bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medical students’ crisis-induced stress and the association with social support
Authors: Broks Vera M.A. , Stegers-Jager Karen M. , van der Waal Jeroen , Van den Broek Walter W. , Woltman Andrea M. 
Published: March 2022

AbstractBackgroundMedical schools are challenged to guard student wellbeing due to the potential negative impact of the COVID-19 outbreak on top of the already high prevalence of mental distress. Whereas social support is generally associated with less crisis-induced stress, it is unknown whether this applies to medical students during the COVID-19 outbreak.ObjectivesThe impact of the COVID-19 outbreak on perceived stress of medical students was assessed by comparing their perceived stress levels during the outbreak to both their own baseline and the previous cohort’s pre-COVID-19 stress levels. Then, the association between social support and COVID-19 induced stress was assessed.MethodsDutch Year-1 medical students of cohort 2019 (n=99) completed the 14-item Perceived Stress Scale (PSS-14) at two time points: baseline (pre-COVID-19) and final measurement (COVID-19). Social support - emotional-informational support and club membership - was assessed during the final measurement. PSS and social support scores were compared to similar measurements of cohort 2018 (n=196). Students’ baseline stress levels, gender and study performance were controlled for when comparing two cohorts.ResultsStress levels did not differ statistically significant between both pre-COVID-19 measurements of cohort 2018 and baseline cohort 2019. During the COVID-19 outbreak, cohort 2019 showed significantly higher stress levels compared to baseline (paired t-test: t=6.07, p<.001) and compared to cohort 2018 (linear regression: B=4.186, p<.001). Only during the COVID-19 outbreak, higher levels of social support - i.e. emotional-informational support (B=-0.75, p<.001) and club membership (B=-3.68, p<.01) - were associated with lower levels of stress.ConclusionsDuring the COVID-19 outbreak, the perceived stress of medical students was higher - especially for students with lower levels of social support. Our results suggest that medical schools should optimize social support to minimize crisis-induced stress.
Missorting of Plasma miRNAs in Aging and Alzheimer’s Disease
Authors: Čarna Maria , Novotny Jan S. , Dragišič Neda , Slavik Hanuš , Sheardova Kateřina , Geda Yonas E. , Vyhnalek Martin , Laczo Jan , Hort Jakub , Mao Zixu , Rissman Robert A. , Hajduch Marian , Dammer Eric B. , Stokin Gorazd B. 
Published: March 2022

AbstractAging is the greatest risk factor for Alzheimer’s disease (AD)1, a pervasive cognitive disorder with unsettled etiology. The precise role of aging in AD, however, remains poorly understood. Accumulating evidence documents the dysregulation of circulating microRNAs (miRNA) separately in aging2,3and AD4. Considering miRNAs play a role in aging and longevity5,6, we comprehensively test which aging-associated miRNA changes are observed in AD, and change in AD beyond aging in the circulating miRNA network. Here we show that plasma miRNAs in aging are downregulated and preferentially targeted to extracellular vesicle (EV) content, while in AD, miRNAs are further downregulated and of exclusive EV origin. We further show that miRNAs in AD display altered proportions of motifs relevant to their loading into EVs7,8and secretion propensity9. Considering endosomes play a role in the genesis of EVs10,11and are compromised early in AD12, these findings implicate endosomal pathology underlying the AD plasma miRNA profile and its potential as a mechanistic AD biomarker. Striking similarities between plasma miRNA profiles in aging and AD further suggest that the AD miRNA network profile reflects a pathological exacerbation of the aging process whereby physiological suppression of AD pathology by plasma miRNAs becomes insufficient.
A 16-Month Longitudinal Investigation of Risk and Protective Factors for Mental Health Outcomes Throughout Three National Lockdowns and a Mass Vaccination Campaign: Evidence from a Weighted Israeli Sample During COVID-19
Authors: Hertz-Palmor Nimrod , Ruppin Shachar , Matalon Noam , Mosheva Mariela , Dorman-Ilan Shirel , Avinir Asia , Mekori-Domachevsky Ehud , Hasson-Ohayon Ilanit , Gross Raz , Gothelf Doron , Pessach Itai M. 
Published: March 2022

