bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of convalescent plasma versus standard care in hospitalized patients with COVID-19 from the Peruvian Social Security Health System: open-label, randomized, controlled clinical trial
Authors: Villanueva Cristian , Neyra Ibeth , Sagastegui Arturo , Chunga Ausberto , Oyanguren Martin , Guillermo-Roman Martina , Soto-Ordoñez Suly , Maguiña Jorge L. , Hurtado-Roca Yamilee , Soto-Becerra Percy , Araujo-Castillo Roger V. 
Published: September 2022

ABSTRACTOBJECTIVESTo assess the efficacy and safety of convalescent plasma plus standard of care (CP + SoC) compared with standard of care (SoC) alone in patients hospitalized for moderate to severe COVID-19 who do not yet require mechanical ventilation.METHODSPhase 2 randomized, parallel-group, randomized, open-label, controlled, superiority, single-center clinical trial. This clinical trial has been registered in REPEC with the following ID: 013-20. Hospitalized adult patients with moderate to severe COVID-19 were enrolled. The allocation ratio was 1:1 in a variable-size permuted block randomization scheme. The primary outcome was death 28 days after the intervention. Secondary outcomes were mortality at 14 and 56 days, time to death at 56 days, time in the ICU at 28 days, time on a mechanical ventilator at 28 days, frequency of adverse events, and frequency of serious adverse events.RESULTSA total of 64 participants were enrolled, 32 were assigned to CP + SoC, and 32 to SoC. One participant assigned to CP + SoC withdrew his informed consent before applying the treatment. At day 28, there were no statistically significant differences for the primary outcome between the CP + SoC and SoC groups (relative risk: 2.06; 95%CI 0.73 to 7.11; p = 0.190). No differences were found in the incidences of mortality at 56 days (hazard ratio: 2.21; 95%CI 0.66 to 7.33; p = 0.182), admission to the ICU at 28 days (sub-hazard ratio: 2.06; 95%CI 0.57 to 8.55; p = 0.250), admission to mechanical ventilation at 28 days (sub-hazard ratio: 2.19; 95%CI 0.57 to 8.51; p = 0.260). Estimates for days 14 were similar. No infusion-related adverse events were reported during the study. There were no statistically significant differences in the frequency of any adverse events (odds ratio: 2.74; 95%CI 0.90 to 9.10; p = 0.085) or the frequency of serious adverse events (odds ratio: 3.60; 95%CI 0.75 to 26.1; p = 0.75).CONCLUSIONSNo evidence was found that CP had a significant effect in reducing 28-day mortality. There was also no evidence that the frequency of adverse events was higher in those who received CP + SoC than those who received only SoC.
The impact of 22q11.2 copy number variants on human traits in the general population
Authors: Zamariolli Malú , Auwerx Chiara , Sadler Marie C , van der Graaf Adriaan , Lepik Kaido , Moysés-Oliveira Mariana , Dantas Anelisa G , Melaragno Maria Isabel , Kutalik Zoltán 
Published: September 2022

ABSTRACTWhile extensively studied in clinical cohorts, the phenotypic consequences of 22q11.2 copy number variants (CNVs) in the general population remain understudied. To address this gap, we performed a phenome-wide association scan in 405’324 unrelated UK Biobank (UKBB) participants using CNV calls from genotyping array. We mapped 236 Human Phenotype Ontology terms linked to any of the 90 genes encompassed by the region to 170 UKBB traits and assessed the association between these traits and the copy-number state of 504 SNP-array probes in the region. We found significant associations for eight continuous and nine binary traits associated under different models (duplication-only, deletion-only, U-shape and mirror model). The causal effect of the expression level of 22q11.2 genes on associated traits was assessed through transcriptome-wide mendelian randomization (TWMR), revealing that increased expression of ARVCF increased BMI. Similarly, increased DGCR6 expression causally reduced mean platelet volume, in line with the corresponding CNV effect. Furthermore, cross-trait multivariable mendelian randomization (MVMR) suggested a predominant role of genuine (horizontal) pleiotropy in the CNV region. Our findings show that within the general population, 22q11.2 CNVs are associated with traits previously linked to genes in the region, with duplications and deletions acting upon traits in different fashion. We also showed that gain or loss of distinct segments within 22q11.2 may impact a trait under different association models. Our results have provided new insights to help further the understanding of the complex 22q11.2 region.
Less invasive SARS-CoV-2 testing for children: A comparison of saliva and a novel Anterior Nasal Swab
Authors: Tosif Shidan , Lee Lai-yang , Nguyen Jill , Selman Chris , Grobler Anneke C , McMinn Alissa , Steer Andrew , Daley Andrew , Crawford Nigel 
Published: September 2022

