tbuckley/cabot-search huggingface dataset:
The effect of population mobility on COVID-19 incidence in 314 Latin American cities: a longitudinal ecological study with mobile phone location data
Authors: Josiah L Kephart, Xavier Delclòs-Alió, Daniel A Rodríguez, Olga L Sarmiento, Tonatiuh Barrientos-Gutiérrez, Manuel Ramirez-Zea, D Alex Quistberg, Usama Bilal, Ana V Diez Roux
Journal: The Lancet Digital Health (2021)

Little is known about the effect of changes in mobility at the subcity level on subsequent COVID-19 incidence, which is particularly relevant in Latin America, where substantial barriers prevent COVID-19 vaccine access and non-pharmaceutical interventions are essential to mitigation efforts. We aimed to examine the longitudinal associations between population mobility and COVID-19 incidence at the subcity level across a large number of Latin American cities.In this longitudinal ecological study, we compiled aggregated mobile phone location data, daily confirmed COVID-19 cases, and features of urban and social environments to analyse population mobility and COVID-19 incidence at the subcity level among cities with more than 100 000 inhabitants in Argentina, Brazil, Colombia, Guatemala, and Mexico, from March 2 to Aug 29, 2020. Spatially aggregated mobile phone data were provided by the UN Development Programme in Latin America and the Caribbean and Grandata; confirmed COVID-19 cases were from national government reports and population and socioeconomic factors were from the latest national census in each country. We used mixed-effects negative binomial regression for a time-series analysis, to examine longitudinal associations between weekly mobility changes from baseline (prepandemic week of March 2-9, 2020) and subsequent COVID-19 incidence (lagged by 1-6 weeks) at the subcity level, adjusting for urban environmental and socioeconomic factors (time-invariant educational attainment, residential overcrowding, population density [all at the subcity level], and country).We included 1031 subcity areas, representing 314 Latin American cities, in Argentina (107 subcity areas), Brazil (416), Colombia (82), Guatemala (20), and Mexico (406). In the main adjusted model, we observed an incidence rate ratio (IRR) of 2·35 (95% CI 2·12-2·60) for COVID-19 incidence per log unit increase in the mobility ratio (vs baseline) during the previous week. Thus, 10% lower weekly mobility was associated with 8·6% (95% CI 7·6-9·6) lower incidence of COVID-19 in the following week. This association gradually weakened as the lag between mobility and COVID-19 incidence increased and was not different from null at a 6-week lag.Reduced population movement within a subcity area is associated with a subsequent decrease in COVID-19 incidence among residents of that subcity area. Policies that reduce population mobility at the subcity level might be an effective COVID-19 mitigation strategy, although they should be combined with strategies that mitigate any adverse social and economic consequences of reduced mobility for the most vulnerable groups.Wellcome Trust.For the Spanish translation of the abstract see Supplementary Materials section.
An epigenetic and transcriptomic signature of immune tolerance in human monocytes through multi-omics integration
Authors: Xanthe Brands, Bastiaan W. Haak, Augustijn M. Klarenbeek, Joe Butler, Fabrice Uhel, Wanhai Qin, Natasja A. Otto, Marja E. Jakobs, Daniël R. Faber, René Lutter, W. Joost Wiersinga, Tom van der Poll, Brendon P. Scicluna
Journal: Genome Medicine (2021)

The plasticity of monocytes enables them to exert multiple roles during an immune response, including promoting immune tolerance. How monocytes alter their functions to convey immune tolerance in the context of lower respiratory tract infections in humans is not well understood. Here, we sought to identify epigenetic and transcriptomic features of cytokine production capacity in circulating monocytes during community-acquired pneumonia (CAP).
Airflow obstruction, impaired lung function and risk of sudden cardiac death: a prospective cohort study
Authors: Yun-Jiu Cheng, Zhen-Guang Chen, Feng-Juan Yao, Li-Juan Liu, Ming Zhang, Su-Hua Wu
Journal: Thorax (2021)

