Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional and Structural Diversity of Bacterial Contact-Dependent Growth Inhibition Effectors

Bacteria live in complex communities and environments, competing for space and nutrients. Within their niche habitats, bacteria have developed various inter-bacterial mechanisms to compete and communicate. One such mechanism is contact-dependent growth inhibition (CDI). CDI is found in many Gram-negative bacteria, including several pathogens. These CDI+ bacteria encode a CdiB/CdiA two-partner secretion system that delivers inhibitory toxins into neighboring cells upon contact. Toxin translocation results in the growth inhibition of closely related strains and provides a competitive advantage to the CDI+ bacteria. CdiB, an outer-membrane protein, secretes CdiA onto the surface of the CDI+ bacteria. When CdiA interacts with specific target-cell receptors, CdiA delivers its C-terminal toxin region (CdiA-CT) into the target-cell. CdiA-CT toxin proteins display a diverse range of toxic functions, such as DNase, RNase, or pore-forming toxin activity. CDI+ bacteria also encode an immunity protein, CdiI, that specifically binds and neutralizes its cognate CdiA-CT, protecting the CDI+ bacteria from auto-inhibition. In Gram-negative bacteria, toxin/immunity (CdiA-CT/CdiI) pairs have highly variable sequences and functions, with over 130 predicted divergent toxin/immunity complex families. In this review, we will discuss biochemical and structural advances made in the characterization of CDI. This review will focus on the diverse array of CDI toxin/immunity complex structures together with their distinct toxin functions. Additionally, we will discuss the most recent studies on target-cell recognition and toxin entry, along with the discovery of a new member of the CDI loci. Finally, we will offer insights into how these diverse toxin/immunity complexes could be harnessed to fight human diseases.
Long Non-Coding RNAs as Molecular Biomarkers in Cholangiocarcinoma

Cholangiocarcinoma (CCA) is a biliary system cancer that has the characteristics of strong invasiveness, poor prognosis, and few therapy choices. Furthermore, the absence of precise biomarkers for early identification and prognosis makes it hard to intervene in the early phase of initial diagnosis or recurring cholangiocarcinoma following surgery. Encouragingly, previous studies found that long non-coding RNA (lncRNA), a subgroup of RNA that is more than 200 nucleotides long, can affect cell proliferation, migration, apoptosis, and even drug resistance by altering numerous signaling pathways, thus reaching pro-cancer or anti-cancer outcomes. This review will take a retrospective view of the recent investigations on the work of lncRNAs in cholangiocarcinoma progression and the potential of lncRNAs serving as promising clinical biomarkers and therapeutic targets for CCA.
Effect of Virtual Reality on Balance Function in Children With Cerebral Palsy: A Systematic Review and Meta-analysis

Virtual Reality (VR) therapy is popular in treating children with Cerebral Palsy (CP) as a new technology for rehabilitation. Nevertheless, no substantial evidence supporting VR therapy promotion has been developed to date. This study aimed to investigate the effects of VR therapy on balance in children with CP. We conducted a systematic search in PubMed and Web of Science (updated to December 30, 2021). The systematic review and meta-analysis included all randomized controlled trials that included children with CP. A total of 18 RCT studies were eligible for inclusion in the systematic review, and meta-analysis was performed on 16 of them. Results showed that the VR intervention was beneficial for balance (SMD 0.47 [95% CI, SD 0.28, 0.66]). We concluded that VR therapy interventions for children with CP have positive effects. However, cautious implementation is needed in clinical applications.
Verbal Suggestion Modulates the Sense of Ownership and Heat Pain Threshold During the “Injured” Rubber Hand Illusion

