Miracle-dz/UniFAR-FTUs huggingface dataset:
Computational approaches to understand transcription regulation in development

Gene regulatory networks (GRNs) serve as useful abstractions to understand transcriptional dynamics in developmental systems. Computational prediction of GRNs has been successfully applied to genome-wide gene expression measurements with the advent of microarrays and RNA-sequencing. However, these inferred networks are inaccurate and mostly based on correlative rather than causative interactions. In this review, we highlight three approaches that significantly impact GRN inference: (1) moving from one genome-wide functional modality, gene expression, to multi-omics, (2) single cell sequencing, to measure cell type-specific signals and predict context-specific GRNs, and (3) neural networks as flexible models. Together, these experimental and computational developments have the potential to significantly impact the quality of inferred GRNs. Ultimately, accurately modeling the regulatory interactions between transcription factors and their target genes will be essential to understand the role of transcription factors in driving developmental gene expression programs and to derive testable hypotheses for validation.
The role of autophagy-related proteins in the pathogenesis of neuromyelitis optica spectrum disorders

ABSTRACT This study aimed to investigate the expression of autophagy-related proteins in a mouse model of neuromyelitis optica (NMO). Mice were assigned to one of four groups: an animal experimental model group (NMO-EAE group, given with exogenous IL-17A), Interleukin-17 monoclonal antibody intervention group (NMO-EAE_0IL17inb), No exogenous interleukin-17 enhanced immune intervention group (NMO-EAE_0IL17), and a control group. Behavioral scores were assessed in each group, and the protein expressions of sequestosome 1 (P62), Beclin-1, the mammalian target of rapamycin (mTOR), phosphoinositide 3-kinase (PI3K-I), and LC3II/LC3I were detected using Western blotting. In the NMO-EAE_0IL17 group, the expression of Beclin-1 decreased, the LC3II/LC3I ratio was lower, and the expressions of P62, mTOR, and PI3K-I increased; after administration of IL-17A inhibitor into the brain tissue, however, the expression of Beclin-1 increased significantly, along with the LC3II/LC3I ratio, while the expressions of P62, mTOR and PI3K-I protein decreased significantly. In terms of behavioral scores, the scores of optic neuritis and myelitis were more serious, onset occurred earlier and the progress was faster, after the administration of IL-17A. In the mechanism of NMO animal model, IL-17A may regulate autophagy and affect the disease process through the activation of the PI3K–mTOR signaling pathway. GRAPHICAL ABSTRACT
Farmers’ beliefs and concerns about climate change, and their adaptation behavior to combat climate change in Saudi Arabia

Climate change threatens the existence of humankind on the planet Earth. Owing to its arid climate and poor natural resources base, Saudi Arabia is particularly susceptible to the negative impact of ongoing climate change. Farmers’ understanding of this global phenomenon is extremely important as it may help determine their adaptation behavior. This study was designed to analyze farmers’ beliefs and concerns about climate change as well as their views about adaptation different obstacles. Data were collected from 80 randomly farmers of the Al-Ahsa region in Eastern Province using structured interviews. The findings revealed that farmers believed that climate change is mainly occurring due to anthropogenic activities. Drought, insects, crop diseases, and heat stress were their main concerns regarding adverse impacts of climate change. Lack of knowledge about adaptation practices, and poor government and financial support are perceived as the major obstacles to adaptation. The results of non-parametric analysis identified no significant differences in farmers’ climate change beliefs and concerns, and their views about obstacles to adaptation in relation to their demographic characteristics. Based on the findings, we suggest that capacity building programs should be undertaken by the government for enhancing the adaptive capacity of the farmers as well the provision of financial incentives wherever deemed necessary for promoting the adoption of sustainable agricultural practices and building a resilient national food system.
Salt stress-induced chloroplastic hydrogen peroxide stimulates pdTPI sulfenylation and methylglyoxal accumulation.

