Miracle-dz/UniFAR-FTUs huggingface dataset:
GCK exonic mutations induce abnormal biochemical activities and result in GCK-MODY

Objective: Glucokinase-maturity-onset diabetes of the young (GCK-MODY; MODY2) is a rare genetic disorder caused by mutations in the glucokinase (GCK) gene. It is often under- or misdiagnosed in clinical practice, but correct diagnosis can be facilitated by genetic testing. In this study, we examined the genes of three patients diagnosed with GCK-MODY and tested their biochemical properties, such as protein stability and half-life, to explore the function of the mutant proteins and identify the pathogenic mechanism of GCK-MODY. Methods: Three patients with increased blood glucose levels were diagnosed with MODY2 according to the diagnostic guidelines of GCK-MODY proposed by the International Society for Pediatric and Adolescent Diabetes (ISPAD) in 2018. Next-generation sequencing (whole exome detection) was performed to detect gene mutations. The GCK gene and its mutations were introduced into the pCDNA3.0 and pGEX-4T-1 vectors. Following protein purification, enzyme activity assay, and protein immunoblotting, the enzyme activity of GCK was determined, along with the ubiquitination level of the mutant GCK protein. Results: Genetic testing revealed three mutations in the GCK gene of the three patients, including c.574C>T (p.R192W), c.758G>A (p.C253Y), and c.794G>A (p.G265D). The biochemical characteristics of the protein encoded by wild-type GCK and mutant GCK were different, compared to wild-type GCK, the enzyme activity encoded by the mutant GCK was reduced, suggesting thermal instability of the mutant GST-GCK. The protein stability and expression levels of the mutant GCK were reduced, and the enzyme activity of GCK was negatively correlated with the levels of fasting blood glucose and HbA1c. In addition, ubiquitination of the mutant GCK protein was higher than that of the wild-type, suggesting a higher degradation rate of mutant GCK than WT-GCK. Conclusion: GCK mutations lead to changes in the biochemical characteristics of its encoded proteins. The enzyme activities, protein expression, and protein stability of GCK may be reduced in patients with GCK gene mutations, which further causes glucose metabolism disorders and induces MODY2.
Does gender moderate the association between socioeconomic status and health? Results from an observational study in persons with spinal cord injury living in Morocco

Background Socioeconomic status (SES) and gender are well-known social determinants of health. However, their impact on health in populations with physical disabilities in low-resource countries is still lacking. Therefore, the objective of this study was to investigate associations of individual SES with health and the moderating effect of gender on this association in a Moroccan population with a physical disability, namely spinal cord injury. Methods Cross-sectional survey data from 385 participants with spinal cord injury living in Morocco were analyzed. SES was operationalized by education level, household income, financial hardship, and subjective social status. Health indicators included secondary conditions, pain, vitality, quality of life, and general health. Associations between SES and health indicators were investigated using linear and logistic regressions. To test the potential moderation of gender, interaction terms between SES and gender were introduced in regression models. Results Financial hardship and lower subjective social status were associated with poorer health outcomes in four out of five indicators in the total sample. In contrast, education and income were inconsistently associated with health. Overall, gender did not moderate the association between SES and health, except that educational inequalities in general health were more pronounced in women, and the observation of a trend for a stronger negative effect of subjective social status on men's than woman's health (p > 0.05). Conclusion This study revealed that subjective indicators of SES negatively impact on health, whereas evidence for the moderating role of gender in this association was weak. These findings underline the importance to reduce social marginalization and poverty in populations with disabilities in low-resource countries to reduce their double burden of living with a disability and encountering social disadvantages through low SES.
Perceived financial burden is indirectly linked to sexual well-being via quality of life among couples seeking medically assisted reproduction

