bluuebunny/crossref_metadata_2025_split huggingface dataset:
The potential for digital patient symptom recording through symptom assessment applications to optimize patient flow and reduce waiting times in Urgent Care Centers: a simulation study
Authors: Montazeri Maryam , Multmeier Jan , Novorol Claire , Upadhyay Shubhanan , Wicks Paul , Gilbert Stephen 
Published: June 2020

AbstractBackgroundOvercrowding can negatively affect the performance of the health care facilities not only for patients in terms of delayed care delivery and increased health risk, but also for health care workers in terms of increased burden and stress. Sometimes overcrowding is a result duplicate activity such as history taking and recording of patients’ symptoms. In this case, using a digital symptom assessment application can prevent duplication of such activities and may decrease the crowding in health care facilities.ObjectiveWe sought to understand the effect of a digital symptom assessment app that facilitates the taking of patient clinical history to optimize patient flow. We hypothesized that waiting times and crowding in an urgent care center could be reduced through the introduction of a digital history taking tool, and that this would be more efficient than simply adding more staff.MethodsA discrete event approach was used to simulate patient flow in an urgent care center during a hypothetical 4-hour time window. The baseline case simulated a small center with 2 triage nurses, 2 doctors, 1 treatment/examination nurse and 1 discharge administrator in service. In addition to the base case, the center is simulated in 32 scenarios either with different number of staff or different assumption on time saved by the app. Target outcomes included average queue length, waiting time, idle time and utilization of staffResultsDiscrete event simulation found that a few minutes saved by a digital history taking app during triage could significantly increase efficiency. An estimated time-saving per patient of 2.5 minutes decreased average patient wait for triage by 26.17%; a 5 minutes time-saving would lead to a 54.88% reduction. Alternatively, adding an additional triage nurse was less efficient, as the additional staff were only required at the busiest times. While reduction in waiting time for triage was similar (approximately 50%) for either approach, adding a triage nurse reduced the median nurse utilization from 97% to 41%, while adding the tool resulted in median nurse utilization of 88%.ConclusionsDigital history taking could result in substantial reduction in patient waiting time for triage nurses, which is associated with reduced patient anxiety, staff anxiety and improved patient care. Patient history taking could be carried out in waiting room (via a check-in kiosk or portable tablet computer) or out at home. This simulation has the potential to impact service provision and approaches to digitalization at scale.
COVID-19 and first trimester spontaneous abortion: a case-control study of 225 pregnant patients
Authors: Cosma Stefano , Carosso Andrea , Cusato Jessica , Borella Fulvio , Carosso Marco , Bovetti Marialuisa , Filippini Claudia , D’Avolio Antonio , Ghisetti Valeria , Di Perri Giovanni , Benedetto Chiara 
Published: June 2020

ABSTRACTBackgroundEvidence for the impact of COVID-19 during the second and the third trimester of pregnancy is limited to a relatively small series, while data on the first trimester are scant. With this study we evaluated COVID-19 infection as a risk factor for spontaneous abortion in first trimester of pregnancy.MethodsBetween February 22 and May 21, 2020, we conducted a case-control study at S. Anna Hospital, Turin, among first trimester pregnant women, paired for last menstruation. The cumulative incidence of COVID-19 was compared between women with spontaneous abortion (case group, n=100) and those with ongoing pregnancy (control group, n=125). Current or past infection was determined by detection of SARS-CoV-2 from nasopharingeal swab and SARS- CoV-2 IgG/IgM antibodies in blood sample. Patient demographics, COVID-19-related symptoms, and the main risk factors for abortion were collected.FindingsTwenty-three (10.2%) of the 225 women tested positive for COVID-19 infection. There was no difference in the cumulative incidence of COVID-19 between the cases (11/100, 11%) and the controls (12/125, 9.6%) (p=0.73). Logistic regression analysis confirmed that COVID-19 was not an independent predictor of abortion (1.28 confidence interval 0.53-3.08).InterpretationCOVID-19 infection during the first trimester of pregnancy does not appear to predispose to abortion; its cumulative incidence did not differ from that of women with ongoing pregnancy.
Sex Moderates the Relationship that Number of Professional Fights has with Cognition and Brain Volumes
Authors: Bennett Lauren L. , Stephen Steve , Bernick Charles , Shan Guogen , Banks Sarah J. 
Published: June 2020

