Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of Function of WFS1 Causes ER Stress-Mediated Inflammation in Pancreatic Beta-Cells

Wolfram syndrome is a rare genetic disorder characterized by juvenile-onset diabetes mellitus, optic nerve atrophy, hearing loss, diabetes insipidus, and progressive neurodegeneration. Pathogenic variants in the WFS1 gene are the main causes of Wolfram syndrome. WFS1 encodes a transmembrane protein localized to the endoplasmic reticulum (ER) and regulates the unfolded protein response (UPR). Loss of function of WFS1 leads to dysregulation of insulin production and secretion, ER calcium depletion, and cytosolic calpains activation, resulting in activation of apoptotic cascades. Although the terminal UPR has been shown to induce inflammation that accelerates pancreatic β-cell dysfunction and death in diabetes, the contribution of pancreatic β-cell inflammation to the development of diabetes in Wolfram syndrome has not been fully understood. Here we show that WFS1-deficiency enhances the gene expression of pro-inflammatory cytokines and chemokines, leading to cytokine-induced ER-stress and cell death in pancreatic β-cells. PERK and IRE1α pathways mediate high glucose-induced inflammation in a β-cell model of Wolfram syndrome. M1-macrophage infiltration and hypervascularization are seen in the pancreatic islets of Wfs1 whole-body knockout mice, demonstrating that WFS1 regulates anti-inflammatory responses in pancreatic β-cells. Our results indicate that inflammation plays an essential role in the progression of β-cell death and diabetes in Wolfram syndrome. The pathways involved in ER stress-mediated inflammation provide potential therapeutic targets for the treatment of Wolfram syndrome.
COVID-19 Induced Misinformation on YouTube: An Analysis of User Commentary

Several scholars have demonstrated a positive link between political polarization and the resistance to COVID-19 prevention measures. At the same time, political polarization has also been associated with the spread of misinformation. This study investigates the theoretical linkages between polarization and misinformation and measures the flow of misinformation about COVID-19 in the comment sections of four popular YouTube channels for over 16 months using big data sources and methods. For the analysis, we downloaded about 3.5M English language YouTube comments posted in response to videos about the pandemic. We then classified the comments into one of the two following categories by applying a supervised Natural Language Processing classifier: (1) fake: comments that contain claims and speculation which are verifiably not true; and (2) legitimate: comments that do not fall into the fake category. The results show that the level of misinformation in YouTube comment sections has increased during the pandemic, that fake comments attract statistically more likes, and that the ratio of fake comments increased by 0.4% per month. These findings suggest that once introduced into an online discussion, misinformation potentially leads to an escalating spiral of misinformation comments, which undermines public policy. Overall, the results signal alarming pandemic-related misinformation and, potentially, rising levels of affective polarization. We place these results in context and point out the limitations of our approach.
Understanding the Drivers of Production in South African Farming Systems: A Case Study of the Vhembe District, Limpopo South Africa

Farming systems in South Africa operate against the backdrop of constantly changing environmental, political, and socio-economic conditions. Farming systems are commonly defined by the Food and Agriculture Organization (FAO) as a population of individual farm systems that have broadly similar resource bases, enterprise patterns, household livelihoods and constraints, and for which similar development strategies and interventions would be appropriate. Historically farming systems in South Africa have been characterised by dualism in which large-scale commercial farmers co-exist with small-scale farmers. Although the two farming systems are impacted by the same drivers of production (land, labour, capital, and enterprise), however, they respond to these drivers differently and the nature of the responses reveal their connectivity and possible approaches to sustaining them. A systems thinking approach is best suited to draw possible scenarios of how farming systems in the Vhembe district located in the Limpopo Province of South Africa will respond to changes with respect to the four drivers. In this area, large-scale commercial farming forms a significant component of the production of a number of subtropical crops that contribute to the country's agricultural economy particularly through exports. Simultaneously 90% of rural communities in the district depend mainly on small-scale agriculture to sustain their livelihoods and generate income. The paper provides an overview of the drivers of production for the two farming systems in the Vhembe district and explores how the government can successfully promote development through agriculture by building capacity for the joint success of the two farming systems.
Comprehensive Analysis of Nasal Polyps Reveals a More Pronounced Type 2 Transcriptomic Profile of Epithelial Cells and Mast Cells in Aspirin-Exacerbated Respiratory Disease

