bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychological Resilience in Adolescence as a function of Genetic Risk for Major Depressive Disorder and Alzheimer’s Disease
Authors: Petrican Raluca , Fornito Alex 
Published: July 2022

AbstractMajor Depressive Disorder (MDD) and Alzheimer’s Disease (AD) are two pathologies linked to prior stress exposure and altered neurodevelopmental trajectories. As a putative antecedent to AD, MDD could be key to understanding the neurobiological changes that precede the clinical onset of AD by decades. To test this hypothesis, we used longitudinal data from the Adolescent Brain and Cognitive Development study (Ntotal = 980, 470 females) and investigated overlapping connectomic, transcriptomic, and chemoarchitectural correlates of adjustment to stressors (i.e., resilience) among adolescents at genetic risk for AD and MDD, respectively. The potential for perinatal adversity to directly and/or indirectly, via accelerated biological ageing, foster resilience (i.e., “inoculation” effects) was also probed. We identified two distinguishable neurodevelopmental profiles predictive of resilience among MDD-vulnerable adolescents. One profile, expressed among the fastest developing youth, overlapped with areas of greater dopamine receptor density and reflected the maturational refinement of the inhibitory control architecture. The second profile distinguished resilient MDD-prone youth from psychologically vulnerable adolescents genetically predisposed towards AD. This profile, associated with elevated GABA, relative to glutamate, receptor density, captured the longitudinal refinement and increasing context specificity of incentive-related brain activations. Its transcriptomic signature implied that poorer resilience among AD-prone youth may be associated with greater expression of MDD-relevant genes. Our findings are compatible with the proposed role of MDD as a precursor to AD and underscore the pivotal contribution of incentive processing to this relationship. They further speak to the key neuromodulatory role of DA-gonadal hormone interactions in fostering resilience in adolescence.Significance StatementEnvironmental stressors can substantially alter brain maturation and incur lifelong costs. Using longitudinal data, we characterise two developmental profiles correlated with positive adjustment to environmental challenges (i.e., resilience) among adolescents at genetic risk for two stress-related conditions, Alzheimer’s Disease (AD) and Major Depressive Disorder (MDD), respectively. One dopamine-related profile typified the fastest developing MDD-prone adolescents and reflected the neural maturation of the inhibitory control architecture. The second profile, neurochemically linked to excitation/inhibition balance, indicated the developmental refinement of motivational pathways, distinguishing resilient MDD-prone from psychologically vulnerable AD-prone teens. Its transcriptomic signature supported the posited role of MDD as an antecedent to AD. Our results unveil candidate neurobiological mechanisms supporting lifespan resilience against both psychiatric and neurological conditions linked to stress exposure.
Active safety surveillance of COVID-19 mRNA vaccines in children aged 5-15 years in Australia
Authors: Wood Nicholas , Lopez Laura K , Glover Catherine , Leeb Alan , Cashman Patrick , Deng Lucy , Macartney Kristine 
Published: July 2022

ABSTRACTAusVaxSafety (Australia’s active safety surveillance system) used SMS/email delivered surveys to actively solicit the short-term (within first 3 days after vaccination) adverse event profile of mRNA COVID-19 vaccines in children (aged 5–15 years) by age, dose, brand and pre-existing comorbidity.392,268 survey responses for children aged 5–15 who received a COVID-19 vaccine between July 2021–May 2022 (211,994 following BNT162b2 10mcg in children aged 5–11 years, 173,329 following BNT162b2 30mcg and 6,945 following mRNA-1273 100mcg in adolescents aged 12–15 years) were analysed.Adverse event rates were higher following dose 2 and 3 compared to dose 1 after all vaccines and highest following dose 2 of mRNA-1273 in 12–15 years. Fever was low in the youngest children (5 years old, any dose; 1,090/26,181 (4%)). Medical review rates remained low (0.3% overall) and impact on daily activities was also low (7% overall). No self-reported cases of myocarditis or pericarditis were identified.Ongoing active safety surveillance of lower dose mRNA vaccines in children under 5 years old is required to better understand safety as the vaccines roll out into this population age-group.
Operant Conditioning of Rectus Femoris H-Reflexes: A Proof-of-Concept with Implications for Post-Stroke Quadriceps Hyperreflexia
Authors: Kim Kyoungsoon , Akbas Tunc , Lee Robert , Manella Kathleen , Sulzer James 
Published: July 2022