Introduction Medically assisted reproduction is a difficult treatment process for couples both financially and sexually. Yet, these two domains have not been examined together among couples seeking treatment, leaving couples and practitioners without guidance on how to address these domains together. Methods In line with Couples and Finance Theory, we tested the hypothesis that perceived financial burden and couple income would predict quality of life during medically assisted reproduction, which would then predict four domains of sexual well-being (i.e., sexual satisfaction, desire, distress, and frequency). We also examined if the results differed by treatment status—that is, between partners who were receiving treatment and those who were not. Cross-sectional data from 120 couples who had undergone medically assisted reproduction in the past six months were analyzed via structural equation modeling through an actor-partner interdependence mediation model. Results An individual’s greater perceived financial burden predicted their own lower quality of life during medically assisted reproduction, which in turn predicted their lower sexual satisfaction, desire and distress, as well as their partner’s lower sexual satisfaction. Household income did not indirectly predict any sexual well-being domains, and results regarding treatment status were inconclusive. Discussion Clinicians can discuss with couples how perceived financial strain of medically assisted reproduction affects their quality of life and what ramifications that may have for their sexual well-being.
Updating the relationship of the Ne/ERN to task-related behavior: A brief review and suggestions for future research

The error negativity/error-related negativity (Ne/ERN) is one of the most well-studied event-related potential (ERP) components in the electroencephalography (EEG) literature. Peaking about 50 ms after the commission of an error, the Ne/ERN is a negative deflection in the ERP waveform that is thought to reflect error processing in the brain. While its relationships to trait constructs such as anxiety are well-documented, there is still little known about how the Ne/ERN may subsequently influence task-related behavior. In other words, does the occurrence of the Ne/ERN trigger any sort of error corrective process, or any other behavioral adaptation to avoid errors? Several theories have emerged to explain how the Ne/ERN may implement or affect behavior on a task, but evidence supporting each has been mixed. In the following manuscript, we review these theories, and then systematically discuss the reasons that there may be discrepancies in the literature. We review both the inherent biological factors of the neural regions that underlie error-processing in the brain, and some of the researcher-induced factors in analytic and experimental choices that may be exacerbating these discrepancies. We end with a table of recommendations for future researchers who aim to understand the relationship between the Ne/ERN and behavior.
Are they still determining? Analysis of associations among ethnicity, gender, socioeconomic status, neighborhood factors, and COVID-19 vaccination

Introduction This study explores associations among adult vaccination, ethnicity, gender, and socioeconomic variables such as educational attainment and income, as well as neighborhood factors. Methods A telephone quota sample of New Jersey adults (N = 1,984) was used to text associations among proposed predictors of vaccination behaviors. Results Our multivariate logistic regression analyses found that certain races/ethnicity, respondents' household income, and perceived safety of one's community were the strongest predictors of COVID-19 vaccination. The odds of COVID-19 vaccination were 52% lower for Black/African American respondents compared to white/Caucasian respondents (p = 0.001) and 44% lower for Hispanic/Latino respondents compared to white/Caucasian respondents (p = 0.001). Discussion The results add new insights to public health communication research and suggest careful interventions across racial groups, considering existing racial disparities in vaccination.
Integrated analysis of SR-like protein kinases Sky1 and Sky2 links signaling networks with transcriptional regulation in Candida albicans

Fungal infections are a major global health burden where Candida albicans is among the most common fungal pathogen in humans and is a common cause of invasive candidiasis. Fungal phenotypes, such as those related to morphology, proliferation and virulence are mainly driven by gene expression, which is primarily regulated by kinase signaling cascades. Serine-arginine (SR) protein kinases are highly conserved among eukaryotes and are involved in major transcriptional processes in human and S. cerevisiae. Candida albicans harbors two SR protein kinases, while Sky2 is important for metabolic adaptation, Sky1 has similar functions as in S. cerevisiae. To investigate the role of these SR kinases for the regulation of transcriptional responses in C. albicans, we performed RNA sequencing of sky1Δ and sky2Δ and integrated a comprehensive phosphoproteome dataset of these mutants. Using a Systems Biology approach, we study transcriptional regulation in the context of kinase signaling networks. Transcriptomic enrichment analysis indicates that pathways involved in the regulation of gene expression are downregulated and mitochondrial processes are upregulated in sky1Δ. In sky2Δ, primarily metabolic processes are affected, especially for arginine, and we observed that arginine-induced hyphae formation is impaired in sky2Δ. In addition, our analysis identifies several transcription factors as potential drivers of the transcriptional response. Among these, a core set is shared between both kinase knockouts, but it appears to regulate different subsets of target genes. To elucidate these diverse regulatory patterns, we created network modules by integrating the data of site-specific protein phosphorylation and gene expression with kinase-substrate predictions and protein-protein interactions. These integrated signaling modules reveal shared parts but also highlight specific patterns characteristic for each kinase. Interestingly, the modules contain many proteins involved in fungal morphogenesis and stress response. Accordingly, experimental phenotyping shows a higher resistance to Hygromycin B for sky1Δ. Thus, our study demonstrates that a combination of computational approaches with integration of experimental data can offer a new systems biological perspective on the complex network of signaling and transcription. With that, the investigation of the interface between signaling and transcriptional regulation in C. albicans provides a deeper insight into how cellular mechanisms can shape the phenotype.
Comprehensive profiling of serotypes, antimicrobial resistance and virulence of Salmonella isolates from food animals in China, 2015–2021