ABSTRACTObjectiveIncidence of concussions and report of symptoms are greater amongst women across sports. While structural brain changes and cognitive declines are associated with repetitive head impact (RHI), the role of sex is not well understood. This study aimed to determine if there is a moderating effect of sex on the relationship number of professional fights has with cognitive functioning and regional brain volumes in a cohort of boxers, mixed martial artists, and martial artists.Methods55 women were matched with 55 men based on age, years of education, ethnicity, and fighting style. Cognition was assessed via CNS Vital Signs computerized cognitive battery and supplemental measures. Structural brain scans, demographic data, and number of professional fights (NoPF) were also considered. Matched pairs were compared via analysis of covariance, accounting for total brain volume. Within-subject moderation models were utilized to assess the moderating effect of sex on the relationship between NoPF and brain volumes and cognitive performance.ResultsMen were observed to have poorer performance on measures of psychomotor speed when compared to women. On a series of analyses assessing the role of sex as a moderator of the relationship between NoPF and regional brain volumes/cognitive performance, a significant moderation effect was observed across multiple measures of cognitive functioning, such that men had poorer performance. Differences in numerous regional brain volumes were also observed, such that the relationship between NoPF and brain volumes was steeper amongst men.ConclusionSex was observed to be an important moderator in the relationship between NoPF, aspects of cognitive functioning, and volumes of numerous brain regions, suggesting that sex differences in neuroanatomic and cognitive response to RHI deserve further attention.
Impact of mental disorders on active tuberculosis treatment outcomes: a systematic review and meta-analysis
Authors: Lee Ga Eun , Scuffell James , Galea Jerome T. , Shin Sanghyuk S. , Magill Elizabeth , Jaramillo Ernesto , Sweetland Annika C. 
Published: June 2020

ABSTRACTBackgroundComorbid mental disorders in patients with tuberculosis (TB) may exacerbate TB treatment outcomes. We systematically reviewed current evidence on the association between mental disorders and TB outcomes.MethodsWe searched eight databases for studies published from 1990-2018 that compared TB treatment outcomes among patients with and without mental disorders. We excluded studies that did not systematically assess mental disorders and studies limited to substance use. We extracted study and patient characteristics and effect measures and performed a meta-analysis using random-effects models to calculate summary odds ratios (OR) with 95% confidence intervals (CI).FindingsOf 7,687 studies identified, ten were included in the systematic review and nine in the meta-analysis. Measurement of mental disorders and TB outcomes were heterogeneous across studies. The pooled association between mental disorders and any poor outcome, loss to follow-up, and non-adherence were OR 2.13 (95% CI: 0.85-5.37), 1.90 (0.33-10.91), and 1.60 (0.81-3.02), respectively. High statistical heterogeneity was present.InterpretationOur review suggests that mental disorders in TB patients increase the risk of poor TB outcomes, but pooled estimates were imprecise due to small number of eligible studies. Integration of psychological and TB services might improve TB outcomes and progress towards TB elimination.
Highly Accurate and Reproducible Diagnosis of Peanut Allergy Using Epitope Mapping
Authors: Kearney Paul , Getts Robert , Hayward Clive , Luta David , Porter Alex , Witmer Marc , du Toit George , Lack Gideon , Chinthrajah R. Sharon , Galli Stephen J , Nadeau Kari , Grishina Galina , Suárez-Fariñas Mayte , Suprun Maria , Sampson Hugh A 
Published: June 2020

AbstractBackgroundMisdiagnosis of peanut allergy is a significant clinical challenge. Here, a novel diagnostic blood-based test using a Bead-Based Epitope Assay (“peanut BBEA”) has been developed on the LEAP cohort and then independently validated on the CoFAR2 and POISED cohorts.MethodsDevelopment of the peanut BBEA followed the National Academy of Medicine’s established guidelines with discovery performed on 133 subjects from the non-interventional arm of the LEAP trial and an independent validation performed on 81 subjects from the CoFAR2 study and 84 subjects from the POISED study. All subject samples were analyzed using the BBEA methodology. The peanut BBEA test measures levels of two Ara h 2 epitopes and compares their combination to a pre=specified threshold. If the combination of the two epitope levels is at or below the threshold, then the subject is ruled “Not Allergic”, otherwise the subject is ruled “Allergic”.All allergic diagnoses were OFC confirmed and subjects’ ages were 7-55 years.ResultsIn validation on the CoFAR2 and POISED cohorts, the peanut BBEA test had a combined sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and accuracy of 91%, 95%, 95%, 91%, 18.2, 0.09 and 93%, respectively.ConclusionThe peanut BBEA test performance in validation demonstrated overall high accuracy and compared very favorably with existing diagnostic tests for peanut allergy including skin prick testing, peanut sIgE and peanut component testing.
Global years of life lost to COVID-19
Authors: i Arolas Héctor Pifarré , Acosta Enrique , Casasnovas Guillem López , Lo Adeline , Nicodemo Catia , Riffe Tim , Myrskylä Mikko 
Published: June 2020

