Miracle-dz/UniFAR-FTUs huggingface dataset:
Biopsychosocial Functions of Human Walking and Adherence to Behaviourally Demanding Belief Systems: A Narrative Review

Human walking is a socially embedded and shaped biological adaptation: it frees our hands, makes our minds mobile, and is deeply health promoting. Yet, today, physical inactivity is an unsolved, major public health problem. However, globally, tens of millions of people annually undertake ancient, significant and enduring traditions of physiologically and psychologically arduous walks (pilgrimages) of days-to-weeks extent. Pilgrim walking is a significant human activity requiring weighty commitments of time, action and belief, as well as community support. Paradoxically, human walking is most studied on treadmills, not ‘in the wild’, while mechanistically vital, treadmill studies of walking cannot, in principle, address why humans walk extraordinary distances together to demonstrate their adherence to a behaviourally demanding belief system. Pilgrim walkers provide a rich ‘living laboratory’ bridging humanistic inquiries, to progressive theoretical and empirical investigations of human walking arising from a behaviourally demanding belief system. Pilgrims vary demographically and undertake arduous journeys on precisely mapped routes of tracked, titrated doses and durations on terrain of varying difficulty, allowing investigations from molecular to cultural levels of analysis. Using the reciprocal perspectives of ‘inside→out’ (where processes within brain and body initiate, support and entrain movement) and ‘outside→in’ (where processes in the world beyond brain and body drive activity within brain and body), we examine how pilgrim walking might shape personal, social and transcendental processes, revealing potential mechanisms supporting the body and brain in motion, to how pilgrim walking might offer policy solutions for physical inactivity.
Replication/Assembly Defective Avian Flavivirus With Internal Deletions in the Capsid Can Be Used as an Approach for Living Attenuated Vaccine

Avian Tembusu virus (TMUV) is a novel flavivirus causing severe egg drop and fatal encephalitis in avian in Asia. In the present study, we screened the structural and functional requirements of TMUV capsid protein (CP) for viral morphogenesis using reverse genetics methods in combination with replicon packaging assays. TMUV-CP showed dramatic functional and structural flexibility, and even though 44 residues were removed from the N-terminus, it was still capable of packaging replicon RNA; in addition, 33 residues were deleted from the C-terminus (containing nearly the entire α4-helix), and infectious particles were still produced, although α4-α4’ is supposedly vital for CP dimerization and nucleocapsid formation. We further analyzed two mutants (ΔC20-43 and ΔC64-96 viruses) with relatively large deletions that still replicated well in BHK-21 cells. Our data indicate that internal deletions within CP impaired viral replication or assembly, resulting in attenuated virus proliferation in cells and attenuated virulence in duck embryos, and these deletion mutations are quite stable in cell culture. An in vivo assay indicated that both ΔC20-43 virus and ΔC64-96 virus were highly attenuated in ducklings but still immunogenic. Single-dose immunization with ΔC20-43 virus or ΔC64-96 virus could protect ducklings from a lethal challenge with good antigen clearance. Together, our data shed light on replication/assembly defective TMUV with internal deletions in CP and provide an effective approach to attenuate viral virulence in live vaccines without changing the antigen composition.
Preparing for Future Adversities: Lessons From the COVID-19 Pandemic in Australia for Promoting Relational Resilience in Families

