Miracle-dz/UniFAR-FTUs huggingface dataset:
Machine learning approach to percolation transitions: global information

Recently, a machine learning (ML) approach has been proposed to determine the percolation threshold and critical behaviors of percolation transitions (PTs), based on the ML algorithm used for the phase transition in thermal equilibrium systems. However, we have observed that the conventional ML approach used for thermal systems does not accurately provide the percolation threshold, in particular when the training regions for ML are asymmetrical with respect to its known value. Here, we remark that percolation is a geometric phase transition, and thus global information, rather than the local configurations used in thermal systems, is needed to determine the percolation threshold. To address this, we assign a parent node index to each node, which is updated during cluster merging, capturing global information on the ancestor of each node. Utilizing this quantity as input data for the convolutional neural network in the ML algorithm, we successfully obtain the correct percolation threshold regardless of whether the training regions are symmetric or asymmetric with respect to the known value. This validity holds independently of the PT type: continuous, hybrid, or discontinuous. As the concept of percolation is applied to various phenomena, this ML algorithm could be used ubiquitously.
In Vivo Stem Cell Imaging Principles and Applications

Stem cells are the foundational cells for every organ and tissue in our body. Cell-based therapeutics using stem cells in regenerative medicine have received attracting attention as a possible treatment for various diseases caused by congenital defects. Stem cells such as induced pluripotent stem cells (iPSCs) as well as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), and neuroprogenitors stem cells (NSCs) have recently been studied in various ways as a cell-based therapeutic agent. When various stem cells are transplanted into a living body, they can differentiate and perform complex functions. For stem cell transplantation, it is essential to determine the suitability of the stem cell-based treatment by evaluating the origin of stem, the route of administration, in vivo bio-distribution, transplanted cell survival, function, and mobility. Currently, these various stem cells are being imaged in vivo through various molecular imaging methods. Various imaging modalities such as optical imaging, magnetic resonance imaging (MRI), ultrasound (US), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) have been introduced for the application of various stem cell imaging. In this review, we discuss the principles and recent advances of in vivo molecular imaging for application of stem cell research.
Language of silence : an ethnographic case study of the expressive language skills of preschool Native American girls

The purpose of this descriptive case study was to describe the expressive language characteristics of the preschool Native American girl. Additionally, the study investigated whether (a) these characteristics are specific to this population as compared to the Anglo children in the Head Start program, (b) these characteristics are gender specific, and (c) these characteristics handicap the preschool Native American girl when she enters a formal education program. The study was conducted in the Head Start programs in Great Falls, Montana, and Havre, Montana. An ethnographic case study method was combined with quantitative test scores. Data were gathered through observation and interview as well as through analysis of test scores. The Expressive One-Word Picture Vocabulary Test was administered to 179 children at the two sites. The research was developed and carried out during the fall and winter of 1991-1992. There were 51 Native American children in the study with 21 being female Native Americans. The findings revealed that there are distinct language patterns of female Native American speakers. The observations indicated that Native American girls speak less than the other groups of children. The interviews revealed that the Native American mothers described their daughters as "shy. " The test scores showed a significant difference between the scores of Native American students and Anglo students, between Native American girls and Anglo boys, and, most significantly, between Native American girls and Anglo girls. LANGUAGE OF SILENCE: AN ETHNOGRAPHIC CASE STUDY OF THE EXPRESSIVE LANGUAGE SKILLS OF PRESCHOOL NATIVE AMERICAN GIRLS by Arlene Marie Hett A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Education MONTANA STATE UNIVERSITY Bozeman, Montana April, 1992
Latent evolutionary potentials under the neutral mutational drift of an enzyme

Biological systems exhibit mutational robustness, or neutrality, whereby the impact of mutations is minimized. Does neutrality hamper their ability to adapt in the face of changing environments? We monitored changes in genotype and phenotype that occur within a neutral mutational network of an enzyme, experimentally and computationally (see accompanying article). Using the enzyme PON1 as a model, we performed random mutagenesis and purifying selection to purge deleterious mutations. We characterized ∼300 variants that are apparently neutral, or close to neutral, with respect to PON1's levels of expression and native lactonase activity. Their activities with promiscuous substrates and ligands indicated significant changes in adaptive potentials. Almost half of the variants exhibited changes in promiscuous activities, specificities, or inhibition, and several of these were found to be one or two mutations, closer to potentially new phenotypes: aryl esterase, thiolactonase, phosphotriesterase, or drug resistance. This empirical measure of phenotypic changes under neutrality supports the notion that sequence changes that are neutral, i.e., non‐adaptive, in a current context can facilitate adaptation under changing circumstances, by both expanding the activity range of existing enzymes and thus providing an immediate advantage, and by reducing the number of mutations required for divergence of new functions.
A Japanese patient with Teebi hypertelorism syndrome and a novel CDH11 EC1 domain variant

