bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced NF-κB signaling in type-2 dendritic cells at baseline predicts non-response to adalimumab in psoriasis
Authors: Andres-Ejarque Rosa , Ale Hira Bahadur , Grys Katarzyna , Tosi Isabella , Solanky Shane , Ainali Chrysanthi , Catak Zeynep , Sreeneebus Hemawtee , Saklatvala Jake , Dand Nick , de Rinaldis Emanuele , Chapman Anna , Nestle Frank O. , Barnes Michael R. , Warren Richard B. , Reynolds Nick J. , Griffiths Christopher E.M. , Barker Jonathan N. , Smith Catherine H. , Di Meglio Paola 
Published: November 2020

AbstractBiological therapies have transformed the management of psoriasis but clinical outcome is variable leaving an unmet clinical need for predictive biomarkers of response. To identify the immune determinants of response to the anti-TNF drug adalimumab and evaluate their predictive value, we performed in-depth immunomonitoring of blood immune cells of 67 psoriasis patients, before and during therapy. We assessed proximal TNF signaling events, by measuring NF-κB nuclear translocation and phosphorylation, and downstream effects, such as cell phenotype and function. Enhanced NF-κBp65 phosphorylation, induced by TNF and LPS in type-2 dendritic cells (DC) before therapy, significantly correlated with lack of clinical response after 12 weeks’ treatment. The heightened NF-κB activation was mechanistically linked to increased DC maturation in vitro and frequency of IL-17+T cells in the blood of non-responders before therapy. Moreover, lesional skin of non-responders contained more activated dermal DC and increased numbers of IL-17+T cells. sFinally, we identified and clinically validated LPS-induced NF-κBp65 phosphorylation before therapy as a predictive biomarker of non-response to adalimumab, with 100% sensitivity and 90.1% specificity in an independent cohort. Our study uncovers key molecular and cellular players underpinning adalimumab mechanisms of action in psoriasis and proposes a blood biomarker for predicting clinical outcome.
Economic impact of the first wave of the COVID-19 pandemic on acute care hospitals in Japan
Authors: Shin Jung-ho , Takada Daisuke , Morishita Tetsuji , Lin Hueiru , Bun Seiko , Teraoka Emi , Okuno Takuya , Itoshima Hisashi , Nagano Hiroyuki , Kishimoto Kenji , Segawa Hiromi , Asami Yuka , Higuchi Takuya , Minato Kenta , Kunisawa Susumu , Imanaka Yuichi 
Published: November 2020

AbstractBackgroundIn response to the coronavirus diseases 2019 (COVID-19) pandemic, the Japanese government declared a state of emergency on April 7, 2020. Six days earlier, the Japan Surgical Society had recommended postponing elective surgical procedures. Along with the growing public fear of COVID-19, hospital visits in Japan decreased.MethodsUsing claims data from the Quality Indicator/Improvement Project (QIP) database, this study aimed to clarify the impact of the first wave of the pandemic, considered to be from March to May 2020, on case volume and claimed hospital charges in acute care hospitals during this period. To make year-over-year comparisons, we considered cases from July 2018 to June 2020.ResultsA total of 2,739,878 inpatient and 53,479,658 outpatient cases from 195 hospitals were included. In the year-over-year comparisons, total claimed hospital charges decreased in April, May, June 2020 by 7%, 14%, and 5%, respectively, compared to the same months in 2019. Our results also showed that per-case hospital charges increased during this period, possibly to compensate for the reduced case volumes. Regression results indicated that the hospital charges in April and May 2020 decreased by 6.3% for hospitals without COVID-19 patients. For hospitals with COVID-19 patients, there was an additional decrease in proportion with the length of hospital stay of COVID-19 patients including suspected cases. The mean additional decrease per COVID-19 patients was estimated to 5.5 million JPY.ConclusionIt is suggested that the hospitals treating COVID-19 patients were negatively incentivized.
Effectiveness of technological interventions to improve upper limb motor function in people with stroke in low- and middle-income countries: Protocol for a systematic review and meta-analysis
Authors: Carbajal-Galarza Meiling Milagros , Chinchihualpa-Paredes Nathaly Olga , Abanto-Perez Sergio Alejandro , Lazo-Porras María 
Published: November 2020

