematic literature review process identified 2897 potential articles, with 85 articles deemed eligible for the final dataset. From the synthesised data, we identified a set of six key domains to be considered during design and reporting of validation studies: target population, criterion measure, index measure, validation conditions, data processing and statistical analysis. Based on these six domains, a set of key variables of interest were identified and a ‘basic’ and ‘advanced’ multistage protocol for the validation of consumer wearable and smartphone step counters was developed. The INTERLIVE consortium recommends that the proposed protocol is used when considering the validation of any consumer wearable or smartphone step counter. Checklists have been provided to guide validation protocol development and reporting. The network also provide guidance for future research activities, highlighting the imminent need for the development of feasible alternative ‘gold-standard’ criterion measures for free-living validation. Adherence to these validation and reporting standards will help ensure methodological and reporting consistency, facilitating comparison between consumer devices. Ultimately, this will ensure that as these devices are integrated into standard medical care, consumers, practitioners, industry and researchers can use this technology safely and to its full potential.
Knowledge Organization Systems for Systematic Chemical Assessments
Authors: Paul Whaley, Stephen W. Edwards, Andrew Kraft, Kate Nyhan, Andrew Shapiro, Sean Watford, Steve Wattam, Taylor Wolffe, Michelle Angrish
Journal: Environmental Health Perspectives (2020)

Although the implementation of systematic review and evidence mapping methods stands to improve the transparency and accuracy of chemical assessments, they also accentuate the challenges that assessors face in ensuring they have located and included all the evidence that is relevant to evaluating the potential health effects an exposure might be causing. This challenge of information retrieval can be characterized in terms of "semantic" and "conceptual" factors that render chemical assessments vulnerable to the streetlight effect. This commentary presents how controlled vocabularies, thesauruses, and ontologies contribute to overcoming the streetlight effect in information retrieval, making up the key components of Knowledge Organization Systems (KOSs) that enable more systematic access to assessment-relevant information than is currently achievable. The concept of Adverse Outcome Pathways is used to illustrate what a general KOS for use in chemical assessment could look like. Ontologies are an underexploited element of effective knowledge organization in the environmental health sciences. Agreeing on and implementing ontologies in chemical assessment is a complex but tractable process with four fundamental steps. Successful implementation of ontologies would not only make currently fragmented information about health risks from chemical exposures vastly more accessible, it could ultimately enable computational methods for chemical assessment that can take advantage of the full richness of data described in natural language in primary studies. https://doi.org/10.1289/EHP6994.
Carotid Physiology and Neck Restraints in Law Enforcement
Authors: Jillian M. Berkman, Joseph A. Rosenthal, Altaf Saadi
Journal: JAMA Neurology (2020)

This Viewpoint reviews the potential neurologic sequelae of any restriction of blood flow or oxygen to the brain and calls for a radical examination on the safety or appropriateness of use of neck restraints by law enforcement.
Kidney Involvement and Outcome of COVID-19 Patients Admitted from a Federal Medical Facility
Authors: Yahya R. Ahmad, Matthew Shea, Mohamed M. Abdalbary, Elijah Kakani, Javier A. Neyra, Amr E. Mohamed
Journal: Journal of the American Society of Nephrology (2020)

Background: Correctional facilities face unique challenges with the COVID-19 pandemic  A COVID-19 outbreak was reported in the Federal Medical Center (FMC) in Lexington, Kentucky, a prison for inmates requiring medical and/or mental health care  We aimed to compare clinical characteristics and kidney related outcomes in inmates from this FMC to other COVID-19 hospitalized patients  Methods: A total of 86 COVID-19 patients were admitted to our hospital between March 1st and June 1st, 2020  Among those, 37 patients were from the same FMC  We examined demographics, clinical and laboratory characteristics, along with the outcomes of this cohort and compared it to other COVID-19 non-prisoners  AKI was determined by KDIGO criteria  Results: All inmates were men and their mean age was 59 8±10 6 years  The majority of them were white (60%) and required ICU admission (54%), while 39% of patients required mechanical ventilation  The prevalent comorbidities were hypertension (81%), obesity (62%), diabetes (41%) and coronary artery disease (CAD) (38%)  Stage 3 CKD was present in 22% of inmates  The mean eGFR was 68±26 ml/min/1 73m2 at time of admission  Significant hematuria and proteinuria were found in 17% and 25% of patients, respectively  Hypertension, heart failure, CAD, COPD, hepatitis C infection, and AKI were more prevalent in the FMC cohort (P= 0 030, 0 001, 0 024, 0 001, 0 017, and 0 011, respectively)  The difference in mortality rates was not statistically significant between groups (12% for inmates vs 17% for non-inmates, p=0 520)  Incident AKI was higher in inmates vs  non-inmates (68% vs  38%, p=0 006) and there was no difference in acute dialysis need (14% vs 12%, respectively)  The overall mortality rates were higher in patients that required dialysis (80% vs  6% for those who did not, p<0 001)  The need for acute dialysis was independently associated with mortality in multivariable models  Conclusions: Incidence of AKI was higher in hospitalized inmates with COVID-19 vs  non-inmates  The need for acute dialysis was strongly associated with mortality in overall COVID-19 hospitalized patients
Determination of fitness and therapeutic options in older patients with acute myeloid leukemia
Authors: Jorge E. Cortes, Priyanka Mehta
Journal: American Journal of Hematology (2020)

