bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying COVID-19 vaccination hesitancy during early vaccination rollout in Canada
Authors: Tang Xuyang , Gelband Hellen , Nagelkerke Nico , Bogoch Isaac I. , Brown Patrick , Morawski Ed , Tam Theresa , Reid Angus , Jha Prabhat ,   for the Action to beat coronavirus/Action pour battre le coronavirus (Ab-C) Study Investigators
Published: May 2021

AbstractBackgroundUnderstanding vaccination hesitancy during early vaccination rollout in Canada can help the government’s vaccination efforts in education and outreach, which may help eventually achieving herd immunity. This study uses an online survey to assess vaccination hesitancy in population subgroups in Canada.MethodPanel members from the nationally representative Angus Reid Forum were randomly invited to complete an online survey on their experiencing with COVID-19 symptoms and testing, as well as intention to vaccination against COVID-19. Respondents were asked “when a vaccine against the coronavirus becomes available to you, will you get vaccinated or not?” Vaccination hesitancy was defined as choosing “No – I will not get a coronavirus vaccination” as a response.Results14,621 panel members (46% male and 53% female) completed the survey. Although the respondents overrepresent age 60+ and higher levels of education, other demographics, the prevalences of smoking, obesity, diabetes and hypertension were comparable to the Canadian national census and health surveys. COVID-19 vaccination hesitancy is relatively low overall (9%). Being a resident of Alberta (predicted probability = 15%), aged 40-59 (OR = 0.87, 0.78 – 0.97, predicted probability = 12%), identifying as a visible minority (OR = 0.56, 0.37 – 0.84, predicted probability = 15%), having some college level education or lower (predicted probability = 14%), or living in households of at least 5 are related to greater vaccination hesitancy (OR = 0.82, 0.76 – 0.88, predicted probability = 13%).ConclusionOur study enhances the understanding of COVID-19 vaccination hesitancy and identifies key population groups with higher vaccination hesitancy. As the Canadian COVID-19 vaccination effort continues, policymakers may focus outreach, education, and other efforts on these groups, which also represent groups with higher risks for contracting and dying from COVID-19. Furthermore, Canada would need to vaccinate virtually the entire population to reach herd immunity due to its relatively low infection level, and a high vaccination hesitancy would be a major hurdle to achieving that.
Women’s views on accepting COVID-19 vaccination during and after pregnancy, and for their babies: A multi-methods study in the UK
Authors: Skirrow Helen , Barnett Sara , Bell Sadie , Riaposova Lucia , Mounier-Jack Sandra , Kampmann Beate , Holder Beth 
Published: May 2021

AbstractBackgroundCOVID-19 vaccines are the cornerstone of the pandemic response and now advised for pregnant women in the United Kingdom(UK) however COVID-19 vaccine acceptance among pregnant women is unknown.MethodsAn online survey and semi-structured interviews were used to investigate pregnant women’s views on COVID-19 vaccine acceptability for themselves when pregnant, not pregnant and for their babies. 1,181 women, aged over 16 years, who had been pregnant since 23rd March 2020, were surveyed between 3rdAugust–11thOctober 2020. Ten women were interviewed.ResultsThe majority of women surveyed (81.2%) reported that they would ‘definitely’ or were ‘leaning towards’ accepting a COVID-19 vaccine when not pregnant. COVID-19 vaccine acceptance was significantly lower during pregnancy (62.1%, p<0.005) and for their babies (69.9%, p<0.005). Ethnic minority women were twice as likely to reject a COVID-19 vaccine for themselves when not pregnant, pregnant and for their babies compared to women from White ethnic groups (p<0.005). Women from lower-income households, aged under 25-years, and from some geographic regions were more likely to reject a COVID-19 vaccine when not pregnant, pregnant and for their babies. Multivariate analysis revealed that income and ethnicity were the main drivers of the observed age and regional differences. Women unvaccinated against pertussis in pregnancy were over four times more likely to reject COVID-19 vaccines when not pregnant, pregnant and for their babies. Thematic analysis of the survey freetext responses and interviews found safety concerns about COVID-19 vaccines were common though wider mistrust in vaccines was also expressed. Trust in vaccines and the health system were also reasons women gave for accepting COVID-19 vaccines.ConclusionSafety information on COVID-19 vaccines must be clearly communicated to pregnant women to provide reassurance and facilitate informed pregnancy vaccine decisions. Targeted interventions to promote COVID-19 vaccine uptake among ethnic minority and lower-income women may be needed.
Predicting remission after internet-delivered psychotherapy in patients with depression using machine learning and multi-modal data
Authors: Wallert John , Boberg Julia , Kaldo Viktor , Mataix-Cols David , Flygare Oskar , Crowley James J , Halvorsen Matthew , Abdesslem Fehmi Ben , Boman Magnus , Andersson Evelyn , Isacsson Nils Hentati , Ivanova Ekaterina , Rück Christian 
Published: May 2021