High salinity, an adverse environmental factor affecting about 20% of irrigated arable land worldwide, inhibits plant growth and development by causing oxidative stress, damaging cellular components, and disturbing global metabolism. However, whether and how reactive oxygen species disturb the metabolism of salt-stressed plants remain elusive. Here, we report that salt-induced hydrogen peroxide (H2O2) inhibits the activity of plastid triose phosphate isomerase (pdTPI) to promote methylglyoxal (MG) accumulation and stimulates the sulfenylation of pdTPI at cysteine 74. We also show that MG is a key factor limiting plant growth, as a decrease in MG levels completely rescued the stunted growth and repressed salt stress tolerance of the pdtpi mutant. Furthermore, targeting CATALASE 2 (CAT2) into chloroplasts to prevent salt-induced overaccumulation of H2O2 conferred salt stress tolerance, revealing a role for chloroplastic H2O2 in salt-caused plant damage. In addition, we demonstrate that the H2O2-mediated accumulation of MG in turn induces H2O2 production, thus forming a regulatory loop that further inhibits pdTPI activity in salt-stressed plants. Our findings therefore illustrate how salt stress induces MG production to inhibit plant growth.
Emerging order of anomalous eye movements with progressive drowsiness

It has been widely recognized that human alertness is reflected in the eyes (e.g., when drowsiness, miosis, slow saccades, divergence, less compensatory vestibulo-ocular reflex, and less-accurate optokinetic response and smooth pursuit emerge). Previous studies that discovered these pupil/oculomotor anomalous behaviors along with lowering alertness evaluated only one or a few of them simultaneously, thus their emergence order is yet unknown. Presently, we focused on the following five pupil/oculomotor behaviors that can be evaluated under a natural stationary environment without giving external sensory stimulations: saccades, slow-phase eye movements, vergence, pupil diameter, and blinks. We demonstrate that their anomalous behaviors emerge in the following order: first: frequent saccades; second: slow saccades; third: divergence & miosis, then slow eye movement, while elongated eyelid closure duration emerges randomly in this sequence. These results provide a basis for the oculo-pupillometry–enabling objective monitoring of progressive drowsiness.
DNA polymorphisms associated with lactase persistence, self‐perceived symptoms of lactose intolerance, milk and dairy consumption, and ancestry, in the Uruguayan population

Uruguay has one of the highest per capita milk intakes worldwide, even with a limited supply of lactose‐free products; furthermore, the admixed nature of its population is well known, and various frequencies of lactase persistence (LP) are observed in the source populations. We aimed to contribute to the understanding of the relation between allelic variants associated with LP, milk consumption, digestive symptoms, and genetic ancestry in the Uruguayan population. Samples of saliva or peripheral blood were collected from 190 unrelated individuals from two regions of Uruguay, genotypes for polymorphic sites in a fragment within the LCT enhancer were determined and allelic frequencies calculated in all of them. Data were collected on frequency of milk and dairy consumption and self‐reported symptoms in a subsample of 153 individuals. Biparental and maternal ancestry was determined by analyzing individual ancestry markers and mitochondrial DNA. Twenty‐nine percentage of individuals reported symptoms attributed to the ingestion of fresh milk, with abdominal pain, bloating and flatulence being the most frequent. European LP‐associated allele T‐13910 showed a frequency of 33%, while other LP‐associated alleles like G‐13915 and T‐14011 were observed in very low frequencies. Associations between self‐reported symptoms, fresh milk intake, and C/T‐13910 genotype were statistically significant. No evidence of association between genetic ancestry and C/T‐13910 was found, although individuals carrying one T‐13910 allele appeared to have more European ancestry. In conclusion, the main polymorphism capable of predicting lactose intolerance in Uruguayans is C/T‐13910, although more studies are required to unravel the relation between genotype and lactase activity, especially in heterozygotes.
Toward a realistic in silico abdominal phantom for QSM

QSM outside the brain has recently gained interest, particularly in the abdominal region. However, the absence of reliable ground truths makes difficult to assess reconstruction algorithms, whose quality is already compromised by additional signal contributions from fat, gases, and different kinds of motion. This work presents a realistic in silico phantom for the development, evaluation and comparison of abdominal QSM reconstruction algorithms.
The need for future research into the assessment and monitoring of eating disorder risk in the context of obesity treatment

Abstract In adolescents and adults, the co‐occurrence of eating disorders and overweight or obesity is continuing to increase, and the prevalence of eating disorders is higher in people with higher weight compared to those with lower weight. People with an eating disorder with higher weight are more likely to present for weight loss than for eating disorder treatment. However, there are no clinical practice guidelines on how to screen, assess, and monitor eating disorder risk in the context of obesity treatment. In this article, we first summarize current challenges and knowledge gaps related to the identification and assessment of eating disorder risk and symptoms in people with higher weight seeking obesity treatment. Specifically, we discuss considerations relating to the validation of current self‐report measures, dietary restraint, body dissatisfaction, binge eating, and how change in eating disorder risk can be measured in this setting. Second, we propose avenues for further research to guide the development and implementation of clinical and research protocols for the identification and assessment of eating disorders in people with higher weight in the context of obesity treatment. Public Significance The number of people with both eating disorders and higher weight is increasing. Currently, there is little guidance for clinicians and researchers about how to identify and monitor risk of eating disorders in people with higher weight. We present limitations of current research and suggest future avenues for research to enhance care for people living with higher weight with eating disorders.
Association of dietary intake with body mass index and glycemic profile among newly diagnosed patients with type 2 diabetes mellitus

