Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Characterization of CLCN4 Variants Associated With X-Linked Intellectual Disability and Epilepsy

Early/late endosomes, recycling endosomes, and lysosomes together form the endo-lysosomal recycling pathway. This system plays a crucial role in cell differentiation and survival, and dysregulation of the endo-lysosomal system appears to be important in the pathogenesis of neurodevelopmental and neurodegenerative diseases. Each endo-lysosomal compartment fulfils a specific function, which is supported by ion transporters and channels that modify ion concentrations and electrical gradients across endo-lysosomal membranes. CLC-type Cl–/H+ exchangers are a group of endo-lysosomal transporters that are assumed to regulate luminal acidification and chloride concentration in multiple endosomal compartments. Heterodimers of ClC-3 and ClC-4 localize to various internal membranes, from the endoplasmic reticulum and Golgi to recycling endosomes and late endosomes/lysosomes. The importance of ClC-4-mediated ion transport is illustrated by the association of naturally occurring CLCN4 mutations with epileptic encephalopathy, intellectual disability, and behavioral disorders in human patients. However, how these mutations affect the expression, subcellular localization, and function of ClC-4 is insufficiently understood. We here studied 12 CLCN4 variants that were identified in patients with X-linked intellectual disability and epilepsy and were already characterized to some extent in earlier work. We analyzed the consequences of these mutations on ClC-4 ion transport, subcellular trafficking, and heterodimerization with ClC-3 using heterologous expression in mammalian cells, biochemistry, confocal imaging, and whole-cell patch-clamp recordings. The mutations led to a variety of changes in ClC-4 function, ranging from gain/loss of function and impaired heterodimerization with ClC-3 to subtle impairments in transport functions. Our results suggest that even slight functional changes to the endosomal Cl–/H+ exchangers can cause serious neurological symptoms.
Cronobacter spp. in Commercial Powdered Infant Formula Collected From Nine Provinces in China: Prevalence, Genotype, Biofilm Formation, and Antibiotic Susceptibility

The purpose of this study was to investigate the prevalence of Cronobacter spp. in commercial powdered infant formula (PIF) from nine provinces in China from March 2018 to September 2020, and to reveal the genotype, biofilm-forming ability, and antibiotic susceptibility of these isolates. A total of 27 Cronobacter strains, consisting of 22 Cronobacter sakazakii strains, 3 Cronobacter malonaticus strains, 1 Cronobacter turicensis strain, and 1 Cronobacter dublinensis strain, were isolated from 3,600 commercial PIF samples with a prevalence rate of 0.75%. Compared with the other 8 provinces, PIF from Shaanxi province had a higher prevalence rate (1.25%) of Cronobacter spp. These isolates were divided into 14 sequence types (STs), and 6 Cronobacter serotypes. The main Cronobacter STs were ST4, ST1, and ST64, and the dominant Cronobacter serotype was C. sakazakii serotype O2. Approximately 88.89% of Cronobacter isolates had a strong ability (OD595 > 1) to form biofilms on tinplate, among which the strains with ST4 were more dominant. All isolates were susceptible to ampicillin-sulbactam, ceftriaxone, cefotaxime, sulfadiazine, sulfadoxine, trimethoprim-sulfamethoxazole, gentamicin, tetracycline, ciprofloxacin, and colistin, while 55.56 and 96.30% isolates were resistant to cephalothin and vancomycin, respectively. Taken together, our findings highlighted the contamination status and characterization of Cronobacter spp. in commercial PIF from nine provinces of China, and provided guidance for the effective prevention and control of this pathogen in the production of PIF.
A Positive Psychology Resource for Students? Evaluation of the Effectiveness of the 6 Minutes Diary in a Randomized Control Trial

