Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring the lived return-to-work experience of individuals with acquired brain injury: use of vocational services and environmental, personal and injury-related influences

Abstract Purpose To explore work outcomes, vocational services, barriers and facilitators for returning to work in individuals with acquired brain injury (ABI) in Queensland, Australia and to identify areas for improvement. Design and methods Ten semi-structured interviews were conducted with individuals with ABI (stroke, traumatic brain injury, tumour). Interviews were analysed using a realist thematic analysis approach. Results Participants either returned to the same work, different work, did not maintain work or did not have any work since their injury. Use of vocational services depended on participants’ needs and insurance. Facilitators for return to work (RTW) were a supportive workplace and family, vocational rehabilitation that met the individual’s needs, insurance coverage and self-motivation. Workplaces that were not understanding of brain injury, employment service providers who were unable to find work for participants, and physical and cognitive deficits were barriers to RTW. Workplaces, employment service providers and individuals require more information about the deficits associated with brain injury. Conclusions The use and effectiveness of vocational services were variable across participants and depended on insurance coverage and needs. Barriers and facilitators for RTW were affected by both the environment and the individual. Implications for vocational rehabilitation were identified. Implications for Rehabilitation A supportive workplace and family, and access to appropriate vocational rehabilitation are important environmental facilitators for RTW in individuals with ABI. Workplaces with a poor understanding of ABI and employment service providers unable to find work for individuals with ABI are environmental barriers to RTW. Workplaces, employment service providers and individuals with ABI require more information about the physical and cognitive deficits associated with ABI. Employment service providers need more training to develop comprehensive strategies to help individuals with ABI find new employment.
Androgen receptor signalling confers clonogenic and migratory advantages in urothelial cell carcinoma of the bladder

Bladder urothelial cell carcinoma (UCC) incidence is about three times higher in men compared with women. There are several indications for the involvement of hormonal factors in the aetiology of UCC. Here, we provide evidence of androgen signalling in UCC progression. Microarray and qPCR analysis revealed that the androgen receptor (AR) mRNA level is upregulated in a subset of UCC cases. In an AR‐positive UCC‐derived cell line model, UM‐UC‐3‐AR, androgen treatment increased clonogenic capacity inducing the formation of big stem cell‐like holoclones, while AR knockdown or treatment with the AR antagonist enzalutamide abrogated this clonogenic advantage. Additionally, blockage of AR signalling reduced the cell migration potential of androgen‐stimulated UM‐UC‐3‐AR cells. These phenotypic changes were accompanied by a rewiring of the transcriptome with almost 300 genes being differentially regulated by androgens, some of which correlated with AR expression in UCC patients in two independent data sets. Our results demonstrate that AR signals in UCC favouring the development of an aggressive phenotype and highlights its potential as a therapeutic target for bladder cancer.
Visualization of neurofibrillary tangle maturity in Alzheimer's disease: A clinicopathologic perspective for biomarker research

Neurofibrillary tangles, one of the neuropathologic hallmarks of Alzheimer's disease, have a dynamic lifespan of maturity that associates with progressive neuronal dysfunction and cognitive deficits. As neurofibrillary tangles mature, the biology of the neuron undergoes extensive changes that may impact biomarker recognition and therapeutic targeting. Neurofibrillary tangle maturity encompasses three levels: pretangles, mature tangles, and ghost tangles. In this review, we detail distinct and overlapping characteristics observed in the human brain regarding morphologic changes the neuron undergoes, conversion from intracellular to extracellular space, tau immunostaining patterns, and tau isoform expression changes across the lifespan of the neurofibrillary tangle. Post‐translational modifications of tau such as phosphorylation, ubiquitination, conformational events, and truncations are discussed to contextualize tau immunostaining patterns. We summarize accumulated and emerging knowledge of neurofibrillary tangle maturity, discuss the current tools used to interpret the dynamic nature in the postmortem brain, and consider implications for cognitive dysfunction and tau biomarkers.
Macrostructural Changes of the Acoustic Radiation in Humans with Hearing Loss and Tinnitus Revealed with Fixel-Based Analysis