Background Growing evidence suggests that compromised lung health may be linked to cardiovascular disease. However, little is known about its association with sudden cardiac death (SCD). Objectives We aimed to assess the link between impaired lung function, airflow obstruction and risk of SCD by race and gender in four US communities. Methods A total of 14 708 Atherosclerosis Risk in Communities (ARIC) study participants who underwent spirometry and were asked about lung health (1987–1989) were followed. The main outcome was physician-adjudicated SCD. Fine-Gray proportional subdistribution hazard models with Firth’s penalised partial likelihood correction were used to estimate the HRs. Results Over a median follow-up of 25.4 years, 706 (4.8%) subjects experienced SCD. The incidence of SCD was inversely associated with FEV 1 in each of the four race and gender groups and across all smoking status categories. After adjusting for multiple measured confounders, HRs of SCD comparing the lowest with the highest quintile of FEV 1 were 2.62 (95% CI 1.62 to 4.26) for white males, 1.80 (95% CI 1.03 to 3.15) for white females, 2.07 (95% CI 1.05 to 4.11) for black males and 2.62 (95% CI 1.21 to 5.65) for black females. The above associations were consistently observed among the never smokers. Moderate to very severe airflow obstruction was associated with increased risk of SCD. Addition of FEV 1 significantly improved the predictive power for SCD. Conclusions Impaired lung function and airflow obstruction were associated with increased risk of SCD in general population. Additional research to elucidate the underlying mechanisms is warranted.
27594 Impact of guselkumab on fatigue and mediation analysis of independent treatment effect of guselkumab on fatigue in patients with active psoriatic arthritis: Results from DISCOVER-1&amp;2
Authors: Proton Rahman, Philip S. Helliwell, Atul Deodhar, Alexa P. Kollmeier, Elizabeth Hsia, Bei Zhou, Xiwu Lin, Chenglong Han, Ya-Wen Yang, Philip J. Mease
Journal: Journal of the American Academy of Dermatology (2021)
Technology dictates algorithms: recent developments in read alignment
Authors: Mohammed Alser, Jeremy Rotman, Dhrithi Deshpande, Kodi Taraszka, Huwenbo Shi, Pelin Icer Baykal, Harry Taegyun Yang, Victor Xue, Sergey Knyazev, Benjamin D. Singer, Brunilda Balliu, David Koslicki, Pavel Skums, Alex Zelikovsky, Can Alkan, Onur Mutlu, Serghei Mangul
Journal: Genome biology (2021)

Aligning sequencing reads onto a reference is an essential step of the majority of genomic analysis pipelines. Computational algorithms for read alignment have evolved in accordance with technological advances, leading to today's diverse array of alignment methods. We provide a systematic survey of algorithmic foundations and methodologies across 107 alignment methods, for both short and long reads. We provide a rigorous experimental evaluation of 11 read aligners to demonstrate the effect of these underlying algorithms on speed and efficiency of read alignment. We discuss how general alignment algorithms have been tailored to the specific needs of various domains in biology.
Eating disorders: Record number of young people wait for treatment as demand soars
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The Royal College of Psychiatrists has warned that the number of children and young people waiting for treatment for an eating disorder has reached record levels as services struggle to meet overwhelming demand.

The college’s analysis of newly published NHS England data1 has found that the numbers of under 19s waiting for urgent and routine treatment are higher than ever before, while more young people are also being treated than ever before.

At the end of the first quarter of 2021-22 (April, May, and June)—a year on from the start of the covid pandemic—207 patients were …
Incidence and Types of Human Papillomavirus Infections in Adolescent Girls and Young Women Immunized With the Human Papillomavirus Vaccine
Authors: Nicolas F. Schlecht, Angela Diaz, Anne Nucci-Sack, Kathleen Shyhalla, Viswanathan Shankar, Mary Guillot, Dominic Hollman, Howard D. Strickler, Robert D. Burk
Journal: JAMA Network Open (2021)

Rates of human papillomavirus (HPV) infection have decreased since the introduction of HPV vaccines in populations with high vaccine uptake. Data are limited for adolescent and young adult populations in US metropolitan centers.
Screening for Prediabetes and Type 2 Diabetes
Authors: Jill Jin
Journal: JAMA (2021)

US Preventive Services Task Force; Karina W. Davidson, PhD, MASc; Michael J. Barry, MD; Carol M. Mangione, MD, MSPH; Michael Cabana, MD, MA, MPH; Aaron B. Caughey, MD, PhD; Esa M. Davis, MD, MPH; Katrina E. Donahue, MD, MPH; Chyke A. Doubeni, MD, MPH; Alex H. Krist, MD, MPH; Martha Kubik, PhD, RN; Li Li, MD, PhD, MPH; Gbenga Ogedegbe, MD, MPH; Douglas K. Owens, MD, MS; Lori Pbert, PhD; Michael Silverstein, MD, MPH; James Stevermer, MD, MSPH; Chien-Wen Tseng, MD, MPH, MSEE; John B. Wong, MD
Antibody Responses to SARS-CoV-2 Variants are Significantly Increased Following BNT162b2 Vaccine Boost in SARS-CoV-2 Exposed and Naïve Individuals
Authors: Richard A Urbanowicz, Theocharis Tsoleridis, Hannah J Jackson, Lola Cusin, Joshua D Duncan, Joseph G Chappell, Alexander W Tarr, Jessica Nightingale, Alan R Norrish, Adeel Ikram, Ben Marson, Simon J Craxford, Anthony Kelly, Guruprasad P Aithal, Amrita Vijay, Patrick J Tighe, Jonathan K Ball, Ana M Valdes, Benjamin J Ollivere
Journal: Science Translational Medicine (2021)