Background: The COVID-19 pandemic has placed considerable pressure on families, testing the quality of relationships and the strength of social support within and beyond the family network. However, little is known about the pre-pandemic factors that predict family relational resilience and social functioning during times of natural disaster or global crisis. Here we use data from one of Australia's longest running studies of social and emotional development to examine the nature and timing of possible relational and social support intervention aimed at preparing families for future adversities. Methods: Data were from the Australian Temperament Project Generation 3 (ATPG3) Study, a population representative three generation cohort study of families established in 1983. A subset of Generation 2 parents completed a COVID-19 specific survey in May-September 2020 (502 parents of 871 children; 60% mothers; 37–38 years). These participants had completed the Quality of Relationships Inventory to assess social support during young adulthood, at 23–24 years (2006) and 27–28 years (2010), before next generation conception. Participants had also completed the Maternity Social Support Scale 1 year postpartum for each child born across the ATPG3 assessment period (2012–2019). In 2020, during the height of the Australian lockdowns, participants rated the quality of their relationships with their partners, children and broader family and friends, in addition to social support within and extended beyond their family. Results: Pre-pandemic partner support was associated with partner relationship quality during the pandemic (β = 0.22). Pre-pandemic support from friends was associated with relationship quality with other family and friends during the pandemic (β = 0.12 – 0.18). Pre-pandemic support (from partner, family and friends) was consistently associated with social support within families during the pandemic (β = 0.11 – 0.21). Pre-pandemic support from friends was also associated with family support extended to others within their local community during the pandemic (β = 0.12 – 0.13). Conclusions: Strengthening supportive relationships during major life transitions, prior to the start of family life and in early parenthood, may have long-term and intergenerational benefits years into the future for both families and communities. This may promote resilience during future crises and other more normative stressful life events.
Corticosterone Can Be an Essential Stress Index in Channel Catfish (Ictalurus punctatus)

Although cortisol is considered the main glucocorticoid involved in regulating stress in fish by elevating the serum glucose, the presence of serum corticosterone and whether its level can be used as an indicator for fish stress activation and reflect the degree of fish stress remains to be determined. To comprehensively and accurately evaluate the performance of two glucocorticoids after stress, in this study, seven of the most common stressors (ammonia nitrogen, high-temperature, acid, alkali, Aeromonas hydrophila, and salinity) in aquaculture were selected. The levels of serum corticosterone, cortisol, and glucose were detected within 48 h, and then the dynamic changes were analyzed. In addition, the kidneys were collected to detect the expression of corresponding proteins involved in corticosterone and cortisol synthesis (3 β-HSD and CYP17A1) for further exploration. From the results obtained, the content of serum corticosterone was about 100 times higher than that of cortisol, and it was found that corticosterone and cortisol showed different dynamic changes within 48 h among the seven kinds of stress. In the subsequent detection of glucose, it was found that the dynamic shift in glucose was not consistent with the dynamic changes of corticosterone or cortisol entirely but seemed to be caused by the combination of the two. In the follow-up protein expression detection, we found that corticosterone seemed to respond to stress earlier. Therefore, it is concluded that the responses of corticosterone and cortisol to stress are independent, corticosterone may be more sensitive in the current seven acute stresses, and then they regulate glucose together to resist stress. The study aimed to fill the vacancy of corticosterone in fish research and provide a reference for the complete evaluation of fish stress degree.
Integrative Longitudinal Analysis of Metabolic Phenotype and Microbiota Changes During the Development of Obesity

Obesity has increased at an alarming rate over the past two decades in the United States. In addition to increased body mass, obesity is often accompanied by comorbidities such as Type II Diabetes Mellitus and metabolic dysfunction-associated fatty liver disease, with serious impacts on public health. Our understanding of the role the intestinal microbiota in obesity has rapidly advanced in recent years, especially with respect to the bacterial constituents. However, we know little of when changes in these microbial populations occur as obesity develops. Further, we know little about how other domains of the microbiota, namely bacteriophage populations, are affected during the progression of obesity. Our goal in this study was to monitor changes in the intestinal microbiome and metabolic phenotype following western diet feeding. We accomplished this by collecting metabolic data and fecal samples for shotgun metagenomic sequencing in a mouse model of diet-induced obesity. We found that after two weeks of consuming a western diet (WD), the animals weighed significantly more and were less metabolically stable than their chow fed counterparts. The western diet induced rapid changes in the intestinal microbiome with the most pronounced dissimilarity at 12 weeks. Our study highlights the dynamic nature of microbiota composition following WD feeding and puts these events in the context of the metabolic status of the mammalian host.
Research on Improved Fault Current Analysis Method for Flexible Direct Current Power Grid Considering Alternating Current Feed

