Miracle-dz/UniFAR-FTUs huggingface dataset:
Twelve-Month Follow-Up to a Fully Automated Internet-Based Cognitive Behavior Therapy Intervention for Rural Adults With Depression Symptoms: Single-Arm Longitudinal Study

Background Internet-based cognitive behavior therapy (iCBT) interventions have the potential to help individuals with depression, regardless of time and location. Yet, limited information exists on the longer-term (>6 months) effects of iCBT and adherence to these interventions. Objective The primary aim of this study was to evaluate the longitudinal (12 months) effectiveness of a fully automated, self-guided iCBT intervention called Thrive, designed to enhance engagement with a rural population of adults with depression symptoms. The secondary aim was to determine whether the program adherence enhanced the effectiveness of the Thrive intervention. Methods We analyzed data from 181 adults who used the Thrive intervention. Using self-reports, participants were evaluated at baseline, 8 weeks, 6 months, and 12 months for the primary outcome of depression symptom severity using the Patient Health Questionnaire-9 (PHQ-9) scale and secondary outcome measures, namely, the Generalized Anxiety Disorder Scale-7 (GAD-7) scores, Work and Social Adjustment Scale (WSAS) scores, Conner-Davidson Resilience Scale-10 (CD-RISC-10) scores, and suicidal ideation (ninth item of the PHQ-9 scale) scores. The Thrive program adherence was measured using the numbers of program logins, page views, and lessons completed. Results The assessment response rates for 8-week, 6-month, and 12-month outcomes were 58.6% (106/181), 50.3% (91/181), and 51.4% (93/181), respectively. By 8 weeks, significant improvements were observed for all outcome measures. These improvements were maintained at 12 months with mean reductions in severities of depression (mean –6.5; P<.001) and anxiety symptoms (mean –4.3; P<.001). Improvements were also observed in work and social functioning (mean –6.9; P<.001) and resilience (mean 4.3; P<.001). Marked decreases were observed in suicidal ideation (PHQ-9 ninth item score >1) at 6 months (16.5%) and 12 months (17.2%) compared to baseline (39.8%) (P<.001). In regard to the program adherence, cumulative counts of page views and lessons completed were significantly related to lower PHQ-9, GAD-7, and WSAS scores and higher CD-RISC-10 scores (all P values <.001 with an exception of page views with WSAS for which P value was .02). Conclusions The Thrive intervention was effective at reducing depression and anxiety symptom severity and improving functioning and resilience among a population of adults from mostly rural communities in the United States. These gains were maintained at 1 year. Program adherence, measured by the number of logins and lessons completed, indicates that users who engage more with the program benefit more from the intervention. Trial Registration ClinicalTrials.gov NCT03244878; https://clinicaltrials.gov/ct2/show/NCT03244878
Growth Factors in the Carotid Body—An Update

The carotid body may undergo plasticity changes during development/ageing and in response to environmental (hypoxia and hyperoxia), metabolic, and inflammatory stimuli. The different cell types of the carotid body express a wide series of growth factors and corresponding receptors, which play a role in the modulation of carotid body function and plasticity. In particular, type I cells express nerve growth factor, brain-derived neurotrophic factor, neurotrophin 3, glial cell line-derived neurotrophic factor, ciliary neurotrophic factor, insulin-like-growth factor-I and -II, basic fibroblast growth factor, epidermal growth factor, transforming growth factor-α and -β, interleukin-1β and -6, tumor necrosis factor-α, vascular endothelial growth factor, and endothelin-1. Many specific growth factor receptors have been identified in type I cells, indicating autocrine/paracrine effects. Type II cells may also produce growth factors and express corresponding receptors. Future research will have to consider growth factors in further experimental models of cardiovascular, metabolic, and inflammatory diseases and in human (normal and pathologic) samples. From a methodological point of view, microarray and/or proteomic approaches would permit contemporary analyses of large groups of growth factors. The eventual identification of physical interactions between receptors of different growth factors and/or neuromodulators could also add insights regarding functional interactions between different trophic mechanisms.
Liver steatosis and non-alcoholic fatty liver disease with fibrosis are predictors of frailty in people living with HIV.