Dietary intake plays an important role in determining body mass index (BMI) and glycemic profile in patients with type 2 diabetes mellitus (T2DM). Our aim was to describe habitual dietary intake and its associations with BMI and glycemic profile in a cohort of patients with newly diagnosed T2DM in Sri Lanka.
A Folk Theorem for Stochastic Games

Abstract In many dynamic economic applications, the appropriate game theoretic structure is that of a stochastic game. A folk theorem for such games is presented. The result subsumes a number of results obtained earlier and applies to a wide range of games studied in the economics literature. The result further establishes an underlying unity between stochastic and purely repeated games from the point of view of aspymptotic analysis, even though stochastic games offer a much richer set of deviation possibilities. Journal of Economic Literature Classification Number: C73, D90.
Backscattering from a Gaussian-distributed perfectly conducting rough surface

An analytical approach to the problem of scattering by composite random surfaces is presented. The surface is assumed to be Gaussian so that the surface height can be split (in the mean-square sense) into large ( \zeta_{l} ) and small ( \zeta_{s} ) scale components relative to the electromagnetic wavelength. A first-order perturbation approach developed by Burrows is used wherein the scattering solution for the large-scale structure is perturbed by the small-scale diffraction effects. The scattering from the large-scale structure (the zeroth-order perturbation solution) is treated via geometrical optics since 4k_{0}^{2}\bar{\zeta_{l}^{2}} \gg 1 . The first-order perturbation result comprises a convolution in wavenumber space of the height spectrum, the shadowing function, a polarization dependent factor, the joint density function for the large-scale slopes, and a truncation function which restricts the convolution to the domain corresponding to the small-scale height spectrum. The only "free" parameter is the surface wavenumber separating the large and small height contributions. For a given surface height spectrum, this wavenumber can be determined by a combination of mathematical and physical arguments.
Models versus pathogens: how conserved is the FtsZ in bacteria?

Abstract Combating anti-microbial resistance by developing alternative strategies is the need of the hour. Cell division, particularly FtsZ, is being extensively studied for its potential as an alternative target for anti-bacterial therapy. Bacillus subtilis and Escherichia coli are the two well-studied models for research on FtsZ, the leader protein of the cell division machinery. As representatives of gram-positive and gram-negative bacteria, respectively, these organisms have provided an extensive outlook into the process of cell division in rod-shaped bacteria. However, research on other shapes of bacteria, like cocci and ovococci, lags behind that of model rods. Even though most regions of FtsZ show sequence and structural conservation throughout bacteria, the differences in FtsZ functioning and interacting partners establish several different modes of division in different bacteria. In this review, we compare the features of FtsZ and cell division in the model rods B. subtilis and E. coli and the four pathogens: Staphylococcus aureus, Streptococcus pneumoniae, Mycobacterium tuberculosis, and Pseudomonas aeruginosa. Reviewing several recent articles on these pathogenic bacteria, we have highlighted the functioning of FtsZ, the unique roles of FtsZ-associated proteins, and the cell division processes in them. Further, we provide a detailed look at the anti-FtsZ compounds discovered and their target bacteria, emphasizing the need for elucidation of the anti-FtsZ mechanism of action in different bacteria. Current challenges and opportunities in the ongoing journey of identifying potent anti-FtsZ drugs have also been described.
Multi-Objective Particle Swarm Optimization with Comparison Scheme and New Pareto-Optimal Search Strategy

In the presented article, a novel multi-objective PSO algorithm, RP-MOPSO has been proposed. The algorithm adopts a new comparison scheme for position upgrading. The scheme is simple but effective in improve algorithms convergence speed. A sigma-density strategy of selecting the global best particle for each particle in swarm based on a new solutions density definition is designed. Experimental results on seven functions show that proposed algorithm show better convergence performance than other classical MOP algorithms. Meanwhile the proposed algorithm is more effective in maintaining the diversity of the solutions.
Induction Immunosuppression Does Not Worsen Tumor Recurrence After Liver Transplantation for Hepatocellular Carcinoma

