bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Content Validation of a Multidisciplinary Standardized Management Pathway for Hypoxemic Respiratory Failure and Acute Respiratory Distress Syndrome
Authors: Parhar Ken Kuljit S. , Zjadewicz Karolina , Knight Gwen E. , Soo Andrea , Boyd Jamie M. , Zuege Danny J. , Niven Daniel J. , Doig Christopher J. , Stelfox Henry T. 
Published: May 2021

Objectives:
Treatment of hypoxemic respiratory failure and acute respiratory distress syndrome is complex. Evidence-based therapies that can improve survival and guidelines advocating their use exist; however, implementation is inconsistent. Our objective was to develop and validate an evidence-based, stakeholder-informed standardized management pathway for hypoxemic respiratory failure and acute respiratory distress syndrome to improve adherence to best practice.

Design:
A standardized management pathway was developed using a modified Delphi consensus process with a multidisciplinary group of ICU clinicians. The proposed pathway was externally validated with a survey involving multidisciplinary stakeholders and clinicians.

Setting:
In-person meeting and web-based surveys of ICU clinicians from 17 adult ICUs in the province of Alberta, Canada.

Intervention:
Not applicable.

Measurements and Main Results:
The consensus panel was comprised of 30 ICU clinicians (4 nurses, 10 respiratory therapists, 15 intensivists, 1 nurse practitioner; median years of practice 17 [interquartile range, 13–21]). Ninety-one components were serially rated and revised over two rounds of online and one in-person review. The final pathway included 46 elements. For the validation survey, 692 responses (including 59% nurses, 33% respiratory therapists, 7% intensivists and 1% nurse practitioners) were received. Agreement of greater than 75% was achieved on 43 of 46 pathway elements.

Conclusions:
A 46-element evidence-informed hypoxemic respiratory failure and acute respiratory distress syndrome standardized management pathway was developed and demonstrated to have content validity.
SARS-CoV-2 Impairs Vision
Authors: Finsterer Josef , Scorza Fulvio A. , Scorza Carla A. , Fiorini Ana C. 
Published: May 2021

Objectives:
Affection of the central nervous system and the eyes is increasingly recognized as manifestations of a SARS-CoV-2 infection (COVID-19). This review aims at summarizing and discussing recent advances concerning causes and locations of impaired vision because of an infection with SARS-CoV-2.

Methods:
On a literature search through PubMed and ScholarOne, all available publications about COVID-19 patients with impaired vision were retrieved.

Results:
Visual impairment in SARS-CoV-2–infected patients may be due to infection of lacrimal glands (dacryoadenitis), conjunctivitis, tonic pupils, vitritis, central retinal artery/venous occlusion, retinitis, retinal bleeding, panuveitis, anterior ischemic optic neuropathy, optic nerve stroke, optic neuritis, optic perineuritis, or occipital ischemic stroke. Visual impairment may be the initial manifestation of SARS-CoV-2.

Conclusions:
This mini review shows that impaired vision may be the initial manifestation of COVID-19, that all sections of the visual tract may be affected and causative for visual impairment in COVID-19 patients, and that SARS-CoV-2 manifests along the visual tract with ischemia, focal infection, and immunological reactions.
New Focus on Endovascular Therapy for Ischemic Stroke
Authors: Kelly Sean , Raz Eytan , Shapiro Maksim , Ishida Koto 
Published: May 2021

Background:
Over the past 2 decades, a growing number of large-scale clinical trials have helped expand the toolkit for emergency management of acute ischemic stroke. This article is intended to be an up-to-date resource to aid nonstroke specialist neurology providers and ophthalmologists in identifying situations and patient populations in which urgent stroke evaluation should be completed with options for emergent reperfusion therapy considered.

Evidence Acquisition:
The literature forming the foundation of the guidelines for early management of patients with acute ischemic stroke was reviewed, annotated, and summarized.

Results:
Data from both initial and follow-up trials investigating the benefits and indications for use of intravenous thrombolysis and endovascular intervention for stroke are reviewed systematically, with an emphasis on new updates to qualifying patient populations and time periods for treatment.