ABSTRACTIntroductionStroke is one of the main causes of disability in low- and middle-income countries (LMIC), frequently presenting with upper extremity paresis and causing major functional dependence. It requires high dose and intense rehabilitation which implies high economic costs, consequently limiting this therapy in LMIC. There are multiple technological interventions that facilitate rehabilitation either in intensity, adherence and motor evaluation; or enable access to rehabilitation such as robots, games or virtual reality, sensors, electronic devices and tele-rehabilitation. Their efficacy has been mainly evaluated in high-income countries, hence the importance of conducting a systematic review in LMIC settings.ObjectivesTo measure the efficacy of technological interventions vs. classical physical rehabilitation in the upper extremity motor function in people who had suffered a first or recurrent episode of stroke in LMIC.Methods and analysisThis protocol is consistent with the methodology recommended by the PRISMA-P and the Cochrane handbook for systematic reviews of interventions. We propose to do a systematic review and meta-analysis. In order to do so, we will perform an electronic search in PubMed, Global Index Medicus and Physiotherapy Evidence Database. No date range parameters will be used. Randomized controlled trials (RCT) published in English, Spanish, French and Portuguese, with the primary outcome focusing on upper limb motor function, will be included. Two reviewers will screen all retrieved titles, abstracts and full texts, perform the evaluation of the risk of bias and extract all data independently. The risk of bias of the included RCT will be evaluated by the Cochrane Collaboration’s tool. A qualitative synthesis will be provided in text and tables, to summarize the main results of the selected publications.The heterogeneity between studies will be assessed through the I2statistic. If there is sufficient homogeneity across outcomes, a meta-analysis will be considered. The outcomes to be evaluated will be motor functionality of the upper extremity, performance for activities of daily living and quality of life, through measurement scales.ConclusionsThis systematic review will provide evidence regarding the efficacy of multiple technological interventions to improve motor function of upper extremity in individuals with stroke in LMIC. Based on this analysis, we will be able to assess whether these interventions are also effective and feasible in the recovery of functionality after stroke in low- and middle-income countries, and thus offer recommendations in these areas.
The Silent Pandemic COVID-19 in the Asymptomatic Population
Authors: Stout Robert L. , Rigatti Steven J. 
Published: November 2020

AbstractAs the COVID-19 pandemic continues to ravage the world there is a great need to understand the dynamics of spread. Currently the seroprevalence of asymptomatic COVID-19 doubles every 3 months, this silent epidemic of new infections may be the main driving force behind the rapid increase in SARS-CoV-2 cases.Public health official quickly recognized that clinical cases were just the tip of the iceberg. In fact a great deal of the spread was being driven by the asymptomatically infected who continued to go out, socialize and go to work. While seropositivity is an insensitive marker for acute infection it does tell us about the prevalence COVID-19 in the population.ObjectiveDescribe the seroprevalence of SARS-CoV-2 infection in the United States over time.MethodologyRepeated convenience samples from a commercial laboratory dedicated to the assessment of life insurance applicants were tested for the presence of antibodies to SARS-CoV-2, in several time periods between May and December of 2020. US census data were used to estimate the population prevalence of seropositivity.ResultsThe raw seroprevalence in the May-June, September, and December timeframes were 3.0%, 6.6% and 10.4%, respectively. Higher rates were noted in younger vs. older age groups. Total estimated seroprevalence in the US is estimated at 25.7 million cases.ConclusionsThe seroprevalence of SARS-CoV-2 demonstrates a significantly larger pool of individuals who have contract COVID-19 and recovered, implying a lower case rate of hospitalizations and deaths than have been reported so far.
Prediction of abnormal left ventricular geometry in patients without cardiovascular disease through machine learning: An ECG-based approach
Authors: Angelaki Eleni , Marketou Maria E. , Barmparis Georgios D. , Patrianakos Alexandros , Vardas Panos E. , Parthenakis Fragiskos , Tsironis Giorgos P. 
Published: November 2020

