bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing false reassurance following negative results from asymptomatic coronavirus (Covid-19) testing: an online experiment
Authors: Batteux Eleonore , Bonfield Stefanie , Jones Leah Ffion , Carter Holly , Gold Natalie , Amlôt Richard , Marteau Theresa M. , Weston Dale 
Published: August 2021

AbstractObjectivesIndividuals who receive a negative lateral flow coronavirus (Covid-19) test result may misunderstand it as meaning ‘no risk of infectiousness’, giving false reassurance. This experiment tested the impact of adding information to negative test result messages about (a) residual risk and (b) need to continue protective behaviours.Design4 (residual risk) × 2 (post-test result behaviours) between-subjects design.SettingOnline.Participants1200 adults from a representative UK sample recruited via Prolific (12-15 March 2021).InterventionsParticipants were randomly allocated to one of eight messages. Residual risk messages were: 1) ‘Your coronavirus test result is negative’ (control); 2) Message 1 plus ‘It’s likely you were not infectious when the test was done’ (Current NHS Test & Trace); 3) Message 2 plus ‘But there is still a chance you may be infectious’ (Elaborated NHS T&T); 4) Message 3 plus infographic depicting residual risk (Elaborated NHS T&T + infographic). Each message contained either no additional information or information about behaviour, i.e. the need to continue following guidelines and protective behaviours.Outcome measures(i) proportion understanding residual risk of infectiousness and (ii) likelihood of engaging in protective behaviours (score range 0-7).ResultsThe control message decreased understanding relative to the current NHS T&T message: 54% vs 71% (AOR=0.37 95% CI [0.22, 0.61], p<.001). Understanding increased with the elaborated NHS T&T (89%; AOR=3.27 95% CI [1.78, 6.02], p<.001) and elaborated NHS T&T + infographic (91%; AOR=4.03 95% CI [2.14, 7.58], p<.001) compared to current NHS T&T message. Likelihood of engaging in protective behaviours was unaffected by information (F(1,1192)=0.43, p=.513), being high (M=6.4, SD=0.9) across the sample.ConclusionsThe addition of a single sentence (‘But there is still a chance you may be infectious’) to current NHS Test & Trace wording increased understanding of the residual risk of infection.Trial registrationOpen Science Framework: https://osf.io/byfz3/
Cryptic Transmission of the Delta Variant AY.3 Sublineage of SARS-CoV-2 among Fully Vaccinated Patients on an Inpatient Ward
Authors: Linsenmeyer Katherine , Gupta Kalpana , Madjarov Rebecca , Charness Michael E. 
Published: August 2021

AbstractBackgroundRecent reports indicate that vaccination is effective in reducing symptomatic infection with the Delta variant of SARS-CoV-2 (DV) but is less protective against asymptomatic transmission of DV in outpatients than for earlier variants.Here we report cryptic transmission associated with high DV viral load among vaccinated patients on an inpatient medical-surgical ward.MethodsThis observational study included all persons diagnosed with breakthrough SARS-CoV-2 infections at the VA Boston Healthcare System (VABHS) from March 11, 2021 to July 31, 2021, including those tested for surveillance, admission, symptoms, and as part of an outbreak investigation in July 2021. SARS-CoV-2 infection was diagnosed by reverse-transcription polymerase chain reaction (PCR) (Cepheid). Variants were identified by MassARRAY SARS-CoV-2 Variant Panel (36-plex PCR, Agena BioScience) for most breakthrough cases after June 2021 Viral genomic sequencing was performed by the Jackson Laboratory.ResultsAn inpatient was diagnosed with asymptomatic DV infection on routine pre-discharge testing. Contact tracing detected infection in 6 of 38 patients (15.8%), 1 of 168 staff (0.6%), and 1 of 6 visitors (16.7%). Infection at the time of diagnosis was asymptomatic in 4 proximate, vaccinated patients, 1 vaccinated visitor, and 1 vaccinated employee caring for 1 undiagnosed, infected, vaccinated patient. Patients were unmasked, whereas staff wore surgical masks. PCR cycle threshold (Ct) for breakthrough infections indicated more than 1000-fold higher viral load for DV (Ct:21.7±4.3; n=15) than for earlier variants (Ct: 31.8±10.9, n=12; p=.003 (t-test)).ConclusionThese findings demonstrate transmission of DV with high viral load between vaccinated inpatients, the continued efficacy of masking and vaccination for protecting healthcare personnel, and the potential need for post-admission surveillance to prevent cryptic DV transmission.
Time-to-event comparative effectiveness of NOACs vs VKAs in newly diagnosed non-valvular atrial fibrillation patients
Authors: Gallego Blanca , Zhu Jie 
Published: August 2021