ABSTRACTBACKGROUNDWhether a patient benefits from psychotherapy or not is arguably a complex process and heterogeneous information extracted from process, genetic, demographic, and clinical data could contribute to the prediction of remission status after psychotherapy. This study applied supervised machine learning with such multi-modal baseline data to predict remission in patients with major depressive disorder (MDD) after completed psychotherapy.METHODSEight-hundred ninety-four genotyped adult patients (65.5% women, age range 18-75 years) diagnosed with MDD and treated with guided Internet-based Cognitive Behaviour Therapy (ICBT) at the Internet Psychiatry Clinic in Stockholm were included (2008-2016). Predictor variables from multiple domains were available: demographic, clinical, process (e.g. time to complete online questionnaires), and genetic (polygenic risk scores for depression, education and more). The outcome was remission status post ICBT (cut-off ≤10 on MADRS-S). Data were split into train (60%) and validation (40%) sets based on treatment start date. Predictor selection employed human domain knowledge followed by Recursive Feature Elimination. Model derivation was internally validated through repeated cross-validation resampling. The final random forest model was externally validated against a (i) null, (ii) logit, (iii) XGBoost, and (iv) blended meta-ensemble model on the hold-out validation set. Model transparency was explored through partial dependence and Local Interpretable Model-agnostic Explanations (LIME) analysis.RESULTSFeature selection retained 45 predictors representing all four predictor types. With unseen validation data, the final random forest model proved reasonably accurate at classifying post ICBT remission (Accuracy 0.656 [0.604, 0.705], P vs null model = 0.004; AUC 0.687 [0.631, 0.743]), slightly better vs logit (bootstrap D =1.730, P = 0.084) but not vs XGBoost (D = 0.463, P = 0.643). Transparency analysis showed model usage of all predictor types at both the group and individual patient level.CONCLUSIONA new, multi-modal classifier for predicting MDD remission status after ICBT treatment in routine psychiatric care was derived and empirically validated. The multi-modal approach to predicting remission may inform tailored treatment, and deserves further investigation.One-sentence SummaryPredicting remission of depression in adults after psychotherapy
Attitude and Perceived Barriers towards Research among Undergraduate Medical Students of Bangladesh
Authors: Ferdoush Jannatul , Johora Fatema , Khan IkramUllah , Towfiq Hossain Sharif Mohammad , Sadia Halima , Jeenia Fatiha Tasmin , Chowdhury Sameera Shafique , Sultana Nagina , Sharmeen Shagorika 
Published: May 2021

AbstractBackgroundUndergraduate research opportunities teach students not only how to conduct research, but they too learn problem-solving aptitudes. Participating in research also increases students’ interest is being involved and making special contributions to the academic field. Therefore, the aim of our study was intended to assess the attitude and perceived barriers toward research among the medical undergraduates of Bangladesh.MethodsA cross-sectional questionnaire survey was conducted among third, fourth, and fifth year students across medical colleges in Bangladesh, during the month of July, 2020 to December, 2020. A Google-linked questionnaire was disseminated to the students via different social platform and the responses were received through Google drive.ResultThe questionnaire survey received responses from 1279 students, with 94% claiming to be familiar with the scientific method. 82.7% of students mentioned they could design and execute a research project as well as can write scientific articles. More than half of the respondents (66.4%) expressed an interest in participating in research. Almost all respondents (96.7%) agreed that research is beneficial as it aid critical thinking and policy implementation. 79.8% of respondents opined that education on research methodology should be required in the medical curriculum. Majority of the respondents reported that lack of time and priorities to do research work because of compact academic tasks (89.1%), insufficient guidance (86.6%), lack of familiarities with research methodology (87.5%) and statistical analysis (85.2%) are the barriers of research.ConclusionOur findings indicated that Bangladeshi medical students have a positive attitude toward research and that research methodology should be taught in undergraduate medical education. In order to increase participation in research, the challenges identified by students should be addressed.
Deubiquitinase-Targeting Chimeras for Targeted Protein Stabilization
Authors: Henning Nathaniel J. , Boike Lydia , Spradlin Jessica N. , Ward Carl C. , Belcher Bridget , Brittain Scott M. , Hesse Matthew , Dovala Dustin , McGregor Lynn M. , McKenna Jeffrey M. , Tallarico John A. , Schirle Markus , Nomura Daniel K. 
Published: May 2021