Conclusions:
Recent studies underscore the conclusion that timely reperfusion in acute ischemic stroke is the most effective available treatment and that there are a growing number of new scenarios and patients for which interventions maybe applied.
Psychosocial and Behavioral Responses and SARS-CoV-2 Transmission Prevention Behaviors while Working during the COVID-19 Pandemic
Authors: Senerat Araliya M. , Pope Zachary , Rydell Sarah , Mullan Aidan , Roger Veronique , Pereira Mark A. 
Published: May 2021

AbstractBackgroundThe impact of coronavirus disease-2019 (COVID-19) on psychosocial and behavioral responses of the non-healthcare workforce is unknown. This study investigated these outcomes in this population during the pandemic while also evaluating transmission prevention behavior implementation at the workplace.MethodsWe deployed the baseline questionnaire of a prospective online survey from November 2020-February 2021 to U.S.-based employees. The survey included questions on psychosocial and behavioral responses in addition to transmission prevention behaviors (e.g., mask wear). Select questions asked employees to report perceptions and behaviors ‘before’ and ‘during’ the COVID-19 pandemic. Data were analyzed descriptively and stratified by work from home (WFH) percentage.ResultsIn total, 3,607 employees completed the survey from eight companies. Most participants (70.0%) averaged ≥90% of their time WFH during the pandemic. Employees reported increases in stress (54.0%), anxiety (57.4%), fatigue (51.6%), and feeling unsafe (50.4%) from before to during the pandemic, while feeling a lack of companionship (60.5%) and isolation from others (69.3%). Productivity was perceived to decrease, and non-work screen time and alcohol consumption to increase, for 43.0%, 50.7%, and 25.1% of employees, respectively, from before to during the pandemic. Adverse changes were worse among those with lower WFH percentages. Most employees reported wearing a mask (98.2%), washing hands regularly (95.7%), and physically distancing (93.6%) when at workplace.ConclusionResults suggested worsened psychosocial and behavioral outcomes from before to during the COVID-19 pandemic and higher transmission prevention behavior implementation among non-healthcare employees. Observations provide novel insight into how the COVID-19 pandemic has impacted non-healthcare employees.
Individuals who were mildly symptomatic following infection with SARS-CoV-2 B.1.1.28 have neutralizing antibodies to the P.1 variant
Authors: Mendes-Correa Maria Cassia , Villas-Boas Lucy S. , Bierrenbach Ana Luiza , de Paula Anderson , Tozetto-Mendoza Tania Regina , Leal Fabio E. , Freire Wilton , Paiao Heuder Gustavo Oliveira , Ferraz Andrea B C , Witkin Steven S. 
Published: May 2021

AbstractObjectivesTo evaluate if antibodies induced by infection with a different SARS-CoV-2 virus strain neutralize the P.1 variant.MethodsConvalescent sera from 60 individuals following a documented SARS-CoV-2 infection were assayed for neutralizing antibody titer against both strains.ResultsFifty-six and 50 sera were positive for neutralizing antibodies against the ancestral and P.1 strains, respectively. Neutralization titers were higher against the ancestral strain, but in the majority of patients differences did not differ by more than a single dilution.ConclusionsNeutralizing antibodies that were generated following infection with SARS-CoV-2 B.1.1.28 were effective in vitro, against the SARS-CoV-2 P.1. variant.
Investigation of gene-environment interactions in relation to tic severity
Authors: Abdulkadir Mohamed , Yu Dongmei , Osiecki Lisa , King Robert A. , Fernandez Thomas V. , Brown Lawrence W. , Cheon Keun-Ah , Coffey Barbara J. , Garcia-Delgar Blanca , Gilbert Donald L. , Grice Dorothy E. , Hagstrøm Julie , Hedderly Tammy , Heyman Isobel , Hong Hyun Ju , Huyser Chaim , Ibanez-Gomez Laura , Kim Young Key , Kim Young-Shin , Koh Yun-Joo , Kook Sodahm , Kuperman Samuel , Leventhal Bennett , Madruga-Garrido Marcos , Maras Athanasios , Mir Pablo , Morer Astrid , Münchau Alexander , Plessen Kerstin J. , Roessner Veit , Shin Eun-Young , Song Dong-Ho , Song Jungeun , Visscher Frank , Zinner Samuel H. , Mathews Carol A. , Scharf Jeremiah M. , Tischfield Jay A. , Heiman Gary A. , Dietrich Andrea , Hoekstra Pieter J. 
Published: May 2021

AbstractTourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N=518) design. We assessed 98 single nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate gene-studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies.
Is mRankin scale correlated with mTICI? A systematic review and meta-regression on RCTs and registries
Authors: De Rubeis Gianluca , Pampana Enrico , Prosperini Luca , Fabiano Sebastiano , Bertaccini Luca , Anticoli Sabrina , Saba Luca , Gasperini Claudio , Cotroneo Enrico 
Published: May 2021

AbstractBackground and PurposemTICI ≥2b/3 is one of the strongest positive predictors of mRS ≤2. Quantitative analysis is poorly investigated. Reconcile results from RCT and registries is still a challenge.The purpose was to evaluate the numeric correlation between mTICI≥2b/3 and mRS≤2 in RCT and registries.MethodsLiterature research was performed on Pubmed for studies in 2015-2020. mTICI, mRS and sample size were recorded. Exclusion criteria were monocentric study, not-human and not-English. Studies quality were assessed with MINORS and RoB2. Meta-logistic and meta-linear regressions were used to correlate mTICI and mRS in both RCTs and registries. Z-test was used for comparing coefficients between RCTs and registries.ResultsTwenty-six studies were evaluated (13 registries; 14 RCTs) for 24423 patients (21914 from registries [average per registry 1685±1277]; 2509 from RCTs [average per RCT 179±160]). RCTs involved anterior circulation only, 7/13 (53.8%) registries considered also posterior one.The OR of obtaining a mRS≤2 for a singular increased of mTICI ≥2b rate was 1.65 (CI95% 1.22-2.01) for all studies, 1.65 (CI95% 1.10-2.46) for RCTs and 1.50 (CI95% 1.00-2.23) for registries. mTICI≥2b and mRS had a positive correlation with a coefficient of 0.49 (CI95% 0.19-0.80, p=0.001) for all studies, 0.54 (CI95% 0.09-1.00) for RCTs and 0.42 (CI 95% 0.04-0.81) for registries. No differences were found in the coefficients between RCTs and registries (p=0.63; p=0.65; respectively).ConclusionsUnitary increased of mTICI≥2b rate correspond to an augment of mRS≤2 by 0.50 (CI95% 0.19-0.89) with OR of obtaining mRS≤2 of 1.65 (CI95% 1.22-2.01), without significantly differences in coefficients.
Clustered Mendelian Randomization analyses identifies distinct and opposing pathways in the causal association between insulin-like growth factor-1 and type 2 diabetes mellitus
Authors: Wang Wenyi , Tesfay Ephrem Baraki , van Dijk Ko Willems , Bartke Andrzej , van Heemst Diana , Noordam Raymond 
Published: May 2021