AbstractReducing procedural discomfort for children requiring respiratory testing for SARS-CoV-2 is important in supporting testing strategies for case identification. Alternative sampling methods to nose and throat swabs, which can be self-collected, may reduce laboratory-based testing requirements and provide rapid results for clearance to attend school or hospital settings. The aim of this study was to compare preference and diagnostic sensitivity of a novel anterior nasal swab (ANS), and saliva, with a standard combined nose and throat (CTN) swab. The three samples were self-collected by children aged 5-18 years who had COVID-19 or were a household close contact. Samples were analysed by reverse transcription polymerase chain reaction (RT-PCR) on the Allplex SARS-CoV-2 Assay. Most children and parents preferred the ANS and saliva swab over the CTN swab for future testing. The ANS was highly sensitive (sensitivity 1.000 (95% Confidence Interval (CI) 0.920, 1.000)) for SARS-CoV-2 detection, compared to saliva (sensitivity 0.886, 95% CI 0.754, 0.962). We conclude the novel ANS is a highly sensitive and more comfortable method for SARS-CoV-2 detection when compared to CTN swab.
Differential WMH progression trajectories in progressive and stable mild cognitive impairment
Authors: Kamal Farooq , Morrison Cassandra , Maranzano Josefina , Zeighami Yashar , Dadar Mahsa ,   Alzheimer’s Disease Neuroimaging Initiative
Published: September 2022

AbstractBackgroundPathological brain changes such as white matter hyperintensities (WMHs) occur with increased age and contribute to cognitive decline. Current research is still unclear regarding the association of amyloid positivity with WMH burden and progression to dementia in people with mild cognitive impairment (MCI).MethodsThis study examined whether WMH burden increases differently in both amyloid-negative (Aβ-) and amyloid-positive (Aβ+) people with MCI who either remain stable or progress to dementia. We also examined regional WMHs differences in all groups: amyloid positive (Aβ+) progressor, amyloid negative (Aβ–) progressor, amyloid positive (Aβ+) stable, and amyloid negative (Aβ–) stable. MCI participants from the Alzheimer’s Disease Neuroimaging Initiative were included if they had APOE ɛ4 status and if they had amyloid measures to determine amyloid status (i.e., positive, or negative). A total of 820 MCI participants that had APOE ɛ4 status and amyloid measures were included in the study with 5054 follow-up time points over a maximum period of 13 years with an average of 5.7 follow-up timepoints per participant. Linear mixed-effects models were used to examine group differences in global and regional WMHs.ResultsPeople who were Aß– stable had lower baseline WMHs compared to both Aß+ progressors and Aß+ stable across all regions. When examining change over time, compared to Aß– stable, all groups had steeper change in WMH burden with Aß+ progressors having the largest change (largest increase in WMH burden over time).ConclusionThese findings suggest that WMH progression is a contributing factor to conversion to dementia both in amyloid-positive and negative people with MCI.
Metabolomic fingerprinting for biomarker discovery in renal amyloidosis
Authors: Ghosh Shreya , Singh Praveen , Govil Samir , Kala Chayanika , Chitkara Shivani , Sengupta Shantanu , Thakur Ashwani Kumar 
Published: September 2022

AbstractNephrotic syndrome (NS) manifested by proteinuria is the primary clinical hallmark of amyloid deposition in the kidney. However, proteinuria is observed in other kidney disorders misleading clinicians and limiting the scope of early diagnosis. We presumed that amyloid-driven pathophysiology could result in the perturbation of downstream cellular and metabolic pathways in these patients with NS. Herein, we have diagnosed one hundred patients with clinical evidence of nephrotic syndrome. Further, the histopathological evaluation identified the presence of amyloid in eleven patients. To decipher the downstream effects underlying amyloid formation, we performed plasma metabolomic profiling of these patients. Fifteen metabolites, including different lipids, carnitines and amino acids, were found altered in the renal amyloidosis patients compared to controls. It is the first study depicting the potential of metabolomics to identify biomarkers for early diagnosis of renal amyloidosis patients.
Sensitivity and Uncertainty Analysis for Two-Stream Capture-Recapture Methods in Disease Surveillance
Authors: Zhang Yuzi , Chen Jiandong , Ge Lin , Williamson John M. , Waller Lance A. , Lyles Robert H. 
Published: September 2022

