bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Interrupted Time-Series Analysis of Pediatric Emergency Department Visits During the Coronavirus Disease 2019 Pandemic
Authors: Irvine Michael A. , Portales-Casamar Elodie , Goldman Ran D. 
Published: April 2021

ObjectiveThe objective of this study was to estimate the impact of the coronavirus disease 2019 pandemic on pediatric emergency department (PED) visits after declaration of stay-at-home orders within British Columbia, Canada, and the change in cases by acuity and age for 6 months during the pandemic.MethodsRetrospective data on PED visits at British Columbia Children's Hospital were collected between December 1, 2019, and August 31, 2020, and for 2 previous years. An interrupted time-series analysis was performed to estimate the difference in daily visits after stay-at-home orders on March 17, 2020, as well as before and after. Further analysis was performed to estimate the drop and recovery of admission and visits by age and acuity.ResultsAfter adjustment for year and seasonality, we documented a drop in the expected number of daily visits of 83 (95% confidence interval [CI], 78–89) after stay-at-home orders. Thereafter, daily visits increased by 12.9 (95% CI, 11.3–14.4) every month. Probability of admission adjusted for seasonality and acuity increased 6.9% (95% CI, 4.9%–9.0%) after stay-at-home orders and decreased in the odds of −0.7% (95% CI, −1% to −0.4%) monthly thereafter.ConclusionsThe coronavirus disease 2019 pandemic has had a dramatic and lasting impact on the number of PED visits, with contracted rates 6 months into the pandemic. Further increase in acuity-adjusted rate of admissions after stay at home orders suggests that individuals may be delaying arrival to the emergency department. Further assessment is needed to determine if patients are seeking care through other venues or not seeking care altogether.
Responding to a Behavioral Health Crisis
Authors: Esposito Jeremy , Lavelle Jane , M'Farrej Mirna , Jhonsa Anik , Perry Erin , Felix Amy , Crescenzo Kelly , Abbadessa Mary Kate F. , Hayes Katie 
Published: April 2021

Objectives
Emergency department (ED) visits for behavioral health (BH) emergencies continue to rise, and institutions across the country encounter barriers and struggle to put BH processes in place to address their needs. After learning of an unanticipated closure of a local psychiatric crisis response center (CRC), our ED implemented quality improvement interventions to respond to an acute surge of BH patients.

Methods
Interventions included an enhanced BH database, the role of social workers as extenders, shared electronic health record documentation, increased staffing, clinical pathway updates, and processes to improve communication. We aimed to develop a care model to maintain safe care with timely evaluation and patient disposition despite an anticipated surge of ED patients.

Results
After the CRC closure, 7383 patients met our cohort definition over 18 months, whereas 4326 patients met the cohort definition in the 18 months prior the CRC closure. Of the total patients seen in the study period, 42% were evaluated by the ED team with psychiatry and social work, and the median length of stay for discharged patients evaluated by this team decreased from 4.2 hours to 3.5 hours after CRC closure.

Conclusions
A multifaceted approach allowed our ED to successfully respond to an unexpected surge of BH patients. Other institutions may be able to apply a population health and quality improvement approach when addressing the rising prevalence of ED BH visits. Future studies and practices should explore the optimal role of the acute care setting in the continuum of care of these patients.
Gadoxetate Disodium-Enhanced Imaging of Gradenigo Syndrome in End-Stage Renal Disease
Authors: Sattarova Victoria , Gencturk Mehmet , Lee Michael S. , McClelland Collin M. 
Published: April 2021