Flexible direct current (DC) grid can realize large-scale renewable energy, wide-area coordinated complementation, and reliable power transmission. It is an important development that can be used to support high-voltage and large-capacity flexible DC transmission in the future. The short-circuit current of the DC line is one of the important bases for the selection of key main equipment parameters such as converter valves, DC circuit breakers, and reactors in the flexible DC grid. In this paper, a flexible DC grid equivalent circuit network model with alternating current (AC) feed-in is established. Aiming at the monopolar ground fault of the flexible DC grid grounded through the metal loop, an optimized traditional matrix calculation method is proposed to obtain the accurate line fault current value. On this basis, with an actual engineering background, the equivalent circuit model of the four-terminal bipolar flexible DC power grid is established, and the influence of grounding position, grounding parameters, and current-limiting reactor on the fault current of the DC line is analyzed. Finally, simulation using the PSCAD software verifies the effectiveness and accuracy of the proposed method. The method proposed in this paper can provide the necessary bases and references for the selection of flexible DC grid equipment.
The Prognosis and Immune Checkpoint Blockade Efficacy Prediction of Tumor-Infiltrating Immune Cells in Lung Cancer

Backgrounds The high morbidity and mortality of lung cancer are serious public health problems. The prognosis of lung cancer and whether to apply immune checkpoint blockade (ICB) are currently urgent problems to be solved. Methods Using R software, we performed Kaplan–Meier (K-M) analysis, Cox regression analysis, functional enrichment analysis, Spearman correlation analysis, and the single-sample gene set enrichment analysis. Results On the Tumor IMmune Estimation Resource (TIMER2.0) website, we calculated the abundance of tumor-infiltrating immune cells (TIICs) of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. B cell and myeloid dendritic cell (DC1) were independent prognostic factors for LUAD and LUSC patients, respectively. Enrichment analysis confirmed that genes highly related to B cell or DC1 were closely related to the immune activation of lung cancer patients. In terms of adaptive immune resistance markers, CD8A, CD8B, immunomodulators (immunostimulants, major histocompatibility complex, receptors, and chemokines), immune-related pathways, tumor microenvironment score, and TIICs, high B cell/DC1 infiltration tissue was inflamed and immune-activated and might benefit more from the ICB. Genes most related to B cell [CD19, toll-like receptor 10 (TLR10), and Fc receptor-like A (FCRLA)] and DC1 (ITGB2, LAPTM5, and SLC7A7) partially clarified the roles of B cell/DC1 in predicting ICB efficacy. Among the 186 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, there were three and four KEGG pathways, which partially explained the molecular mechanisms by which B cell and DC1 simultaneously predicted the prognosis and efficacy of immunotherapy, respectively. Among five immune subtypes, the abundance of B cell/DC1 and expression of six hub genes were higher in immune C2, C3, and C6. Conclusion B cell and DC1 could predict the prognosis and ICB efficacy of LUAD and LUSC patients, respectively. The six hub genes and seven KEGG pathways might be novel immunotherapy targets. Immune C2, C3, and C6 subtypes of lung cancer patients might benefit more from ICB therapy.
Morphology, Formation, and Activity of Three Different Pockmark Systems in Peri-Alpine Lake Thun, Switzerland

Pockmarks are crater-like depressions formed by upward fluid flow (gas and/or liquid) through the unconsolidated sediment column on the floor of oceans and lakes. While pockmarks are well described in the marine realm, they have essentially been overlooked in lacustrine settings, likely due to a lack in economic interest to apply high-resolution hydroacoustic techniques in lakes. A swath-bathymetry survey on Lake Thun, Switzerland, revealed the existence of three pockmark systems. One pockmark (110 m in diameter) was discovered near a big karst system at Beatenberg at a water depth of ~217 m. Its activity is probably associated with episodic groundwater seepage induced by earthquakes, floods and snowmelt. At another site, Daerligen, we detected at ~60 m water depth the presence of multiple smaller pockmarks (~1.5 to 10 m in diameter) that seem to be active, continuously liberating CH4 gas by bubble ebullition. The CH4 displayed a biogenic carbon isotopic signature, however, the exact origin of the gas remains unknown. The third site, Tannmoos (~35 m water depth), comprises two large pockmarks (20–43 m in diameter) connected to a karst system in gypsum-carrying bedrock. One of these pockmarks is constituted of several unit pockmarks (e.g., sub-pockmarks; 0.3 to 0.8 m in diameter). While strong evidence is still lacking, we suggest that groundwater discharge occasionally occurs through these unit pockmarks during periods of intense precipitation. Hence, this study reveals the existence of three pockmark systems of variable morphology and mechanisms of formation within the same lake, reflecting different hydrological and biogeochemical regimes. Moreover, it underscores the potential importance of pockmarks in influencing hydrological and CH4 budgets in lakes. Clearly more work on quantifying seasonal fluxes of groundwater and CH4 release via lacustrine pockmarks is required, and it needs to be seen whether the observations made in Lake Thun are universal and apply also to many other lacustrine environments worldwide.
ANK3 Gene Polymorphism Rs10994336 Influences Executive Functions by Modulating Methylation in Patients With Bipolar Disorder