Introduction Salmonella is a ubiquitous foodborne pathogen and mainly transmitted to human farm-to-fork chain through contaminated foods of animal origin. Methods In this study, we investigated the serotypes, antimicrobial resistance and virulence of Salmonella from China. Results A total of 617 Salmonella isolates were collected from 4 major food animal species across 23 provi nces in China from 2015-2021. Highest Salmonella prevalence were observed in Guangdong (44.4%) and Sandong (23.7%). Chickens (43.0%) was shown to be the major source of Salmonella contamination, followed by pigs (34.5%) and ducks (18.5%). The number of Salmonella increased significantly from 5.51% to 27.23% during 2015–2020. S. Derby (17.3%), S. Enteritidis (13.1%) and S. Typhimurium (11.4%) were the most common serotypes among 41 serotypes identifiedin this study. Antibiotic susceptibility testing showing that the majority of the Salmonella isolates were resistant to neomycin (99.7%), tetracycline (98.1%), ampicillin (97.4%), sulfadiazine/trimethoprim (97.1%), nalidixic acid (89.1%), doxycycline (83.1%), ceftria xone (70.3%), spectinomycin (67.7%), florfenicol (60.0%), cefotaxime (52.0%) and lomefloxacin (59.8%). The rates of resistance to multiple antibiotics in S. Derby and S.Typhimurium were higher than that in S. Enteritidis. However, the rate of resistance to fosfomycin were observed from higher to lower by S. Derby, S. Enteritidis, and S. Typhimurium. Biofilm formation ability analysis found that 88.49%of the Salmonella were able to produce biofilms, of which 236 Salmonella isolates were strong biofilm producer. Among the 26 types of antibiotics resistance genes (ARGs) were identified in this study, 4 ARGs (tetB,sul2,aadA2, and aph(3’)-IIa) were highly prevalent. In addition, 5 β-lactam resistance genes (blaTEM, blaSHV, blaCMY-2, blaCTX-M, and blaOXA) and 7 quinolone resistance genes (oqxA, oqxB, qnrB, qnrC, qnrD, qnrS, and qeqA) were detected among these isolates. 12 out of 17 virulence genes selected in this study were commonly presented in the chromosomes of tested isolate, with a detection rate of over 80%, including misL, spiA, stn, pagC, iroN, fim, msgA, sopB, prgH, sitC, ttrC, spaN. Discussion This study provided a systematical updating on surveillance on prevalence of Salmonella from food animals in China, shedding the light on continued vigilance for Salmonella in food animals.
Comparing Regression Coefficients Between Same-sample Nested Models Using Logit and Probit

Logit and probit models are widely used in empirical sociological research. However, the common practice of comparing the coefficients of a given variable across differently specified models fitted to the same sample does not warrant the same interpretation in logits and probits as in linear regression. Unlike linear models, the change in the coefficient of the variable of interest cannot be straightforwardly attributed to the inclusion of confounding variables. The reason for this is that the variance of the underlying latent variable is not identified and will differ between models. We refer to this as the problem of rescaling. We propose a solution that allows researchers to assess the influence of confounding relative to the influence of rescaling, and we develop a test to assess the statistical significance of confounding. A further problem in making comparisons is that, in most cases, the error distribution, and not just its variance, will differ across models. Monte Carlo analyses indicate that other methods that have been proposed for dealing with the rescaling problem can lead to mistaken inferences if the error distributions are very different. In contrast, in all scenarios studied, our approach performs as least as well as, and in some cases better than, others when faced with differences in the error distributions. We present an example of our method using data from the National Education Longitudinal Study.
Endothelial dysfunction and immunothrombosis in sepsis