Abstract:
A 65-year-old man with end-stage renal disease on peritoneal dialysis was admitted for new onset binocular double vision, failure to thrive, and debilitating right-sided headaches. Medical history was significant for tympanomastoidectomy for polymicrobial mastoiditis and treatment with IV antibiotics. MRI brain without contrast was read by radiology initially as showing expected postsurgical changes; however, given patient's history of mastoiditis infection, there was a high clinical suspicion for Gradenigo syndrome. MRI brain was repeated with gadoxetate contrast to minimize the risk of nephrogenic systemic fibrosis (NSF) in a patient with severe renal disease and this revealed an intracranial empyema involving both the trigeminal and abducens nerves confirming the diagnosis of Gradenigo syndrome. This case presented a diagnostic challenge because of suboptimal visualization on initial nonenhanced MRI. Gadoxetate was chosen because of its unique properties including high hepatobiliary excretion making it a safer form of gadolinium-based contrast agent that may not have the potential to precipitate NSF.
Shared genetic etiology between cortical brain morphology and tobacco, alcohol, and cannabis use
Authors: Rabinowitz Jill A. , Campos Adrian I. , Ong Jue-Sheng , García-Marín Luis M. , Alcauter Sarael , Mitchell Brittany L. , Grasby Katrina S. , Cuéllar-Partida Gabriel , Gillespie Nathan A. , Huhn Andrew S. , Martin Nicholas G. , Thompson Paul M. , Medland Sarah E. , Maher Brion S. , Rentería Miguel E. 
Published: April 2021

ABSTRACTGenome-wide association studies (GWAS) have independently identified hundreds of genomic regions associated with brain morphology and substance use. However, the genetic overlap between brain structure and substance use has not been characterized. Here we leverage GWAS summary data of 71 brain imaging measures and alcohol, tobacco, and cannabis use to investigate their genetic overlap using LD score regression. We also used genomic structural equation modeling to model a ‘substance use common genetic factor’ and examined its genetic overlap with brain structure. After accounting for multiple testing, we identified eight significant negative genetic correlations, including between alcoholic drinks per week and average cortical thickness and intracranial volume with the age of smoking initiation; and five positive genetic correlations, including between insula surface area and lifetime cannabis use, and between the common factor with pericalcarine surface area. Our findings highlight a shared genetic etiology between variation in cortical brain morphology and substance use.
Sex Differences in Brain Structures and Functional Connectivity among Patients with Bipolar I Disorder
Authors: Li Ming-Yang , Tsai Shih-Jen , Yang Albert C. 
Published: April 2021

AbstractObjectivesStudies have demonstrated that sex differences may play a crucial role in the alternations of brain structures in individuals with bipolar disorder, but findings are not consistent. The current study identified sex differences in brain structure and function among a large sample of individuals with bipolar I disorder (BD-I).MethodsStructural and functional magnetic resonance imaging datasets were acquired from 105 individuals with BD-I (36 men and 69 women) and 210 healthy adults (72 men and 138 women). A general linear regression model was used for voxel-wise analysis of grey matter (GM) and functional connectivity. Age, sex, diagnosis, and sex-by-diagnosis interaction were defined as predictors.ResultsIn GM, the left caudate (p < .001), left thalamus (p < .001), right caudate (p = .003), right thalamus (p < .001), left anterior cingulate gyrus (p = .015), and left middle/posterior cingulate gyrus (p = .022) exhibited sex-by-diagnosis interaction. Furthermore, by using these six brain regions as seeds, we observed sex-by-diagnosis interaction in the alteration of functional connectivity between the left thalamus and right angular gyrus (p = .019).ConclusionsOur data revealed a sex-by-diagnosis interaction associated with structure and function of the limbic system in individuals with BD-I. These findings may serve as reference for future studies on the pathophysiology of bipolar disorder.
Simultaneous Monitoring of Disease and Microbe Dynamics Through Plasma DNA Sequencing in Pediatric Patients with Acute Lymphoblastic Leukemia
Authors: Barsan Valentin , Xia Yuntao , Klein David , Gonzalez-Pena Veronica , Youssef Sarah , Inaba Yuki , Mahmud Ousman , Natarajan Sivaraman , Agarwal Vibhu , Pang Yakun , Autry Robert , Pui Ching-Hon , Inaba Hiroto , Evans William , Gawad Charles 
Published: April 2021