Emergence of SARS-Cov-V2 variants during the Covid-19 pandemic has raised concerns; understanding the impact of exposure and vaccination on the effectiveness of immune responses to variants of concern is an urgent priority. From a large cohort of healthcare workers followed serologically since April 2020 we purposively sampled 20 with and 25 without confirmed previous SARS-CoV-2 infection. All 45 had received two doses of the Pfizer BTN162b2 vaccine with a delayed booster at 10 weeks. Absolute and neutralizing antibody titres against lineage A, B.1 and B.1.351 variants were measured using enzyme immunoassays and a pseudotype neutralization assay, respectively. We observed significant increases in ID50 against lineage A, B.1.351 and P.1 variants with increasing antigenic exposure (either through vaccination or natural infection) and this superiority was confirmed in neutralization assays using a fixed dilution of each serum. The impact of antigenic exposure was even more evident in enzyme immunoassays measuring spike-specific IgG antibody levels. Our data show that multiple exposures (vaccine or natural infection) when utilizing a delayed booster significantly expand the neutralizing breadth of the antibody response to neutralization-resistant SARS-CoV-2 variants, suggesting that additional boosts would be highly beneficial in reducing the impact of future waves of SARS-CoV-2 including those related to the variants.
Macrophage-derived IL-6 trans-signalling as a novel target in the pathogenesis of bronchopulmonary dysplasia
Authors: Dharmesh Hirani, Cristina M. Alvira, Soula Danopoulos, Carlos Milla, Michele Donato, Lu Tian, Jasmine Mohr, Katharina Dinger, Christina Vohlen, Jaco Selle, Silke v. Koningsbruggen-Rietschel, Verena Barbarino, Christian Pallasch, Stefan Rose-John, Margarete Odenthal, Gloria S. Pryhuber, Siavash Mansouri, Rajkumar Savai, Werner Seeger, Purvesh Khatri, Denise Al Alam, Jörg Dötsch, Miguel A. Alejandre Alcazar
Journal: European Respiratory Journal (2021)

Rationale Premature infants exposed to oxygen are at risk for bronchopulmonary dysplasia (BPD), which is characterised by lung growth arrest. Inflammation is important, but the mechanisms remain elusive. Here, we investigated inflammatory pathways and therapeutic targets in severe clinical and experimental BPD. Methods and results First, transcriptomic analysis with in silico cellular deconvolution identified a lung-intrinsic M1-like-driven cytokine pattern in newborn mice after hyperoxia. These findings were confirmed by gene expression of macrophage-regulating chemokines ( Ccl2 , Ccl7 , Cxcl5 ) and markers ( Il6 , Il17A , Mmp12 ). Secondly, hyperoxia-activated interleukin 6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signalling was measured in vivo and related to loss of alveolar epithelial type II cells (ATII) as well as increased mesenchymal marker. Il6 null mice exhibited preserved ATII survival, reduced myofibroblasts and improved elastic fibre assembly, thus enabling lung growth and protecting lung function. Pharmacological inhibition of global IL-6 signalling and IL-6 trans-signalling promoted alveolarisation and ATII survival after hyperoxia. Third, hyperoxia triggered M1-like polarisation, possibly via Krüppel-like factor 4; hyperoxia-conditioned medium of macrophages and IL-6-impaired ATII proliferation. Finally, clinical data demonstrated elevated macrophage-related plasma cytokines as potential biomarkers that identify infants receiving oxygen at increased risk of developing BPD. Moreover, macrophage-derived IL6 and active STAT3 were related to loss of epithelial cells in BPD lungs. Conclusion We present a novel IL-6-mediated mechanism by which hyperoxia activates macrophages in immature lungs, impairs ATII homeostasis and disrupts elastic fibre formation, thereby inhibiting lung growth. The data provide evidence that IL-6 trans-signalling could offer an innovative pharmacological target to enable lung growth in severe neonatal chronic lung disease.
DDX56 modulates post-transcriptional Wnt signaling through miRNAs and is associated with early recurrence in squamous cell lung carcinoma
Authors: Qingqing Wu, Xiaoyang Luo, Mikkel G. Terp, Qingrun Li, Yuan Li, Lei Shen, Ying Chen, Kirstine Jacobsen, Trever G. Bivona, Haiquan Chen, Rong Zeng, Henrik J. Ditzel
Journal: Molecular Cancer (2021)