This study investigated the effects of the 6 Minutes Journal (6MT), a commercial diary combining several positive psychology interventions, including gratitude, goal-setting, and self-affirmation exercises, on several mental health outcome measures. In a randomized controlled trial, university students (N = 157) were randomly assigned to one of two groups: 6MT (n = 77) and a wait list control group (n = 80). Participants in the intervention group were instructed to follow the instructions of the 6MT for 4 weeks. Participants in both groups completed measures of perceived stress, positive and negative affect, self-efficacy and resilience at baseline, after 2 (t1), and 4 (t2) weeks. We used path-analyses with autoregressive and cross-lagged effects to test our hypotheses of the effects of the 6MT. Participants in the intervention group reported decreased levels of perceived stress and negative affect, as well as increased levels of resilience and self-efficacy compared to the control group. Positive affect was not statistically significantly influenced. The data showed a statistically significant increased levels of self-efficacy and resilience only after 4 weeks, suggesting that changing these constructs needs more time. The 6-minute diary does not appear to make individuals fundamentally more positive. However, the intervention may have a protective function against negative influences on well-being.
Early Abusive Relationships–Influence of Different Maltreatment Types on Postpartum Psychopathology and Mother-Infant Bonding in a Clinical Sample

Postpartum psychopathology is a well-documented risk factor for impaired mother-infant bonding and thus child development. Increasingly, the focus of research in this area lies on maternal adverse childhood experiences that mothers bring into the relationship with their own baby, especially regarding the possible intergenerational transmission of traumatic experiences. Several studies showed that there is no direct link between child maltreatment and mother-infant bonding as one part of mother-child relationship, but that this link is mediated by postpartum psychopathology. To date, few studies examined differential effects between sexual, physical, and emotional abuse, and physical and emotional neglect, especially in a clinical sample. The aim of this study is to investigate whether the relationship between child maltreatment, psychopathology, and mother-infant bonding can be found for different forms of child maltreatment in patients of a mother-baby unit. Our sample consisted of 330 mothers of a mother-baby-unit in a psychosomatic clinic, who filled out self-report measures at time of admission. Mothers reported on maternal child maltreatment history with the Childhood Trauma Questionnaire, on current psychopathology with the Brief Symptom Inventory, and on mother-infant bonding with the Postpartum Bonding Questionnaire. Mediation analyses were performed with psychopathology as mediator, child maltreatment history as independent, and mother-infant bonding as dependent variable. There was no total effect of child maltreatment on mother-infant bonding. However, there were significant indirect effects of child maltreatment in general (ab = 0.09) and of the various forms of child maltreatment on mother-infant bonding via psychopathology (0.16 ≤ ab ≤ 0.34). The strongest effect was found for emotional abuse. After controlling for psychopathology, the direct effect of physical abuse on mother-infant bonding presented as a negative significant effect. This indicates that the more severe the physical abuse experienced, the better the self-reported bonding. A similar, but non-significant trend was found for sexual abuse. Our findings highlight the importance of assessing neglect forms of child maltreatment as well as abuse in women during the perinatal period. It further supports initial findings that different forms of child maltreatment can have differential effects on mother-infant bonding as one aspect of the mother-child relationship. Further research should include observational data to compare with self-report measures.
Perspectives: SARS-CoV-2 Spike Convergent Evolution as a Guide to Explore Adaptive Advantage

Viruses rapidly co-evolve with their hosts. The 9 million sequenced SARS-CoV-2 genomes by March 2022 provide a detailed account of viral evolution, showing that all amino acids have been mutated many times. However, only a few became prominent in the viral population. Here, we investigated the emergence of the same mutations in unrelated parallel lineages and the extent of such convergent evolution on the molecular level in the spike (S) protein. We found that during the first phase of the pandemic (until mid 2021, before mass vaccination) 31 mutations evolved independently ≥3-times within separated lineages. These included all the key mutations in SARS-CoV-2 variants of concern (VOC) at that time, indicating their fundamental adaptive advantage. The omicron added many more mutations not frequently seen before, which can be attributed to the synergistic nature of these mutations, which is more difficult to evolve. The great majority (24/31) of S-protein mutations under convergent evolution tightly cluster in three functional domains; N-terminal domain, receptor-binding domain, and Furin cleavage site. Furthermore, among the S-protein receptor-binding motif mutations, ACE2 affinity-improving substitutions are favoured. Next, we determined the mutation space in the S protein that has been covered by SARS-CoV-2. We found that all amino acids that are reachable by single nucleotide changes have been probed multiple times in early 2021. The substitutions requiring two nucleotide changes have recently (late 2021) gained momentum and their numbers are increasing rapidly. These provide a large mutation landscape for SARS-CoV-2 future evolution, on which research should focus now.
All-Fiber Wideband Supercontinuum Generation in Short Hybrid Highly Nonlinear Fibers With a Femtosecond Erbium-Doped Fiber Laser