AbstractTreatment of acute lymphoblastic leukemia (ALL) necessitates continuous risk assessment of leukemic disease burden as well as infections that arise in the setting of immunosuppression and myelosuppression. This study was performed to assess the feasibility of a hybrid capture NGS panel to longitudinally measure molecular leukemic disease clearance and microbial species abundance in 20 pediatric patients with ALL throughout induction chemotherapy. This proof-of-concept helps establish a technical and conceptual framework that we anticipate will be expanded and applied to additional patients with leukemias, as well as extended to additional cancers. Molecular monitoring can help to accelerate the attainment of insights into the temporal biology of host-microbe-leukemia interactions, including how those changes correlate with and alter anticancer therapy efficacy. We also anticipate fewer invasive bone marrow aspirations or biopsies will be required as these methods improve with standardization and are validated for clinical use.Key PointsA custom-designed hybridization capture next generation sequencing (NGS) panel noninvasively and quantitatively measures leukemic disease burden and microbial species abundance through serial peripheral blood draws throughout induction chemotherapy.Sequencing of circulating tumor DNA (ctDNA) alongside microbial cell free DNA (mcfDNA) in the same sample reveals the effectiveness of chemotherapy alongside the immunosuppressive consequences of cytotoxic therapy.Efforts to incorporate ctDNA and mcfDNA NGS monitoring in higher risk patient populations have the potential to uncover mechanisms of response, resistance, and infectious complications that correlate with patient outcomes.
Factors associated with nonessential workplace attendance during the Covid-19 pandemic in the UK in early 2021: evidence from cross-sectional surveys
Authors: Michie Susan , Potts Henry WW , West Robert , Amlot Richard , Smith Louise E , Fear Nicola T , Rubin G James 
Published: April 2021

AbstractBackground and aimsWorking from home where possible is important in reducing spread of Covid-19. In early 2021, a quarter of people in England who believed they could work entirely from home reported attending their workplace. To inform interventions to reduce this, this study examined associated factors.MethodsData from the ongoing CORSAIR survey series of nationally representative samples of people in the UK aged 16+ years in January-February 2021 were used. The study sample was 1422 respondents who reported that they could work completely from home. The outcome measure was self-reported workplace attendance at least once during the preceding week. Factors of interest were analysed in three blocks: 1) sociodemographic variables, 2) variables relating to respondents’ circumstances, and 3) psychological variables.Results26.8% (95%CI=24.5%-29.1%) of respondents reported having attended their workplace at least once in the preceding week. Sociodemographic variables and living circumstances significantly independently predicted non-essential workplace attendance: male gender (OR=1.85,95%CI=1.33-2.58), dependent children in the household (OR=1.65,95%CI=1.17-2.32), financial hardship (OR=1.14,95%CI=1.08-1.21), socio-economic grade C2DE (OR=1.74, 95%CI=1.19-2.53), working in sectors such as health or social care (OR=4.18, 95%CI=2.56-6.81), education and childcare (OR=2.45, 95%CI=1.45-4.14) and key public service (OR=3.78, 95%CI=1.83-7.81), and having been vaccinated (OR=2.08,95%CI=1.33-3.24).ConclusionsNon-essential workplace attendance in the UK in early 2021 during the Covid-19 pandemic was significantly independently associated with a range of sociodemographic variables and personal circumstances. Having been vaccinated, financial hardship, socio-economic grade C2DE, having a dependent child at home, working in certain key sectors were associated with higher likelihood of workplace attendance.
Genomic monitoring unveil the early detection of the SARS-CoV-2 B.1.351 lineage (20H/501Y.V2) in Brazil
Authors: Slavov Svetoslav Nanev , Leister Patané José Salvatore , Santos Bezerra Rafael dos , Giovanetti Marta , Fonseca Vagner , Martins Antonio Jorge , Viala Vincent Louis , Rodrigues Evandra Strazza , dos Santos Elaine Vieira , dos Santos Barros Claudia Renata , Marqueze Elaine Cristina , Santos Bibiana , Aburjaile Flavia , Neto Raul Machado , Moretti Debora Botequio , Haddad Ricardo , Calado Rodrigo Tocantins , Paulo Kitajima João , Freitas Erika , Schlesinger David , de Alcantara Luiz Carlos Junior , Elias Maria Carolina , Sampaio Sandra Coccuzzo , Kashima Simone , Covas Dimas Tadeu 
Published: April 2021