Abstract Background Early recurrence is a major obstacle to prolonged postoperative survival in squamous cell lung carcinoma (SqCLC). The molecular mechanisms underlying early SqCLC recurrence remain unclear, and effective prognostic biomarkers for predicting early recurrence are needed. Methods We analyzed primary tumor samples of 20 SqCLC patients using quantitative proteomics to identify differentially-expressed proteins in patients who experienced early versus late disease recurrence. The expression and prognostic significance of DDX56 was evaluated using a SqCLC tumor tissue microarray and further verified using different online databases. We performed in vitro and in vivo experiments to obtain detailed molecular insight into the functional role of DDX56 in SqCLC. Results We found that DDX56 exhibited increased expression in tumors of patients who experienced early versus late disease recurrence. Increased DDX56 expression in SqCLC tumors was subsequently confirmed as an independent prognostic factor of poor recurrence-free survival in independent SqCLC cohorts. Functionally, DDX56 promotes SqCLC cell growth and migration in vitro, and xenograft tumor progression in vivo. Mechanistically, DDX56 post-transcriptionally promotes expression of multiple Wnt signaling pathway-related genes, including CTNNB1, WNT2B, and represses a subset of miRNAs, including miR-378a-3p, a known suppressor of Wnt signaling. Detailed analysis revealed that DDX56 facilitated degradation of primary miR-378a, leading to down-regulation of mature miR-378a-3p and thus derepression of the target gene WNT2B. Conclusion We identified DDX56 as a novel independent prognostic biomarker that exerts its oncogenic effects through miRNA-mediated post-transcriptional regulation of Wnt signaling genes to promote early SqCLC recurrence. DDX56 may assist in identifying SqCLC patients at increased risk of early recurrence and who could benefit from Wnt signaling-targeted therapies.
Multimodal intervention for preventing peripheral intravenous catheter failure in adults (PREBACP): a multicentre, cluster-randomised, controlled trial
Authors: Ian Blanco-Mavillard, Joan Ernest de Pedro-Gómez, Miguel Ángel Rodríguez-Calero, Miquel Bennasar-Veny, Gaizka Parra-García, Ismael Fernández-Fernández, Jesús Bujalance-Hoyos, Ana Belén Moya-Suárez, José Luis Cobo-Sánchez, Francisco Ferrer-Cruz, Enrique Castro-Sánchez
Journal: The Lancet Haematology (2021)
Novel Paracrine Action of Endothelium Enhances Glucose Uptake in Muscle and Fat
Authors: Hema Viswambharan, Nadira Y. Yuldasheva, Helen Imrie, Katherine Bridge, Natalie J. Haywood, Anna Skromna, Karen E. Hemmings, Emily R. Clark, V. Kate Gatenby, Paul Cordell, Katie J. Simmons, Natallia Makava, Yilizila Abudushalamu, Naima Endesh, Jane Brown, Andrew M.N. Walker, Simon T. Futers, Karen E. Porter, Richard M. Cubbon, Khalid Naseem, Ajay M. Shah, David J. Beech, Stephen B. Wheatcroft, Mark T. Kearney, Piruthivi Sukumar
Journal: Circulation Research (2021)