Age-related hearing loss is the most prevalent sensory impairment in the older adult population and is related to noise-induced damage or age-related deterioration of the peripheral auditory system. Hearing loss may affect the central auditory pathway in the brain, which is a continuation of the peripheral auditory system located in the ear. A debilitating symptom that frequently co-occurs with hearing loss is tinnitus. Strikingly, investigations into the impact of acquired hearing loss, with and without tinnitus, on the human central auditory pathway are sparse. This study used diffusion-weighted imaging (DWI) to investigate changes in the largest central auditory tract, the acoustic radiation, related to hearing loss and tinnitus. Participants with hearing loss, with and without tinnitus, and a control group were included. Both conventional diffusion tensor analysis and higher-order fixel-based analysis were applied. The fixel-based analysis was used as a novel framework providing insight into the axonal density and macrostructural morphologic changes of the acoustic radiation in hearing loss and tinnitus. The results show tinnitus-related atrophy of the left acoustic radiation near the medial geniculate body. This finding may reflect a decrease in myelination of the auditory pathway, instigated by more profound peripheral deafferentation or reflecting a preexisting marker of tinnitus vulnerability. Furthermore, age was negatively correlated with the axonal density in the bilateral acoustic radiation. This loss of fiber density with age may contribute to poorer speech understanding observed in older adults. SIGNIFICANCE STATEMENT Age-related hearing loss is the most prevalent sensory impairment in the older adult population. Older individuals are subject to the cumulative effects of aging and noise exposure on the auditory system. A debilitating symptom that frequently co-occurs with hearing loss is tinnitus: the perception of a phantom sound. In this large DWI-study, we provide evidence that in hearing loss, the additional presence of tinnitus is related to degradation of the acoustic radiation. Additionally, older age was related to axonal loss in the acoustic radiation. It appears that older adults have the aggravating circumstances of age, hearing loss, and tinnitus on central auditory processing, which may partly be because of the observed deterioration of the acoustic radiation with age.
Gut microbiota from mice with cerebral ischemia-reperfusion injury affects the brain in healthy mice

Gut microorganisms can profoundly influence brain function in the host and their behavior. Since altered brain functional connectivity (FC) has been implicated in various cerebrovascular disorders, including cerebral ischemia-reperfusion (I/R) injury, we hypothesized that gut microbiota in mice with cerebral I/R injury would affect brain FC when transplanted into germ-free mice. Metagenomic analysis of germ-free male C57BL/6J mice colonized with microbiota from mice with and without cerebral I/R injury showed a clear distinction in microbiota composition between mice colonized with control and I/R microbiota. The I/R microbiota-colonized mice showed decreased FC in the cingulate cortex, hippocampus, and thalamus, and exhibited increased anxiety as well as diminished spatial learning and memory and short-term object recognition memory. I/R microbiota-colonized mice also had significantly reduced dendritic spine density and synaptic protein levels and exhibited increased hippocampal inflammation. These results indicate that gut microbiota components from mice with cerebral I/R injury can alter animal behavior, brain functional connectivity, hippocampal neuronal plasticity, and neuroinflammation. Moreover, they increase our understanding of the mechanisms through which the gut microbiome contributes to the pathobiology of cerebrovascular diseases.
Systems genetic analysis of nicotine withdrawal deficits in hippocampus‐dependent learning

Cognitive deficits, such as disrupted learning, are a major symptom of nicotine withdrawal. These deficits are heritable, yet their genetic basis is largely unknown. Our lab has developed a mouse model of nicotine withdrawal deficits in learning, using chronic nicotine exposure via osmotic minipumps and fear conditioning. Here, we utilized the BXD genetic reference panel to identify genetic variants underlying nicotine withdrawal deficits in learning. Male and female mice (n = 6–11 per sex per strain, 31 strains) received either chronic saline or nicotine (6.3 mg/kg per day for 12 days), and were then tested for hippocampus‐dependent learning deficits using contextual fear conditioning. Quantitative trait locus (QTL) mapping analyses using GeneNetwork identified a significant QTL on Chromosome 4 (82.13 Mb, LRS = 20.03, p < 0.05). Publicly available hippocampal gene expression data were used to identify eight positional candidates (Snacpc3, Mysm1, Rps6, Plaa, Lurap1l, Slc24a2, Hacd4, Ptprd) that overlapped with our behavioral QTL and correlated with our behavioral data. Overall, this study demonstrates that genetic factors impact cognitive deficits during nicotine withdrawal in the BXD recombinant inbred panel and identifies candidate genes for future research.
The Congregational Structure of Homonegativity: Why Place of Worship May Matter More than Frequency of Worship