AbstractSao Paulo State, the most populous area in Brazil, currently experiences a second wave of the COVID-19 pandemic which overwhelmed the healthcare system. Recently, due to the paucity of SARS-CoV-2 complete genome sequences, we established a Network for Pandemic Alert of Emerging SARS-CoV-2 Variants to rapidly understand the spread of SARS-CoV-2 and monitor in nearly real-time the circulating SARS-CoV-2 variants into the state. Through full genome analysis of 217 SARS-CoV-2 complete genome sequences obtained from the largest regional health departments we were able to identify the co-circulation of multiple SARS-CoV-2 lineages such as i) B.1.1 (0.92%), ii) B.1.1.1 (0.46%), iii) B.1.1.28 (25.34%), iv) B.1.1.7 (5.99%), v) B.1.566 (1.84%), vi) P.1 (64.05%), and P.2 (0.92%). Further our analysis allowed the detection, for the first time in Brazil of the South African variant of concern (VOC), the B.1.351 (501Y.V2) (0.46%). The identified lineage was characterized by the presence of the following mutations: ORF1ab: T265I, R724K, S1612L, K1655N, K3353R, SGF 3675_F3677del, P4715L, E5585D; Spike: D80A, D215G, L242_L244del, A262D, K417N, E484K, N501Y, D614G, A701V, C1247F; ORF3a: Q57H, S171L, E: P71L; ORF7b: Y10F, N: T205I; ORF14: L52F. Origin of the most recent common ancestor of this genomic variant was inferred to be between middle October to late December 2020. Analysis of generated sequences demonstrated the predominance of the P.1 lineage and allowed the early detection of the South African strain for the first time in Brazil. Our findings highlight the importance to increase active monitoring to ensure the rapid detection of new SARS-CoV-2 variants with a potential impact in pandemic control and vaccination strategies.
Use of multiple Polygenic Risk Scores for distinguishing Schizophrenia-spectrum disorder and Affective psychosis categories; the EUGEI study
Authors: Rodriguez Victoria , Alameda Luis , Quattrone Diego , Tripoli Giada , Gayer-Anderson Charlotte , Spinazzola Edoardo , Trotta Giulia , Jongsma Hannah E , Stilo Simona , Cascia Caterina La , Ferraro Laura , Barbera Daniele La , Lasalvia Antonio , Tosato Sarah , Tarricone Ilaria , Bonora Elena , Jamain Stéphane , Selten Jean-Paul , Velthorst Eva , de Haan Lieuwe , Llorca Pierre-Michel , Arrojo Manuel , Bobes Julio , Bernardo Miguel , Arango Celso , Kirkbride James , Jones Peter B , Rutten Bart P , Richards Alexander , Sham Pak C , O’Donovan Michael , Van Os Jim , Morgan Craig , Forti Marta Di , Murray Robin M , Vassos Evangelos 
Published: April 2021

ABSTRACTSchizophrenia (SZ), Bipolar Disorder (BD) and Depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUGEI case-control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD). Participants (573 cases, 1005 controls) of european ancestry from 17 sites as part of the EUGEI study were successfully genotyped following standard quality control procedures. Using standardised PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons. In case-control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case-case comparison, both PRS-SZ (OR=0.7, 95 %CI 0.53-0.92) and PRS-D (OR=1.29, 95%CI 1.05-1.6) differentiated global AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR=2.38, 95%CI 1.32-4.29). Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards potential usefulness of PRSs for diagnostic prediction in specific populations such as high-risk or early psychosis phases.
SARS-CoV-2 infectivity by viral load, S gene variants and demographic factors and the utility of lateral flow devices to prevent transmission
Authors: Lee Lennard YW , Rozmanowski Stefan , Pang Matthew , Charlett Andre , Anderson Charlotte , Hughes Gareth J , Barnard Matthew , Peto Leon , Vipond Richard , Sienkiewicz Alex , Hopkins Susan , Bell John , Crook Derrick W , Gent Nick , Walker A Sarah , Peto Tim EA , Eyre David W 
Published: April 2021