AbstractHyperreflexia is common after neurological injury such as stroke, yet clinical interventions have had mixed success. Our previous research has shown that hyperreflexia of the rectus femoris (RF) during pre-swing is closely associated with reduced swing phase knee flexion in those with post-stroke Stiff-Knee gait (SKG). Thus, reduction of RF hyperreflexia may improve walking function in those with SKG after stroke. A non-pharmacological and non-surgical procedure for reducing hyperreflexia has emerged based on operant conditioning of spinal reflexes elicited using electrical stimulation of the peripheral nerve, known as an H-reflex. Operant H-reflex conditioning training of the soleus has improved clinical gait function in those with spinal cord injury. It is currently unknown whether operant conditioning can be applied to the RF or those after stroke. This feasibility study trained 7 participants (5 neurologically intact, 2 post-stroke) over a period of 3 months, up to 3 times per week, to down-condition the RF H-reflex using visual feedback. We found an overall decrease in average RF H-reflex amplitude among 7 participants (44% drop, p<0.001, paired t-test), of which the post-stroke individuals contributed (49% drop). We observed a generalized training effect across quadriceps muscles. Post-stroke individuals exhibited improvements in peak knee-flexion velocity, reflex excitability during walking, and clinical measures of spasticity. These aforementioned neuromuscular outcomes provide promising initial results that operant RF H-reflex conditioning is feasible both in healthy and post-stroke individuals. This procedure could provide a targeted alternative to spasticity management and avoid the drawbacks of drugs and surgery.
Novel genomic loci influence patterns of structural covariance in the human brain
Authors: Wen Junhao , Nasrallah Ilya M. , Abdulkadir Ahmed , Satterthwaite Theodore D. , Yang Zhijian , Erus Guray , Robert-Fitzgerald Timothy , Singh Ashish , Sotiras Aristeidis , Boquet-Pujadas Aleix , Mamourian Elizabeth , Doshi Jimit , Cui Yuhan , Srinivasan Dhivya , Skampardoni Ioanna , Chen Jiong , Hwang Gyujoon , Bergman Mark , Bao Jingxuan , Veturi Yogasudha , Zhou Zhen , Yang Shu , Dazzan Paola , Kahn Rene S. , Schnack Hugo G. , Zanetti Marcus V. , Meisenzahl Eva , Busatto Geraldo F. , Crespo-Facorro Benedicto , Pantelis Christos , Wood Stephen J. , Zhuo Chuanjun , Shinohara Russell T. , Gur Ruben C. , Gur Raquel E. , Koutsouleris Nikolaos , Wolf Daniel H. , Saykin Andrew J. , Ritchie Marylyn D. , Shen Li , Thompson Paul M. , Colliot Olivier , Wittfeld Katharina , Grabe Hans J. , Tosun Duygu , Bilgel Murat , An Yang , Marcus Daniel S. , LaMontagne Pamela , Heckbert Susan R. , Austin Thomas R. , Launer Lenore J. , Espeland Mark , Masters Colin L , Maruff Paul , Fripp Jurgen , Johnson Sterling C. , Morris John C. , Albert Marilyn S. , Bryan R. Nick , Resnick Susan M. , Fan Yong , Habes Mohamad , Wolk David , Shou Haochang , Davatzikos Christos ,   the iSTAGING,   the BLSA,   the BIOCARD,   the PHENOM,   the ADNI studies,   the AI4AD consortium
Published: July 2022