Wideband supercontinuum (SC) generation has attracted considerable attention due to its various practical applications in many fields. We report on all-fiber SC generation in hybrid highly nonlinear fibers (HNLFs) pumped with a femtosecond erbium-doped fiber laser (EDFL). Based on the nonlinear polarization rotation (NPR) technique, the EDFL is compactly constructed with a hybrid device integrating a wavelength-division multiplexing (WDM) coupler, a tap coupler, and a polarization-sensitive isolator. The SC emission in HNLFs with different dispersions is characterized and the optimum length of HNLF is found. The SC in the hybrid HNLF, constructed by two sections of HNLFs with positive and zero dispersions, could approximately span an octave spanning in the 20 dB bandwidth. Our system suggests an inexpensive, effective and compact construction for SC generation.
Type and Severity of Migraine Determines Risk of Atrial Fibrillation in Women

Objective To evaluate sex differences in the risk of atrial fibrillation (AF) according to the type and severity of migraine. Methods We analyzed the nationwide health screening recipients in 2009 without previous AF diagnosis from the Korean National Health Insurance Service data. The diagnosis, type, and severity of migraine were determined using claims data. Newly developed AF was identified during a 10-year follow-up. Sex-difference in the effect of migraine on AF was evaluated. Results A total of 4,020,488 subjects were enrolled from January 1, to December 31, 2009 and followed-up through December 31, 2018; 4,986 subjects had migraine with aura (age 50.6 ± 14.0 years, men 29.3%); and 105,029 had migraine without aura (age 51.6 ± 14.3 years, men 30.9%). Risk of AF in a mild degree of migraine was similar to that in the control group, regardless of sex or the presence of aura. Severe migraine without aura modestly but significantly increased the risk of AF in both men and women compared to controls, with increase in AF risk being most prominent in women who had severe migraine with aura [incidence rate (IR) = 3.39, hazard ratio (HR)adjust = 1.48, 95% confidence intervals (CI) = 1.18–1.85]. No significant association according to aura was observed in men with severe migraines (p for interaction 0.011). Conclusion Severe migraine with aura significantly increased the risk of incident AF in women, but not in men. Surveillance for incident AF and prompt lifestyle modification may be beneficial, particularly for young women suffering from severe migraine with aura.
The Fractional Investigation of Some Dynamical Systems With Caputo Operator

In the present work, an Elzaki transformation is combined with a decomposition technique for the solutions of fractional dynamical systems. The targeted problems are related to the systems of fractional partial differential equations. Fractional differential equations are useful for more accurate modeling of various phenomena. The Elzaki transform decomposition method is implemented in a very simple and straightforward manner to solve the suggested problems. The proposed technique requires fewer calculations and needs no discretization or parametrization. The derivative of fractional order is represented in a Caputo form. To show the conclusion, which is drawn from the results, some numerical examples are considered for their approximate analytical solution. The series solutions to the targeted problems are obtained having components with a greater rate of convergence toward the exact solutions. The new results are represented by using tables and graphs, which show the sufficient accuracy of the present method as compared to other existing techniques. It is shown through graphs and tables that the actual and approximate results are very close to each other, which shows the applicability of the presented method. The fractional-order solutions are in best agreement with the dynamics of the given problems and provide infinite choices for an optimal solution to the suggested mathematical model. The novelty of the present work is that it applies an efficient procedure with less computational cost and attains a higher degree of accuracy. Furthermore, the proposed technique can be used to solve other nonlinear fractional problems in the future, which will be a scientific contribution to research society.
Relationships Between Body Composition and Performance in the High-Intensity Functional Training Workout “Fran” are Modulated by Competition Class and Percentile Rank