AbstractBackgroundThe COVID-19 pandemic is an ongoing global crisis, with a multitude of factors that affect mental health worldwide. Here, we explore potential predictors for the emergence and maintenance of depression, anxiety, and posttraumatic stress symptoms (PTSS) in the general population in Israel.MethodsAcross the span of 16 months, 2,478 people completed a repeated self-report survey which inquired psychiatric symptoms and pandemic related stress factors (PRSF). PRSF were divided into four clusters of environmental stressors: financial, health-related, fatigue and sense of protection by authorities. We applied mixed-effects linear models to assess how each stressor contributes to depression, anxiety and PTSS at each time point, alongside a longitudinal exploration among participants who completed at least two consecutive surveys (n=400).ResultsFatigue was the strongest predictor for depression, anxiety and PTSS at all time points (standardized βbetween 0.28-0.60,p<.0001), and predicted deterioration overtime (βbetween 0.22-0.36,p<.0001). Financial concerns associated with depression and anxiety at all time points (βbetween 0.13- 0.26,p<.01), and with their deterioration overtime (βbetween 0.16-0.18,p<.0001), while health related concerns were uniquely associated with anxiety and PTSS at all time points (βbetween 0.14-0.29,p<.01) and their deterioration (βbetween 0.11-0.16,p<.001), but not with depression. Improvement in sense of protection overtime associated with decrease in depression and anxiety (βbetween −0.09 to −0.16,p<.01).ConclusionsOur findings accentuate the multitude of risk factors for psychiatric morbidity during COVID-19, and the dynamics in their association with different aspects of psychopathology at various time points.
Comparison of Phase Angle Using Bioelectrical Impedance Analysis According to Device Type and Examination Posture
Authors: Yang Jihyun , Chun Byung Chul , Kim Jeehyun , Lee Jae-myeong 
Published: March 2022

AbstractBackgroundBioelectrical impedance analysis (BIA) is gaining popularity as a body composition assessment tool for patients. Although it has been studied and validated in different populations, age groups, and clinical settings, including critically ill patients, there are concerns about BIA reproducibility and reliability in different device types and postures. This study aimed to evaluate the reliability of BIA according to different devices, postures, and lead types.MethodsCross-sectional observational data of 74 healthy volunteers (32 women and 42 men) were collected. We used two types of devices, three types of postures (standing, sitting, and lying), and two lead types (clamp lead and adhesive lead) to measure the whole-body phase angle (phA) at a single frequency of 50 kHz. The measurements were validated using the intraclass correlation coefficient (ICC) and Bland–Altman plot analysis.ResultsAll phA measurements recorded with two types of devices, three different postures, and two types of leads were equivalent to each other (mean ICC = 0.9932, 95% confidence interval (CI) 0.9905–0.0053). The average mean difference in phA was 0.31 (95% CI 0.16– 0.46). The largest phA value was measured using BWA with an adhesive-type lead in the lying position. There were no differences between standing and sitting positions.ConclusionThis is the first study to show the consistency and reliability of BIA in measuring phA using different devices, lead types, and postures. This could provide the confidence that BIA can be used in various clinical settings.
Who Does What to Whom? Graph Representations of Action-Predication in Speech Relate to Psychopathological Dimensions of Psychosis
Authors: Nikzad Amir H. , Cong Yan , Berretta Sarah , Hänsel Katrin , Cho Sunghye , Pradhan Sameer , Behbehani Leily , DeSouza Danielle , Liberman Mark Y. , Tang Sunny X. 
Published: March 2022

AbstractGraphical representations of speech generate powerful computational measures related to psychosis. Previous studies have mostly relied on structural relations between words as the basis of graph formation, i.e. connecting each word to the next in a sequence of words. Here, we introduced a method of graph formation grounded in semantic relationships by identifying elements that act upon each other (action relation) and contents of those actions (predication relation). Speech from picture description and open-ended narrative tasks were collected from a cross-diagnostic group of healthy volunteers and people with psychotic as well as non-psychotic disorders. Recordings were transcribed and underwent automated language processing, including semantic role labeling to identify action and predication relations. Structural and semantic graph features were computed using static and dynamic (moving-window) techniques. Compared to structural graphs, semantic graphs were more highly correlated with dimensional psychosis symptoms. Dynamic features also outperformed static features, and samples from picture descriptions were more informative than narrative responses for psychosis diagnoses and symptom dimensions. Overall, semantic graphs capture unique and clinically meaningful information about psychosis and related symptom dimensions. These features, particularly when derived from semi-structured tasks using dynamic measurement, are meaningful additions to the repertoire of computational linguistic methods in psychiatry.
Hemispheric lateralization in older adults who habitually play darts: a cross-sectional study using functional near-infrared spectroscopy
Authors: Toyofuku Koki , Hiwa Satoru , Tanioka Kensuke , Hiroyasu Tomoyuki , Takeda Masaki 
Published: March 2022