OBJECTIVE The aim was to investigate the contribution of liver steatosis and significant fibrosis alone and in association (NAFLD with fibrosis) to frailty as a measure of biological age in people living with HIV (PLWH). DESIGN This was a cross-sectional study of consecutive patients attending Modena HIV Metabolic Clinic in 2018-2019. METHODS Patients with hazardous alcohol intake and viral hepatitis co-infection were excluded. Liver steatosis was diagnosed by controlled attenuation parameter (CAP), while liver fibrosis was diagnosed by liver stiffness measurement (LSM). NAFLD was defined as presence of liver steatosis (CAP≥248), while significant liver fibrosis or cirrhosis (stage ≥F2) as LSM≥7.1 kPa. Frailty was assessed using a 36-Item frailty index (FI). Logistic regression was used to explore predictors of frailty using steatosis and fibrosis as covariates. RESULTS We analyzed 707 PLWH (mean age 53.5 years, 76.2% males, median CD4 700 μL, 98.7% with undetectable HIV RNA). NAFLD with fibrosis was present in 10.2%; 18.9% and 3.9% of patients were classified as frail and most-frail, respectively. Univariate analysis demonstrated that neurocognitive impairment (OR = 5.1, 1.6-15), vitamin D insufficiency (OR = 1.94, 1.2-3.2), obesity (OR = 8.1, 4.4-14.6), diabetes (OR = 3.2, 1.9-5.6) and osteoporosis (OR = 0.37, 0.16-0.76) were significantly associated with NAFLD with fibrosis. Predictors of FI included: steatosis (OR = 2.1, 1.3-3.5), fibrosis (OR = 2, 1-3.7), NAFLD with fibrosis (OR = 9.2, 5.2-16.8), diabetes (OR = 1.7, 1-2.7) and multimorbidity (OR = 2.5, 1.5-4). CONCLUSION Liver steatosis and NAFLD with fibrosis were associated with frailty. NAFLD with fibrosis exceeded multimorbidity in the prediction of frailty, suggesting the former as an indicator of metabolic age in PLWH.
Community-Level Factors and HIV Health Among Older People Living With HIV (PLWH) in Alabama, United States: A Qualitative Analysis

Abstract As the number of older people living with HIV (PLWH) is increasing, there is an urgent need for research on community-level factors to better understand the health care needs of this population. In-depth interview transcripts of 20 older PLWH who participated in a community-based participatory research study conducted in Alabama, in the United States, were analyzed through a phenomenological research approach. Results suggest that crime, lack of resources, and social isolation experienced at the community levels were found to be associated with the wellbeing of older PLWH. Moreover, community characteristics may confound older PLWH's comorbid conditions and resultant polypharmacy. An increased understanding of the impact of contextual factors on HIV health can inform more holistic individual- and community-level interventions aimed at addressing barriers to retention or re-engagement in HIV medical care and viral suppression among older PLWH.
An Assessment of Earth's Climate Sensitivity Using Multiple Lines of Evidence

We assess evidence relevant to Earth's equilibrium climate sensitivity per doubling of atmospheric CO2, characterized by an effective sensitivity S. This evidence includes feedback process understanding, the historical climate record, and the paleoclimate record. An S value lower than 2 K is difficult to reconcile with any of the three lines of evidence. The amount of cooling during the Last Glacial Maximum provides strong evidence against values of S greater than 4.5 K. Other lines of evidence in combination also show that this is relatively unlikely. We use a Bayesian approach to produce a probability density function (PDF) for S given all the evidence, including tests of robustness to difficult‐to‐quantify uncertainties and different priors. The 66% range is 2.6–3.9 K for our Baseline calculation and remains within 2.3–4.5 K under the robustness tests; corresponding 5–95% ranges are 2.3–4.7 K, bounded by 2.0–5.7 K (although such high‐confidence ranges should be regarded more cautiously). This indicates a stronger constraint on S than reported in past assessments, by lifting the low end of the range. This narrowing occurs because the three lines of evidence agree and are judged to be largely independent and because of greater confidence in understanding feedback processes and in combining evidence. We identify promising avenues for further narrowing the range in S, in particular using comprehensive models and process understanding to address limitations in the traditional forcing‐feedback paradigm for interpreting past changes.
Effect of energy intake on the performance of different types of pig from 45 to 100 kg body weight. 2. Tissue gain