Rationale: A hallmark of type 2 diabetes is insulin resistance, which leads to increased endothelial cell (EC) production of superoxide and a simultaneous reduction in the availability of the vasoprotective signaling radical NO. We recently demonstrated in preclinical models that type 2 diabetes simultaneously causes resistance to IGF-1 (insulin-like growth factor-1)–mediated glucose lowering and endothelial NO release. Objective: To examine the effect of insulin and IGF-1 resistance specifically in ECs in vivo. Methods and Results: We generated mice expressing mIGF-1Rs (mouse IGF-1 receptors), which form nonfunctioning hybrid receptors with native IRs (insulin receptors) and IGF-1R, directed to ECs under control of the Tie2 promoter-enhancer. Despite EC insulin and IGF-1 resistance, mIGFREO (mutant IGF-1R EC overexpressing) mice had enhanced insulin and IGF-1–mediated systemic glucose disposal, lower fasting free fatty acids, and triglycerides. In hyperinsulinemic-euglycemic clamp studies, mIGFREO had increased glucose disposal and increased glucose uptake into muscle and fat, in response to insulin. mIGFREO had increased Nox (NADPH oxidase)-4 expression due to reduced expression of the microRNA, miR-25. Consistent with increased Nox4, mIGFREO ECs generated increased hydrogen peroxide (H 2 O 2 ), with no increase in superoxide. Treatment with catalase—a H 2 O 2 dismutase—restored insulin tolerance to WT (wild type) levels in mIGFREO. Conclusions: Combined insulin and IGF-1 resistance restricted to the endothelium leads to a potentially favorable adaptation in contrast to pure insulin resistance, with increased Nox4-derived H 2 O 2 generation mediating enhanced whole-body insulin sensitivity.
27560 Interpreting the relationship between pruritus, sleep, and work productivity: Results from JADE MONO-2
Authors: Melinda J. Gooderham, Sonja Ständer, Jacek C. Szepietowski, Giampiero Girolomoni, Andrew G. Bushmakin, Joseph C. Cappelleri, Pinaki Biswas, Claire Feeney, Gary Chan, Marco DiBonaventura, Daniela E. Myers
Journal: Journal of the American Academy of Dermatology (2021)
Self-assembly nanovaccine containing TLR7/8 agonist and STAT3 inhibitor enhances tumor immunotherapy by augmenting tumor-specific immune response
Authors: Lele Zhang, Jiacheng Huang, Xiaona Chen, Caixu Pan, Yong He, Rong Su, Danjing Guo, Shengyong Yin, Shuai Wang, Lin Zhou, Jianxiang Chen, Shusen Zheng, Yiting Qiao
Journal: Journal for ImmunoTherapy of Cancer (2021)

Cancer vaccines are a promising strategy for cancer immunotherapy. Cancer vaccines elicits a specific cytotoxic immune response to tumor antigens. However, the efficacy of traditional peptide-based cancer vaccines is limited due to the inefficient delivery of antigens and adjuvants to dendritic cells (DCs). Therefore, it is necessary to develop a novel rationally designed cancer vaccine to maximize its desired effects.A Self-assembling Vehicle-free Multi-component Antitumor nanoVaccine (SVMAV) was constructed by using an unsaturated fatty acid docosahexaenoic acid (DHA)-conjugated antigen and R848 (a Toll-like receptor 7/8 agonist) to encapsulate stattic (a signal transducer and activator of transcription 3 inhibitor). The characteristics of SVMAV were investigated. The ability of SVMAV to promote DC functions was examined by in vitro analysis. The antitumor effects of SVMAV and its combination with antiprogrammed cell death protein 1 antibody (aPD-1) were also investigated in vivo. The potential application of SVMAV for neoantigen-targeted, personalized cancer vaccines was examined in an orthotopic hepatocellular carcinoma model.The obtained SVMAV efficiently migrated into lymph nodes and primed CD8+ T cells for exert neoantigen-specific killing by promoting the antigen uptake by DCs, stimulating DC maturation, and enhancing antigen cross-presentation, due to the simultaneous delivery of the antigen, R848 and stattic. SVMAV could not only yield a robust antitumor effect for primary melanoma allografts, but also exert a protective effect for lung metastases. Moreover, combination treatment of SVMAV and aPD-1 exerted synergistic antitumor activity and extended the survival duration of melanoma-bearing mice. Notably, a cell line-specific neoantigen-based SVMAV was designed according to predicted neoantigens for Hepa1-6 cells to examine the potential application of SVMAV for personalized cancer vaccine. Encouragingly, neoantigen-specific SVMAV achieved stronger antitumor activity than aPD-1 in an orthotopic hepatocellular cancer model established with Hepa1-6 cells.In summary, this study offers an efficient codelivery platform for neoantigens and immunoregulatory compounds to enhance immune responses during cancer immune therapy.
Abstract 12731: Cardiac Resynchronization Therapy Improves Diastolic Function and Reduces New Onset Atrial Fibrillation in Patients With Prolonged Atrioventricular Interval: The Pilot Randomized Controlled Real-crt Study
Authors: Giovanni L Botto, Assunta Iuliano, Eraldo Occhetta, Giuseppina Belotti, Giovanni Russo, Monica Campari, Sergio Valsecchi, Giuseppe Stabile
Journal: Circulation (2019)

Introduction: A prolonged PR interval is known to be associated with an increase in mortality and higher risk of developing atrial fibrillation. Hypothesis: We tested the hypothesis that cardiac re...
26268 M89, a combination of 89% of Vichy volcanic mineralizing water and hyaluronic acid improves signs and symptoms of subjects with rosacea/sensitive/reactive skin: Results from an open-label, observational, international study
Authors: Jerry Tan, Julieta Spada, Martina Kerscher, Maryna Anfilova, Sonya Abdulla, Anita Altmeyer, Catherine Delva, Delphine Kerob, Elena Araviiskaia
Journal: Journal of the American Academy of Dermatology (2021)