Chronic rhinosinusitis with nasal polyps is affecting up to 3% of Western populations. About 10% of patients with nasal polyps also suffer from asthma and intolerance to aspirin, a syndrome called aspirin-exacerbated respiratory disease. Although eosinophilic inflammation is predominant in polyps of both diseases, phenotypic differences in the tissue-derived microenvironment, elucidating disease-specific characteristics, have not yet been identified. We sought to obtain detailed information about phenotypic and transcriptional differences in epithelial and immune cells in polyps of aspirin-tolerant and intolerant patients. Cytokine profiles in nasal secretions and serum of patients suffering from aspirin-exacerbated respiratory disease (n = 10) or chronic rhinosinusitis with nasal polyps (n = 9) were assessed using a multiplex mesoscale discovery assay. After enrichment for immune cell subsets by flow cytometry, we performed transcriptomic profiling by employing single-cell RNA sequencing. Aspirin-intolerant patients displayed significantly elevated IL-5 and CCL17 levels in nasal secretions corresponding to a more pronounced eosinophilic type 2 inflammation. Transcriptomic profiling revealed that epithelial and mast cells not only complement one another in terms of gene expression associated with the 15-lipoxygenase pathway but also show a clear type 2-associated inflammatory phenotype as identified by the upregulation of POSTN, CCL26, and IL13 in patients with aspirin-exacerbated respiratory disease. Interestingly, we also observed cellular stress responses indicated by an increase of MTRNR2L12, MTRNR2L8, and NEAT1 across all immune cell subsets in this disease entity. In conclusion, our findings support the hypothesis that epithelial and mast cells act in concert as potential drivers of the pathogenesis of the aspirin-exacerbated respiratory disease.
Effects of Exposure to Heat Stress During Late Gestation on the Daily Time Budget of Nulliparous Holstein Heifers

Exposure of dairy cows to heat stress negatively affects welfare and performance during all phases of the lactation cycle. Detrimental effects include decreased milk and reproductive performance, reduced immune status and health, and altered natural behaviors. While we understand how mature cows respond to heat stress, the effects of late gestation heat stress on pregnant heifers is still unknown. Automated monitoring devices were used to document the behavioral activity of heifers during the pre- (final 60 d of gestation) and postpartum (first 60 d of lactation) periods. Twenty-five pregnant Holstein heifers were housed in a free-stall barn and enrolled to heat stress (HT; shade; n = 13) or cooling (CL; shade, soakers and fans; n = 12) treatments during the last 60 days of gestation. All animals were provided active cooling postpartum. Upon enrollment, heifers were fitted with a leg tag, which measured daily lying time, number of steps, and standing bouts, and a neck tag that measured eating and rumination times. Rectal temperatures (RT) and respiration rates (RR) were measured thrice weekly during the prepartum period. Relative to CL, HT heifers had elevated RT (38.8 vs. 38.7 ± 0.04°C) and RR (59.6 vs. 44.4 ± 1.9 breaths/min) during the prepartum period. Heat-stressed heifers tended to spend more time eating (224 vs. 183 min/d) and less time ruminating (465 vs. 518 min/d) during the prepartum period compared to CL, but dry matter intake did not differ. During the postpartum period, HT heifers spent more time eating (209 vs. 180 min/d) during weeks 1–4 of lactation, but rumination time was similar. Lying time was reduced by 59 and 88 min per day during weeks −7 and −6 prepartum and 84 and 50 min per day during weeks 2 and 3 postpartum in HT heifers, relative to CL. The number of steps was greater for HT during the postpartum period, from weeks 2 to 9 (3019 vs. 2681 steps/d). Eating frequency was similar during pre- and postpartum periods, however, based on semi quantitative visualization of the smarttag reports, HT consumed larger meals at night during the pre- and postpartum periods compared with CL heifers. In summary, late-gestation exposure to heat stress affects the daily time budget of first lactation heifers during both the pre- and postpartum periods. Current insights of heat stress effects on behavioral responses of dairy heifers may contribute to the development of more effective management strategies to mitigate heat load.
Community Structure and Ecological Network's Changes of Vaginal Microbiome in Women Right After Delivery

Objectives Vaginal microbiota is not only an important source of bacterial colonization for neonates, but also plays a crucial role in maternal and neonatal health. This study aimed to investigate the vaginal microbial community structure right after delivery and its impact on the neonatal oral microbiome. Methods In this study, 27 women were recruited from Bao'an Maternal and Child Health Hospital. Bacterial compositions of vaginal samples before and right after delivery and neonatal oral samples right after birth were investigated using 16S rRNA sequencing of V3–V4 hyperregions. Results Vaginal microbiome before delivery was dominated by the genus Lactobacillus. After delivery, the vaginal microbial community was altered, with significantly decreased proportion of Lactobacillus, increased alpha-diversity, and a more diverse ecological network. A large number subjects dominated by Lactobacillus species before delivery shifted to CST (community state type) IV after delivery. In addition, similar changes were observed in the neonatal oral microbiome, and its community profile was closer to vaginal samples after delivery than before delivery with principal coordinates analysis and microbial source tracking analysis. Conclusion The vaginal microbiome was altered right after delivery and impacted the colonization of the neonatal oral microbiome in China. Further, it is vital to understand the longitudinal influence on maternal and neonatal health of vaginal microbiome community changes after delivery.
Evolutionary Trajectories of Complex Traits in European Populations of Modern Humans