ABSTRACT Using 239 congregants from 14 randomly selected places of worship in the Southern United States—and a mega-analysis of 577 congregants from 34 similarly-located places of worship—we examined the relationship between religiousness and homonegativity. Multilevel models examining the effects of religiousness on homonegativity indicated that service attendance was more strongly related to homonegativity as a congregation-level variable than as an individual-level variable. Interaction effects between service attendance and the affirmativeness of a congregation were not significant, suggesting that the frequency of participation with a homonegative congregation is not related to homonegativity. These findings imply that the religiousness of a congregation is more closely related to homonegativity than the religiousness of an individual and that individuals may select a congregation that matches their views on same-sex sexuality. Homonegativity may serve a signaling function, enabling congregants to affiliate with a congregation with attitudes toward same-sex sexuality similar to their own.
DNA hypo-methylation facilitates anti-inflammatory responses in severe ulcerative colitis

Severe ulcerative colitis (UC) is a potentially life-threatening disease with a potential colorectal cancer (CRC) risk. The aim of this study was to explore the relationship between transcriptomic and genome-wide DNA methylation profiles in a well-stratified, treatment-naïve severe UC patient population in order to define specific epigenetic changes that could be responsible for the grade of disease severity. Mucosal biopsies from treatment-naïve severe UC patients (n = 8), treatment-naïve mild UC (n = 8), and healthy controls (n = 8) underwent both whole transcriptome RNA-Seq and genome-wide DNA bisulfite- sequencing, and principal component analysis (PCA), cell deconvolutions and diverse statistical methods were applied to obtain a dataset of significantly differentially expressed genes (DEGs) with correlation to DNA methylation for severe UC. DNA hypo-methylation correlated with approximately 80% of all DEGs in severe UC when compared to mild UC. Enriched pathways of annotated hypo-methylated genes revealed neutrophil degranulation, and immuno-regulatory interactions of the lymphoid system. Specifically, hypo-methylated anti-inflammatory genes found for severe UC were IL10, SIGLEC5, CD86, CLMP and members of inflammasomes NLRP3 and NLRC4. Hypo-methylation of anti-inflammatory genes during severe UC implies an interplay between the epithelium and lamina propria in order to mitigate inflammation in the gut. The specifically DNA hypo-methylated genes found for severe UC can potentially be useful biomarkers for determining disease severity and in the development of new targeted treatment strategies for severe UC patients.
Stress and odorant receptor feedback during a critical period after hatching regulates olfactory sensory neuron differentiation in Drosophila

Here, we reveal that the regulation of Drosophila odorant receptor (OR) expression during the pupal stage is permissive and imprecise. We found that directly after hatching an OR feedback mechanism both directs and refines OR expression. We demonstrate that, as in mice, dLsd1 and Su(var)3-9 balance heterochromatin formation to direct OR expression. We show that the expressed OR induces dLsd1 and Su(var)3-9 expression, linking OR level and possibly function to OR expression. OR expression refinement shows a restricted duration, suggesting that a gene regulatory critical period brings olfactory sensory neuron differentiation to an end. Consistent with a change in differentiation, stress during the critical period represses dLsd1 and Su(var)3-9 expression and makes the early permissive OR expression permanent. This induced permissive gene regulatory state makes OR expression resilient to stress later in life. Hence, during a critical period OR feedback, similar to in mouse OR selection, defines adult OR expression in Drosophila.
Association between renal urolithiasis after extracorporeal shock wave lithotripsy therapy and new-onset hypertension: an updated meta-analysis