AbstractObjectiveTo investigate the difference in the time-to-event probabilities of ischaemic events, major bleeding and death of NOAC vs VKAs in newly diagnosed non-valvular atrial fibrillation patients.DesignRetrospective observational cohort study.SettingUK’s Clinical Practice Research Data linked to the Hospital Episode Statistics inpatient and outpatient data, mortality data and the Patient Level Index of Multiple Deprivation.ParticipantsPatients over 18 years of age, with an initial diagnosis of atrial fibrillation between 1st-Mar-2011 and 31-July-2017, without a record for a valve condition, prosthesis or procedure previous to initial diagnosis, and without a record of oral anticoagulant treatment in the previous year.InterventionOral anticoagulant treatment with either vitamin K antagonists (VKAs) or the newer target-specific oral anticoagulants (NOACs).Main Outcome MeasuresIschaemic event, major bleeding event and death from 15 days from initial prescription up to two years follow-up.Statistical AnalysisTreatment effect was defined as the difference in time-to-event probability between NOAC and VKA treatment groups. Treatment and outcomes were modelled using an ensemble of parametric and non-parametric models, and the average and conditional average treatment effects were estimated using one-step Targeted Maximum Likelihood Estimation (TMLE). Heterogeneity of treatment effect was examined using variable importance methods in Bayesian Additive Regression Trees (BART).ResultsThe average treatment effect of NOAC vs VKA was consistently close to zero across all times, with a temporal average of 0.00[95%0.00, 0.00] for ischaemic event, 0.00%[95%−0.01, 0.01] for major bleeding and 0.00[95%−0.01, 0.01] for death. Only history of major bleeding was found to influence the distribution of treatment effect for major bleeding, but its impact on the associated conditional average treatment effect was not significant.ConclusionsThis study found no statistically significant difference between NOAC and VKA users up to two years of medication use for the prevention of ischaemic events, major bleeding or death.
Clenbuterol Attenuates Immune Reaction to Lipopolysaccharide and Its Relationship to Anhedonia in Adolescents
Authors: Nguyen Tram N. B. , Ely Benjamin A. , Pick Danielle , Patel Manishkumar , Xie Hui , Kim-Schulze Seunghee , Gabbay Vilma 
Published: August 2021

AbstractWhile inflammation has been implicated in psychopathology, relationships between immune-suppressing processes and psychiatric constructs remain elusive. This study sought to assess whether β2-agonist clenbuterol (CBL) would attenuate immune activation in adolescents with mood and anxiety symptoms following ex vivo exposure of whole blood to lipopolysaccharide (LPS). Our focus on adolescents aimed to target a critical developmental period when psychiatric conditions often emerge and prior to chronicity effects. To capture a diverse range of immunologic and symptomatologic phenotypes, we included 97 psychotropic-medication free adolescents with mood and anxiety symptoms and 33 healthy controls. All participants had comprehensive evaluations and dimensional assessments of psychiatric symptoms. Fasting whole-blood samples were collected and stimulated with LPS in the presence and absence of CBL for 6 hours, then analyzed for 41 cytokines, chemokines, and hematopoietic growth factors. Comparison analyses used Bonferroni-corrected nonparametric tests. Levels of nine immune biomarkers—including IL-1RA, IL-1β, IL-6, IP-10, MCP-1, MIP-1α, MIP-1β, TGF-α, and TNF-α—were significantly reduced by CBL treatment compared to LPS alone. Exploratory factor analysis reduced 41 analytes into 5 immune factors in each experimental condition, and their relationships with psychiatric symptoms were examined as a secondary aim. CBL+LPS Factor 4—comprising EGF, PDGF-AA, PDGF-AB/BB, sCD40L, and GRO—significantly correlated with anticipatory and consummatory anhedonia, even after controlling for depression severity. This study supports the possible inhibitory effect of CBL on immune activation. Using a data-driven method, distinctive relationships between CBL-affected immune biomarkers and dimensional anhedonia were reported, further elucidating the role of β2-agonism in adolescent affective symptomatology.
Patient Informed Domain Adaptation Improves Clinical Drug Response Prediction
Authors: Anastopoulos Ioannis , Seninge Lucas , Ding Hongxu , Stuart Joshua 
Published: August 2021

