Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of abnormalities at the neuromuscular junction in the SOD1-G93A mouse model of ALS: dysfunction then disruption of postsynaptic structure precede overt motor symptoms

Introduction The ultimate deficit in amyotrophic lateral sclerosis (ALS) is neuromuscular junction (NMJ) loss, producing permanent paralysis, ultimately in respiratory muscles. However, understanding the functional and structural deficits at NMJs prior to this loss is crucial for therapeutic strategy design. Should early interventions focus on reversing denervation, or supporting largely intact NMJs that are functionally impaired? We therefore determined when functional and structural deficits appeared in diaphragmatic NMJs relative to the onset of hindlimb tremor (the first overt motor symptoms) in vivo in the SOD1-G93A mouse model of ALS. Materials and methods We employed electrophysiological recording of NMJ postsynaptic potentials for spontaneous and nerve stimulation-evoked responses. This was correlated with fluorescent imaging microscopy of the postsynaptic acetylcholine receptor (AChR) distribution throughout the postnatal developmental timecourse from 2 weeks to early symptomatic ages. Results Significant reduction in the amplitudes of spontaneous miniature endplate potentials (mEPPs) and evoked EPPs emerged only at early symptomatic ages (in our colony, 18-22 weeks). Reductions in mEPP frequency, number of vesicles per EPP, and EPP rise time were seen earlier, at 16weeks, but this reversed by early symptomatic ages. However, the earliest and most striking impairment was an inability to maintain EPP amplitude during a 20 Hz stimulus train, which appeared 6 weeks before overt in vivo motor symptoms. Despite this, fluorescent α-bungarotoxin labelling revealed no systematic, progressive changes in 11 comprehensive NMJ morphological parameters (area, shape, compactness, number of acetylcholine receptor, AChR, regions, etc.) with disease progression. Rather, while NMJs were largely normally-shaped, from 16 weeks there was a progressive and substantial disruption in AChR concentration and distribution within the NMJ footprint. Discussion Thus, NMJ functional deficits appear at least 6 weeks before motor symptoms in vivo, while structural deficits occur 4 weeks later, and predominantly within NMJs. These data suggest initial therapies focused on rectifying suboptimal NMJ function could produce effective relief of symptoms of weakness.
Social capital and loneliness among older adults in community dwellings and nursing homes in Zhejiang Province of China

Background Loneliness is an important problem afflicting the health of older adults, and has been proven to be associated with social capital. Previous research in China rarely investigated the differences of social capital and loneliness between older adults living in community dwellings and nursing homes. This study aims to examine the status of social capital and loneliness among older adults living in community dwellings and nursing homes, and analyze the relationship between them. Methods A total of 1,278 older adults were recruited for the study from the cities of Hangzhou, Huzhou, and Lishui in Zhejiang Province of China from July to October 2021 by using multi-stage stratified random sampling. Questionnaires were used to collect data on the participants’ sociodemographic characteristics, social capital, and loneliness. Hierarchical multiple regression was used to examine the relationship between social capital and loneliness. The interaction of social capital and institutionalization on loneliness was also explored. Results Compared with community-dwelling older adults, institutionalized older adults had higher levels of loneliness and lower degrees of social support, social connection, trust, cohesion, and reciprocity. A further analysis of the social capital showed that low levels of social support, trust, and cohesion were related to high levels of loneliness among adults in both community dwellings and nursing homes. Social connection was negatively correlated with loneliness among older adults living in community dwellings. Institutionalization itself demonstrated a strong effect on loneliness. Conclusion Health-related policies should help older adults gain more social support, trust and cohesion to alleviate their loneliness. This is particularly crucial for older adults living in nursing homes, as they have higher levels of loneliness and lower levels of social capital than noninstitutionalized older adults.
Hepatokines, bile acids and ketone bodies are novel Hormones regulating energy homeostasis