AbstractCapture-recapture methods are widely applied in estimating the number (N) of prevalent or cumulatively incident cases in disease surveillance. Here, we focus the bulk of our attention on the common case in which there are two data streams. We propose a sensitivity and uncertainty analysis framework grounded in multinomial distribution-based maximum likelihood, hinging on a key dependence parameter that is typically non-identifiable but is epidemiologically interpretable. Focusing on the epidemiologically meaningful parameter unlocks appealing data visualizations for sensitivity analysis and provides an intuitively accessible framework for uncertainty analysis designed to leverage the practicing epidemiologist’s understanding of the implementation of the surveillance streams as the basis for assumptions driving estimation of N. By illustrating the proposed sensitivity analysis using publicly available HIV surveillance data, we emphasize both the need to admit the lack of information in the observed data and the appeal of incorporating expert opinion about the key dependence parameter. The proposed uncertainty analysis is an empirical Bayes-like approach designed to more realistically acknowledge variability in the estimated N associated with uncertainty in an expert’s opinion about the non-identifiable parameter, together with the statistical uncertainty. We demonstrate how such an approach can also facilitate an appealing general interval estimation procedure to accompany capture-recapture methods. Simulation studies illustrate the reliable performance of the proposed approach for quantifying uncertainties in estimating N in various contexts. Finally, we demonstrate how the recommended paradigm has the potential to be directly extended for application to data from more than two surveillance streams.
MicroRNA-146a polymorphisms are Associated with Psoriasis Vulgaris
Authors: Zhu Kunju , Li Shijie , Liang Lifan 
Published: September 2022

AbstractMicroRNA-146a acts as a critical physiological brake role to prevent the overactivation of inflammatory response pathways and was a key negative regulator of autoimmunity. Ets-1 could bind to the MicroRNA-146a promoter region as a regulator of MicroRNA-146a expression in vitro. IRAK1 is a prominent target of MicroRNA-146a that help it to negatively regulate the release of IL8. This study aimed to investigate the association of MicroRNA-146a, Ets-1(negative regulator) and IRAK1(target) polymorphisms with Psoriasis Vulgaris(PsV), the most prevalent chronic inflammatory skin disease in adults, in a Southern Chinese cohort. Seven SNPs in microRNA-146a (rs2431697; rs2910164; rs57095329), Ets-1(rs10893872; rs1128334) and IRAK1(rs1059703; rs3027898) genes were genotyped in 673 subjects (360 PsV cases and 313 controls) by SNaPshot Multiplex Kit (Applied Biosystems Co., USA). We found significant difference in the genotype and allele frequencies of rs2431697 and rs2910164 in MicroRNA-146a gene between the PsV cases and the controls. The dominant model genotype (CC+CT) (p=0.019; OR=1.463) and allele (C) (p=0.027; OR=1.496) of rs2431697 and the GG genotype (p= 0.027; OR=1.582) and allele (G) of rs2910164 were associated with an increased risk of PsV. There was no association of the SNPs with the clinical traits of PsV. Our data provide preliminary evidence that the rs2431697 and rs2910164 polymorphism in the microRNA-146a gene may be involved in the genetic susceptibility to PsV in Southern Chinese. Although further function studies will be required to identify the details of the process, the findings could make a significant step forward in our understanding of the genetic contribution to psoriasis.What’s already known about this topic?MicroRNA-146a is one of the most highly associated MicroRNA to psoriasis.MicroRNA-146a acts as a critical physiological brake role to prevent the overactivation of inflammatory response pathways and was a key negative regulator of autoimmunity.What does this study add?Our data provide preliminary evidence that the rs2431697 and rs2910164 polymorphism in the microRNA-146a gene are involved in the genetic susceptibility to PsV in Southern Chinese.
Assessment tools and incidence of hospital-associated disability: a rapid systematic review
Authors: Giacomino Katia , Hilfiker Roger , Beckwée David , Taeymans Jan , Sattelmayer Karl Martin 
Published: September 2022