ABSTRACTCardiac remodeling is recognized as an important aspect of cardiovascular disease (CVD) progression. Machine learning (ML) techniques were applied on basic clinical parameters and electrocardiographic features for detecting abnormal left ventricular geometry (LVG), even before the onset of left ventricular hypertrophy (LVH), in a population without established CVD. After careful screening, we enrolled 528 subjects with and without essential hypertension, but no other indications of CVD. All patients underwent a full echocardiographic evaluation and were classified into 3 groups; normal geometry (NG), concentric remodeling without LVH (CR), and LVH. Abnormal LVG was identified as increased relative wall thickness (RWT) and/or left ventricular mass index (LVMi). We trained nonlinear predictive ML models, to classify subjects with abnormal LVG and calculated SHAP values to perform feature importance and interaction analysis. Hypertension, age, body mass index over the Sokolow-Lyon voltage, QRS-T angle, and QTc duration were some of the most important features. Our model was able to distinguish NG from all others (CR+LVH), with accuracy 86%, specificity 75%, sensitivity 95%, and area under the receiver operating curve (AUC/ROC) 0.89. We also trained our model to classify NG and CR (NG+CR) against those with established LVH, with accuracy 89%, specificity 97%, sensitivity 50%, and AUC/ROC 0.85. Our ML algorithm effectively detects abnormal LVG even at early stages. Innovative solutions are needed to improve risk stratification of patients without established CVD, especially in primary care settings, and ML may enable this direction.
Rural Disparities in Early Childhood Well Child Visit Attendance
Authors: DeGuzman Pamela B. , Huang Guoping , Lyons Genevieve , Snitzer Joseph , Keim-Malpass Jessica 
Published: November 2020

AbstractPurposeChildren should attend well child visits (WCVs) during early childhood so that developmental disorders may be identified as early as possible, and if indicated treatment can begin. The aim of this research was to determine if rurality impacts access to WCV during early childhood, and if altering rurality measurement methods impacts outcomes.Design and MethodsWe utilized a longitudinal correlational design with early childhood data gathered from the Virginia All Payer Claims Database, which contains claims data from Medicaid and the majority of Virginia commercial insurance payers (n=6349). WCV attendance was evaluated against three rurality metrics: a traditional metric using Rural-Urban Commuting Area codes, a developed land variable, and a distance to care variable, at a zip code level.ResultsTwo of the rurality methods revealed that rural children attend fewer WCVs than their urban counterparts, (67% vs. 50% respectively, using a traditional metric; and a 0.035 increase in WCV attendance for every percent increase in developed land). Differences were attenuated by insurance payer; children with Medicaid attend fewer WCVs than those with private insurance.ConclusionsYoung children in rural Virginia attend fewer WCVs than their non-rural counterparts, placing them at higher risk for missing timely developmental disorder screenings. The coronavirus disease pandemic has been associated with an abrupt and significant reduction in vaccination rates, which likely indicates fewer WCVs and concomitant developmental screenings. Pediatric nurses should encourage families of young children to develop a plan for continued WCVs, so that early identification of developmental disorders can be achieved.
Psychometric properties and factor invariance for the General Health Questionnaire (GHQ-28): study in Peruvian population exposed to the COVID-19 pandemic
Authors: Ames-Guerrero Rita J. , Barreda-Parra Victoria A. , Huamani-Cahua Julio C. 
Published: November 2020

AbstractLarge-scale epidemics are known to significantly disrupt the mental health and perceived well-being of most populations. In spite of the wide range of screening tools, there are not many reliable and widespread tools for the identification of psychological symptoms in non-clinical populations during a health crisis.ObjectiveThe aim of this study was to conduct a psychometric analysis of the Goldberg’s GHQ-28 (1) through a sample of Peruvian adults using confirmatory factor analysis.Materials and methods434 individuals have been examined, studying the goodness and structure of the Goldberg GHQ-28 questionnaire.ResultWe found high reliability indicating optimal values (α by Cronbach = .829), also there are four correlated factors that show strict invariance among the 28 items. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were used to examine the structure of the subscales. There are high levels of anxiety (X=1.01) and social dysfunction (X=1.21) in the assessed sampling.ConclusionThe factorial structure obtained in this study is similar to that originally described by the researchers involved in the original questionnaire. It is concluded that GHQ-28 is suitable to explore prevalence of psychopathologies in emergency contexts and social isolation for general non-psychiatric population.
Systemic blockade of Clever-1 elicits lymphocyte activation alongside checkpoint molecule downregulation in patients with solid tumors
Authors: Virtakoivu Reetta , Rannikko Jenna , Viitala Miro , Vaura Felix , Takeda Akira , Lönnberg Tapio , Koivunen Jussi , Jaakkola Panu , Pasanen Annika , Shetty Shishir , de Jonge Maja , Robbrecht Debbie , Ma Yuk Ting , Skyttä Tanja , Minchom Anna , Jalkanen Sirpa , Karvonen Matti K. , Mandelin Jami , Bono Petri , Hollmén Maija 
Published: November 2020