Current views show that an impaired balance partly explains the fat accumulation leading to obesity. Fetal malnutrition and early exposure to endocrine-disrupting compounds also contribute to obesity and impaired insulin secretion and/or sensitivity. The liver plays a major role in systemic glucose homeostasis through hepatokines secreted by hepatocytes. Hepatokines influence metabolism through autocrine, paracrine, and endocrine signaling and mediate the crosstalk between the liver, non-hepatic target tissues, and the brain. The liver also synthetizes bile acids (BAs) from cholesterol and secretes them into the bile. After food consumption, BAs mediate the digestion and absorption of fat-soluble vitamins and lipids in the duodenum. In recent studies, BAs act not simply as fat emulsifiers but represent endocrine molecules regulating key metabolic pathways. The liver is also the main site of the production of ketone bodies (KBs). In prolonged fasting, the brain utilizes KBs as an alternative to CHO. In the last few years, the ketogenic diet (KD) became a promising dietary intervention. Studies on subjects undergoing KD show that KBs are important mediators of inflammation and oxidative stress. The present review will focus on the role played by hepatokines, BAs, and KBs in obesity, and diabetes prevention and management and analyze the positive effects of BAs, KD, and hepatokine receptor analogs, which might justify their use as new therapeutic approaches for metabolic and aging-related diseases.
Drosophila photoreceptor systems converge in arousal neurons and confer light responsive robustness

Lateral ventral neurons (LNvs) in the fly circadian neural circuit mediate behaviors other than clock resetting, including light-activated acute arousal. Converging sensory inputs often confer functional redundancy. The LNvs have three distinct light input pathways: (1) cell autonomously expressed cryptochrome (CRY), (2) rhodopsin 7 (Rh7), and (3) synaptic inputs from the eyes and other external photoreceptors that express opsins and CRY. We explored the relative photoelectrical and behavioral input contributions of these three photoreceptor systems to determine their functional impact in flies. Patch-clamp electrophysiology measuring light evoked firing frequency (FF) was performed on large LNvs (l-LNvs) in response to UV (365 nm), violet (405 nm), blue (450 nm), or red (635 nm) LED light stimulation, testing controls versus mutants that lack photoreceptor inputs gl60j, cry-null, rh7-null, and double mutant gl60j-cry-null flies. For UV, violet, and blue short wavelength light inputs, all photoreceptor mutants show significantly attenuated action potential FF responses measured in the l-LNv. In contrast, red light FF responses are only significantly attenuated in double mutant gl60j-cry-null flies. We used a light-pulse arousal assay to compare behavioral responses to UV, violet, blue and red light of control and light input mutants, measuring the awakening arousal response of flies during subjective nighttime at two different intensities to capture potential threshold differences (10 and 400 μW/cm2). The light arousal behavioral results are similar to the electrophysiological results, showing significant attenuation of behavioral light responses for mutants compared to control. These results show that the different LNv convergent photoreceptor systems are integrated and together confer functional redundancy for light evoked behavioral arousal.
Deciphering the mechanism of jujube vinegar on hyperlipoidemia through gut microbiome based on 16S rRNA, BugBase analysis, and the stamp analysis of KEEG