AbstractNormal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization method to a diverse population of 50,699 individuals (12 studies, 130 sites) and derive data-driven, multi-scale PSCs of regional brain size. PSCs were significantly correlated with 915 genomic loci in the discovery set, 617 of which are novel, and 72% were independently replicated. Key pathways influencing PSCs involve reelin signaling, apoptosis, neurogenesis, and appendage development, while pathways of breast cancer indicate potential interplays between brain metastasis and PSCs associated with neurodegeneration and dementia. Using support vector machines, multi-scale PSCs effectively derive imaging signatures of several brain diseases. Our results elucidate new genetic and biological underpinnings that influence structural covariance patterns in the human brain.Significance statementThe coordinated patterns of changes in the human brain throughout life, driven by brain development, aging, and diseases, remain largely unexplored regarding their underlying genetic determinants. This study delineates 2003 multi-scale patterns of structural covariance (PSCs) and identifies 617 novel genomic loci, with the mapped genes enriched in biological pathways implicated in reelin signaling, apoptosis, neurogenesis, and appendage development. Overall, the 2003 PSCs provide new genetic insights into understanding human brain morphological changes and demonstrate great potential in predicting various neurologic conditions.
Geographical disparities and differences in medical specialty prescribing of dronabinol in Medicare from 2014 to 2019
Authors: DeSalve Dayna S , McCall Kenneth L , Piper Brian J 
Published: July 2022

AbstractPurposeThe purpose of our study was to investigate dronabinol prescribing in Medicare from 2014 to 2019 by provider specialty and state.MethodsData was collected and analyzed from the Centers for Medicare & Medicaid Services databases from 2014 to 2019. The mean number of prescriptions for each area of practice, each individual year, and for 2014 to 2019 overall for the 50 United States and District of Columbia was determined. The prescriptions were separated by state and the state totals were determined. Individual states with dronabinol prescriptions ≥1.96 standard deviations (SD) from the mean were identified as significant.ResultsThe total number of dronabinol prescriptions decreased 9.1% from 2014 to 2019. Dronabinol prescriptions were more concentrated in the eastern United States in 2019 than compared to 2014 [Tennessee (107.2), Kentucky (94.2), and West Virginia (87.6) (>1.96 SD)]. The largest portion of dronabinol prescriptions originated from primary care (1,736) compared to specialty areas of practice (1,233). Internal medicine (789.5), family medicine (608.8), hematology-oncology (343.3), nurse practitioners (337.3), and infectious disease (271.0) had the highest average number of dronabinol prescriptions per year (p<0.05). The areas of practice with the highest ratio of percent dronabinol prescriptions to percent Medicare utilization were infectious disease (15.8), hematology-oncology (12.2), and medical oncology (12.1).ConclusionDronabinol usage declined among Medicare patients and became more concentrated in the eastern United States. Most prescriptions originated from primary care, although after accounting for Medicare patient utilization, the highest ratios originated from infectious disease, hematology-oncology, and medical oncology.
Theory-based determinants of modern contraceptive use in sub-Saharan Africa: an analysis of demographic and health surveys
Authors: Adu-Gyamfi Raphael , Enos Juliana , Yeboah Dorcas Obiri , Torpey Kwasi 
Published: July 2022