AbstractTargeted protein degradation is a powerful therapeutic modality that uses heterobifunctional small-molecules to induce proximity between E3 ubiquitin ligases and target proteins to ubiquitinate and degrade specific proteins of interest. However, many proteins are ubiquitinated and degraded to drive disease pathology; in these cases targeted protein stabilization (TPS), rather than degradation, of the actively degraded target using a small-molecule would be therapeutically beneficial. Here, we present the Deubiquitinase-Targeting Chimera (DUBTAC) platform for TPS of specific proteins. Using chemoproteomic approaches, we discovered the covalent ligand EN523 that targets a non-catalytic allosteric cysteine C23 in the K48 ubiquitin-specific deubiquitinase OTUB1. We then developed a heterobifunctional DUBTAC consisting of our EN523 OTUB1 recruiter linked to lumacaftor, a drug used to treat cystic fibrosis that binds ΔF508-CFTR. We demonstrated proof-of-concept of TPS by showing that this DUBTAC robustly stabilized ΔF508-CFTR in human cystic fibrosis bronchial epithelial cells in an OTUB1-dependent manner. Our study underscores the utility of chemoproteomics-enabled covalent ligand discovery approaches to develop new induced proximity-based therapeutic modalities and introduces the DUBTAC platform for TPS.Editorial summaryWe have developed the Deubiquitinase Targeting Chimera (DUBTAC) platform for targeted protein stabilization. We have discovered a covalent recruiter against the deubiquitinase OTUB1 that we have linked to the mutant ΔF508-CFTR targeting cystic fibrosis drug Lumacaftor to stabilize mutant CFTR protein in cells.
GLUCOCORTICOIDS REGULATE MITOCHONDRIAL FATTY ACID OXIDATION IN FETAL CARDIOMYOCYTES
Authors: Ivy Jessica R. , Carter Roderic N. , Zhao Jin-Feng , Buckley Charlotte , Urquijo Helena , Rog-Zielinska Eva A. , Panting Emma , Hrabalkova Lenka , Nicholson Cara , Agnew Emma J. , Kemp Matthew W. , Morton Nicholas M. , Stock Sarah J. , Wyrwoll Caitlin , Ganley Ian G. , Chapman Karen E. 
Published: May 2021

ABSTRACTThe late gestational rise in glucocorticoids contributes to the structural and functional maturation of the perinatal heart. Here, we hypothesised that glucocorticoid action contributes to the metabolic switch in perinatal cardiomyocytes from carbohydrate to fatty acid oxidation. In primary mouse fetal cardiomyocytes, dexamethasone treatment induced expression of genes involved in fatty acid oxidation and increased mitochondrial oxidation of palmitate, dependent upon glucocorticoid receptor (GR). Dexamethasone did not, however, induce mitophagy or alter the morphology of the mitochondrial network. In neonatal mice, dexamethasone treatment induced cardiac expression of fatty acid oxidation genesin vivo.However, dexamethasone treatment of pregnant C57Bl/6 mice at embryonic day (E)13.5 or E16.5 failed to induce fatty acid oxidation genes in fetal hearts assessed 24 hours later. Instead, at E17.5, fatty acid oxidation genes were down-regulated by dexamethasone, as was GR itself. PGC-1α, required for glucocorticoid-induced maturation of primary mouse fetal cardiomyocytesin vitro, was down-regulatedin vivoin fetal hearts at E17.5, 24 hours after dexamethasone administration. Similarly, following a course of antenatal corticosteroids in a sheep model of preterm birth, both GR and PGC-1α were down-regulated in fetal heart. These data suggest endogenous glucocorticoids support the perinatal switch to fatty acid oxidation in cardiomyocytes through changes in gene expression rather than gross changes in mitochondrial volume or mitochondrial turnover. Moreover, our data suggest that treatment with exogenous glucocorticoids may interfere with normal fetal heart maturation, possibly by down-regulating GR. This has implications for clinical use of antenatal corticosteroids when preterm birth is considered a possibility.
Myofibroblast transcriptome indicates SFRP2+ fibroblast progenitors in systemic sclerosis skin
Authors: Tabib Tracy , Huang Mengqi , Morse Nina , Papazoglou Anna , Behera Rithika , Jia Minxue , Bulik Melissa , Monier Daisy E. , Benos Panayiotis V. , Chen Wei , Domsic Robyn , Lafyatis Robert 
Published: May 2021