The appearance of the self-body influences the feeling that one’s body belongs to oneself, that is, a sense of ownership (SoO) and pain perception. This can be identified by measuring the SoO and pain thresholds after performing the rubber hand illusion (RHI) with an injured rubber hand. The generation of SoO is thought to be caused by multisensory integration of bottom-up factors (vision, proprioceptive, and touch), and by top-down factors, such as the context effect. The appearance is one of the context effects which may become more effective when used simultaneously with other context effects (e.g., verbal suggestion). However, in the RHI, when appearance and other context effects are used simultaneously, the effect is unclear. In this study, we attempted to identify the influence of verbal suggestion on the SoO and heat pain threshold (HPT). As a preliminary step, in Experiment 1, the “normal” rubber hand and “penetrated nail” as injured rubber hand were used to clarify the context effect with appearance alone during RHI (synchronous/asynchronous), which was conducted within-subjects. In Experiment 2, we only used the “penetrated nail” rubber hand to clarify the context effect with verbal suggestion and appearance during RHI. We randomly classified participants into two suggestion groups (“fear” and “no-fear”). The RHI (synchronous/asynchronous) was conducted for each group. In each experiment, the effect of each condition was assessed by subjective measures of SoO, such as questionnaire, and objective measures of SoO, such as proprioceptive drift and electrodermal activity. Following RHI in each condition, HPT was measured. The main finding was that, in the synchronous condition, the “penetrated nail” appearance with “fear” verbal suggestion modulated questionnaire and HPT, but not electrodermal activity. We conclude that the context-included multisensory integration affected the subjective factors because it contains a higher cognitive process by verbal suggestion.
Knockout of Nur77 Leads to Amino Acid, Lipid, and Glucose Metabolism Disorders in Zebrafish

Orphan nuclear receptor Nur77 has been reported to be implicated in a diverse range of metabolic processes, including carbohydrate metabolism and lipid metabolism. However, the detailed mechanism of Nur77 in the regulation of metabolic pathway still needs to be further investigated. In this study, we created a global nur77 knockout zebrafish model by CRISPR/Cas9 technique, and then performed whole-organism RNA sequencing analysis in wildtype and nur77-deficient zebrafish to dissect the genetic changes in metabolic-related pathways. We found that many genes involved in amino acid, lipid, and carbohydrate metabolism changed by more than twofold. Furthermore, we revealed that nur77−/− mutant displayed increased total cholesterol (TC) and triglyceride (TG), alteration in total amino acids, as well as elevated glucose. We also demonstrated that the elevated glucose was not due to the change of glucose uptake but was likely caused by the disorder of glycolysis/gluconeogenesis and the impaired β-cell function, including downregulated insb expression, reduced β-cell mass, and suppressed insulin secretion. Importantly, we also verified that targeted expression of Nur77 in the β cells is sufficient to rescue the β-cell defects in global nur77−/− larvae zebrafish. These results provide new information about the global metabolic network that Nur77 signaling regulates, as well as the role of Nur77 in β-cell function.
Evaluation of the Effects of a Short Supplementation With Tannins on the Gut Microbiota of Healthy Subjects

Western diet, high in fats and sugars and low in greens, contributes to dysbiosis of the gut microbiota, which can lead to a variety of chronic diseases related with inflammation. Supplementation with bioactive compounds can help to maintain a healthy eubiotic state. Thus, we performed a 4-weeks nutritional intervention on healthy volunteers to investigate whether a blend of natural tannin extracts could induce healthy changes in the microbial intestinal ecosystem. Changes in the composition and functionality of the microbiota could be observed from the first two weeks onward. 16S rRNA amplicon next-generation sequencing (NGS) revealed a significant increase in microbial diversity at the end of the intervention, as well as trends toward increases in the relative abundances of several beneficial taxa, such as Ruminococcus bicirculans, Faecalibacterium prausnitzii, Lachnospiraceae UCG 010, Lachnospiraceae NK4A136, Bacteroides thetaiotaomicron and B. uniformis. Remarkably, some of the identified taxa were also identified as responsible for an increase in the production of short-chain fatty acids (SCFAs), microbial metabolites that contribute to the modulation of the immune system and have various other anti-inflammatory functions in the gut. Taken together, these results suggest that the tannin supplementation could exert a prebiotic effect by selectively stimulating the growth and the activity of bacteria that are advantageous for the host.
Work, train, win: work-based learning design and management for productivity gains