Humans have a great diversity in phenotypes, influenced by genetic, environmental, nutritional, cultural, and social factors. Understanding the historical trends of physiological traits can shed light on human physiology, as well as elucidate the factors that influence human diseases. Here we built genome-wide polygenic scores for heritable traits, including height, body mass index, lipoprotein concentrations, cardiovascular disease, and intelligence, using summary statistics of genome-wide association studies in Europeans. Subsequently, we applied these scores to the genomes of ancient European populations. Our results revealed that after the Neolithic, European populations experienced an increase in height and intelligence scores, decreased their skin pigmentation, while the risk for coronary artery disease increased through a genetic trajectory favoring low HDL concentrations. These results are a reflection of the continuous evolutionary processes in humans and highlight the impact that the Neolithic revolution had on our lifestyle and health.
A Neurometabolic Pattern of Elevated Myo-Inositol in Children Who Are HIV-Exposed and Uninfected: A South African Birth Cohort Study

Introduction Exposure to maternal HIV in pregnancy may be a risk factor for impaired child neurodevelopment during the first years of life. Altered neurometabolites have been associated with HIV exposure in older children and may help explain the mechanisms underlying this risk. For the first time, we explored neurometabolic profiles of children who are HIV-exposed and uninfected (CHEU) compared to children who are HIV-unexposed (CHU) at 2-3 years of age. Methods The South African Drakenstein Child Health Study enrolled women during pregnancy and is following mother-child pairs through childhood. MRI scans were acquired on a sub-group of children at 2-3 years. We used single voxel magnetic resonance spectroscopy to measure brain metabolite ratios to total creatine in the parietal grey matter, and left and right parietal white matter of 83 children (36 CHEU; 47 CHU). Using factor analysis, we explored brain metabolite patterns in predefined parietal voxels in these groups using logistic regression models. Differences in relative concentrations of individual metabolites (n-acetyl-aspartate, myo-inositol, total choline, and glutamate) to total creatine between CHEU and CHU groups were also examined. Results Factor analysis revealed four different metabolite patterns, each one characterized by covarying ratios of a single metabolite in parietal grey and white matter. The cross-regional pattern dominated by myo-inositol, a marker for glial reactivity and inflammation, was associated with HIV exposure status (OR 1.63; 95% CI 1.11–2.50) which held after adjusting for child age, sex, and maternal alcohol use during pregnancy (OR 1.59; 95% CI 1.07 –2.47). Additionally, higher relative concentrations of myo-inositol to total creatine were found in left and right parietal white matter of CHEU compared to CHU (p=0.025 and p=0.001 respectively). Discussion Increased ratios of myo-inositol to total creatine in parietal brain regions at age 2-3 years in CHEU are suggestive of early and ongoing neuroinflammatory processes. Altered relative concentrations of neurometabolites were found predominantly in the white matter, which is sensitive to neuroinflammation, and may contribute to developmental risk in this population. Future work on the trajectory of myo-inositol over time in CHEU, alongside markers of neurocognitive development, and the potential for specific neurodevelopmental interventions will be useful.
Examining Inhibitory Affective Processing Within the Rostral Anterior Cingulate Cortex Among Abstinent Cannabis-Using Adolescents and Young Adults

Cannabis use has been associated with deficits in self-regulation, including inhibitory control. Cannabis users have previously exhibited both structural and functional deficits in the rostral anterior cingulate cortex (rACC), a region involved in self-regulation of emotional response and inhibitory control. The present study aimed to examine whether abstinent cannabis users demonstrated abnormal functional activation and connectivity of the bilateral rACC during an emotional inhibitory processing task, and whether gender moderated these relationships. Cannabis-using (N = 34) and non-using (N = 32) participants ages 16–25 underwent at least 2-weeks of monitored substance use abstinence (excluding tobacco) and fMRI scanning while completing a Go/No-go task using fearful and calm emotional faces as non-targets. Multiple linear regression and ANCOVA were used to determine if cannabis group status was related to rACC activation and context-dependent functional connectivity, and whether gender moderated these relationships. Results showed decreased bilateral rACC activation in cannabis users during fearful response inhibition, although groups did not show any context-dependent connectivity differences between the left or right rACC during calm or fearful inhibition. Gender findings revealed that cannabis-using females compared to males did show aberrant connectivity between the right rACC and right cerebellum. These results are consistent with literature demonstrating aberrant structural and functional rACC findings and suggest that chronic cannabis use may disrupt typical rACC development—even after abstinence—potentially conferring risk for later development of mood disorders. Marginal gender-specific connectivity findings bolster continued findings regarding female vulnerability to effects of cannabis on cognition and affect. Findings should be assessed in longitudinal studies to determine causality and timing effects.
Exploring Purchasing Determinants for a Low Fat Content Salami: Are Consumers Willing to Pay for an Additional Premium?