ABSTRACTSkin and lung fibrosis in systemic sclerosis (SSc) is driven by myofibroblasts, alpha-smooth muscle actin expressing cells that arise from a variety of cell types in murine fibrosis models. Utilizing single cell RNA-sequencing to examine the transcriptome changes, we show that SSc dermal myofibroblasts arise from an SFRP2/DPP4-expressing progenitor fibroblast population that globally upregulates expression of transcriptome markers, such as PRSS23 and THBS1. Only a fraction of SSc fibroblasts differentiate into myofibroblasts, as shown by expression of additional markers, SFRP4 and FNDC1. The myofibroblast transcriptome implicates upstream transcription factors that drive myofibroblast differentiation.
A Novel In Situ Activity Assay for Lysyl Oxidases
Authors: Wang Huilei , Poe Alan , Pak Lydia , Jandu Sandeep , Nandakumar Kavitha , Steppan Jochen , Löser Reik , Santhanam Lakshmi 
Published: May 2021

AbstractThe lysyl oxidase family of enzymes (LOXs) catalyze oxidative deamination of lysine side chains on collagen and elastin to initialize cross-linking that is essential for the formation of the extracellular matrix (ECM). Elevated expression of LOXs is highly associated with diverse disease processes. To date, the inability to detect total LOX catalytic function in situ has limited the ability to fully elucidate the role of LOXs in pathobiological mechanisms. Using LOXL2 as a representative member of the LOX family, we developed an in situ activity assay by utilizing the strong reaction between hydrazide and aldehyde to label the LOX-catalyzed allysine (-CHO) residues with biotin-hydrazide. The biotinylated ECM proteins are then labeled via biotin-streptavidin interaction and detected by fluorescence microscopy. This assay detects the total LOX activity in situ for both overexpressed and endogenous LOXs in cells and tissue samples and can be used for studies of LOXs as therapeutic targets.
Incidence and outcome of delirium during Helmet CPAP treatment in COVID-19 patients
Authors: Samartin Federica , Salvi Emanuele , Brambilla Anna Maria , Torre Alessandro , Ingrassia Stella , Gidaro Antonio 
Published: May 2021

AbstractIt is estimated that almost one-third of patients with COVID-19 develop delirium in the course of disease, actually it may be the only presenting symptom, especially in dementia patients. In COVID-19 patients delirium is associated with higher mortality rate, increased length of stay and a greater rate of admission in Intensive Care Unit and ventilator utilisation. We hypothesized a greater rate of delirium in Helmet CPAP COVID-19 ventilated patients because many known risk factors for delirium co-exist in these kind of patients (i.e. isolation, noise, dehydration). The first aim of our study is to investigate the incidence of delirium occurring during Helmet CPAP therapy in COVID-19 patients. Moreover, we wanted to verify if there are predictable risk factors for delirium and to determine if delirium increases the risk of adverse outcomes (need of endotracheal intubation and death). The cohort of CPAP ventilated COVID-19 patients were composed by 194 patients. Of them, 57 patients (29.3%) developed delirium during CPAP, more than two third in the first 48h. Age over 70 years, previous diagnosis of dementia or psychiatric condition, P/F < 150 after starting CPAP and Gr/Lys >8 resulted risk factors for delirium. Delirium group had a significantly higher mortality rate (47% vs 23%) and lower intubation rate (12% vs 26%) compared to non-delirious ones. Despite many potential predisposing factors are common in CPAP ventilated patients, delirium incidence in our population seems not to differ from what reported by other studies. Moreover, the occurrence of delirium seems not to be related to prolonged CPAP treatment, indeed no correlation between time spent in CPAP and delirium onset was found.
Naming Human Diseases: Ethical Principles of Curating Exclusive Substitute for Inopportune Nosology
Authors: Hu Zhiwen , Chen Ya , Song Yuling , Yang Zhongliang , Huang Hui 
Published: May 2021