AbstractIntroductionDespite improved access to modern contraceptives in sub-Saharan Africa (SSA), the region has the highest fertility rate. Although modern contraceptive usage and its determinants in SSA have been assessed, most authors were not guided by behavioral change theories. This study sought to assess the modern contraceptive coverage in SSA and identify the theory-based determinants that need to be considered in demand creation interventions.MethodsData was obtained from the most recent demographic and health surveys conducted across 37 countries in SSA. Estimates of country-specific and pooled Regional modern contraceptive coverage were generated from 501,324 responses. Logistic regression was used to assess the relationship between modern contraceptive use and determinants selected based on the Health Belief and Social-Ecological behavior change models.ResultsModern contraceptive coverage in SSA was 22.26% (95% CI: 17.91, 26.60). The health belief model determinants of modern contraceptive use included last birth by caesarian section (AOR=1.44, 95% CI:1.31,1.59), hearing of family planning at the health facility (AOR=1.18, 95% CI:1.12,1.24), or from at least one media source, being able to negotiate condom use (AOR=1.65, 95% CI: 1.55,1.76), and having a previous terminated pregnancy (AOR=0.76, 95%CI: 0.71, 0.81). The social ecological model determinants of modern contraceptive use included being above 24 years, having at least primary education, non-urgent need for a last child, and being involved in decision-making concerning personal health (AOR=1.81,95% CI:1.71,1.92).DiscussionModern contraceptive coverage in SSA is low. Age, educational status, past obstetric history, exposure to family planning information, ability to negotiate condom use or make personal health-related decisions, and the need for a child were the determinants for modern contraceptive use in the region. Countries need to develop context-specific interventions considering these determinants to help improve coverage and reduce the poor maternal and child health outcomes and the developmental gaps resulting from unplanned pregnancies.
Promotion and Validation of Flipped Teaching Based on Video Conference in Standardized Training for Internal Medicine Residents
Authors: Zhang Xiao-Yu 
Published: July 2022

AbstractObjectiveI aimed to verify the training effect of Flipped Teaching with Video Conference as carrier in the training of infectious diseases, and promote the application of this teaching mode in the standardized training for resident physicians.MethodsThe vertical management mode was adopted to carry out Flipped Teaching in the training, and the training of infectious diseases was carried out according to the requirements of the standardized training program for internal medicine resident. The residents trained in April were included in the trial group, and those trained in June were included in the validation group. The evaluation indexes of both groups were compared and analyzed.ResultsA total of 43 resident physicians participated in the training of infectious diseases by the Flipped Teaching based on Video Conference, all from tertiary hospitals. There were 19 participants in the trial group and 24 participants in the validation group, who carried out Flip Teaching with Video Conference as carrier for 31 times and 24 times respectively. The implementation rate of teaching plan was above 91% in both groups, and the attendance rate was above 98%; There was no significant difference on the attendance rate between the both groups, P>0.05. 952 effective feedback questionnaires were collected, including 395 in the trial group and 557 in the validation group. In terms of teaching quality, the indicators of “Rigorous teaching attitude” and “Punctual class” in the validation group were lower than those in the trial group, P < 0.05; And the other indicatiors were no significant difference, P>0.05; All feedback of the teaching quality indexes “good and very good” accounted for more than 96%. In the overall evaluation, there was no significant difference between the both groups on the index of “Suggestions for improvement”, P>0.05; And the “Praise highlight” of the validation group was higher than that of the trial group, P<0.05.ConclusionThe Flipped Teaching based on Video Conference is generally effective for internal medicine residents to carry out training of infectious diseases, with good feedback and strong feasibility. This teaching model can be further promoted and applied in the standardized training for resident physicians.
Rickettsiainfection rate along an altitudinal gradient as influenced by population genetic structure of Ixodid ticks
Authors: Regilme Maria Angenica F. , Sato Megumi , Tamura Tsutomu , Arai Reiko , Sato Marcello Otake , Ikeda Sumire , Watanabe Kozo 
Published: July 2022

AbstractIxodid ticks, such asIxodes ovatusandHaemaphysalis flava,are important vectors of tick-borne diseases in Japan, such as Japanese spotted fever caused byRickettsia japonica. This study describes the population genetic structure and gene flow ofI. ovatusandH. flavaand theirRickettsiainfection rates along an altitudinal gradient. A total of 346 adultI. ovatusand 243H. flavawere analyzed for the presence ofRickettsiaby nested PCR targeting the 17kDA,gltA, rOmpA,andrOmpBgenes. Population genetic structure was performed using the mitochondrial cytochrome oxidase 1 (cox1) marker. TheRickettsiainfection rates were 13.26% inI. ovatusand 6.17% inH. flava.ForI. ovatus,the globalFSTvalue revealed significant genetic differentiation among the different populations, whereasH. flavashowed non-significant genetic differentiation. Thecox1 I. ovatuscluster dendrogram showed two cluster groups, while the haplotype network and phylogenetic tree showed three genetic groups. The two cluster groups and the three genetic groups found inI. ovatusshowed a significant difference in theirRickettsiainfection rates and mean altitude per group. No significant differences were found in the mean altitude orRickettsiainfection rates ofH. flava. Our results suggest that low gene flow in theI. ovatuspopulations has caused spatially heterogenousRickettsiainfection rates along the altitudinal gradient. This information can be used in understanding the relationship between the tick vector, its pathogen, and environmental factors, such as altitude, and for the control of tick-borne diseases in Japan.
Single Photon smFRET. I. Theory and Conceptual Basis
Authors: Saurabh Ayush , Fazel Mohamadreza , Safar Matthew , Sgouralis Ioannis , Pressé Steve 
Published: July 2022