Background: A large body of evidence suggests that epigenetic modification including DNA methylation plays a critical role in BD's pathogenesis while the identification of methylation quantitative trait loci (meQTLs) shed light on the interpretation of the function of genetic variants in non-coding regions. The intronic single nucleotide polymorphism (SNP) rs10994336 within the ANK3 has emerged as one of the most replicated risk variants for bipolar disorder (BD) in genome-wide association studies. Whether rs10994336 functions as a meQTL to mediate the association between genotype and phenotype remains unclear. Method: A total of 154 patients with BD and 181 healthy controls (HC) were recruited. The genotypes of rs10994336 and methylation levels of CpG sites within ANK3 were tested. Executive functions were assessed using a computerized version of the Wisconsin Card Sorting Test (WCST). Results: Bipolar disorder patients with the risk-T allele of rs10994336 scored lower on tests of executive function compared to homozygous CC carriers, after controlling for age, gender, and education level. No significant difference was found in HC individuals. The risk-T allele is associated with a lower methylation level of CpG site cg02172182 in HC after multiple corrections and replicated in the BD group in the same direction. Further mediation analysis revealed that the cg02172182 methylation significantly mediated the association between the polymorphism rs10994336 and PE index of WCST in patients with BD. Conclusion: Our study suggests that BD-related genetic variant rs10994336 in ANK3 impacts executive functions by modulating ANK3 methylation, supporting the theory that methylation acts as a mediator between genotype and phenotype.
Wrist, but Not Back, Isometric Contraction Induced Widespread Hypoalgesia in Healthy Participants

Objective: Exercise may reduce pain sensitivity. This phenomenon called exercise-induced hypoalgesia is observed in different types of exercises and involves the activation of endogenous pain modulation systems. Although the effect of limb exercise on pain sensitivity has often been tested, few studies explored the impact of back exercises that are often used to treat low back pain. The main objective is to measure the effect of back-muscle exercise on pain sensitivity and compare it to the effect of a limb-muscle exercise. Methods: Twenty-three participants who were pain-free performed a 4-min wrist flexion isometric contraction followed by a 4-min low back extension, separated by a 20-min break. Pressure pain thresholds were tested at two low back (S1 spinous process, lumbar erector spinae muscle) and two wrist (capitate bone, wrist flexor muscles) sites before and after each exercise. For each exercise, sites were considered as remote or local in relation to the muscles contracted during the exercise. An independent sample of 11 participants was recruited to confirm the influence of low back extension on pain sensitivity. Results: Wrist exercise induced a larger increase in pain sensitivity than back exercise at the remote site. Only wrist exercise induced a hypoalgesia effect at both the local and the remote sites. Back exercise induced a similar effect in the independent sample. Conclusions: This study showed that back and wrist exercises induced a distinct effect on pain sensitivity in participants who were pain-free. The wrist exercise induced a systemic reduction in pain sensitivity (locally and remotely), whereas the back exercise did not. This differential effect may be present because wrist exercise induced most fatigue compared with the back exercise.
Risk Stratification Tool for Ischemic Stroke: A Risk Assessment Model Based on Traditional Risk Factors Combined With White Matter Lesions and Retinal Vascular Caliber