AbstractMacrophages are critical in driving an immunosuppressive tumor microenvironment that counteracts the efficacy of T-cell targeting therapies. Thus, agents that can reprogram macrophages towards a proinflammatory state hold promise as novel immunotherapies for solid cancers. Here, we report that immunotherapeutic targeting of the macrophage scavenger receptor Clever-1 in heavily pretreated metastatic cancer patients was able to induce a significant increase and activation of peripheral T-cells. Anti-Clever-1 (FP-1305) administration led to suppression of nuclear lipid signaling pathways and a proinflammatory phenotypic switch in blood monocytes. Mechanistically, Clever-1 inhibition impaired multiprotein vacuolar ATPase–mediated endosomal acidification and improved macrophage cross-presentation of scavenged antigens. Our results reveal a non-redundant role played by the receptor Clever-1 in suppressing adaptive immune cell activation in humans. We provide evidence that targeting macrophage scavenging activity can promote an immune switch potentially leading to intratumoral proinflammatory responses in metastatic cancer patients.
ADHERENCE TO NATIONAL HEALTHCARE REFERRAL GUIDELINES AND ITS EFFECT ON THE MANAGEMENT OUTCOMES AMONG CHILDREN SEEN AT A TEACHING HOSPITAL IN WESTERN KENYA
Authors: Njanwe Paul Jairus , Marete Irene , Ayaya Samuel 
Published: November 2020

ABSTRACTIntroductionReferral guidelines are meant to ensure coordination and continuity across all levels of healthcare. Poor adherence to these guidelines could result in increased morbidity and mortality among the patients who are denied access; especially in the resource constrained healthcare settings in developing economies.AimTo determine adherence to the national healthcare referral guidelines and immediate outcomes of children seen at a tertiary teaching hospital in Western Kenya.Materials and methodsA Cross-sectional study conducted at the Pediatric emergency department of Moi Teaching and Referral Hospital in Western Kenya between February to June 2016. A total of 422 children aged below 15 years were recruited systematically. Sociodemographic and clinical data were collected using interviewer administered questionnaires and clinical chart reviews respectively. Checklists were used to collect information from ambulances. Pearson chi-square tests and odds ratios were used to test for association between predictor and outcome variables using statistical package for social science (SPSS) version-24.ResultsMore than half (55.5%) of the 422 children enrolled were male while 51.4% were aged between 5 to 14 years. Hospital referrals accounted for 15.9% (n=67) with the rest being self-referrals and no counter referrals seen. Adherence to all the four transfer guideline requirements was observed in 46.3% (n=31) of the 67 hospital referrals. Less than half (46.3%) of the hospital referrals had their referring facilities calling the receiving facility prior to initiating the referral; 83.6% had a referral document; 64.2% were transferred in ambulances while 68.7% (n=46) were accompanied by health care workers. Most (88.1%) of the hospital referrals were admitted. Lower level of parental education (p= 0.025), residing outside the host county (p<0.001) and a child being older than five years (p = 0.015) were significantly associated with hospital referrals. Hospital referrals were nearly three times (AOR = 2.932; 95% CI: 2.422 – 3.550; p<0.001) more likely to be admitted compared to children who were self-referred.ConclusionThere is low adherence to national healthcare referral guidelines among children seen at the second largest national hospital in Kenya; with less than half of hospital referrals transferred as per the transfer process guidelines.
Multiomics and digital monitoring during lifestyle changes reveal independent dimensions of human biology and health
Authors: Marabita Francesco , James Tojo , Karhu Anu , Virtanen Heidi , Kettunen Kaisa , Stenlund Hans , Boulund Fredrik , Hellström Cecilia , Neiman Maja , Mills Robert , Perheentupa Teemu , Laivuori Hannele , Helkkula Pyry , Byrne Myles , Jokinen Ilkka , Honko Harri , Kallonen Antti , Ermes Miikka , Similä Heidi , Lindholm Mikko , Widen Elisabeth , Ripatti Samuli , Perälä-Heape Maritta , Engstrand Lars , Nilsson Peter , Moritz Thomas , Miettinen Timo , Sallinen Riitta , Kallioniemi Olli 
Published: November 2020