ABSTRACTIn-silico modeling of patient clinical drug response (CDR) promises to revolutionize personalized cancer treatment. State-of-the-art CDR predictions are usually based on cancer cell line drug perturbation profiles. However, prediction performance is limited due to the inherent differences between cancer cell lines and primary tumors. In addition, current computational models generally do not leverage both chemical information of a drug and a gene expression profile of a patient during training, which could boost prediction performance. Here we develop a Patient Adapted with Chemical Embedding (PACE) dual convergence deep learning framework that a) integrates gene expression along with drug chemical structures, and b) is adapted in an unsupervised fashion by primary tumor gene expression. We show that PACE achieves better discrimination between sensitive and resistant patients compared to the state-of-the-art linear regularized method (9/12 VS 3/12 drugs with available clinical outcomes) and alternative methods.
Enterococcus spp. have higher fitness for survival, in a pH-dependent manner, in pancreatic juice among duodenal bacterial flora
Authors: Itoyama Saki , Noda Emika , Takamatsu Shinji , Kondo Jumpei , Kawaguchi Rui , Shimosaka Munefumi , Fukuoka Tomoya , Motooka Daisuke , Nakamura Shota , Tanemura Masahiro , Mitsufuji Suguru , Iwagami Yoshifumi , Akita Hirofumi , Tobe Toru , Kamada Yoshihiro , Eguchi Hidetoshi , Miyoshi Eiji 
Published: August 2021

AbstractObjectivesBacterial infection is involved in the progression of many gastrointestinal diseases, including cancer; however, how and which bacteria colonize in pancreatic juice and tissue have yet to be elucidated. Recently, we reported that Enterococcus faecalis exists in the pancreatic juice and tissues of patients with chronic pancreatic disease. Here, we investigated the survival of E. faecalis in duodenal juice with different pH conditions.MethodsPancreatic juice samples from 62 patients with cancers of the duodeno-pancreato-biliary region were evaluated for the presence of E. faecalis. 16S ribosomal RNA PCR and 16S-based metagenome analyses were performed to determine the bacterial composition. The survival of E. faecalis in various pancreatic juice conditions was evaluated.ResultsOf 62 samples, 27% (17/62) were positive for Enterococcus spp., among which 71% (12/17) contained E. faecalis. Enterococcus spp. showed the highest fitness for survival in alkaline pancreatic juice among various bacterial species. The microbiome of pancreatic juice from patients with pancreatic and bile duct cancer showed diversity, but Enterococcus spp. were enriched among duodenal tumors and intraductal papillary mucinous neoplasms.ConclusionsAlkalinity is important for the selective survival of E. faecalis among microbiota. E. faecalis may induce pancreatic inflammation with changes in pancreatic juice conditions.
A Tethered Ligand Assay to Probe SARS-CoV-2:ACE2 Interactions
Authors: Bauer Magnus S. , Gruber Sophia , Hausch Adina , Milles Lukas F. , Nicolaus Thomas , Schendel Leonard C. , López Navajas Pilar , Procko Erik , Lietha Daniel , Bernardi Rafael C. , Gaub Hermann E. , Lipfert Jan 
Published: August 2021

ABSTRACTSARS-CoV-2 infections are initiated by attachment of the receptor-binding domain (RBD) on the viral Spike protein to angiotensin-converting enzyme-2 (ACE2) on human host cells. This critical first step occurs in dynamic environments, where external forces act on the binding partners and multivalent interactions play critical roles, creating an urgent need for assays that can quantitate SARS-CoV-2 interactions with ACE2 under mechanical load and in defined geometries. Here, we introduce a tethered ligand assay that comprises the RBD and the ACE2 ectodomain joined by a flexible peptide linker. Using magnetic tweezers and atomic force spectroscopy as highly complementary single-molecule force spectroscopy techniques, we investigate the RBD:ACE2 interaction over the whole physiologically relevant force range. We combine the experimental results with steered molecular dynamics simulations and observe and assign fully consistent unbinding and unfolding events across the three techniques, enabling us to establish ACE2 unfolding as a molecular fingerprint. Measuring at forces of 2-5 pN, we quantify the force dependence and kinetics of the RBD:ACE2 bond in equilibrium. We show that the SARS-CoV-2 RBD:ACE2 interaction has higher mechanical stability, larger binding free energy, and a lower dissociation rate in comparison to SARS-CoV-1, which helps to rationalize the different infection patterns of the two viruses. By studying how free ACE2 outcompetes tethered ACE2, we show that our assay is sensitive to prevention of bond formation by external binders. We expect our results to provide a novel way to investigate the roles of mutations and blocking agents for targeted pharmaceutical intervention.
Adulthood Deficiency of the Insulin-like Growth Factor-1 Receptor in Hippocampal Neurons Impairs Cell Structure and Spatial Learning and Memory in Male and Not Female Mice
Authors: Hayes Cellas A. , Hodges Erik L. , Marshall Jessica P. , Logan Sreemathi , Farley Julie A. , Owens Daniel B. , Sonntag William E. , Ashpole Nicole M. 
Published: August 2021