AbstractBackgroundHow SARS-CoV-2 infectivity varies with viral load is incompletely understood. Whether rapid point-of-care antigen lateral flow devices (LFDs) detect most potential transmission sources despite imperfect sensitivity is unknown.MethodsWe combined SARS-CoV-2 testing and contact tracing data from England between 01-September-2020 and 28-February-2021. We used multivariable logistic regression to investigate relationships between PCR-confirmed infection in contacts of community-diagnosed cases and index case viral load, S gene target failure (proxy for B.1.1.7 infection), demographics, SARS-CoV-2 incidence, social deprivation, and contact event type. We used LFD performance to simulate the proportion of cases with a PCR-positive contact expected to be detected using one of four LFDs.Results231,498/2,474,066 (9%) contacts of 1,064,004 index cases tested PCR-positive. PCR-positive results in contacts independently increased with higher case viral loads (lower Ct values) e.g., 11.7%(95%CI 11.5-12.0%) at Ct=15 and 4.5%(4.4-4.6%) at Ct=30. B.1.1.7 infection increased PCR-positive results by ∼50%, (e.g. 1.55-fold, 95%CI 1.49-1.61, at Ct=20). PCR-positive results were most common in household contacts (at Ct=20.1, 8.7%[95%CI 8.6-8.9%]), followed by household visitors (7.1%[6.8-7.3%]), contacts at events/activities (5.2%[4.9-5.4%]), work/education (4.6%[4.4-4.8%]), and least common after outdoor contact (2.9%[2.3-3.8%]). Contacts of children were the least likely to test positive, particularly following contact outdoors or at work/education. The most and least sensitive LFDs would detect 89.5%(89.4-89.6%) and 83.0%(82.8-83.1%) of cases with PCR-positive contacts respectively.ConclusionsSARS-CoV-2 infectivity varies by case viral load, contact event type, and age. Those with high viral loads are the most infectious. B.1.1.7 increased transmission by ∼50%. The best performing LFDs detect most infectious cases.Key pointsIn 2,474,066 contacts of 1,064,004 SARS-CoV-2 cases, PCR-positive tests in contacts increased with higher index case viral loads, the B.1.1.7 variant and household contact. Children were less infectious. Lateral flow devices can detect 83.0-89.5% of infections leading to onward transmission.
Phage infection restores PQS signaling and enhances growth of aPseudomonas aeruginosa lasIquorum-sensing mutant
Authors: Høyland-Kroghsbo Nina Molin , Bassler Bonnie L. 
Published: April 2021

AbstractBacteriophage (phage) therapy is reemerging as a valuable tool to combat multidrug resistant bacteria. A major hurdle in developing efficacious bacteriophage therapies is that bacteria acquire resistance to phage killing. In this context, it is noteworthy that quorum sensing (QS), the bacterial cell-to-cell communication mechanism that promotes collective undertaking of group behaviors including anti-phage defenses, enhances bacterial survival in the face of phage attack. QS relies on the production, release, accumulation, and detection of signal molecules called autoinducers. In the opportunistic pathogenPseudomonas aeruginosa, the LasI/R QS system induces the RhlI/R QS system, and these two systems control, in opposing manners, the PQS QS system that relies on the autoinducer called PQS. A ΔlasImutant is impaired in PQS synthesis, leading to accumulation of the precursor molecule HHQ. HHQ suppresses growth of theP. aeruginosaΔlasIstrain. We uncover a phage infection-induced mechanism that restores expression of thepqsHgene in theP. aeruginosaΔlasIQS mutant. PqsH converts HHQ into PQS, preventing HHQ-mediated growth inhibition. Thus, phage-infectedP. aeruginosaΔlasIcells exhibit superior growth compared to uninfected cells. Phage infection also restores expression of virulence factors and the CRISPR-casanti-phage defense system in theP. aeruginosaΔlasIstrain. This study highlights a challenge for phage therapy, namely that phage infection may make particular bacterial strains faster growing, more virulent, and resistant to phage killing.ImportanceThe emergence of multidrug resistant bacteria necessitates development of new antimicrobial therapies. Phage therapy relies on exploiting phages, natural enemies of bacteria, in the fight against pathogenic bacteria. For successful phage therapy development, potent phages that exhibit low propensity for acquisition of bacterial resistance are desired. Here, we show that phage infection restores QS, a cell-to-cell communication mechanism in aP. aeruginosaQS mutant, which increases its virulence and resistance to phage killing. Importantly, clinical isolates ofP. aeruginosafrequently harbor mutations in particular QS genes. Thus, phage therapies against suchP. aeruginosastrains may inadvertently increase bacterial virulence. Our study underscores the importance of characterizing phage-host interactions in the context of bacterial mutants that are relevant in clinical settings prior to selecting phages for therapy.