Treatment of older patients with AML remains challenging. Although age, performance status, and comorbidities are commonly employed to determine fitness for intensive treatment, several studies have demonstrated improved outcomes with treatment in older and classically unfit patients, highlighting the importance of other disease-related and patient-related factors that have prognostic value for treatment outcome in AML. However, consistent and objective assessments for fitness are lacking. Multi-parameter geriatric assessment tools offer more comprehensive evaluation, but are limited by the required resources and lack of standardization and consensus regarding prognostic value. These assessments are particularly important considering the emerging new AML therapies that represent a spectrum of intensities. Patients should therefore be evaluated holistically for fitness to receive a specific treatment, with the aim of providing individualized care, and such definitions of fitness should also consistently be applied to clinical trials. This review will examine evolving criteria for the determination of fitness among AML patients and discuss treatment options for older and/or unfit patients with AML.
Reducing the Global Burden of Myopia by Delaying the Onset of Myopia and Reducing Myopic Progression in Children
Authors: Bobeck S. Modjtahedi, Richard L. Abbott, Donald S. Fong, Flora Lum, Donald Tan, Marcus Ang, Susan Chiarito, Susan A. Cotter, Angela Maria Fernandez, Andrzej Grzybowski, Mingguang He, Deborah S. Jacobs, Jost B. Jonas, Alex Kemper, Katherine A. Lee, Andrea Delia Molinari, Ian Morgan, Kyoko Ohno-Matsui, Michael X. Repka, Sarwat Salim, Pei-Chang Wu, Ke Yao, Karla Zadnik
Journal: Ophthalmology (2020)
Investigator Use of Social Media for Recruitment of Patients for Cancer Clinical Trials
Authors: Mina S. Sedrak, Can-Lan Sun, Dawn L. Hershman, Joseph M. Unger, Jennifer Liu, William Dale, Don S. Dizon
Journal: JAMA Network Open (2020)

The use of social media has been explored as a potential strategy to improve enrollment in cancer clinical trials. However, significant barriers to implementation of this recruitment approach remain, including investigator reluctance to use social media for patient recruitment.1,2 We conducted a survey study to assess the prevalence of and attitudes toward the use of social media in clinical trial recruitment among cancer investigators.
ABC of heart failure: Non-drug management
Authors: G Jackson
Journal: BMJ (2000)

Effective counselling and education of patients, and of the relatives or carers, is important and may enhance long term adherence to management strategies. Simple explanations about the symptoms and signs of heart failure, including details on drug and other treatment strategies, are valuable. Emphasis should be placed on self help strategies for each patient; these should include information on the need to adhere to drug treatment. Some patients can be instructed how to monitor their weight at home on a daily basis and how to adjust the dose of diuretics as advised; sudden weight increases ( > 2 kg in 1-3 days), for example, should alert a patient to alter his or her treatment or seek advice.
Genetic variation in the Middle East—an opportunity to advance the human genetics field
Authors: Ahmad N. Abou Tayoun, Heidi L. Rehm
Journal: Genome Medicine (2020)

We highlight the current lack of representation of the Middle East from large genomic studies and emphasize the expected high impact of cataloging its variation. We discuss the limiting factors and possible solutions to generating and accessing research and clinical sequencing data from this part of the world.