Objective The long-term effect of extracorporeal shock wave lithotripsy (SWL) is still controversial. A previous meta-analysis showed no association between new-onset hypertension and entire upper urinary urolithiasis after SWL. Recently, there have been some reports on this topic. Therefore, we aimed to examine the association between new-onset hypertension and nephrolithiasis after SWL therapy. Methods Embase, the Cochrane Central Search Library, and PubMed were used to search for reports on new-onset hypertension and patients with nephrolithiasis after SWL. A meta-analysis of the association between new-onset hypertension and nephrolithiasis after SWL was carried out. The data of relevant research were synthesized and the relative risk was computed. Results Seven eligible studies were included in our meta-analysis. There was a significant association between nephrolithiasis after SWL and new-onset hypertension. The overall relative risk with a 95% confidence interval was 1.21 (1.11–1.31) in a fixed-effects model. Conclusion Our meta-analysis suggests an association between new-onset hypertension and patients with nephrolithiasis after SWL, which is in contrast with the finding of a previous meta-analysis.
Computed Tomography–Derived Fractional Flow Reserve in Patients With Chronic Coronary Syndrome: A Real-World Cohort Study

Supplemental digital content is available in the text. Objective This study aimed to investigate the outcome of computed tomography (CT) angiography with optional CT-derived fractional flow reserve (FFRCT) of intermediate-range coronary artery disease in non-emergent patients referred on a suspicion of chronic coronary syndrome. Methods Patients were classified as high risk and low-intermediate risk according to the presence of typical angina or either atypical or nonangina chest pain. Outcome was assessed as the cumulative incidence proportion of a composite end point of unstable angina pectoris, unplanned revascularization, nonfatal myocardial infarction, and all-cause mortality. Results The study included 743 patients. Mean follow-up was 2.2 (range, 0.1–2.5) years. Low-intermediate–risk and high-risk patients who had invasive coronary angiography deferred had comparable proportions of adverse events (1.4% vs 2.6% [P = 0.27]). Adverse events in high-risk patients with FFRCT >0.80 was 3.3% versus 1.4% in patients where no additional testing was performed (P = 0.79). Conclusions Computed tomography–derived fractional flow reserve >0.8 conveys an excellent prognosis. Computed tomography angiography with optional FFRCT allows for the safe cancellation of invasive coronary angiography in high-risk patients.
Ocular Manifestations in Patients of HIV(Human Immunodeficiency Virus) Infection on Combined Anti-Retroviral Therapy (CART)

ABSTRACT Aim To determine the prevalence and spectrum of ocular manifestations in PLHIV (people living with Human Immunodeficiency Virus) on cART (combined Antiretroviral Therapy) and correlate them with WHO clinical staging, CD4 count, duration & type of cART. Methods Observational cross-sectional study. Ophthalmic evaluation of 350 PLHIV on cART (at least 6 months) was done. Logistic regression was done to correlate ocular findings with different variables. Results: Prevalence of ocular, anterior & posterior segment manifestations was 15.71%, 10.86%, and 4.00%, respectively. Dry eye(8.00%) being the most common finding. PLHIV with CD4 count ≤350 (OR = 3.1,p < 0.001), in WHO stage 3 (OR = 26.9,p = 0.004) & 4(OR = 60.7,p < 0.001) & on 3rdlineART were at much higher risk of ocular manifestations as compared to those on 2nd (OR = 2.83) and 1stline (OR = 6.6) of therapy. Duration of treatment had a protective (p = 0.01) effect on bilateral manifestations. Conclusion With early initiation of ART, there is significant reduction in the overall prevalence of ocular findings, in the number of opportunistic ophthalmic infections and blinding disorders. Of all the reported ocular findings, anterior segment disorder emerged more often.
Prevalence of anxiety, depression, and psychological distress among the general population during the COVID-19 pandemic: A systematic review and meta-analysis