AbstractWe present a unified conceptual framework and the associated software package for single molecule Förster Resonance Energy Transfer (smFRET) analysis from single photon arrivals leveraging Bayesian nonparametrics, BNP-FRET. This unified framework addresses the following key physical complexities of a single photon smFRET experiment, including: 1) fluorophore photophysics; 2) continuous time kinetics of the labeled system with large timescale separations between photophysical phenomena such as excited photophysical state lifetimes and events such as transition between system states; 3) unavoidable detector artefacts; 4) background emissions; 5) unknown number of system states; and 6) both continuous and pulsed illumination. These physical features necessarily demand a novel framework that extends beyond existing tools. In particular, the theory naturally brings us to a hidden Markov model (HMM) with a second order structure and Bayesian nonparametrics (BNP) on account of items 1, 2 and 5 on the list. In the second and third companion manuscripts, we discuss the direct effects of these key complexities on the inference of parameters for continuous and pulsed illumination, respectively.Why It MatterssmFRET is a widely used technique for studying kinetics of molecular complexes. However, until now, smFRET data analysis methods required specifyinga priorithe dimensionality of the underlying physical model (the exact number of kinetic parameters). Such approaches are inherently limiting given the typically unknown number of physical configurations a molecular complex may assume. The methods presented here eliminate this requirement and allow estimating the physical model itself along with kinetic parameters, while incorporating all sources of noise in the data.
Phenotypic profile of Mycobacterium tuberculosis-specific CD4 T cell responses in HIV-positive patients who develop Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome
Authors: Moseki Raymond M , Barber Daniel L , Bruyn Elsa Du , Shey Muki , Van der Plas Helen , Wilkinson Robert J , Meintjes Graeme , Riou Catherine 
Published: July 2022

ABSTRACTBackgroundTuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of co-treatment for TB and HIV-1. We characterized Mtb-specific CD4 T cell phenotype and transcription factor profile associated with the development of TB-IRIS.MethodsWe examined the role of CD4 T-cell transcription factors in a murine model of mycobacterial IRIS. In humans, we compared longitudinally on antiretroviral therapy (ART) the magnitude, activation, transcription factor profile and cytotoxic potential of Mtb-specific CD4 T cells between TB-IRIS (n=25) and appropriate non-IRIS control patients (n=18) using flow cytometry.ResultsIn the murine model, CD4 T cell expression of Eomes, but not Tbet, was associated with experimentally induced IRIS. In patients, TB-IRIS onset was associated with the expansion of Mtb-specific IFNγ+CD4 T cells (p=0.039). TB-IRIS patients had higher HLA-DR expression (p=0.016), but no differences in the expression of T-bet or Eomes were observed. At TB-IRIS onset, Eomes+Tbet+Mtb-specific IFNγ+CD4+ T cells showed higher expression of Granzyme B in TB-IRIS patients (p=0.026).ConclusionWhile the murine model of MAC-IRIS suggests that Eomes+CD4 T cells underly IRIS, TB-IRIS was not associated with Eomes expression in patients. Mtb-specific IFNγ+CD4 T cell responses in TB-IRIS patients are differentiated, highly activated and potentially cytotoxic.