AbstractExercise training integrating physical and cognitive activities is gaining attention because of its potential benefits for brain health. This study focuses on exercise training using a dart game called Wellness Darts. Wellness Darts is a sport involving throwing darts and walking to pull them out of the board, memorizing the score, and subtracting it from the total score, thus allowing the performance of two tasks simultaneously: exercise and calculation. It is expected to maintain and improve cognitive function, and whether the continual dart training affects brain function is of great interest. Before conducting the longitudinal study revealing its effect on brain function, we aimed to cross-sectionally confirm the difference in hemispheric lateralization between expert and non-expert players. Functional near-infrared spectroscopy (fNIRS) was used to measure brain activity for three groups: an expert older group who practiced darts continually, a non-expert older control group, and a non-expert younger control group. Their brain activity patterns were quantified by lateralization index (LI) and compared between groups. The results showed that the younger and the expert older groups had significantly higher LI values than the non-expert older group and did not differ between the expert older and the younger groups. Our results suggest that the Wellness Darts possibly promote hemispheric lateralization.
Frequency-specific neural signatures of perceptual content and perceptual stability
Authors: Hardstone Richard , Flounders Matthew , Zhu Michael , He Biyu J. 
Published: March 2022

ABSTRACTIn the natural environment, we often form stable perceptual experiences from ambiguous and fleeting sensory inputs. Which neural activity underlies the content of perception and which neural activity supports perceptual stability remains an open question. We used a bistable perception paradigm involving ambiguous images to behaviorally dissociate perceptual content from perceptual stability, and magnetoencephalography (MEG) to measure whole-brain neural dynamics in humans. Combining multivariate decoding and neural state-space analyses, we found frequency band-specific neural signatures that underlie the content of perception and promote perceptual stability, respectively. Across different types of images, non-oscillatory neural activity in the slow cortical potential (SCP, <5 Hz) range supported the content of perception. By contrast, perceptual stability is influenced by the amplitude of alpha and beta oscillations. In addition, neural activity underlying perceptual memory, which supports perceptual stability when sensory input is temporally removed from view, also encodes elapsed time. Together, these results reveal distinct neural mechanisms that support the content vs. stability of visual perception.
Epigenetic changes associated with hyperglycaemia exposure in the longitudinal D.E.S.I.R. cohort
Authors: Khamis Amna , Ning Lijiao , Balkau Beverley , Bonnefond Amélie , Canouil Mickaёl , Roussel Ronan , Froguel Philippe 
Published: March 2022

AbstractAimUnderstanding DNA methylation dynamics associated with progressive hyperglycaemia exposure could provide early diagnostic biomarkers and an avenue for delaying type 2 diabetes (T2D) disease. We aimed to identify DNA methylation changes during a 6-year period associated with early hyperglycaemia exposure using the longitudinal D.E.S.I.R. cohort.MethodsWe selected individuals with progressive hyperglycaemia exposure based on T2D diagnostic criteria: 27 with long-term exposure, 34 with short-term exposure and 34 normoglycaemic controls. DNA from blood at inclusion and at the 6-years visit was subjected to methylation analysis using 850K methylation-EPIC arrays. A linear mixed model was used to perform an epigenome-wide association study (EWAS) and identify methylated changes associated with hyperglycaemia exposure during 6-year time-period.ResultsWe did not identify differentially methylated sites that reached FDR-significance in our cohort. Based on EWAS, we focused our analysis on methylation sites that had a constant effect during the 6-years across the hyperglycaemia groups compared to controls and found the most statistically significant site was the reported cg19693031 probe (TXNIP). We also performed an EWAS with HbA1c, using the inclusion and the 6-years methylation data and did not identify any FDR-significant CpGs.ConclusionsOur study reveals that DNA methylation changes are not robustly associated with hyperglycaemia exposure or HbA1c during a short-term period, however, our top loci indicate potential interest and should be replicated in larger cohorts.
Young adults who improve performance during dual-task walking show more flexible reallocation of cognitive resources: A Mobile Brain-Body Imaging (MoBI) study
Authors: Patelaki Eleni , Foxe John J. , Mazurek Kevin A. , Freedman Edward G. 
Published: March 2022