ABSTRACTReductions in insulin-like growth factor-1 (IGF-1) are associated with cognitive impairment and increased risk of neurodegenerative disease in advanced age. In mouse models, reduced IGF-1 early-in-life leads to memory impairments and synaptic dysfunction; however, these models are limited by systemic reductions in IGF-1. We hypothesized that IGF-1 continues to promote hippocampal neuron structure and function after development, and as such, the loss of IGF-1 signaling in adult neurons would lead to impaired spatial learning and memory. To test this, the IGF-1 receptor (IGF-1R) was genetically targeted in hippocampal neurons of adult male and female mice. Male mice deficient in neuronal IGF-1R exhibited spatial learning impairments as evidenced by increased pathlength and errors in the radial arm water maze. No differences in learning and memory were observed in female mice. Golgi-Cox staining revealed a reduced number of dendritic boutons of neurons the CA1 region of the hippocampus in male mice. Decreased MAPK and increased ROCK activity were also observed in these tissues. In vitro studies revealed that impaired neurite outgrowth due to inhibited IGF-1R signaling could be rescued by pharmacological inhibitors of ROCK. However, ROCK inhibition in neuronal IGF-1R-deficient mice did not fully rescue learning impairments or bouton numbers. Together, our study highlights that IGF-1 continues to support spatial learning and memory and neuronal structure in adulthood.
Professional Commitment and Its Associated Factors Among Institutional Delivery Services Providers In Public Health Facilities, In Shone District, Southern Ethiopia
Authors: Anshebo Melaku Wolde , Tessema Tesfaye Gobeana , Gebremariam Yosef Haile 
Published: August 2021

AbstractBackgroundThere is paucity of information on level of commitment among health professionals attending delivery service in public health facilities of low-income countries including Ethiopia.ObjectiveTo assess the level and factors associated with professional commitment among institutional delivery services providers at public health facilities in Shone District, Southern Ethiopia.MethodsA facility-based cross-sectional study design was conducted at primary level public health facilities in Shone District. All health facilities (one primary hospital and 7 health centers) were included in the study. 503 study participants who fulfilled inclusion criteria in proportion to obstetric care providers in each public health facilities were selected by applying simple random sampling. Self-administered Likert scale type of questionnaire was used. Data were analyzed using SPSS version 20. Bivariate and multivariable logistic regression analyses were done to see the association between dependent and explanatory variables.ResultsThe magnitude of professional commitment for obstetric care providers working in public health facilities of Shone district was 69.4%. In this study, those who worked at hospital, those who had positive attitude toward organizational commitment, and those who had positive attitude toward personal characteristics were 2.4, 2.3 and 1.76 times more likely committed to profession compared with the counterparts respectively.ConclusionThe professional commitment among institutional delivery service provision was medium. All health professional should manage their own personal characteristics to behave in good way to be committed for their profession. Organizational commitment had great influence on professional commitment.
Observational study of HPV genitalia and oral infection in an unvaccinated population of men who have sex with men infected with HIV in Northwest Spain
Authors: Pérez-González Alexandre , Pérez Sonia , Carballo Raquel , López-Diez Elena , Limeres-Posse Jacobo , Ocampo Antonio 
Published: August 2021