Background Growing data indicate that the gut microbiome may contribute to the rising incidence of hyperlipoidemia. Jujube vinegar lowers lipids, protects the liver, and reduces oxidant capacity, however, it is unknown whether this is due to the gut flora. To further research the role of the gut microbiome in treating hyperlipidemia with jujube vinegar, we looked into whether the action of jujube vinegar is related to the regulation of the gut microbiome. Method Thirty male ICR mice were used. The control group (CON), the high-fat diet (HFD) group, and the vinegar group (VIN) each consisted of ten female ICR mice fed consistently for eight weeks. For each treatment, we kept track of body mass, liver index, blood lipid levels, and oxidative stress state. We also analyzed mouse feces using high-throughput 16srRNA sequencing to examine the relationship between jujube vinegar’s hypolipidemic effect and antioxidant activity and how it affects the gut microbiome. Results Jujube vinegar reduced body weight by 19.92%, serum TC, TG, and LDL-C by 25.09%, 26.83%, and 11.66%, and increased HDL-C by 1.44 times, serum AST and ALT decreased by 26.36% and 34.87% respectively, the blood levels of SOD and GSH-Px increased 1.35-fold and 1.60-fold, respectively. While blood MDA decreased 33.21%, the liver’s SOD and GSH-Px increased 1.32-fold and 1.60-fold, respectively, and the liver’s MDA decreased 48.96% in HFD mice. The gut microbiome analysis revealed that jujube vinegar increased the intestinal microbial ASV count by 13.46%, and the F/B (Firmicutes/Bacteroidota) ratio by 2.08-fold in high-fat diet mice, and the proportion was significantly inversely correlated with TC, TG, and LDL-C and positively correlated with HDL-C. Biomarker bacteria in the vinegar group included Lactobacillaceae and Lactobacillus, which correlated favorably with HDL-C, SOD, and GSH-Px and negatively with LDL-C, TC, and TG. Jujube vinegar increased the abundance of the Aerobic, Contains Mobile Elements, and Facultative Aerobic by 2.84 times, 1.45 times, and 2.40 times, while decreased the abundance of Potential pathogens by 44.72%, according to the BugBase study. The KEGG analysis showed that jujube vinegar was predominantly reflected in the biological process of gene function and related to signal transduction pathways, including glucagon signaling system, HIF-1 signaling pathway, adipocytokine signaling pathway, amino sugar, and nucleotide sugar metabolism, and so forth. Conclusion Based on these findings, jujube vinegar may reduce hyperlipoidemia by controlling the gut microbiome and enhancing antioxidant capacity.
Failure pattern and radiotherapy exploration in malignant pleural effusion non-small cell lung cancer treated with targeted therapy

Purpose Actionable mutations are common in non-small cell lung cancer(NSCLC)with malignant pleural effusion(MPE)(MPE-NSCLC). The pattern of failure in MPE-NSCLC treated with targeted therapy after MPE control remains unclear. We aimed to investigate the failure pattern of such patients in a cohort study and explore the possibility of radiotherapy. Patients and methods Computed tomography scans of 86 patients were reviewed in this study. We classified first pattern of failure after MPE control as initial disease sites only (IF), new distant sites only (NF), or IF and NF detected simultaneously (INF). Patients evaluated suitable for radiotherapy after disease progression were divided into two groups: D group without radiotherapy and RD group with radiotherapy. The Kaplan-Meier method and log-rank test were used for survival analyses. Results Disease progression after MPE control was observed in 42 patients with complete serial imaging. Median time to any progression was 9.5 months. Rate of the IF, NF and INF were 50%, 17% and 33% for all patients,60%,0% and 40% for patients with MPE recurrence (n=10,23.8%) and 47%, 22% and 31% for patients (n=32,76.2%) without MPE recurrence, respectively. Out of 10 patients(23.8%) with MPE recurrence, 7 patients simultaneous underwent primary tumor progression and 5 MPE were cytologically confirmed in 7 patients with examination. The overall survival (OS )rates at 1, 2, 3 years for the RD group and D group were 88.2%, 50.5%, 21.7% and 80.0%, 20.3%, 0%, respectively; the corresponding MST were 26.1 months and 17.5 months, respectively (χ2 = 4.959, p =0.026) Conclusions Our data indicates that 50% of patients with actionable mutations MPE- NSCLC after MPE control are likely to fail at their initial sites of disease and the use of radiotherapy may bring OS benefits during the course of their disease. Multicenter RCT is necessary to confirm the result in the future.
Neuroimaging mechanisms of acupuncture on functional reorganization for post-stroke motor improvement: a machine learning-based functional magnetic resonance imaging study