AbstractBackgroundIn the medical sphere, understanding naming conventions strengthen the integrity of naming human diseases remains nominal rather than substantial yet. Since the current nosology-based standard for human diseases could not offer a one-size-fits-all corrective mechanism, many idiomatic but flawed names frequently appear in scientific literature and news outlets at the cost of sociocultural impacts.ObjectiveWe attempt to examine the ethical oversights of current naming practices and propose heuristic rationales and approaches to determine a pithy name instead of an inopportune nosology.MethodsFirst, we examined the compiled global online news volumes and emotional tones on some inopportune nosology likeGerman measles, Middle Eastern Respiratory Syndrome, Spanish flu, Hong Kong flu, andHuntington’s diseasein the wake of COVID-19. Second, we prototypically scrutinize the lexical dynamics and pathological differentials ofGerman measlesand common synonyms by leveraging the capacity of the Google Books Ngram Corpus. Third, we demonstrated the empirical approaches to curate an exclusive substitute for an anachronistic nosologyGerman measlesbased on deep learning models andpost-hocexplanations.ResultsThe infodemiological study shows that the public informed the offensive names with extremely negative tones in textual and visual narratives. The findings of the historiographical study indicate that many synonyms ofGerman measlesdid not survive, whileGerman measlesbecame an anachronistic usage, andrubellahas taken the dominant place since 1994. The PubMedBERT model could identifyrubellaas a potential substitution forGerman measleswith the highest semantic similarity. The results of the semantic drift experiments further indicate thatrubellatends to survive during the ebb and flow of semantic drift.ConclusionsOur findings indicate that the nosological evolution of anachronistic names could result in sociocultural impacts without a corrective mechanism. To mitigate such impacts, we introduce some ethical principles for formulating an improved naming scheme. Based on deep learning models andpost-hocexplanations, our illustrated experiments could provide hallmark references to the remedial mechanism of naming practices and pertinent credit allocations.
Detection of SARS-CoV-2 infection in gargle, spit and sputum specimens
Authors: Poukka Eero , Mäkelä Henna , Hagberg Lotta , Vo Thuan , Nohynek Hanna , Ikonen Niina , Liitsola Kirsi , Helve Otto , Savolainen-Kopra Carita , Dub Timothée 
Published: May 2021

AbstractThe gold standard for SARS-CoV-2 infection diagnosis is RT-PCR from nasopharyngeal specimen (NPS). Its collection involves a close contact between patients and healthcare workers requiring a significant amount of workforce and putting them at risk of infection. We evaluated self-collection of alternative specimens and compared their sensitivity and Ct values to NPS. We visited acute COVID-19 outpatients to collect concomitant nasopharyngeal and gargle specimens and had patients self-collect a gargle and either sputum or spit specimens on the next morning.We included 40 patients and collected 40 concomitant nasopharyngeal and gargle specimens, as well as 40 gargle, 22 spit and 16 sputum specimens on the next day, as 2 patients could not produce sputum.All specimens were as sensitive as NPS. Gargle specimens had a sensitivity of 0.97 (CI 95% 0.92-1,00), whether collected concomitantly to NPS or on the next morning. Next morning spit and sputum specimens showed a sensitivity of 1.00 CI (95% 1.00-1.00) and 0.94 (CI 95% 0.87-1.00), respectively. The gargle specimens had a significantly higher mean cycle threshold (Ct) values, 29.89 (SD 4.63) (p-value <0.001) and 29.25 (SD 3.99) (p-value <0.001) when collected concomitantly and on the next morning compared to NPS (22.07, SD 4.63). Ct value obtained with spit (23.51, SD 4.57, p-value 0.11) and sputum (25.82, SD 9.21, p-value 0.28) specimens were close to NPS.All alternative specimen collection methods were as sensitive as NPS, but spit collection appeared more promising, with a low Ct value and ease of collection. Our findings warrant further investigation.
Reconstructing co-dependent cellular crosstalk in lung adenocarcinoma using REMI
Authors: Yu Alice , Li Yuanyuan , Li Irene , Yeh Christine , Chiou Aaron E. , Ozawa Michael G. , Taylor Jonathan , Plevritis Sylvia K. 
Published: May 2021

AbstractCellular crosstalk in tissue microenvironments is fundamental to normal and pathological biological processes. Global assessment of cell-cell interactions (CCI) is not yet technically feasible, but computational efforts to reconstruct these interactions have been proposed. Current computational approaches that identify CCI often make the simplifying assumption that pairwise interactions are independent of one another, which can lead to reduced accuracy. We present REMI (REgularized Microenvironment Interactome), a graph-based algorithm that predicts ligand-receptor (LR) interactions by accounting for LR dependencies on high-dimensional, small sample size datasets. We apply REMI to reconstruct the human lung adenocarcinoma (LUAD) interactome from a bulk flow-sorted RNA-seq dataset, then leverage single-cell transcriptomics data to increase its resolution and identify LR prognostic signatures. We experimentally confirmed colocalization of CTGF:LRP6 as an interaction predicted to be associated with LUAD progression. Our work presents a novel way to reconstruct interactomes and a new approach to identify clinically-relevant cell-cell interactions.