AbstractIn order to explore opportunities for personalized and predictive health care, we collected serial clinical measurements, health surveys and multiomics profiles (genomics, proteomics, autoantibodies, metabolomics and gut microbiome) from 96 individuals. The participants underwent data-driven health coaching over a 16-month period with continuous digital monitoring of activity and sleep. Multiomics factor analysis resulted in an unsupervised, data-driven and integrated view of human health, revealing distinct and independent molecular factors linked to obesity, diabetes, liver function, cardiovascular disease, inflammation, immunity, exercise, diet and hormonal effects. The data revealed novel and previously uncovered associations between risk factors, molecular pathways, and quantitative lifestyle parameters. For example, ethinyl estradiol use had a distinct impact on metabolites, proteins and physiology. Multidimensional molecular and digital health signatures uncovered biological variability between people and quantitative effects of lifestyle changes, hence illustrating the value of the combined use of molecular and digital monitoring of human health.
The repurposed drugs suramin and quinacrine inhibit cooperativelyin vitroSARS-CoV-2 3CLpro
Authors: Eberle Raphael J. , Olivier Danilo S. , Amaral Marcos S. , Willbold Dieter , Arni Raghuvir K. , Coronado Monika A. 
Published: November 2020

AbstractSince the first report of a new pneumonia disease in December 2019 (Wuhan, China) up to now WHO reported more than 50 million confirmed cases and more than one million losses, globally. The causative agent of COVID-19 (SARS-CoV-2) has spread worldwide resulting in a pandemic of unprecedented magnitude. To date, no clinically safe drug or vaccine is available and the development of molecules to combat SARS-CoV-2 infections is imminent. A well-known strategy to identify molecules with inhibitory potential against SARS-CoV-2 proteins is the repurposing of clinically developed drugs, e.g., anti-parasitic drugs. The results described in this study demonstrate the inhibitory potential of quinacrine and suramin against SARS-CoV-2 main protease (3CLpro). Quinacrine and suramin molecules present a competitive and non-competitive mode of inhibition, respectively, with IC50and KDvalues in low μM range. Using docking and molecular dynamics simulations we identified a possible binding mode and the amino acids involved in these interactions. Our results suggested that suramin in combination with quinacrine showed promising synergistic efficacy to inhibit SARS-CoV-2 3CLpro. The identification of effective, synergistic drug combinations could lead to the design of better treatments for the COVID-19 disease. Drug repositioning offers hope to the SARS-CoV-2 control.
Frustration in protein complexes leads to interaction versatility
Authors: Freiberger Maria I. , Wolynes Peter G. , Ferreiro Diego U. , Fuxreiter Monika 
Published: November 2020

AbstractDisordered proteins can fold into a well-defined structure upon binding but these complexes are often fuzzy: the originally disordered partner adopts different binding modes when bound to different partners. Here we perform a systematic analysis of 160 proteins that form fuzzy complexes and demonstrate that the disordered partner displays a high degree of frustration in both the free and bound states. Although the folding of disordered regions upon binding reduces frustration relative to that of the unbound state, the interactions at the binding interface do not become fully optimized. In addition, we show that sub-optimal interactions lead to alternative frustration patterns in the complexes with different partners. These results demonstrate that disordered proteins do not always achieve fully optimal interactions in their complexes and their residual frustration leads to interaction versatility with different partners.