This study examined relationships between body composition and high-intensity functional training (HIFT) workout performance. Fifty-seven men (31.4 ± 6.9 years, 177.2 ± 7.5 cm, 84.7 ± 8.5 kg) and thirty-eight women (29.2 ± 6.4 years, 166.6 ± 6.1 cm, 66.5 ± 7.7 kg) with HIFT experience (≥6 months) reported completing “Fran” (21-15-9 repetitions of barbell thrusters and pull-ups) in 4.78 ± 2.22 min and 6.05 ± 2.84 min, respectively, and volunteered to complete dual-energy X-ray absorptiometry assessments. Participants were grouped by competition class (men, women, master’s men, master’s women) and percentile rank in “Fran” (≤25th percentile, 25–75th percentiles, ≥75th percentile). Two-way analyses of variance revealed expected differences (p < 0.001) between men and women in non-bone lean mass (NBLM), fat-free mass index, and fat mass, and more NBLM (10.6–10.8 kg) and less fat mass (2.7–5.2 kg) in >75th percentile compared to other percentiles. Most body composition measures were significantly (p < 0.05) related to performance in men and women but limited in master’s men; no relationships were seen in master’s women. “Fran” time was negatively correlated to NBLM and fat-free mass index in all percentile groups (ρ = -0.37 to -0.64) and bone mineral characteristics for >25th percentile (ρ = −0.41 to −0.63), and positively correlated to fat mass in 25–75th percentiles (ρ = 0.33–0.60). No other relationships were seen in ≤25th percentile. The influence of body composition on “Fran” time appears to vary by both competition class and percentile rank. Though training to increase lean mass always seems relevant, reducing body fat only appears relevant in mid-skilled trainees and when it is outside healthy parameters.
Tuning the Properties of Protein-Based Polymers Using High-Performance Orthogonal Translation Systems for the Incorporation of Aromatic Non-Canonical Amino Acids

The incorporation of non-canonical amino acids (ncAAs) using engineered aminoacyl-tRNA synthetases (aaRSs) has emerged as a powerful methodology to expand the chemical repertoire of proteins. However, the low efficiencies of typical aaRS variants limit the incorporation of ncAAs to only one or a few sites within a protein chain, hindering the design of protein-based polymers (PBPs) in which multi-site ncAA incorporation can be used to impart new properties and functions. Here, we determined the substrate specificities of 11 recently developed high-performance aaRS variants and identified those that enable an efficient multi-site incorporation of 15 different aromatic ncAAs. We used these aaRS variants to produce libraries of two temperature-responsive PBPs—elastin- and resilin-like polypeptides (ELPs and RLPs, respectively)—that bear multiple instances of each ncAA. We show that incorporating such aromatic ncAAs into the protein structure of ELPs and RLPs can affect their temperature responsiveness, secondary structure, and self-assembly propensity, yielding new and diverse families of ELPs and RLPs, each from a single DNA template. Finally, using a molecular model, we demonstrate that the temperature-responsive behavior of RLPs is strongly affected by both the hydrophobicity and the size of the unnatural aromatic side-chain. The ability to efficiently incorporate multiple instances of diverse ncAAs alongside the 20 natural amino acids can help to elucidate the effect of ncAA incorporation on these and many other PBPs, with the aim of designing additional precise and chemically diverse polymers with new or improved properties.
When Do Coworkers’ Idiosyncratic Deals Trigger Social Undermining?—The Moderating Roles of Core Self-Evaluations and Conscientiousness