The effect of energy supply on physical composition of body weight gain between 45 and 100 kg was studied in Large White castrated males (cLW), crossbred Pietrain × Large White castrated males (cPPX) and boars (bPPX). The pigs were either given food ad libitum and kept in individual pens in experiment 1, or allocated to four energy levels (0·70, 0·80, 0·90, and 1·00 ad libitum ) and kept in metabolism cages in experiment 2. Daily protein supplies were calculated to be the same at the four energy levels within each type of pig and non-limiting for growth. Five additional animals for each type of pig were slaughtered at 45 kg. Daily tissue gain was measured according to the comparative slaughter technique. The daily lean gain increased with metabolizable energy (ME) intake according to a linear-plateau relationship whereas the daily fat gain increased linearly. The type of pig significantly affected the slope of the relationship between lean gain and ME intake (from 15 to 22 g per extra MJ ME) but not the slope of the relationship between fat gain and ME intake (10 g per extra MJ ME on average). Increased energy intake was associated with increased fatness of body-weight gain, which was higher in cLW and cPP× than in bPP×.
Genetic diversity analysis for quantitative traits in hermaphrodite ridge gourd (Luffa acutangula (Roxb.) L.)

A study was carried out to determine variability, heritability, genetic advance, correlation and path analysis in hermaphrodite ridge gourd for eight quantitative characters. The fruit length had the highest heritability (93.5%) followed by node at which first hermaphrodite flower appeared (78.0%). This trait provides ample scope for varietal improvement through selection. Significant positive correlation was found between fruit yield per plant and fruit weight (0.877), number of fruits per cluster (0.590) and fruit length (0.356) at phenotypic level. Significantly negative and desirable correlation at phenotypic level was observed between fruit yield per plant and days to first fruit harvest (−0.403), days to first hermaphrodite flower (−0.337) and node at which first hermaphrodite flower appeared (−0.315). The maximum direct and desirable effect on fruit yield per plant was exerted by fruit length (0.850), number of fruits (0.334), days to first fruit harvest (−0.019) and node at which first hermaphrodite flower appeared (−0.057) at phenotypic level.
New boundaries and dissociation of the mouse hippocampus along the dorsal‐ventral axis based on glutamatergic, GABAergic and catecholaminergic receptor densities

In rodents, gene‐expression, neuronal tuning, connectivity and neurogenesis studies have postulated that the dorsal, the intermediate and the ventral hippocampal formation (HF) are distinct entities. These findings are underpinned by behavioral studies showing a dissociable role of dorsal and ventral HF in learning, memory, stress and emotional processing. However, up to now, the molecular basis of such differences in relation to discrete boundaries is largely unknown. Therefore, we analyzed binding site densities for glutamatergic AMPA, NMDA, kainate and mGluR2/3, GABAergic GABAA (including benzodiazepine binding sites), GABAB, dopaminergic D1/5 and noradrenergic α1 and α2 receptors as key modulators for signal transmission in hippocampal functions, using quantitative in vitro receptor autoradiography along the dorsal‐ventral axis of the mouse HF. Beside general different receptor profiles of the dentate gyrus (DG) and Cornu Ammonis fields (CA1, CA2, CA3, CA4/hilus), we detected substantial differences between dorsal, intermediate and ventral subdivisions and individual layers for all investigated receptor types, except GABAB. For example, striking higher densities of α2 receptors were detected in the ventral DG, while the dorsal DG possesses higher numbers of kainate, NMDA, GABAA and D1/5 receptors. CA1 dorsal and intermediate subdivisions showed higher AMPA, NMDA, mGluR2/3, GABAA, D1/5 receptors, while kainate receptors are higher expressed in ventral CA1, and noradrenergic α1 and α2 receptors in the intermediate region of CA1. CA2 dorsal was distinguished by higher kainate, α1 and α2 receptors in the intermediate region, while CA3 showed a more complex dissociation. Our findings resulted not only in a clear segmentation of the mouse hippocampus along the dorsal‐ventral axis, but also provides insights into the neurochemical basis and likely associated physiological processes in hippocampal functions. Therein, the presented data has a high impact for future studies modeling and investigating dorsal, intermediate and ventral hippocampal dysfunction in relation to neurodegenerative diseases or psychiatric disorders.
Blood neurofilament light chain in Parkinson disease and atypical parkinsonisms