AbstractAims/hypothesisThere is inconsistent evidence for the causal role of serum insulin-like growth factor-1 (IGF-1) concentration in the pathogenesis of type 2 diabetes. Here, we investigated the association between IGF-1 and type 2 diabetes using a combination of multivariable-adjusted and (clustered) Mendelian Randomization (MR) analyses in the UK Biobank.MethodsWe conducted Cox proportional hazard analyses in 451,232 European-ancestry individuals of the UK Biobank (55.3% women, mean age at recruitment 56.6 years), among which 13,247 individuals developed type 2 diabetes during up to 12 years of follow-up. In addition, we conducted two-sample MR analyses based on independent SNPs associated with IGF-1. Given the heterogeneity between the causal estimates of individual instruments (P-value for Q statistic=4.03e-145), we also conducted clustered MR analyses. Biological pathway analyses of the identified clusters were performed by overrepresentation analyses.ResultsIn the Cox proportional hazard models, with IGF-1 concentrations stratified in quintiles, we observed that participants in the lowest quintile had the highest relative risk of type 2 diabetes (HR: 1.31; CI: 1.23-1.39). In contrast, in the two-sample MR analyses, higher genetically-influenced IGF-1 was associated with a higher risk of type 2 diabetes. Based on the heterogeneous distribution of causal effect estimates, six clusters associated either with a lower or a higher risk of type 2 diabetes were identified. The main clusters in which a higher IGF-1 was associated with a lower risk of type 2 diabetes consisted of instruments mapping to genes in the growth-hormone signaling pathway, whereas the main clusters in which a higher IGF-1 was associated with a higher risk of type 2 diabetes consisted of instruments mapping to genes in pathways related to amino acid metabolism and genomic integrity.ConclusionThe IGF-1 associated SNPs used as genetic instruments in MR analyses showed a heterogeneous distribution of causal effect estimates on the risk of type 2 diabetes. This was likely explained by differences in the underlying molecular pathways that increase IGF-1 concentration and differentially mediate the effects of IGF-1 on type 2 diabetes.
A Model to Introduce Medical Students to the Use of Artificial Intelligence and Genomics for Precision Medicine
Authors: Alderson Philip O. , Donlin Maureen J. , Morrison Lynda A. 
Published: May 2021

ABSTRACTObjectiveDespite the significant medical impact of artificial intelligence (AI) in healthcare, emergence of AI-related topics in medical curricula has been slow. The authors sought to introduce pre-clinical students to the importance of AI methodologies and medical applications using modular short courses focused on active learning with precision medicine as a primary use case.Materials and MethodsA short elective course was designed to introduce first-year students to how various bioinformatic and AI-related processes work and how they help classify medical data, facilitate genomic analysis and predict clinical outcomes. The course covers gene sequencing and variants, neural networks, natural language processing, medical computer vision and the limitations and ethical concerns related to use of AI in precision medicine. Online content serves as major source material. After a faculty-led introduction, sessions focus on teams of students who present course content to one another and lead discussions with faculty guidance. A related short AI course focused on gene variants was given to the entire second-year class.ResultsThe elective course has been taken by 74 first- year students over 8 consecutive semesters (2017-2021). The course achieved average satisfaction scores of 4.4/5.0 (n = 13) when the active learning approach became dominant in 2018. Students were able to describe accurately how bioinformatics and AI make personalized medicine possible. Students also did well on the gene variants exercise given to the entire second year class (2018), but the full class short AI course was not continued in subsequent years. Students have created a school-approved interest group in medical AI.ConclusionsThis experience shows that AI-related materials can be sustainably introduced into pre- clinical medical education with precision medicine as the primary use case. This modular course design and content could be adapted easily for educational use in medical subspecialties and other health professions.
Design and Formative Evaluation of a Voice-based Virtual Coach for Problem-Solving Treatment
Authors: Kannampallil Thomas , Ronneberg Corina R. , Wittels Nancy , Kumar Vikas , Lv Nan , Smyth Joshua M. , Gerber Ben S. , Kringle Emily , Johnson Jillian A. , Yu Philip , Steinman Lesley E. , Ajilore Olu , Ma Jun 
Published: May 2021

AbstractArtificial intelligence (AI)-based voice technology offers considerable promise in healthcare; however, its application for behavioral therapy in a real-world or research setting has yet to be determined. We describe the design and evaluation of 1Lumen™, a fully functional voice-only virtual coach that delivers evidence-based, problem-solving treatment (PST) for patients with mild-to-moderate depression and/or anxiety. Participants (N=26) completed surveys and semi-structured interviews after two therapy sessions with Lumen. Participants found Lumen to provide high pragmatic usability and favorable user experience, with marginal task load during interactions. Participants emphasized its on-demand accessibility and the delivery of a complex PST task with a simplistic structure for achieving therapy goals. Suggestions for improvement included streamlining and improved personalization and pacing of conversations and providing additional context during therapy sessions. Lumen offers a realistic and cognitively plausible verbal interaction that can potentially lead to personalized and accessible mental health care, filling a gap in traditional mental health services.
MiR-139-5p is a causal biomarker for type 2 diabetes; Results from genome-wide microRNA profiling and Mendelian randomization analysis in a population-based study
Authors: Mens Michelle M.J. , Mustafa Rima , Ahmadizar Fariba , Ikram M. Arfan , Evangelou Marina , Kavousi Maryam , Dehghan Abbas , Ghanbari Mohsen 
Published: May 2021