Idiosyncratic deals are personalized work arrangements negotiated between enterprises and employees based on employees’ abilities and needs, previous studies have focused more on their positive effects on i-dealers and neglected the negative effects on peers in the process of interpersonal interaction. In view of this, this study explores the effects of coworkers’ idiosyncratic deals on employees’ social undermining and the internal mechanism based on social comparison theory. This study tested the theoretical model with a sample of 331 employees from six enterprises in China. The results showed that the interaction between perceptions of coworkers’ receiving idiosyncratic deals and low core self-evaluations stimulated employees’ feelings of relative deprivation, which triggered social undermining toward i-dealers. At the same time, employees’ conscientiousness could weaken the positive effect of relative deprivation on social undermining. Therefore, it reveals the negative peer effect of idiosyncratic deals and provides theoretical and practical implications for preventing the interpersonal harm doing caused by idiosyncratic deals.
Effects of Inappropriate Administration of Empirical Antibiotics on Mortality in Adults With Bacteraemia: Systematic Review and Meta-Analysis

Introduction Bloodstream infections are associated with high mortality rates and contribute substantially to healthcare costs, but a consensus on the prognostic benefits of appropriate empirical antimicrobial therapy (EAT) for bacteraemia is lacking. Methods We performed a systematic search of the PubMed, Cochrane Library, and Embase databases through July 2021. Studies comparing the mortality rates of patients receiving appropriate and inappropriate EAT were considered eligible. The quality of the included studies was assessed using Joanna Briggs Institute checklists. Results We ultimately assessed 198 studies of 89,962 total patients. The pooled odds ratio (OR) for the prognostic impacts of inappropriate EAT was 2.06 (P < 0.001), and the funnel plot was symmetrically distributed. Among subgroups without between-study heterogeneity (I2 = 0%), those of patients with severe sepsis and septic shock (OR, 2.14), Pitt bacteraemia scores of ≥4 (OR, 1.88), cirrhosis (OR, 2.56), older age (OR, 1.78), and community-onset/acquired Enterobacteriaceae bacteraemia infection (OR, 2.53) indicated a significant effect of inappropriate EAT on mortality. The pooled adjusted OR of 125 studies using multivariable analyses for the effects of inappropriate EAT on mortality was 2.02 (P < 0.001), and the subgroups with low heterogeneity (I2 < 25%) exhibiting significant effects of inappropriate EAT were those of patients with vascular catheter infections (adjusted OR, 2.40), pneumonia (adjusted OR, 2.72), or Enterobacteriaceae bacteraemia (adjusted OR, 4.35). Notably, the pooled univariable and multivariable analyses were consistent in revealing the negligible impacts of inappropriate EAT on the subgroups of patients with urinary tract infections and Enterobacter bacteraemia. Conclusion Although the current evidence is insufficient to demonstrate the benefits of prompt EAT in specific bacteraemic populations, we indicated that inappropriate EAT is associated with unfavorable mortality outcomes overall and in numerous subgroups. Prospective studies designed to test these specific populations are needed to ensure reliable conclusions. Systematic Review Registration https://www.crd. york.ac. uk/prospero/, identifier: CRD42021270274.
The Mitochondrial tRNAPhe 625G>A Mutation in Three Han Chinese Families With Cholecystolithiasis

In this study, we assessed three Chinese families with inherited cholecystolithiasis and conducted the clinical, genetic, and molecular characterization of these subjects. Eight of eighteen matrilineal relatives had a clinical phenotype in these three families. Sequence analysis of complete mitochondrial genomes in these probands identified the homoplasmic tRNAPhe 625 G > A mutation and distinct sets of mtDNA polymorphisms belonging to haplogroups H2, F4b, and M10a. The 625G > A mutation disturbed the classic G-C base-pairings at a highly conserved position 49 in the T-stem of mitochondrial tRNAs. Molecular dynamics simulation showed that the structure of tRNAphe with 625 G > A mutation was noticeably remodeled while compared with the isoform of the wild type. The occurrence of tRNAPhe 625 G > A mutation in these various genetically unrelated subjects strongly indicates that this mutation is involved in the pathogenesis of cholecystolithiasis. This is the first evidence that tRNA mutations are associated with cholecystolithiasis, and it provided more insights into the genetic mechanism of cholecystolithiasis.