Understanding the mortality impact of COVID-19 requires not only counting the dead, but analyzing how premature the deaths are. We calculate years of life lost (YLL) across 42 countries due to COVID-19 attributable deaths, and also conduct an analysis based on estimated excess deaths. As of June 13th 2020, YLL in heavily affected countries are 2 to 6 times the average seasonal influenza; over two thirds of the YLL result from deaths in ages below 75 and one quarter from deaths below 55; and men have lost 47% more life years than women. The results confirm the large mortality impact of COVID-19 among the elderly. They also call for heightened awareness in devising policies that protect vulnerable demographics losing the largest number of life-years.One Sentence SummaryAcross 42 countries, the years of life lost due to COVID-19 are up to 6 times that of the average seasonal flu.
Real-time assessment of daytime sleepiness in drivers with multiple sclerosis
Authors: Devos Hannes , Alissa Nesreen , Lynch Sharon , Sadeghi Maryam , Akinwuntan Abiodun E. , Siengsukon Catherine 
Published: June 2020

AbstractBackgroundDaytime sleepiness is a common symptom of multiple sclerosis (MS) that may jeopardize safe driving. The aim of this study was to compare daytime sleepiness, recorded in real-time through eyelid tracking, in a simulated drive between individuals with MS (iwMS) and healthy controls.MethodsFifteen iwMS (age = median (Q1 – Q3), 55 (50 – 55); EDSS = 2.5 (2 – 3.5); 12 (80%) female) were matched for age, sex, education, and cognitive status with 15 controls. All participants completed self-reported fatigue and sleepiness scales including the Modified Fatigue Impact Scale (MFIS), Pittsburg Sleep Quality Inventory (PSQI), and Epworth Sleepiness Scale (ESS). Percentage of eyelid closure (PERCLOS) was extracted from a remote eye tracker while completing a simulated drive of 25 minutes.ResultsAlthough iwMS reported more symptoms of fatigue (MFIS, p =0.003) and poorer sleep quality (PSQI, p = 0.008), they did not report more daytime sleepiness (ESS, p = 0.45). Likewise, there were no differences between groups in real-time daytime sleepiness, indexed by PERCLOS (p = 0.82). Both groups exhibited more real-time daytime sleepiness as they progressed through the drive (time effect, p< 0.0001). The interaction effect of group*time (p = 0.05) demonstrated exacerbated symptoms of daytime sleepiness towards the end of the drive in iwMS compared to controls.PERCLOS correlated strongly (Spearman ρ = 0.76, p = 0.001) with distance out of lane in iwMS.ConclusionIwMS show exacerbated symptoms of daytime sleepiness during monotonous, simulate drive. Future studies are warranted to investigate the effect of MS on daytime sleepiness during real-world driving.
CD14 (C-159T) polymorphism is associated with increased susceptibility to SLE, and plasma levels of soluble CD14 is a novel biomarker of disease activity: a hospital-based case-control study
Authors: Panda Aditya K , Tripathy Rina , Das Bidyut K 
Published: June 2020