Abstract Background: Neurofilament light chain (NfL), an index of neuroaxonal injury, is a promising diagnostic and prognostic fluid biomarker with high translational value in many neurodegenerative disorders. Blood NfL measurement has been an exciting and active field of research in idiopathic Parkinson disease (PD) and atypical parkinsonisms. However, blood NfL levels in these parkinsonisms from existing literature were inconsistent. No comprehensive meta-analysis has ever been conducted. Methods: Three major biomedical electronic databases PubMed, Embase, and Web of Science were comprehensively searched from inception to July 10, 2020. This protocol will be prepared based on the guidelines recommended by the statement of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Original observational studies that measured blood (serum/plasma) NfL concentrations in patients with parkinsonisms (multiple system atrophy [MSA], progressive supranuclear palsy [PSP], corticobasal syndrome [CBS], and dementia with Lewy bodies [DLB]), and healthy controls (HCs) will be included. Quality assessment of the included studies will be performed using the Newcastle Ottawa Scale (NOS). Meta-analyses will be conducted using the STATA software version 13.0. The standardized mean differences as the measure of effect size and 95% confidence intervals were calculated for each comparison of blood NfL levels. Heterogeneity analysis, sensitivity analysis, publication bias, subgroup analysis, and meta-regression analysis will be carried out to test the robustness of the results. Results: The meta-analysis will obtain the effect sizes of blood NfL levels in the following comparisons: PD versus HC, MSA versus HC, PSP versus HC, CBS versus HC, DLB versus HC, MSA versus PD, PSP versus PD, CBS versus PD, and DLB versus PD. Conclusions: The present meta-analysis will provide the quantitative evidence of NfL levels in idiopathic PD and atypical parkinsonisms, hoping to facilitate differential diagnoses in clinical practice. Registration number: INPLASY202070091.
The Protective Effect of Exercise in Neurodegenerative Diseases: The Potential Role of Extracellular Vesicles

Physical activity has systemic effects on the body, affecting almost every organ. It is important not only for general health and wellbeing, but also in the prevention of diseases. The mechanisms behind the therapeutic effects of physical activity are not completely understood; however, studies indicate these benefits are not confined to simply managing energy balance and body weight. They also include systemic factors which are released into the circulation during exercise and which appear to underlie the myriad of benefits exercise can elicit. It was shown that along with a number of classical cytokines, active tissues also engage in inter-tissue communication via extracellular vesicles (EVs), specifically exosomes and other small EVs, which are able to deliver biomolecules to cells and alter their metabolism. Thus, EVs may play a role in the acute and systemic adaptations that take place during and after physical activity, and may be therapeutically useful in the treatment of a range of diseases, including metabolic disorders such as type 2 diabetes and obesity; and the focus of this review, neurological disorders such as Alzheimer’s disease.
Functional Transcription Factor Target Networks Illuminate Control of Epithelial Remodelling

Cell identity is governed by gene expression, regulated by transcription factor (TF) binding at cis-regulatory modules. Decoding the relationship between TF binding patterns and gene regulation is nontrivial, remaining a fundamental limitation in understanding cell decision-making. We developed the NetNC software to predict functionally active regulation of TF targets; demonstrated on nine datasets for the TFs Snail, Twist, and modENCODE Highly Occupied Target (HOT) regions. Snail and Twist are canonical drivers of epithelial to mesenchymal transition (EMT), a cell programme important in development, tumour progression and fibrosis. Predicted “neutral” (non-functional) TF binding always accounted for the majority (50% to 95%) of candidate target genes from statistically significant peaks and HOT regions had higher functional binding than most of the Snail and Twist datasets examined. Our results illuminated conserved gene networks that control epithelial plasticity in development and disease. We identified new gene functions and network modules including crosstalk with notch signalling and regulation of chromatin organisation, evidencing networks that reshape Waddington’s epigenetic landscape during epithelial remodelling. Expression of orthologous functional TF targets discriminated breast cancer molecular subtypes and predicted novel tumour biology, with implications for precision medicine. Predicted invasion roles were validated using a tractable cell model, supporting our approach.
Dual-Time Point [68Ga]Ga-PSMA-11 PET/CT Hybrid Imaging for Staging and Restaging of Prostate Cancer