AbstractBackgroundHuman papillomavirus (HPV) infection is the most common sexual transmitted disease (STD) and a risk factor for penile, oral and anal cancer. Human immunodeficiency virus (HIV) coinfection increases the risk of cancer. While HPV anal infection is well studied in men-who-have-sex-with-men (MSM), HPV genitalia and oral infection is less known.MethodsThis prevalence study of HPV infection in genitalia and oral cavity in HIV-MSM patients included 107 HPV non-vaccinated subjects. HPV-DNA was detected with Anyplex™ II HPV28 method. Participants completed a questionnaire on lifestyle and sexual behavior.ResultsMedian age was 43 years (range 35-54 years); 97 patients were on antiretroviral treatment (ART); 81 (75.7%) had undetectable HIV-RNA; median CD4-lymphocyte count was 746 cell/mm3; 70 (65.4%) participants had a previous STD. HPV was detected in genitalia in 37 (34.6%) subjects; 26 (24.3%) in oral cavity and 12 (11.2%) in both locations. High-risk HPV genotypes were detected in 24 (22.4%) patients in genitalia and 15 (14%) in oral cavity.ConclusionsHPV infection is common in unvaccinated HIV-MSM patients. Detectable HIV-RNA was associated with higher HPV prevalence in genitalia. High oncogenic risk HPV genotypes were more common in genitalia than in mouth.Summary textHPV infection is common in HIV infected subjects and it is a risk factor for many types of cancer. Although anal conduct is the most studied location, HPV can also infect genitalia and oral cavity. However, the frequency and distribution of HPV strains is different in both locations.
Lead-OR: A Multimodal Platform for Deep Brain Stimulation Surgery
Authors: Oxenford Simón , Roediger Jan , Milosevic Luka , Güttler Christopher , Spindler Philipp , Vajkoczy Peter , Neumann Wolf-Julian , Kühn Andrea , Horn Andreas 
Published: August 2021

AbstractDeep Brain Stimulation (DBS) electrode implant trajectories are stereotactically defined using preoperative neuroimaging. To validate the correct trajectory, microelectrode recordings (MER) can be used to match the neuroanatomy with expected neurophysiological activity patterns, commonly using up to five trajectories in parallel. However, understanding their location in relationship to basal ganglia anatomy can be challenging. Here we present a tool that integrates resources from stereotactic planning, neuroimaging, MER and high-resolution atlas data to create a real-time visualization of the implant trajectory. We show a general correspondence between features derived from neuroimaging and electrophysiological recordings and present example use cases that demonstrate the functionality of the tool. The software toolbox is made openly available, extendable and holds translational potential in the field of stereotactic neurosurgery.
Quantitative Restoration of Immune Defense in Old Animals Determined by Naïve Antigen-Specific CD8 T cell Numbers
Authors: Uhrlaub Jennifer L. , Jergović Mladen , Bradshaw Christine M. , Sonar Sandip , Coplen Christopher P. , Dudakov Jarrod , Murray Kristy O. , Lanteri Marion C. , Busch Michael P. , van den Brink Marcel R. M. , Nikolich-Žugich Janko 
Published: August 2021

ABSTRACTOlder humans and animals often exhibit reduced immune responses to infection and vaccination, and this often directly correlates to the numbers and frequency of naïve T (Tn) cells. We found such a correlation between reduced numbers of blood CD8+ Tn cells and severe clinical outcomes of West Nile virus (WNV) in both humans naturally exposed to, and mice experimentally infected with, WNV.To examine possible causality, we sought to increase the number of CD8 Tn cells by treating C57BL/6 mice with IL-7 complexes (IL-7C, anti-IL-7 mAb bound to IL-7), shown previously to efficiently increase peripheral T cell numbers by homeostatic proliferation. T cells underwent robust expansion following IL-7C administration to old mice increasing the number of total T cells (>four-fold) and NS4b:H-2Db-restricted antigen-specific CD8 T cells (two-fold). This improved the numbers of NS4b-specific CD8 T cells detected at the peak of the response against WNV, but not survival of WNV challenge. IL-7C treated old animals also showed no improvement in WNV-specific effector immunity (neutralizing antibody and in vivo T cell cytotoxicity). To test quantitative limits to which CD8 Tn cell restoration could improve protective immunity, we transferred graded doses of Ag-specific precursors into old mice and showed that injection of 5,400 (but not of 1,800 or 600) adult naïve WNV-specific CD8 T cells significantly increased survival after WNV. These results set quantitative limits to the level of Tn reconstitution necessary to improve immune defense in older organisms and are discussed in light of targets of immune reconstitution.