Realising the potential of work-based learning schemes as a driver of productivity requires careful design and support. The length of work-based learning schemes should be adapted to the profile of productivity gains. A scheme that is too long for a given skill set might be unattractive for learners and waste public resources, but a scheme that is too short will fail to attract employer interest. Ensuring that the design of work-based learning schemes balances the interests of both employer and trainee is key to successful implementation. Carefully organising what trainees do while in the workplace and integrating learning into productive work can yield higher benefits for firms, while maintaining the quality of learning. Strengthening capacity within firms to effectively manage work-based learning can help achieve this. Enhancing that capacity, for example through training for trainee supervisors can help employers reap more benefits from work-based learning schemes while meeting quality requirements. Les programmes d’apprentissage en milieu professionnel doivent etre concus avec soin et mis en oeuvre de facon appropriee si l’on veut exploiter pleinement les possibilites qu’ils offrent en tant que moteurs de la productivite. La duree de ces programmes devrait etre adaptee au profil des gains de productivite. Un programme qui est trop long pour acquerir un ensemble donne de competences risque de ne pas attirer les apprentis et de gaspiller les ressources publiques, tandis qu’un programme trop court ne suscitera pas l’interet des employeurs. Il est donc essentiel a la bonne mise en oeuvre des programmes d’apprentissage en milieu professionnel qu’ils soient concus de facon a repondre aux besoins a la fois des employeurs et des stagiaires. Le fait d’organiser avec soin les tâches des stagiaires sur le lieu de travail et d’integrer l’apprentissage dans un travail productif peut procurer aux entreprises des avantages accrus, tout en maintenant la qualite de l’apprentissage. La capacite des entreprises a gerer l’apprentissage efficacement en interne contribue a atteindre ces objectifs. Renforcer cette capacite, par exemple en offrant une formation aux maitres de stage, peut aider les employeurs a tirer davantage profit des programmes d’apprentissage en milieu professionnel tout en repondant a des exigences de qualite.
A 13-Gene Signature Based on Estrogen Response Pathway for Predicting Survival and Immune Responses of Patients With UCEC

Background: Accumulating evidence suggests that anti-estrogens have been effective against multiple gynecological diseases, especially advanced uterine corpus endometrial carcinoma (UCEC), highlighting the contribution of the estrogen response pathway in UCEC progression. This study aims to identify a reliable prognostic signature for potentially aiding in the comprehensive management of UCEC. Methods: Firstly, univariate Cox and LASSO regression were performed to identify a satisfying UCEC prognostic model quantifying patients’ risk, constructed from estrogen-response-related genes and verified to be effective by Kaplan-Meier curves, ROC curves, univariate and multivariate Cox regression. Additionally, a nomogram was constructed integrating the prognostic model and other clinicopathological parameters. Next, UCEC patients from the TCGA dataset were divided into low- and high-risk groups according to the median risk score. To elucidate differences in biological characteristics between the two risk groups, pathway enrichment, immune landscape, genomic alterations, and therapeutic responses were evaluated to satisfy this objective. As for treatment, effective responses to anti-PD-1 therapy in the low-risk patients and sensitivity to six chemotherapy drugs in the high-risk patients were demonstrated. Results: The low-risk group with a relatively favorable prognosis was marked by increased immune cell infiltration, higher expression levels of HLA members and immune checkpoint biomarkers, higher tumor mutation burden, and lower copy number alterations. This UCEC prognostic signature, composed of 13 estrogen-response-related genes, has been identified and verified as effective. Conclusion: Our study provides molecular signatures for further functional and therapeutic investigations of estrogen-response-related genes in UCEC and represents a potential systemic approach to characterize key factors in UCEC pathogenesis and therapeutic responses.
Importance of Echocardiography and Clinical “Red Flags” in Guiding Genetic Screening for Fabry Disease