Background: The COVID-19 pandemic is a worldwide epidemic declared by the world health organization as a public health emergency of concern and consequently inducing huge mental health and psychological reactions. Aims: This study is aimed to summarize the existing data regarding anxiety, depression, and psychological distress during the covid-19 pandemic among the wider population so that effective intervention strategies will be initiated. Methods: Pieces of literature that assessed anxiety, depression, and psychological distress among the general population during the COVID pandemic period were systematically gathered. Data extraction in Microsoft excel was done by two independent reviewers using predefined criteria. The analysis was done using a stata-11 and random effect model. A sub-group and sensitivity analysis was done. Besides, the funnel plot and eggers publication bias test was tested. Results: Sixteen studies that assessed 78,225 participants were included. Nine studies were included in the meta-analysis for anxiety prevalence. The average prevalence of anxiety was found to be 38.12%. A sub-group analysis showed that anxiety was 33.33% in China and 47.70% in other countries (Italy, Turkey, and India). Anxiety prevalence in studies measured with the DASS-21 scale, GAD-7 scale, and other tools (SAS, HADS, and 5-point Likert scale) was 23.4%, 40.73%, and 44.47% respectively. The prevalence of anxiety in studies that assessed a sample size above 2,000 participants was 40.33%. The average prevalence of depression among included studies was 34.31% and a sub-group analysis showed that depression was higher in China (36.32%) than in other countries (28.3%). Moreover, six studies reported psychological distress and the average prevalence was 37.54%. Conclusion: This study revealed that anxiety, depression, and psychological distress are potential public mental health problems of the global community that suggests the need for early recognition and initiation of interventions during the COVID-19 pandemic period.
Sensitization or inoculation: Investigating the effects of early adversity on personality traits and stress experiences in adulthood

Cumulative evidence has been found for the associations between personality traits and stress experiences in adulthood. However, less is known about the moderating mechanisms underlying these associations. The present study tested whether the stress sensitization and stress inoculation hypotheses could be applied to the relationship between early adversity and personality in adulthood. Specifically, we tested the linear and curvilinear relations between early adversity (measured retrospectively) and adulthood personality traits, as well as the linear and curvilinear moderating effects of early adversity on the associations between adulthood stress and personality traits. Samples of older adults from the Health and Retirement Study (HRS; N = 6098) and middle-aged adults from the Midlife in the United States Survey (MIDUS; N = 6186) were used. Across the two samples, positive linear associations were found between retrospective early adversity and neuroticism. The results also suggested significant linear effects of early adversity on the association between ongoing chronic stressors and neuroticism such that individuals with moderate exposure to early adversity showed stronger associations between ongoing chronic stressors and neuroticism. Results from the current research were more in line with the stress sensitization model. No support was found for the stress inoculation effects on personality.
CD40 signaling augments IL-10 expression and the tolerogenicity of IL-10-induced regulatory dendritic cells

CD40 expressed on stimulatory dendritic cells (DC) provides an important accessory signal for induction of effector T cell responses. It is also expressed at lower levels on regulatory DC (DCreg), but there is little evidence that CD40 signaling contributes to the tolerogenic activity of these cells. Indeed, CD40 silencing within DCreg has been reported to induce T cell tolerance in multiple disease models, suggesting that CD40 is superfluous to DC-induced tolerance. We critically assessed whether CD40 does have a role in tolerance induced by IL-10-differentiated DC (DC10) by using DC10 generating from the bone marrow of wild-type (w.t.) or CD40-/- donor mice, or IL-10-complemented CD40-/- DC10 to treat asthmatic mice. Wild-type DC10 ablated the OVA-asthma phenotype via induction of Foxp3+ Treg responses, but CD40-/- DC10 had no discernible effects on primary facets of the phenotype (e.g., IL-5, IL-9, IL-13 levels, IgE & IgG1 antibodies; p>0.05) and were ≤40% effective in reversal of others. Foxp3+ T cells from the lungs of CD40-/- DC10-treated mice expressed reduced levels of a panel of six Treg-specific activation markers relative to Treg from w.t. DC10-treated mice. Coculture with effector T cells from asthmatic mice induced a marked upregulation of cell surface CD40 on w.t. DC10. While untreated CD40-/- and w.t. DC10 secreted equally low levels of IL-10, stimulation of w.t. DC10 with anti-CD40 for 72 h increased their expression of IL-10 by ≈250%, with no parallel induction of IL-12. Complementing IL-10 expression in CD40-/- DC10 by IL-10 mRNA transfection fully restored the cells’ abilities to suppress the asthma phenotype. In summary, CD40 signaling in DC10 contributes importantly to their expression of IL-10 and to a robust induction of tolerance, including activation of induced Treg.