Background. Prior studies are inconsistent regarding the impact of antibody induction therapy on outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). Methods. Adults transplanted with HCC exception priority were identified from February 27, 2002, to March 31, 2019, using the United Network for Organ Sharing database. Time-to-event analyses evaluated the association of antibody induction therapy (none, nondepleting induction [NDI], depleting induction [DI]) with overall post-LT patient survival and HCC recurrence. Separate multivariable models adjusted for tumor characteristics on either last exception or on explant. The interaction of induction and maintenance regimen at LT discharge was investigated. Results. Among 22 535 LTs for HCC, 17 688 (78.48%) received no antibody induction, 2984 (13.24%) NDI, and 1863 (8.27%) DI. Minimal differences in patient and tumor characteristics were noted between induction groups, and there was significant center variability in practices. NDI was associated with improved survival, particularly when combined with a calcineurin inhibitor (CNI) and antimetabolite (hazard ratio [HR] 0.73 versus no induction plus 3-drug therapy in the last exception model [P < 0.001]; HR 0.64 in the explant model [P = 0.011]). The combination of DI with CNI alone was also protective (HR 0.43; P = 0.003). Neither NDI nor DI was associated with tumor recurrence (all P > 0.1). However, increased HCC recurrence was observed with no induction plus CNI monotherapy (HR 1.47, P = 0.019; versus no induction plus 3-drug therapy). Conclusions. In conclusion, induction immunosuppression was not associated with worse post-LT outcomes in patients transplanted with HCC exception priority. An improvement in survival was possibly observed with NDI.
A homozygous truncating ETV4 variant in a Nigerian family with congenital anomalies of the kidney and urinary tract

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most prevalent cause of chronic kidney disease that manifests in children. To date ~23 different monogenic causes have been implicated in isolated forms of human CAKUT, but the vast majority remains elusive. In a previous study, we identified a homozygous missense variant in E26 transformation‐specific (ETS) Variant Transcription Factor 4 (ETV4) causing CAKUT via dysregulation of the transcriptional function of ETV4, and a resulting abrogation of GDNF/RET/ETV4 signaling pathway. This CAKUT family remains the only family with an ETV4 variant reported so far. Here, we describe one additional CAKUT family with a homozygous truncating variant in ETV4 (p.(Lys6*)) that was identified by exome sequencing. The variant was found in an individual with isolated CAKUT displaying posterior urethral valves and renal dysplasia. The newly identified stop variant conceptually truncates the ETS_PEA3_N and ETS domains that regulate DNA‐binding transcription factor activity. The variant has never been reported homozygously in the gnomAD database. To our knowledge, we here report the first CAKUT family with a truncating variant in ETV4, potentially causing the isolated CAKUT phenotype observed in the affected individual.
Extension of the bi‐epitaxial Josephson junction process to various substrates

We report an extension of the bi‐epitaxial Josephson junction process that permits the use of a variety of substrate materials and allows junctions to be placed at any level of a multilayer structure. The new materials, SrTiO3, MgO, and CeO2, serve as a base layer, a seed layer, and a buffer layer, respectively, and replace Al2O3, MgO, and SrTiO3 in the original bi‐epitaxial process. This new process offers much more flexibility in designing a circuit. Bi‐epitaxial junctions made with the new set of materials show much improved electrical properties, especially at 77 K. We attribute the improved electrical characteristics to a better thermal expansion match between the substrate and the thin‐film layers. Important junction properties such as critical currents and junction resistances are compared to other types of grain boundary junctions.
Life Styles and Consumption Patterns

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Renally inappropriate medications in elderly outpatients and inpatients with an impaired renal function

ABSTRACT Background and aims The purpose of this study was to investigate differences in the frequency of renally inappropriate medications (RIMs) in outpatient and inpatient among three institutions. Methods We collected prescription and renal function data for patients over 65 years of age from the drug department system. We selected 50 kinds of the most frequently used medicines which require dose adjustment according to a patient’s renal function. Results Outpatient RIM was seen in 611 cases (6.17%), and inpatient prescription RIM was seen in 317 cases (5.29%), showing a significant difference between the groups (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.02–1.35). However, in a multivariate analysis, when the renal function was included, that difference between outpatients and inpatients became insignificant (OR 1.16, 95% CI 0.98–1.37). The distribution of prescription with or without RIM in outpatient and inpatient settings depended on the CKD stage. Outpatients with a better CKD stage (stage 1–3) had a higher rate of RIM than inpatients, while patients with a worse CKD stage (stage 4 or 5) had a higher rate of RIM than outpatients. Conclusion The rate of RIM in outpatients tends to be high, and attention should be paid to RIM in inpatients with a severe CKD stage.