AbstractBackgroundDuring hospitalization older people have a high risk of developing functional impairments unrelated to the reasons for their admission. This is termed hospital-associated disability. This systematic review aimed to assess the incidence of hospital-associated disability among older patients admitted to acute care, to identify the tools used to assess activities of daily living in these patients, and evaluate which functional task is most sensitive for detecting changes in disability among older hospitalized patients.MethodsA rapid systematic review was performed according to the recommendations of the Cochrane Rapid Reviews Methods Group and the PRISMA statement. A literature search was performed in Medline (via Ovid), EMBASE, and Cochrane Central Register of Controlled Trials databases on 26 August 2021. Inclusion criteria: older people, assessment of activities of daily living at baseline and discharge. Exclusion criterion: diseases affecting functional decline.ResultsEleven studies were included in the final review. Incidence of hospital-associated disability (overall score) was 37% (95% CI 0.31–0.42). Insufficient data prevented meta-analysis of the individual items. The most sensitive measure for detecting changes in disability was the overall score of assessment of activities of daily living.ConclusionsIncidence of hospital-associated disability in older patients might be overestimated, due to the combination of disease-related disability and hospital-associated disability. The tools used to assess these patients presented some limitations. These results should be interpreted with caution, as a limited number of studies reported adequate information to assess the incidence of hospital-associated disability. Risk of bias in the included studies raised some concerns.
Natural language processing and modeling of clinical disease trajectories across brain disorders
Authors: Mekkes Nienke , Groot Minke , Wehrens Sophie , Hoekstra Eric , Herbert Megan K , Brummer Maaike , Wever Dennis ,   Netherlands Neurogenetics Database Consortium, Eggen Bart J.L. , Rozemuller Annemieke , Huitinga Inge , Holtman Inge R. 
Published: September 2022

AbstractBrain disorders, including neurodegenerative diseases and mental illnesses, are often difficult to diagnose and study due to clinical and pathological heterogeneity, overlap in clinical manifestations between disorders, and frequent comorbidities, hampering drug development and fundamental research. Hence, there is a clear need for data-driven approaches to disentangle these complex disorders. Here, we established a computational pipeline to process clinical summaries from donors with a wide range of brain disorders that were neuropathologically diagnosed by the Netherlands Brain Bank. First, we identified and defined 90 cross-disorder signs and symptoms within cognitive, motor, sensory, psychiatric, and general domains. Second, we trained and optimized natural language processing (NLP) models to identify these signs and symptoms in individual sentences of the extensive clinical summaries from donors of the NBB, resulting in temporal disease trajectories. Third, we studied the temporal manifestation and survival profiles across rare and complex dementias, alpha-synucleinopathies, frontotemporal dementia subtypes, and mental illnesses, giving new insight into how symptomatology differs in manifestation and temporal profiles across brain disorders. Lastly, we trained a recurrent neural network to predict the Neuropathological Diagnosis. Taken together, this integrated approach resulted in a highly unique resource that can facilitate research into cross-disorder symptomatology.
Data-driven identification of unusual prescribing behaviour: an analysis and interactive data tool using six months of primary care data from 6500 practices in England
Authors: Hopcroft Lisa EM , Massey Jon , Curtis Helen , MacKenna Brian , Croker Richard , Macdonald Orla , Evans David , Inglesby Peter , Bacon Seb , O’Dwyer Tom , Goldacre Ben , Walker Alex J 
Published: September 2022

AbstractBackgroundApproaches to addressing unwarranted variation in healthcare service delivery have traditionally relied on the prospective identification of activities and outcomes, based on a hypothesis, with subsequent reporting against defined measures. Practice-level prescribing data in England are made publicly available by the NHS Business Services Authority for all general practices. There is an opportunity to adopt a more data-driven approach to capture variability and identify outliers by applying hypothesis free data driven algorithms to national datasets.ObjectivesTo develop and apply a hypothesis free algorithm to identify unusual prescribing behaviour in primary care data at multiple administrative levels in the NHS in England, and to visualise these results using organisation-specific interactive dashboards.MethodsHere we report a new data-driven approach to quantify how ‘unusual’ prescribing rates of a particular chemical within an organisation are as compared to peer organisations, over a period of six months (June-December 2021). This is followed by ranking to identify which chemicals are the most notable outliers in each organisation. These outlying chemicals are calculated for all practices, primary care networks, clinical commissioning groups and sustainability and transformation partnerships in England. Results are presented via organisation-specific interactive dashboards, the iterative development of which has been informed by user feedback.ResultsUser feedback and internal review of case studies demonstrate that our methodology identifies chemicals that are in line with local policies and internal reporting.ConclusionsData-driven approaches overcome existing biases with regards to the planning and execution of audits, interventions and policy-making within NHS organisations, potentially revealing new targets for improved healthcare service delivery. We provide our dashboards as a candidate list for the consideration of expert users to prioritise for further interpretation and qualitative research in terms of potential targets for improved performance.
Intensity of sample processing methods impacts wastewater SARS-CoV-2 whole genome amplicon sequencing outcomes
Authors: Feng Shuchen , Owens Sarah M. , Shrestha Abhilasha , Poretsky Rachel , Hartmann Erica M. , Wells George 
Published: September 2022