Objective Motor recovery is crucial in stroke rehabilitation, and acupuncture can influence recovery. Neuroimaging and machine learning approaches provide new research directions to explore the brain functional reorganization and acupuncture mechanisms after stroke. We applied machine learning to predict the classification of the minimal clinically important differences (MCID) for motor improvement and identify the neuroimaging features, in order to explore brain functional reorganization and acupuncture mechanisms for motor recovery after stroke. Methods In this study, 49 patients with unilateral motor pathway injury (basal ganglia and/or corona radiata) after ischemic stroke were included and evaluated the motor function by Fugl–Meyer Assessment scores (FMA) at baseline and at 2-week follow-up sessions. Patients were divided by the difference between the twice FMA scores into one group showing minimal clinically important difference (MCID group, n = 28) and the other group with no minimal clinically important difference (N-MCID, n = 21). Machine learning was performed by PRoNTo software to predict the classification of the patients and identify the feature brain regions of interest (ROIs). In addition, a matched group of healthy controls (HC, n = 26) was enrolled. Patients and HC underwent magnetic resonance imaging examination in the resting state and in the acupuncture state (acupuncture at the Yanglingquan point on one side) to compare the differences in brain functional connectivity (FC) and acupuncture effects. Results Through machine learning, we obtained a balance accuracy rate of 75.51% and eight feature ROIs. Compared to HC, we found that the stroke patients with lower FC between these feature ROIs with other brain regions, while patients in the MCID group exhibited a wider range of lower FC. When acupuncture was applied to Yanglingquan (GB 34), the abnormal FC of patients was decreased, with different targets of effects in different groups. Conclusion Feature ROIs identified by machine learning can predict the classification of stroke patients with different motor improvements, and the FC between these ROIs with other brain regions is decreased. Acupuncture can modulate the bilateral cerebral hemispheres to restore abnormal FC via different targets, thereby promoting motor recovery after stroke. Clinical trial registration https://www.chictr. org.cn/showproj.html? proj=37359, ChiCTR1900022220.
The Effect of Using Relative and Absolute Criteria to Decide Students’ Passing or Failing a Course

In the formation education that is carried out within the scope of undergraduate and non-thesis graduate programs within the same university, different criteria are used to evaluate students’ success. In this study, classification accuracy of letter grades that are generated to evaluate students’ success using relative and absolute criteria and decisions for students’ passing or failing a course were examined. Within the scope of this study, it was also intended to determine the cut-off point required for students to pass a course. In this regard, midterm and final grades of a total of 141 students. First, correct classification percentages of the letter grades that the students scored with absolute and relative evaluations were calculated. Then, classification percentages for decisions regarding passing or failing a course were examined. Then, a cut-off point that decisions for students’ passing or failing a course will be based on was determined using cluster analysis. At the end of the study, it was determined that the relative criterion provided a more accurate classification than the absolute criterion in determining letter grades, whereas the absolute criterion provided a more accurate classification in decisions for students’ passing or failing courses. The relative criterion was found to have provided more benefits to students than the absolute criterion both in terms of letter grading and decision making process for students' passing a course. It was determined that the cut-off points required to decide students’ passing a course is more parallel to the absolute criterion.
Future horizons in the analysis of technical-tactical performance in women’s football: a mixed methods approach to the analysis of in-depth interviews with professional coaches and players

Introduction Scientific knowledge about the criteria that determine success in women’s football is beginning to develop. Methods This study was carried out with the aim of detecting regularities in the offensive success in elite women’s football, as well as carrying out an interrelational analysis of linked behaviors, based on in-depth interviews with professional coaches and players. Eight in-depth interviews were conducted with professional Spanish coaches and players. The interviews were analyzed by indirect observation from a process of “quantitizing,” through the construction of an indirect observation ad hoc instrument. The segmentation of the transcription of the interviews was carried out in textual units, and the creation of a matrix of codes. Two types of analysis were performed: first, a lag sequential analysis (LSA) was performed and, then, a polar coordinates analysis (PCA), which allowed to find, respectively, a wide number of established communicative patterns with offensive performance in women’s football, as well as an interrelational map between the established codes. Results The results obtained allowed us to suggest a statistically significant association between success in women’s football and criteria such as the physical characteristics of a particular player, the individual action space, the duration of the attack, the type of dynamic start, individual and collective technical and tactical aspects, decision making and the type of attack used. Discussion Based on these results, the influence of these criteria on performance in women’s soccer can be studied in future studies. In addition, with the aim of increasing the validity of these conclusions, new studies on this subject may be carried out following strategies such as the Delphi Method.
Field evaluation of the sex pheromone of the cacao pod borer (Conopomorpha cramerella Snellen) in the Philippines