AbstractIn young adults, pairing a taxing cognitive task with walking can have different effects on gait and cognitive task performance. In some cases, performance clearly declines whereas in others compensatory mechanisms maintain performance even under dual-task conditions. This study set out to investigate the preliminary finding of behavioral improvement in Go-NoGo response inhibition task performance during walking compared to sitting, which was observed at the piloting stage. Mobile Brain/Body Imaging (MoBI) was used to record electroencephalographic (EEG) activity, three-dimensional (3D) gait kinematics and behavioral responses in the cognitive task, during sitting or walking on a treadmill. In a cohort of twenty-six (26) young adults, fourteen (14) participants improved in measures of cognitive task performance while walking compared to sitting. These participants exhibited walking-related EEG amplitude reductions over frontal brain scalp regions during key stages of inhibitory control (conflict monitoring, control implementation and pre-motor stages), accompanied by reduced stride-to-stride variability and faster responses to stimuli compared to those who did not improve. In contrast, the twelve (12) participants who did not improve exhibited no EEG amplitude differences across physical condition. The neural activity changes associated with performance improvement during dual tasking hold promise as cognitive flexibility markers that can potentially help assess cognitive decline in aging and neurodegeneration.
Durable protection against SARS-CoV-2 Omicron induced by an adjuvanted subunit vaccine
Authors: Arunachalam Prabhu S. , Feng Yupeng , Ashraf Usama , Hu Mengyun , Edara Venkata Viswanadh , Zarnitsyna Veronika I. , Aye Pyone Pyone , Golden Nadia , Green Kristyn W. M. , Threeton Breanna M. , Maness Nicholas J. , Beddingfield Brandon J. , Bohm Rudolf P. , Dufour Jason , Russell-Lodrigue Kasi , Miranda Marcos C. , Walls Alexandra C. , Rogers Kenneth , Shirreff Lisa , Ferrell Douglas E , Deb Adhikary Nihar R. , Fontenot Jane , Grifoni Alba , Sette Alessandro , O’Hagan Derek T. , Van Der Most Robbert , Rappuoli Rino , Villinger Francois , Kleanthous Harry , Rappaport Jay , Suthar Mehul S. , Veesler David , Wang Taia T. , King Neil P. , Pulendran Bali 
Published: March 2022

SummaryDespite the remarkable efficacy of COVID-19 vaccines, waning immunity, and the emergence of SARS-CoV-2 variants such as Omicron represents a major global health challenge. Here we present data from a study in non-human primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine, consisting of RBD (receptor binding domain) on the I53-50 nanoparticle, adjuvanted with AS03, currently in Phase 3 clinical trial (NCT05007951). Vaccination induced robust neutralizing antibody (nAb) titers that were maintained at high levels for at least one year after two doses (Pseudovirus nAb GMT: 2207, Live-virus nAb GMT: 1964) against the ancestral strain, but not against Omicron. However, a booster dose at 6-12 months with RBD-Wu or RBD-β (RBD from the Beta variant) displayed on I53-50 elicited equivalent and remarkably high neutralizing titers against the ancestral as well as the Omicron variant. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Importantly, vaccination resulted in protection against Omicron infection in the lung (no detectable virus in any animal) and profound suppression of viral burden in the nares (median peak viral load of 7567 as opposed to 1.3×107 copies in unvaccinated animals) at 6 weeks post final booster. Even at 6 months post vaccination, there was significant protection in the lung (with 7 out of 11 animals showing no viral load, 3 out of 11 animals showing ~20-fold lower viral load than unvaccinated controls) and rapid control of virus in the nares. These results highlight the durable cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine platform.
Herpesvirus Reactivations in Critically-Ill COVID-19 Patients with Autoantibodies Neutralizing Type I Interferons
Authors: Busnadiego Idoia , Abela Irene A. , Frey Pascal M. , Hofmaenner Daniel A. , Scheier Thomas C. , Schuepbach Reto A. , Buehler Philipp K. , Brugger Silvio D. , Hale Benjamin G. 
Published: March 2022

ABSTRACTAutoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with pre-disposition to severe COVID-19. Here, we screened for such autoantibodies in 103 critically-ill COVID-19 patients in a tertiary intensive care unit in Switzerland. Eleven patients (10.7%), but no healthy donors, had neutralizing anti-IFNα or anti-IFNα/anti-IFNω IgG in plasma/serum, but anti-IFN IgM or IgA was rare. One patient had non-neutralizing anti-IFNα IgG. Strikingly, all patients with plasma anti-IFNα IgG also had anti-IFNα IgG in tracheobronchial secretions, identifying these autoantibodies at anatomical sites relevant for SARS-CoV-2 infection. Longitudinal analyses revealed patient heterogeneity in terms of increasing, decreasing, or stable anti-IFN IgG levels throughout the length of hospitalization. Notably, presence of anti-IFN autoantibodies in this critically-ill COVID-19 cohort appeared to predict herpesvirus (herpes simplex viruses types 1 and 2, HSV-1/-2; and/or cytomegalovirus, CMV) reactivations, which are linked to worse clinical outcomes. Indeed, all seven tested COVID-19 patients with anti-IFN IgG in our cohort (100%) suffered from one or more herpesvirus reactivations, and analysis revealed that these patients were substantially more likely to experience CMV reactivation than COVID-19 patients without anti-IFN autoantibodies, even when adjusting for systemic steroid treatment (odds ratio 7.28, 95%-CI 1.14-46.31, p=0.036). As the IFN system deficiency caused by neutralizing anti-IFN autoantibodies likely directly and indirectly exacerbates herpesvirus reactivations in critically-ill patients, early diagnosis of anti-IFN IgG could be rapidly used to inform risk-group stratification and treatment options.
De novo mutation hotspots in homologous protein domains identify function-altering mutations in neurodevelopmental disorders
Authors: Wiel Laurens , Hampstead Juliet E. , Venselaar Hanka , Vissers Lisenka E. L. M. , Brunner Han G. , Pfundt Rolph , Vriend Gerrit , Veltman Joris A. , Gilissen Christian 
Published: March 2022

AbstractVariant interpretation remains a major challenge in medical genetics. We developed Meta-Domain HotSpot (MDHS) to identify mutational hotspots across homologous protein domains. We applied MDHS to a dataset of 45,221 de novo mutations (DNMs) from 31,058 patients with neurodevelopmental disorders (NDDs) and identified three significantly enriched missense DNM hotspots in the ion transport protein domain family (PF00520). The 37 unique missense DNMs that drive enrichment affect 25 genes, 19 of which were previously associated with NDDs. 3D protein structure modelling supports function-altering effects of these mutations. Hotspot genes have a unique expression pattern in tissue, and we used this pattern alongside in silico predictors and population constraint information to identify candidate NDD-associated genes. We also propose a lenient version of our method, which identifies 32 hotspot positions across 16 different protein domains. These positions are enriched for likely pathogenic variation in clinical databases and DNMs in other genetic disorders.
Treatment response prediction: Is model selection unreliable?
Authors: Augustin David , Wang Ken , Walz Antje-Christine , Lambert Ben , Clerx Michael , Robinson Martin , Gavaghan David 
Published: March 2022

AbstractQuantitative modelling has become an essential part of the drug development pipeline. In particular, pharmacokinetic and pharmacodynamic models are used to predict treatment responses in order to optimise clinical trials and assess the safety and efficacy of dosing regimens across patients. It is therefore crucial that treatment response predictions are reliable. However, the data available to fit models are often limited, which can leave considerable uncertainty about the best model to use. Common practice is to select the model that is most consistent with the observed data based on the Akaike information criterion (AIC). Another popular approach is to average the predictions across the subset of models consistent with the data. In this article, we argue that both approaches can lead to unreliable predictions, as treatment responses typically display nonlinear dynamics, so models can be consistent with the observed dynamics, whilst predicting incorrect treatment responses. This is especially the case when predicting treatment responses for either times or dosing regimens that go beyond the observed dynamics. Across a range of experiments on both real laboratory data and synthetically derived data onNeisseria gonorrhoeaeresponse to ciprofloxacin, we show that probabilistic averaging of models results in more reliable treatment response predictions.