Simple Summary Early diagnosis and tumor characterization of prostate cancer (PCa) are important for accurate treatment. [68Ga]Ga-PSMA-11 PET/CT turns out to constitute a major step toward improved diagnostic procedures to detect primary, recurrent, and metastatic PCa. The aim of our study is to evaluate the effect of a second imaging modality for the staging and restaging of PCa by possibly detecting additional PCa lesions due to the well-known increase of PSMA uptake over time. There was a significant increase in tracer uptake on delayed images in comparison to early [68Ga]Ga-PSMA-11 PET/CT in our study, but the lesion positivity rate was comparable. However, in a few individual cases, additional delayed scans provided an information advantage in PCa lesion detection. The findings of our study are likely to be of major interest to clinicians as well as to researchers defining the algorithms that are necessary to implement this promising method with its specific tracer into clinical routine. Abstract Routine [68Ga]Ga-PSMA-11 PET/CT (one hour post-injection) has been shown to accurately detect prostate cancer (PCa) lesions. The goal of this study is to evaluate the benefit of a dual-time point imaging modality for the staging and restaging of PCa patients. Biphasic [68Ga]Ga-PSMA-11 PET/CT of 233 patients, who underwent early and late scans (one/three hours post-injection), were retrospectively studied. Tumor uptake and biphasic lesion detection for 215 biochemically recurrent patients previously treated for localized PCa (prostatectomized patients (P-P)/irradiated patients (P-I) and 18 patients suspected of having primary PCa (P-T) were separately evaluated. Late [68Ga]Ga-PSMA-11 PET/CT imaging detected 554 PCa lesions in 114 P-P patients, 187 PCa lesions in 33 P-I patients, and 47 PCa lesions in 13 P-T patients. Most patients (106+32 P-P/P-I, 13 P-T) showed no additional PCa lesions. However, 11 PSMA-avid lesions were only detected in delayed images, and 33 lesions were confirmed as malignant by a SUVmax increase. The mean SUVmax of pelvic lymph node metastases was 25% higher (p < 0.001) comparing early and late PET/CT. High positivity rates from routine [68Ga]Ga-PSMA-11 PET/CT for the staging and restaging of PCa patients were demonstrated. There was no decisive influence of additional late imaging with PCa lesion detection on therapeutic decisions. However, in a few individual cases, additional delayed scans provided an information advantage in PCa lesion detection due to higher tracer uptake and improved contrast.
Per‐ and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research

Reports of environmental and human health impacts of per‐ and polyfluoroalkyl substances (PFAS) have greatly increased in the peer‐reviewed literature. The goals of the present review are to assess the state of the science regarding toxicological effects of PFAS and to develop strategies for advancing knowledge on the health effects of this large family of chemicals. Currently, much of the toxicity data available for PFAS are for a handful of chemicals, primarily legacy PFAS such as perfluorooctanoic acid and perfluorooctane sulfonate. Epidemiological studies have revealed associations between exposure to specific PFAS and a variety of health effects, including altered immune and thyroid function, liver disease, lipid and insulin dysregulation, kidney disease, adverse reproductive and developmental outcomes, and cancer. Concordance with experimental animal data exists for many of these effects. However, information on modes of action and adverse outcome pathways must be expanded, and profound differences in PFAS toxicokinetic properties must be considered in understanding differences in responses between the sexes and among species and life stages. With many health effects noted for a relatively few example compounds and hundreds of other PFAS in commerce lacking toxicity data, more contemporary and high‐throughput approaches such as read‐across, molecular dynamics, and protein modeling are proposed to accelerate the development of toxicity information on emerging and legacy PFAS, individually and as mixtures. In addition, an appropriate degree of precaution, given what is already known from the PFAS examples noted, may be needed to protect human health. Environ Toxicol Chem 2021;40:606–630. © 2020 SETAC