Cacao is a promising high-value crop in the Philippines and is considered one of the key players globally in providing the raw materials for chocolate making. However, before the Philippines can take this market opportunity, production constraints from various pests should be addressed. The cacao pod borer (CPB), Conopomorpha cramerella, is one of the major insect pests of cacao in the Philippines, which can cause up to 50% annual loss or even higher if proper management is not employed. Management of CPB heavily relies on chemical control but is becoming unpopular because of its high cost and health risk to people and the environment. A number of efforts have been made to develop sex pheromones to monitor and control CPB. A field bioassay of the new blend of CPB sex pheromones was conducted in southern Philippines to determine its efficiency and identify the appropriate trap height placement in a cacao field, which is important in maximizing the efficiency of the sex pheromone traps for inclusion in the integrated pest management (IPM) program of CPB. Pheromone lures at four different trap heights (1.0 m, 0.5 m above the canopy, 0.0 m or along the canopy, and 0.5 m below the canopy) and a blank lure (control) placed 1.0 m above the canopy were evaluated in terms of male CPB trap catches. Results showed significantly higher male CPB trap catches when installed at least 0.5 m above the canopy while minimal to zero male CPB catches were obtained from the control traps with blank lures, confirming the attractiveness of the new blend of the CPB sex pheromone in the field. This suggests the reliability of the pheromone-based method to monitor and control CPB and as a major component of the IPM program.
The role of marketing stimuli and attitude in determining post-COVID buying decisions toward organic food products: evidence from retail consumers in Beijing, China

Customers are diverse, and their preferences have changed tremendously, especially post-pandemic, as many business organizations are facing major challenges in meeting those needs. Therefore, an in-depth understanding of consumer buying decisions plays a vital role to develop effective strategies. The aim of this study is to determine whether the marketing mix (4Ps) elements and their attitude have a significant effect on organic food product buying decisions among retail consumers in Beijing, China. A quantitative method was used in this study, whereby 334 questionnaires were physically collected randomly from walk-in customers at Walmart, Darunfa, and Yonghui supermarkets in Beijing, China. Based on the results of the hypothesis test using PLS-SEM, it was confirmed that product, place and promotional strategies had a significant positive relationship with attitude and consumer buying decisions. Interestingly, price had no effect and income was not a moderator. The results of this study provided relevant suggestions to marketing practitioners, especially organic food producers and retail stores on developing and implementing marketing strategies effectively to address changing consumer preferences.
Critical roles of m6A methylation in cardiovascular diseases

Cardiovascular diseases (CVDs) have been established as a major cause of mortality globally. However, the exact pathogenesis remains obscure. N6-methyladenosine (m6A) methylation is the most common epigenetic modification on mRNAs regulated by methyltransferase complexes (writers), demethylase transferases (erasers) and binding proteins (readers). It is now understood that m6A is a major player in physiological and pathological cardiac processes. m6A methylation are potentially involved in many mechanisms, for instance, regulation of calcium homeostasis, endothelial function, different forms of cell death, autophagy, endoplasmic reticulum stress, macrophage response and inflammation. In this review, we will summarize the molecular functions of m6A enzymes. We mainly focus on m6A-associated mechanisms and functions in CVDs, especially in heart failure and ischemia heart disease. We will also discuss the potential application and clinical transformation of m6A modification.