Consumers today are increasingly moving toward healthier lifestyles and food purchasing habits. This new awareness has also prompted the meat industry, usually indicted for the use of harmful compounds and ingredients such as additives, salt, and fat, to introduce innovative measures to meet demand. This study aims to assess consumer willingness to pay an additional price premium (APP) for a healthy salami by identifying which factors are more likely to have an effect on the willingness to purchase, such as socio-demographic and product and market-related attributes. An Ordered Logit model has been applied to define factors influencing consumers' willingness to pay for a low-fat salami. Results show a favorable consumer acceptance of reduced-fat salami conveyed by the willingness of consumers to pay an additional price for this product and confirm that the health awareness of consumers is an important driving force in cured meat marketing strategies.
Be in Your Element: The Joint Effect of Human Resource Management Strength and Proactive Personality on Employee Creativity

Employee creativity is fast becoming a part and parcel in the wake of the increasing volatility of the employment market and the complexity of job demands. Drawing from the actor-context interactionist theoretical approach and career construction theory, this paper adds to current research by exploring the serial mediating effect of job crafting (JC) and career adaptability (CA) in the impact of human resource management strength (HRMS) on employee creativity. Furthermore, we suggest that proactive personality interacts with HRMS to jointly influence creativity. Survey data from samples of 297 (Study 1) and 390 (Study 2) employees largely confirm our model. Our findings show that HRMS positively impacts employee creativity via serial mediation of job crafting and career adaptability, and proactive personality negatively moderates the process. The paper confirms and expands the interactionist theoretical perspective of creativity, highlights the significance of integration of contextual factors, individual characteristics, and career construction, and makes certain practical sense.
Lights, Camera, Reaction: Evaluating Extent of Transformative Learning and Emotional Engagement Through Viewer-Responses to Environmental Films

In sustainability education affective responses to climate change are rarely discussed, and this is to the detriment of students. One way to address this gap in higher education for sustainability is learner-centred teaching using transformative learning principles. The processes for implementation may vary. Our preliminary study evaluated the contribution of environmental films paired with viewer-response activities, such as reflections and discussions, to create emotional engagement and facilitate transformative learning in an online course where content focused on sustainability and climate change. Data for the study were gathered through two questionnaires, student reflections, and interviews. Our study found that the process of film watching, reflection writing, and engaging in discussion was conducive to incorporating five of the six elements of transformative learning: individual experience, promoting critical reflection, awareness of context, dialogue, and authentic relationships. We conclude that films are an effective means of conveying complex content in an online course pertaining to climate change and sustainability. We propose pairing films with viewer-response strategies, especially reflections to allow students to identify their feelings, biases, and preconceived frames of references and stimulate the path toward transformative learning in higher education.
Case Report: Repeated Stereotactic Radiotherapy of Recurrent Ventricular Tachycardia: Reasons, Feasibility, and Safety

Stereotactic body radiotherapy (SBRT) has been reported as an attractive option for cases of failed catheter ablation of ventricular tachycardia (VT) in structural heart disease. However, even this strategy can fail for various reasons. For the first time, this case series describes three re-do cases of SBRT which were indicated for three different reasons. The purpose in the first case was the inaccuracy of the determination of the treatment volume by indirect comparison of the electroanatomical map and CT scan. A newly developed strategy of co-registration of both images allowed precise targeting of the substrate. In this case, the second treatment volume overlapped by 60% with the first one. The second reason for the re-do of SBRT was an unusual character of the substrate–large cardiac fibroma associated with different morphologies of VT from two locations around the tumor. The planned treatment volumes did not overlap. The third reason for repeated SBRT was the large intramural substrate in the setting of advanced heart failure. The first treatment volume targeted arrhythmias originating in the basal inferoseptal region, while the second SBRT was focused on adjacent basal septum without significant overlapping. Our observations suggested that SBRT for VT could be safely repeated in case of later arrhythmia recurrences (i.e., after at least 6 weeks). No acute toxicity was observed and in two cases, no side effects were observed during 32 and 22 months, respectively. To avoid re-do SBRT due to inaccurate targeting, the precise and reproducible strategy of substrate identification and co-registration with CT image should be used.