ABSTRACTWastewater SARS-CoV-2 surveillance has been deployed since the beginning of the COVID-19 pandemic to monitor dynamics in virus burden in local communities. Genomic surveillance of SARS-CoV-2 in wastewater, particularly the efforts for whole genome sequencing for variant tracking or identification, are comparatively challenging due to low target concentration, complex microbial and chemical background, and lack of robust nucleic acid recovery experimental procedures. The intrinsic sample limitations are inherent to wastewater. In this study, we evaluated impacts from sample types, certain sample intrinsic features, and processing and sequencing methods on sequencing outcomes with a specific focus on the breadth of genome coverage. We collected 184 composite and grab wastewater samples from the Chicago area between March to October 2021 for SARS-CoV-2 quantification and genomic surveillance. Samples were processed using a mixture of processing methods reflecting different homogenization intensities (HA+Zymo beads, HA+glass beads, and Nanotrap), and were sequenced using two sequencing library preparation kits (the Illumina COVIDseq kit and the QIAseq DIRECT kit). A synthetic SARS-CoV-2 RNA experiment was performed to validate the potential impacts of processing methods on sequencing outcomes. Our findings suggested that 1) wastewater SARS-CoV-2 whole genome sequencing outcomes were associated with sample types and processing methods 2) in less intensive method processed samples (HA+glass beads), higher genome breadth of coverage in sequencing (over 80%) was associated with N1 concentration > 105 cp/L, while in intensive method (HA+Zymo beads), qPCR results were inconsistent with sequencing outcomes, and 3) sample processing methods and sequencing kits, rather than the extraction methods or intrinsic features of wastewater samples, played important roles in wastewater SARS-CoV-2 amplicon sequencing. Overall, extra attention should be paid to wastewater sample processing (e.g., concentration and homogenization) for sufficient, good quality RNA yield for downstream sequencing.
Effects of SARS-CoV-2 Infection on Attention, Memory, and Sensorimotor Performance
Authors: O’Connor Erin E. , Rednam Nikita , O’Brien Rory , O’Brien Shea , Rock Peter , Levine Andrea , Zeffiro Thomas A. 
Published: September 2022

AbstractBackgroundRecovery after SARS-CoV-2 infection is extremely variable, with some individuals recovering quickly, and others experiencing persistent long-term symptoms or developing new symptoms after the acute phase of infection, including fatigue, poor concentration, impaired attention, or memory deficits. Many existing studies reporting cognitive deficits associated with SARS-CoV-2 infection are limited by the exclusive use of self-reported measures or a lack of adequate comparison groups.MethodsForty-five participants, ages 18-70, (11 Long-COVID, 14 COVID, and 20 No-COVID) underwent behavioral testing with the NIH Toolbox Neuro-Quality of Life survey and selected psychometric tests, including a flanker interference task and the d2 Test of Attention.ResultsWe found greater self-reported anxiety, apathy, fatigue, emotional dyscontrol, sleep disturbance and cognitive dysfunction in COVID compared No-COVID groups. After categorizing COVID patients according to self-reported concentration problems, we observed declining performance patterns in multiple attention measures across No-COVID controls, COVID and Long-COVID groups. COVID participants, compared to No-COVID controls, exhibited worse performance on NIH Toolbox assessments, including the Eriksen Flanker, Nine-Hole Pegboard and Auditory Verbal Learning tests.ConclusionThis study provides convergent evidence that previous SARS-CoV-2 infection is associated with impairments in sustained attention, processing speed, self-reported fatigue and concentration. The finding that some patients have cognitive and visuomotor dysfunction in the absence of self-reported problems suggests that SARS-CoV-2 infection can have unexpected and persistent subclinical consequences.