The gene CDH11 encodes cadherin‐11, a Type II cadherin superfamily member that contains five extracellular cadherin (EC) domains. Cadherin‐11 undergoes trans‐dimerization via the EC1 domain to generate cadherin complexes. Compound heterozygous and homozygous loss‐of‐function CDH11 variants are observed in Elsahy–Waters syndrome (EWS), which shows characteristic craniofacial features, vertebral abnormalities, cutaneous syndactyly in 2–3 digits, genitourinary anomalies, and intellectual disability. Heterozygous CDH11 variants can cause Teebi hypertelorism syndrome (THS), which features widely spaced eyes and hypospadias. We report a THS patient with a novel CDH11 variant involving the EC1 domain. The patient was a 10‐month‐old male with normal developmental milestones, but had widely spaced eyes, strabismus, hypospadias, shawl scrotum, broad thumbs (right bifid thumb in x‐ray), polysyndactyly of the left fourth finger, and cutaneous syndactyly of left third/fourth fingers. Exome sequencing identified a de novo heterozygous CDH11 variant (NM_001797.4:c.229C > T [p.Leu77Phe] NC_000016.9:g.64998856G > A). Clinical features were consistent with previously reported THS patients, but polysyndactyly, broad thumb, and cutaneous syndactyly overlapped phenotypic features of EWS. THS and EWS may represent a spectrum of CDH11‐related disorders. Residue Leu77 in this novel CDH11 variant lines a large hydrophobic pocket where side chains of the partner cadherin‐11 insert to trans‐dimerize, suggesting that the cadherin‐11 structure might be altered in this variant.
Risk management actions following genetic testing in the Cancer Health Assessments Reaching Many (CHARM) Study: A prospective cohort study

Genetic testing can identify cancer risk early, enabling prevention and early detection. We describe use of risk management interventions following genetic testing in the Cancer Health Assessment Reaching Many (CHARM) study. CHARM assessed risk and provided genetic testing to low income, low literacy, and other underserved populations that historically face barriers to accessing cancer genetic services.
Factors associated with sharing email information and mental health survey participation in large population cohorts

People who opt to participate in scientific studies tend to be healthier, wealthier, and more educated than the broader population. While selection bias does not always pose a problem for analysing the relationships between exposures and diseases or other outcomes, it can lead to biased effect size estimates. Biased estimates may weaken the utility of genetic findings because the goal is often to make inferences in a new sample (such as in polygenic risk score analysis). We used data from UK Biobank and Generation Scotland and conducted phenotypic and genome-wide association analyses on two phenotypes that reflected mental health data availability: (1) whether participants were contactable by email for follow-up) and (2) whether participants responded to a follow-up surveys of mental health. We identified nine genetic loci associated with email contact and 25 loci associated with mental health survey completion. Both phenotypes were positively genetically correlated with higher educational attainment and better health and negatively genetically correlated with psychological distress and schizophrenia. Recontact availability and follow-up participation can act as further genetic filters for data on mental health phenotypes.
Adverse Childhood Experiences and Alcohol Use among Black College Students: Examining the Mediating Roles of Depression and Coping Drinking Motives

Abstract Background: Over the past two decades, research has linked adverse childhood experiences (ACEs) to adult health-risk behaviors such as excessive alcohol use. Yet, few have investigated health-risk behaviors among Black college students. Research suggests that Black college students are at lower risk for hazardous drinking patterns, yet ACEs appear to alter the drinking patterns of Black students. Other studies have also shown depressive symptoms and coping-motivated drinking to predict greater alcohol consumption for this ethnic group. Objective: The current study investigated the relationship between ACEs and hazardous patterns of drinking, including frequency of alcohol use, binge, and heavy drinking episodes, using a sample of 282 Black students attending a historically black college/university (HBCU). Results: Depressive symptoms and coping drinking motives were tested as serial mediators between ACEs and the three drinking patterns. Results revealed a significant indirect effect of ACEs on the frequency of alcohol use, binge, and heavy drinking episodes, through depressive symptoms and coping drinking motives. Depressive symptoms also independently mediated the relationship between ACEs and heavy drinking episodes. Conclusion: The finding suggested that drinking perhaps serves as a maladaptive coping strategy to address underlying early life stress and depression for Black students.
Analysis of secondary failure time responses in studies with response‐dependent sampling schemes