Introduction Aim of this study was to evaluate, in a metropolitan area not already explored, the prevalence of Anderson–Fabry disease, by genetic screening, in patients with echocardiographic evidence of left ventricular hypertrophy (LVH) of unknown origin and “clinical red flags”. Methods From August 2016 to October 2017, all consecutive patients referring to our echo-lab for daily hospital practices with echocardiographic evidence of LVH of unknown origin in association with history of at least one of the classical signs and symptoms related to Fabry disease (FD) (neuropathic pain, anhidrosis/hypohidrosis, angiokeratomas, gastrointestinal problems, chronic kidney disease, or cerebrovascular complications) were considered eligible for the FD genetic screening program. Through dried blood spot testing, α-Galactosidase A (α-Gal A) activity and analysis of the GLA gene were performed. Results Among 3,360 patients who underwent transthoracic echocardiography in our echo-lab during the study period, 30 patients (0.89%; 19 men, mean age 58 ± 18.2 years) were selected. FD was diagnosed in 3 (10%) unrelated patients. Three different GLA gene mutations were detected, one of them [mutation c.388A > G (p.Lys130Glu) in exon 3] never described before. Moreover, probands' familiar genetic screening allowed the identification of 5 other subjects affected by FD. Conclusion In a metropolitan area not previously investigated, among patients with LVH of unknown origin associated with other “red flags,” undergoing genetic screening, the prevalence of FD was very high (10%). Our results highlight the importance of an echocardiographic- and clinical-oriented genetic screening for FD in patients with uncommon cause of LVH.
Succession Challenges Facing Family Businesses in Saudi Arabia

The aim of this study is to examine how succession planning is carried out in family-owned businesses in Saudi Arabia. The study adopts a qualitative methodology which involves semi-structured, face-to-face interviews. The major findings of the research is that most of the family businesses in Saudi Arabia do not have a proper succession plan due mainly to socio-cultural issues such as mistrust and conflict of interest between the older and the younger members of the family and also subservience of women in the society generally. The implications of the study are discussed including a paradigm shift where women are encouraged and given the opportunity to get involved in the running of their family businesses.
Mitochondrial ROS in Slc4a11 KO Corneal Endothelial Cells Lead to ER Stress

Recent studies from Slc4a11 −/− mice have identified glutamine-induced mitochondrial dysfunction as a significant contributor toward oxidative stress, impaired lysosomal function, aberrant autophagy, and cell death in this Congenital Hereditary Endothelial Dystrophy (CHED) model. Because lysosomes are derived from endoplasmic reticulum (ER)—Golgi, we asked whether ER function is affected by mitochondrial ROS in Slc4a11 KO corneal endothelial cells. In mouse Slc4a11 −/− corneal endothelial tissue, we observed the presence of dilated ER and elevated expression of ER stress markers BIP and CHOP. Slc4a11 KO mouse corneal endothelial cells incubated with glutamine showed increased aggresome formation, BIP and GADD153, as well as reduced ER Ca2+ release as compared to WT. Induction of mitoROS by ETC inhibition also led to ER stress in WT cells. Treatment with the mitochondrial ROS quencher MitoQ, restored ER Ca2+ release and relieved ER stress markers in Slc4a11 KO cells in vitro. Systemic MitoQ also reduced BIP expression in Slc4a11 KO endothelium. We conclude that mitochondrial ROS can induce ER stress in corneal endothelial cells.
Neuroevolution Guided Hybrid Spiking Neural Network Training