AbstractMicroRNAs (miRNAs) have emerged as key regulators of gene expression. Differential expression of miRNAs has been linked to diabetes, but underlying pathways remain poorly understood. We performed genome-wide miRNAs profiling and tested the causal associations between miRNAs and type 2 diabetes in the general population. Subsequently, we investigated target genes and metabolites of miRNAs to provide insight into the metabolic disturbances that emerge with type 2 diabetes. Between 2002 and 2005, plasma levels of 2083 circulatory miRNAs were profiled in 1900 participants (mean age 71.4 years) of the population-based Rotterdam Study cohort. The associations of 591 well-expressed miRNAs with prevalent and incident type 2 diabetes were examined until 2015. Two-sample Mendelian Randomization (MR) was conducted to investigate the causal associations and miRNA-target genes and metabolites were studied in relation to type 2 diabetes. At baseline, higher plasma levels of miR-139-5p and miR-193a-5p were associated (FDR<0.05) with prevalent type 2 diabetes (n=253 cases). During a follow-up of >9.0 years, 209 participants developed type 2 diabetes. Plasma levels of miR-99a-5p, miR-4664-3p, miR-29a-3p, miR-122-5p, and miR-125b-5p were significantly associated with incident type 2 diabetes (n=209). Two-sample MR confirmed a causal effect for miR-139-5p (MR-IWV-beta=0.10, p=3.51×10−4) on type 2 diabetes. We found several target genes and metabolites that could link miR-139-5p to pathways underlying type 2 diabetes. Our study indicates a causal relationship between miR-139-5p and type 2 diabetes and suggests this miRNA as a plasma biomarker of type 2 diabetes.
Current challenges of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence studies among blood donors: A scoping review
Authors: Saeed Sahar , Uzicanin Samra , Lewin Antoine , Lieshout-Krikke Ryanne , Faddy Helen , Erikstrup Christian , Osiowy Carla , Seed Clive , Steele Whitney , Davidson Katy , Custer Brian , O’Brien Sheila 
Published: May 2021

BackgroundBlood donors are increasingly being recognized as an informative resource for surveillance. We aimed to review and characterize SARS-CoV-2 seroprevalence studies conducted using blood donors to investigate methodology and provide guidance for future research.MethodsWe conducted a scoping review of peer-reviewed and preprint publications between January 2020 to January 2021. Two reviewers used standardized forms to extract seroprevalence estimates and data on methodology pertaining to population sampling, periodicity, assay characteristics and antibody kinetics. National data on cumulative incidence and social distancing policies were extracted from publicly available sources and summarized.ResultsThirty-three studies representing 1,323,307 blood donations from 20 countries worldwide were included (sample size per study ranged from 22 to 953,926 donations). Seroprevalence rates ranged from 0% to 76% (after adjusting for waning antibodies). Overall, less than 1 in 5 studies reported standardized seroprevalence rates to reflect the demographics of the general population. Stratification by age and sex were most common (64% of studies), followed by region (48%). 52% of studies reported seroprevalence at a single time point. Overall, 27 unique assay combinations were identified, 55% of studies used a single assay and only 39% adjusted seroprevalence rates for imperfect test characteristics. Among the eight nationally representative studies case detection was most underrepresented in Kenya (1:1264).ConclusionAs of December 11, 2020, 79% of studies reported seroprevalence rates <10%; thresholds far from reaching herd immunity. In addition to differences in community transmission and diverse public health policies, study designs and methodology were likely contributing factors to seroprevalence heterogeneity.