Response‐dependent sampling is routinely used as an enrichment strategy in the design of family studies investigating the heritable nature of disease. In addition to the response of primary interest, investigators often wish to investigate the association between biomarkers and secondary responses related to possible comorbidities. Statistical analysis regarding genetic biomarkers and their association with the secondary outcome must address the biased sampling scheme involving the primary response. In this article, we develop composite likelihoods and two‐stage estimation procedures for such secondary analyses in which the within‐family dependence structure for the primary and secondary outcomes is modeled via a Gaussian copula. The dependence among responses within family members is modeled based on kinship coefficients. Auxiliary data from independent individuals are exploited by augmenting the composite likelihoods to increase precision of marginal parameter estimates and enhance the efficiency of estimators of the dependence parameters. Simulation studies are carried out to evaluate the finite sample performance of the proposed method, and an application to a motivating family study in psoriatic arthritis is given for illustration.
Iron‐responsive element of Divalent metal transporter 1 (Dmt1) controls Notch‐mediated cell fates

Notch receptor activation is regulated by the intramembrane protease γ‐secretase, which cleaves and liberates the Notch intracellular domain (Nicd) that regulates gene transcription. While γ‐secretase cleavage is necessary, we demonstrate it is insufficient for Notch activation and requires vesicular trafficking. Here, we report Divalent metal transporter 1 (Dmt1, Slc11A2) as a novel and essential regulator of Notch signalling. Dmt1‐deficient cells are defective in Notch signalling and have perturbed endolysosomal trafficking and function. Dmt1 encodes for two isoforms, with and without an iron response element (ire). We show that isoform‐specific silencing of Dmt1‐ire and Dmt1+ire has opposite consequences on Notch‐dependent cell fates in cell lines and intestinal organoids. Loss of Dmt1‐ire suppresses Notch activation and promotes differentiation, whereas loss of Dmt1+ire causes Notch activation and maintains stem‐progenitor cell fates. Dmt1 isoform expression correlates with Notch and Wnt signalling in Apc‐deficient intestinal organoids and human colorectal cancers. Consistently, Dmt1‐ire silencing induces Notch‐dependent differentiation in colorectal cancer cells. These data identify Dmt1 isoforms as binary switches controlling Notch cell fate decisions in normal and tumour cells.
Emery–Dreifuss muscular dystrophy Type 1 is associated with a high risk of malignant ventricular arrhythmias and end-stage heart failure

Abstract Background and Aims Emery–Dreifuss muscular dystrophy (EDMD) is caused by variants in EMD (EDMD1) and LMNA (EDMD2). Cardiac conduction defects and atrial arrhythmia are common to both, but LMNA variants also cause end-stage heart failure (ESHF) and malignant ventricular arrhythmia (MVA). This study aimed to better characterize the cardiac complications of EMD variants. Methods Consecutively referred EMD variant-carriers were retrospectively recruited from 12 international cardiomyopathy units. MVA and ESHF incidences in male and female variant-carriers were determined. Male EMD variant-carriers with a cardiac phenotype at baseline (EMDCARDIAC) were compared with consecutively recruited male LMNA variant-carriers with a cardiac phenotype at baseline (LMNACARDIAC). Results Longitudinal follow-up data were available for 38 male and 21 female EMD variant-carriers [mean (SD) ages 33.4 (13.3) and 43.3 (16.8) years, respectively]. Nine (23.7%) males developed MVA and five (13.2%) developed ESHF during a median (inter-quartile range) follow-up of 65.0 (24.3–109.5) months. No female EMD variant-carrier had MVA or ESHF, but nine (42.8%) developed a cardiac phenotype at a median (inter-quartile range) age of 58.6 (53.2–60.4) years. Incidence rates for MVA were similar for EMDCARDIAC and LMNACARDIAC (4.8 and 6.6 per 100 person-years, respectively; log-rank P = .49). Incidence rates for ESHF were 2.4 and 5.9 per 100 person-years for EMDCARDIAC and LMNACARDIAC, respectively (log-rank P = .09). Conclusions Male EMD variant-carriers have a risk of progressive heart failure and ventricular arrhythmias similar to that of male LMNA variant-carriers. Early implantable cardioverter defibrillator implantation and heart failure drug therapy should be considered in male EMD variant-carriers with cardiac disease.
Effectiveness of ultraviolet-C disinfection systems for reduction of multi-drug resistant organism infections in healthcare settings: A systematic review and meta-analysis