Objective: This study aims to establish a risk assessment model based on traditional risk factors combined with the Fazekas classification of white matter lesions and retinal vascular caliber for screening the patients at high risk of ischemic stroke. Methods: This study included 296 patients (128 cases of ischemic stroke and 168 cases in the normal control group). The basic data of the patients were collected. Color fundus photography was performed after pupil dilation, and the retinal vascular caliber was measured using semiautomated vascular measurement software (IVAN Software, Sydney, Australia). The severity of white matter lesions (WML) on cranial nuclear magnetic fluid-attenuated inversion recovery images were assessed using the Fazekas scale. Moreover, logistic regression analysis was used to establish different risk assessment models for ischemic stroke. The effects of models were evaluated through the receiver operating characteristic (ROC) curve and the Delong test compared area under the curve. Results: The sensitivity and specificity of models 1 (the traditional risk factor model), 2 (the retinal vascular caliber model), 3 (the WML model), and 4 (the combined the traditional risk factor, WML and central retinal artery equivalent (CRAE) model) were 71 and 55%, 48 and 71%, 49 and 67%, and 68 and 68.5% with areas under the curve of 0.658, 0.586, 0.601, and 0.708, respectively. The area under the receiver operating characteristic curve in models 1, 2, 3, and 4 showed statistically significant differences. Moreover, no statistical significance exists in the pairwise comparison of other models. Conclusion: The risk assessment model of ischemic stroke combined with Fazekas grade of WML and CRAE is superior to the traditional risk factor and the single-index model. This model is helpful for risk stratification of high-risk stroke patients.
Intestinal Regulatory T Cells as Specialized Tissue-Restricted Immune Cells in Intestinal Immune Homeostasis and Disease

FOXP3+ regulatory T cells (Treg cells) are a specialized population of CD4+ T cells that restrict immune activation and are essential to prevent systemic autoimmunity. In the intestine, the major function of Treg cells is to regulate inflammation as shown by a wide array of mechanistic studies in mice. While Treg cells originating from the thymus can home to the intestine, the majority of Treg cells residing in the intestine are induced from FOXP3neg conventional CD4+ T cells to elicit tolerogenic responses to microbiota and food antigens. This process largely takes place in the gut draining lymph nodes via interaction with antigen-presenting cells that convert circulating naïve T cells into Treg cells. Notably, dysregulation of Treg cells leads to a number of chronic inflammatory disorders, including inflammatory bowel disease. Thus, understanding intestinal Treg cell biology in settings of inflammation and homeostasis has the potential to improve therapeutic options for patients with inflammatory bowel disease. Here, the induction, maintenance, trafficking, and function of intestinal Treg cells is reviewed in the context of intestinal inflammation and inflammatory bowel disease. In this review we propose intestinal Treg cells do not compose fixed Treg cell subsets, but rather (like T helper cells), are plastic and can adopt different programs depending on microenvironmental cues.
Potential of PINK1 and PARKIN Proteins as Biomarkers for Active Multiple Sclerosis: A Japanese Cohort Study

Background Mitochondrial dysfunction has been suggested to play an important role in all stages of multiple sclerosis (MS). Objective To determine the expression of two mitophagy-related proteins, PTEN-induced kinase 1 (PINK1) and PARKIN, in a cohort of Japanese patients with different neuroinflammatory disorders. Methods Protein concentrations were measured using commercial ELISA in paired cerebrospinal fluid (CSF) and serum samples from patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein antibody disorders (MOGAD), and from age- and sex-matched controls. Results CSF and serum concentrations of PINK1 were higher in patients with MS than in patients with NMOSD (p = 0.004 and p < 0.001, respectively), MOGAD (p = 0.008 and p = 0.011, respectively), and controls (p = 0.021 and p = 0.002, respectively). CSF and concentrations of PARKIN were elevated in patients with MS in comparison with those in controls (p = 0.016 and p = 0.05, respectively). Conclusions Our study highlighted the importance of mitophagy in MS and suggested the potential application of PINK1 and PARKIN as biomarkers to predict disease activity.