Sepsis is a life-threatening clinical syndrome characterized by multiorgan dysfunction caused by a dysregulated or over-reactive host response to infection. During sepsis, the coagulation cascade is triggered by activated cells of the innate immune system, such as neutrophils and monocytes, resulting in clot formation mainly in the microcirculation, a process known as immunothrombosis. Although this process aims to protect the host through inhibition of the pathogen’s dissemination and survival, endothelial dysfunction and microthrombotic complications can rapidly lead to multiple organ dysfunction. The development of treatments targeting endothelial innate immune responses and immunothrombosis could be of great significance for reducing morbidity and mortality in patients with sepsis. Medications modifying cell-specific immune responses or inhibiting platelet–endothelial interaction or platelet activation have been proposed. Herein, we discuss the underlying mechanisms of organ-specific endothelial dysfunction and immunothrombosis in sepsis and its complications, while highlighting the recent advances in the development of new therapeutic approaches aiming at improving the short- or long-term prognosis in sepsis.
External and internal training load comparison between sided-game drills in professional soccer

This study aims to quantify and compare the external and internal training load demands of sided-game drills in professional team players during the competitive season. Twenty-four male professional soccer players of the same club were enrolled in this study. Drills were categorized as large-sided games (LSG): 10vs10 (84 × 60 m or 72 × 60 m), Hexagon possession 9vs9 + 3 (36 × 48 m), Possession gate 8vs8 + 2 (36 × 44 m), Possession 7vs7 + 3 (30 × 32 m) or as Small-sided games (SSG): 6vs6 (48 × 42 m), and Possession 6vs4 (30 × 60 m). A total of 7 drills and 279 individual data points were included in this analysis. Distance covered, high-speed running (HSR), and sprinting distance were all calculated in meters per minute (m.min−1) while total accelerations (>3 m.s−2) and total decelerations (− < 3 m.s−2) were calculated in number of actions per minute (n.min−1). All external load was measured with global navigation satellite systems (GNSS) STATSports Apex units. Players’ internal load was quantified using their rating of perceived exertion (RPE). We found that distance covered (p < 0.01, large), HSR (p < 0.01, large), and sprinting distance (p < 0.01, large) changed between drills (e.g., greater in LSG formats), acceleration (p < 0.01, large) and deceleration (p < 0.01, large) demands were greater in smaller formats (e.g., SSG 6vs6, and Possession 6vs4), while RPE was lower in the Possession gate 8vs8 + 2 format (p < 0.01, large). This study found that sided-games can replicate and sometimes exceed some match-specific intensity parameters, however, HSR and sprinting were consistently lower compared to official matches.
Meta-analysis of the association between dietary inflammatory index and cognitive health

Background Some studies have shown that a pro-inflammatory diet may be associated with cognitive function, but their conclusions have varied considerably. We here present a meta-analysis of the current published literature on DII score and its association with cognitive health. Methods In this meta-analysis, the PubMed, Embase, Web of Science, and Cochrane databases were searched in September 2022. The reported indexes, specifically OR, RR, and β, were extracted and analyzed using R version 3.1. 0. Results A total of 636 studies in databases were identified, and 12 were included in the meta-analysis. Higher DII was associated with an increased risk of AD and MCI (OR = 1.34; 95% CI = 1.21–1.49). Meanwhile, it may also cause global function impairment (categorical: OR = 1.63; 95% CI = 1.36–1.96) and verbal fluency impairment (continuous: OR = 0.18; 95% IC = 0.08–0.42). But there was no significant association between DII and executive function (categorical: OR = 1.12; 95% IC = 0.84–1.49; continuous: OR = 0.48; 95% IC = 0.19–1.21) or episodic memory (continuous: OR = 0.56; 95% IC = 0.30–1.03). Conclusion A pro-inflammatory diet is related to AD, MCI, and the functions of some cognitive domains (specifically global function and verbal fluency). However, the current evidence on the role of diet-induced inflammation in different cognitive domains should be supported by further studies in the future.
Microbiome and metabolome associated with white spot lesions in patients treated with clear aligners