ABSTRACTBackgroundCluster of differentiation 14 (CD14) plays a crucial role in the innate immune response of the host in protection against various pathogens. The importance of soluble CD14 in autoimmune disorders has been described in different populations. However, the role of sCD14 in systemic lupus erythematosus (SLE) is poorly understood. Further, the association of functional variants at the promoter region of the CD14 gene (−159 C>T) with susceptibility to SLE or disease severity needs to be defined.MethodsTwo hundred female SLE patients diagnosed on SLICC classification criteria and age, sex, matched healthy controls were enrolled in the present study. PCR-RFLP method was used to genotype CD14 (C-159 T) polymorphism. Plasma levels of IFN-α, TNF-α, and sCD14 were quantified by ELISA.ResultsPrevalence of mutant genotypes (CT and TT) and minor allele of CD14 (C-159T) polymorphism was significantly higher in SLE cases compared to healthy controls (CT:P<0.0001; OR=3.26, TT:P<0.0001; OR=3.39; T:P=0.0009, OR=1.62). Further, lupus nephritis patients had a higher prevalence of homozygous mutants (TT) and mutant allele (T)(TT: P=0.0002, OR=8.07; T: P=0.001, OR=1.32). SLE patients displayed significantly increased plasma sCD14, TNF-α, and IFN-α levels in comparison to healthy controls. These cytokines were significantly elevated in patients of lupus nephritis compared to those without kidney involvement. Interestingly, sCD14 levels correlated positively with SLEDAI-2K scores and 24 hours proteinuria.ConclusionCD14 (C-159T) polymorphism is associated with an increased predisposition to the development of SLE and lupus nephritis: sCD14 is a promising novel biomarker for assessing disease activity and lupus nephritis.
Structural variability, expression profile and pharmacogenetics properties of TMPRSS2 gene as a potential target for COVID-19 therapy
Authors: Zarubin Aleksei , Stepanov Vadim , Markov Anton , Kolesnikov Nikita , Marusin Andrey , Khitrinskaya Irina , Swarovskaya Maria , Litvinov Sergey , Ekomasova Natalia , Dzhaubermezov Murat , Maksimova Nadezhda , Sukhomyasova Aitalina , Shtygasheva Olga , Khusnutdinova Elza , Radjabov Magomed , Kharkov Vladimir 
Published: June 2020

AbstractThe human serine protease TMPRSS2 gene is involved in the priming of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins being one of the possible targets for COVID-19 therapy. TMPRSS2 gene is possibly co-expressed with SARS-CoV-2 cell receptor genes ACE2 and BSG, but only TMPRSS2 demonstrates tissue-specific expression in alveolar cells according to single cell RNA sequencing data. Our analysis of the structural variability of the TMPRSS2 gene based on genome-wide data of 76 human populations demonstrates that functionally significant missense mutation in exon 6/7 in TMPRSS2 gene, was found in many human populations in relatively high frequency, featuring region-specific distribution patterns. The frequency of the missense mutation encoded by the rs12329760, which previously was found to be associated with prostate cancer, is ranged between 10% and 63% being significantly higher in populations of Asian origin compared to European populations. In addition to SNPs, two copy numbers variants (CNV) were detected in the TMPRSS2 gene. Number of microRNAs have been predicted to regulate TMPRSS2 and BSG expression levels, but none of them is enriched in lung or respiratory tract cells. Several well studied drugs can downregulate the expression of TMPRSS2 in human cells, including Acetaminophen (Paracetamol) and Curcumin. Thus TMPRSS2 interaction with the SARS-CoV-2, its structural variability, gene-gene interactions, and expression regulation profiles, and pharmacogenomics properties characterize this gene as a potential target for COVID-19 therapy.
Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19
Authors: Graham Simon P. , McLean Rebecca K. , Spencer Alexandra J. , Belij-Rammerstorfer Sandra , Wright Daniel , Ulaszewska Marta , Edwards Jane C. , Hayes Jack W. P. , Martini Veronica , Thakur Nazia , Conceicao Carina , Dietrich Isabelle , Shelton Holly , Waters Ryan , Ludi Anna , Wilsden Ginette , Browning Clare , Bialy Dagmara , Bhat Sushant , Stevenson-Leggett Phoebe , Hollinghurst Philippa , Gilbride Ciaran , Pulido David , Moffat Katy , Sharpe Hannah , Allen Elizabeth , Mioulet Valerie , Chiu Chris , Newman Joseph , Asfor Amin S. , Burman Alison , Crossley Sylvia , Huo Jiandong , Owens Raymond J. , Carroll Miles , Hammond John A. , Tchilian Elma , Bailey Dalan , Charleston Bryan , Gilbert Sarah C. , Tuthill Tobias J. , Lambe Teresa 
Published: June 2020

AbstractClinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres.
D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity
Authors: Hu Jie , He Chang-Long , Gao Qing-Zhu , Zhang Gui-Ji , Cao Xiao-Xia , Long Quan-Xin , Deng Hai-Jun , Huang Lu-Yi , Chen Juan , Wang Kai , Tang Ni , Huang Ai-Long 
Published: June 2020

AbstractCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein that mediates SARS-CoV-2 entry into host cells is a major target for vaccines and therapeutics. Thus, insights into its sequence variations are key to understanding the infection and antigenicity of SARS-CoV-2. A dominant mutational variant at position 614 of the S protein (aspartate to glycine, D614G mutation) was observed in the SARS-CoV-2 genome sequence obtained from the Nextstrain database. Using a pseudovirus-based assay, we identified that S-D614 and S-G614 protein pseudotyped viruses share a common receptor, human angiotensin-converting enzyme 2 (ACE2), which could be blocked by recombinant ACE2 with the fused Fc region of human IgG1. However, S-D614 and S-G614 protein demonstrated functional differences. First, S-G614 protein could be cleaved by serine protease elastase-2 more efficiently. Second, S-G614 pseudovirus infected 293T-ACE2 cells significantly more efficiently than did the S-D614 pseudovirus, especially in the presence of elastase-2. Third, an elastase inhibitor approved for clinical use blocked elastase-enhanced S-G614 pseudovirus infection. Moreover, 93% (65/70) convalescent sera from patients with COVID-19 could neutralize both S-D614 and S-G614 pseudoviruses with comparable efficiencies, but about 7% (5/70) convalescent sera showed reduced neutralizing activity against the S-G614 pseudovirus. These findings have important implications for SARS-CoV-2 transmission and immune interventions.
Scalable recombinase-based gene expression cascades
Authors: Kim Tackhoon , Weinberg Benjamin , Wong Wilson , Lu Timothy K. 
Published: June 2020

AbstractTemporal modulation of multiple genes underlies sophisticated biological phenomena. However, there are few scalable and generalizable gene circuit architectures for the programming of sequential genetic perturbations. We describe a modular recombinase-based gene circuit architecture, comprising tandem gene perturbation cassettes (GPCs), that enables the sequential expression of multiple genes in a defined temporal order by alternating treatment with just two orthogonal ligands. We used tandem GPCs to sequentially express single-guide RNAs to encode transcriptional cascades and trigger the sequential accumulation of mutations. We built an all-in-one gene circuit that sequentially edits genomic loci, synchronizes cells at a specific stage within a gene expression cascade, and deletes itself for safety. Tandem GPCs offer a multi-tiered cellular programming tool for modeling multi-stage genetic changes, such as tumorigenesis and cellular differentiation.
Selective linkage of mitochondrial enzymes to intracellular calcium stores differs between human induced pluripotent stem cells, neural stem cells and neurons
Authors: Chen Huanlian , Thakkar Ankita , Cross Abigail C. , Xu Hui , Li Aiqun , Pauli Dan , Noggle Scott A. , Kruger Laken , Denton Travis T. , Gibson Gary E. 
Published: June 2020

AbstractThe coupling of the endoplasmic reticulum (ER) with mitochondria modulates neuronal calcium signaling. Whether this link changes with neuronal development is unknown. The current study first determined whether ER calcium stores are similar during development of human neurons, and then tested if the ER/mitochondrial coupling varied with development. The release of ER calcium to the cytosol by the IP3agonist bradykinin was determined in human induced-pluripotent stem cells (iPSC), neural stem cells (NSC) and neurons. The concentration dependence for the release of ER calcium was similar at different stages of development. Metabolism changes dramatically with development. Glycolysis is the main energy source in iPSC and NSC whereas mitochondrial metabolism is more prominent in neurons. To test whether the coupling of mitochondria and ER changed with development, bombesin or bradykinin releasable calcium stores (BRCS) were monitored after inhibiting either of two key mitochondrial enzyme complexes: the alpha-ketoglutarate dehydrogenase complex (KGDHC) or the pyruvate dehydrogenase complex (PDHC). Inhibition of KGDHC did not alter BRCS in either iPSC or NSC. Inhibition of PDHC in neurons diminished BRCS whereas decreased KGDHC activity exaggerated BRCS. The latter finding may help understand the pathology of Alzheimer’s disease (AD). BRCS is exaggerated in cells from AD patients and KGDHC is reduced in brains of patients with AD. In summary, a prominent ER/mitochondrial link in neurons is associated with selective mitochondrial enzymes. The ER/mitochondrial link changes with human neuronal development and plausibly links ER calcium changes to AD.