Neuromorphic computing algorithms based on Spiking Neural Networks (SNNs) are evolving to be a disruptive technology driving machine learning research. The overarching goal of this work is to develop a structured algorithmic framework for SNN training that optimizes unique SNN-specific properties like neuron spiking threshold using neuroevolution as a feedback strategy. We provide extensive results for this hybrid bio-inspired training strategy and show that such a feedback-based learning approach leads to explainable neuromorphic systems that adapt to the specific underlying application. Our analysis reveals 53.8, 28.8, and 28.2% latency improvement for the neuroevolution-based SNN training strategy on CIFAR-10, CIFAR-100, and ImageNet datasets, respectively in contrast to state-of-the-art conversion based approaches. The proposed algorithm can be easily extended to other application domains like image classification in presence of adversarial attacks where 43.2 and 27.9% latency improvements were observed on CIFAR-10 and CIFAR-100 datasets, respectively.
Weed Identification by Single-Stage and Two-Stage Neural Networks: A Study on the Impact of Image Resizers and Weights Optimization Algorithms

The accurate identification of weeds is an essential step for a site-specific weed management system. In recent years, deep learning (DL) has got rapid advancements to perform complex agricultural tasks. The previous studies emphasized the evaluation of advanced training techniques or modifying the well-known DL models to improve the overall accuracy. In contrast, this research attempted to improve the mean average precision (mAP) for the detection and classification of eight classes of weeds by proposing a novel DL-based methodology. First, a comprehensive analysis of single-stage and two-stage neural networks including Single-shot MultiBox Detector (SSD), You look only Once (YOLO-v4), EfficientDet, CenterNet, RetinaNet, Faster Region-based Convolutional Neural Network (RCNN), and Region-based Fully Convolutional Network (RFCN), has been performed. Next, the effects of image resizing techniques along with four image interpolation methods have been studied. It led to the final stage of the research through optimization of the weights of the best-acquired model by initialization techniques, batch normalization, and DL optimization algorithms. The effectiveness of the proposed work is proven due to a high mAP of 93.44% and validated by the stratified k-fold cross-validation technique. It was 5.8% improved as compared to the results obtained by the default settings of the best-suited DL architecture (Faster RCNN ResNet-101). The presented pipeline would be a baseline study for the research community to explore several tasks such as real-time detection and reducing the computation/training time. All the relevant data including the annotated dataset, configuration files, and inference graph of the final model are provided with this article. Furthermore, the selection of the DeepWeeds dataset shows the robustness/practicality of the study because it contains images collected in a real/complex agricultural environment. Therefore, this research would be a considerable step toward an efficient and automatic weed control system.
Influence of an Acute Exposure to a Moderate Real Altitude on Motoneuron Pool Excitability and Jumping Performance

The aim of the study was to test whether ascending to a moderate real altitude affects motoneuron pool excitability at rest, as expressed by a change in the H-reflex amplitude, and also to elucidate whether a possible alteration in the motoneuron pool excitability could be reflected in the execution of lower-body concentric explosive (squat jump; SJ) and fast eccentric-concentric (drop jump; DJ) muscle actions. Fifteen participants performed four experimental sessions that consisted of the combination of two real altitude conditions [low altitude (low altitude, 690 m), high altitude (higher altitude, 2,320 m)] and two testing procedures (H-reflex and vertical jumps). Participants were tested on each testing day at 8, 11, 14 and 17 h. The only significant difference (p < 0.05) detected for the H-reflex was the higher H-reflex response (25.6%) obtained 15 min after arrival at altitude compared to baseline measurement. In terms of motor behavior, DJ height was the only variable that showed a significant interaction between altitude conditions (LA and HA) and time of measurement (8, 11, 14 and 17 h) as DJ height increased more during successive measurements at HA compared to LA. The only significant difference between the LA and HA conditions was observed for DJ height at 17 h which was higher for the HA condition (p = 0.04, ES = 0.41). Although an increased H-reflex response was detected after a brief (15–20 min) exposure to real altitude, the effect on motorneuron pool excitability could not be confirmed since no significant changes in the H-reflex were detected when comparing LA and HA. On the other hand, the positive effect of altitude on DJ performance was accentuated after 6 h of exposure.