White spot lesions (WSLs) have long been a noteworthy complication during orthodontic treatment. Recently, an increasing number of orthodontists have found that adolescents undergoing orthodontic treatment with clear aligners are at a higher risk of developing WSLs. The oral microbiota and metabolites are considered the etiologic and regulatory factors of WSLs, but the specific impact of clear aligners on the oral microbiota and metabolites is unknown. This study investigated the differences in the salivary microbiome and metabolome between adolescents with and without WSLs treated with clear aligners. Fifty-five adolescents (aged 11-18) with Invisalign appliances, 27 with and 28 without WSLs, were included. Saliva samples were analyzed using 16S rRNA gene sequencing and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS); the data were further integrated for Spearman correlation analysis. The relative abundances of 14 taxa, including Actinobacteria, Actinomycetales, Rothia, Micrococcaceae, Subdoligranulum, Capnocytophaga, Azospira, Olsenella, Lachnoanaerobaculum, and Abiotrophia, were significantly higher in the WSL group than in the control group. Metabolomic analysis identified 27 potential biomarkers, and most were amino acids, including proline and glycine. The metabolites were implicated in 6 metabolic pathways, including alanine, aspartate and glutamate metabolism; glycine, serine and threonine metabolism; and aminoacyl-tRNA biosynthesis. There was a correlation between the salivary microbial and metabolomic datasets, reflecting the impact of clear aligners on the metabolic activity of the oral flora. A concordant increase in the levels of Lachnoanaerobaculum, Rothia, Subdoligranulum and some amino acids had predictive value for WSL development. In summary, when adolescents undergo long-term clear aligner therapy with poor oral hygiene habits, clear aligners can disrupt the balance of the oral microecosystem and lead to oral microbiota dysbiosis, thereby increasing the risk of developing WSLs. Our findings might contribute to the understanding of the pathogenesis of WSLs and provide candidate biomarkers for the diagnosis and treatment of WSLs associated with clear aligners.
Association of miR-196a2 and miR-27a polymorphisms with gestational diabetes mellitus susceptibility in a Chinese population

Introduction MiR-196a2 and miR-27a play a key role in the regulation of the insulin signaling pathway. Previous studies have indicated that miR-27a rs895819 and miR-196a2 rs11614913 have a strong association with type 2 diabetes (T2DM), but very few studies have investigated their role in gestational diabetes mellitus (GDM). Methods A total of 500 GDM patients and 502 control subjects were enrolled in this study. Using the SNPscan™ genotyping assay, rs11614913 and rs895819 were genotyped. In the data treatment process, the independent sample t test, logistic regression and chi-square test were used to evaluate the differences in genotype, allele, and haplotype distributions and their associations with GDM risk. One-way ANOVA was conducted to determine the differences in genotype and blood glucose level. Results There were obvious differences in prepregnancy body mass index (pre-BMI), age, systolic blood pressure (SBP), diastolic blood pressure (DBP) and parity between GDM and healthy subjects (P < 0.05). After adjusting for the above factors, the miR-27a rs895819 C allele was still associated with an increased risk of GDM (C vs. T: OR=1.245; 95% CI: 1.011-1.533; P = 0.039) and the TT-CC genotype of rs11614913-rs895819 was related to an increased GDM risk (OR=3.989; 95% CI: 1.309-12.16; P = 0.015). In addition, the haplotype T-C had a positive interaction with GDM (OR=1.376; 95% CI: 1.075-1.790; P=0.018), especially in the 18.5 ≤ pre-BMI < 24 group (OR=1.403; 95% CI: 1.026-1.921; P=0.034). Moreover, the blood glucose level of the rs895819 CC genotype was significantly higher than that of the TT and TC genotypes (P < 0.05). The TT-CC genotype of rs11614913-rs895819 showed that the blood glucose level was significantly higher than that of the other genotypes. Discussion Our findings suggest that miR-27a rs895819 is associated with increased GDM susceptibility and higher blood glucose levels.