Abstract This study aimed to summarise the findings of the studies assessing the effectiveness of ultraviolet C (UV-C) room disinfection in reducing the incidence rate of healthcare-associated multi-drug-resistant organism (MDRO) infections. A systematic screening was conducted using PubMed, EMBASE, and Scopus for randomised controlled trials (RCTs), quasi-experimental studies, and before–after studies, which assessed the efficacy of the UV-C disinfectant system in reducing the incidence of MDRO infections. A random-effects model was used for the analysis. Effect sizes were described as incidence rate ratio (IRR) with 95% confidence intervals (CI). Nine studies were included, all of which were conducted in the USA. No statistically significant reduction in Clostridioides difficile (CD) (IRR: 0.90, 95% CI; 0.62–1.32) and vancomycin-resistant enterococcal (VRE) infection rates (IRR 0.72, 95% CI; 0.38–1.37) was observed with the use of UV-C, but the risk of Gram-negative rod infection was reduced (IRR 0.82, 95% CI; 0.68–0.99).
Clustering of systemic lupus erythematosus mortality in southwestern Spain

Objective To analyse time trends in systemic lupus erythematosus (SLE) mortality and explore possible provincial clustering of SLE mortality in Spain (2001–2020). Methods We conducted an ecological study using deaths registered in SLE at the Spanish National Institute of Statistics between 2001 and 2020. Jointpoint regression models have been used to evaluate temporal trends. To analyse the spatial pattern of SLE mortality in men and women in Spain, crude rates, age-standardised mortality rates (ASMRs), smooth relative risk (RR) and posterior probabilities (PP) for RR greater than one for the period 2001–2020 were calculated. The Global Moran I index was used to assess the existence of global spatial autocorrelation. Local indicators of spatial association (LISA) and Kulldorff’s spatial scan statistic were used to identify clusters. Results Over the 20 years analyzed in this study, the SLE average ASMR for the period was 2.7 for women and 0.7 for men, with a sex ratio (female/male) of 3.8. In men, no province showed a RR>1. Conversely, in women, eight provinces showed values of RR> 1 with a PP greater than 0.8 (Seville, Cadiz, Huelva and Murcia in the south, Barcelona, Zaragoza, Huesca and Leon in the north). In men, neither of the two methods detected a clustering of provinces. However, in women, both methods identified a cluster of provinces located in the southwest of the country (Huelva, Cádiz, Seville and Malaga) as a cluster with significant excess mortality. In the second cluster (centred on the province of Huelva) obtained with the Kulldorff method, two more provinces were added (Badajoz and Cordoba, also located in the southwest). Conclusions We detected a cluster of provinces with an excess risk of female SLE mortality in the southwest of Spain.
Vomeronasal receptors: from monogenic expression to axon guidance

Le systeme olfactif fait face a un devoir remarquable: extraire une information coherente d'un monde qu'il n'a jamais rencontre. Les outils moleculaires lui permettant d'effectuer cette tâche sont representes par differents types de chimiorecepteurs, qui sont exprimes par des neurones sensoriels localises dans le nez. Ceux-ci sont codes par de tres grandes familles de genes, et incluent les recepteurs a odeurs (plus de 1000 genes chez la souris), les recepteurs TAAR, V1R et V2R, et les recepteurs a formyl peptide. Les deux premieres familles sont exprimees dans le systeme olfactif majeur, alors que les trois dernieres sont transcrites dans l'organe vomeronasal.
A cost‐effectiveness analysis of avelumab plus best supportive care versus best supportive care alone as first‐line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma in Taiwan

Patients with locally advanced or metastatic urothelial carcinoma have limited treatment options and a poor prognosis. The JAVELIN Bladder 100 trial showed that avelumab as first‐line maintenance plus best supportive care significantly prolonged overall survival and progression‐free survival versus best supportive care alone in patients with locally advanced or metastatic urothelial carcinoma that had not progressed with first‐line platinum‐containing chemotherapy.
Molecular binding of different classes of organophosphates to methyl parathion hydrolase from Ochrobactrum species

Methyl parathion hydrolase (MPH) is an enzyme of the metallo‐β‐lactamase superfamily, which hydrolyses a wide range of organophosphates (OPs). Recently, MPH has attracted attention as a promising enzymatic bioremediator. The crystal structure of MPH enzyme shows a dimeric form, with each subunit containing a binuclear metal ion center. MPH also demonstrates metal ion‐dependent selectivity patterns. The origins of these patterns remain unclear but are linked to open questions about the more general role of metal ions in functional evolution and divergence within enzyme superfamilies. We aimed to investigate and compare the binding of different OP pesticides to MPH with cobalt(II) metal ions. In this study, MPH was modeled from Ochrobactrum sp. with different OP pesticides bound, including methyl paraoxon and dichlorvos and profenofos. The docked structures for each substrate optimized by DFT calculation were selected and subjected to atomistic molecular dynamics simulations for 500 ns. It was found that alpha metal ions did not coordinate with all the pesticides. Rather, the pesticides coordinated with less buried beta metal ions. It was also observed that the coordination of beta metal ions was perturbed to accommodate the pesticides. The binding free energy calculations and structure‐based pharmacophore model revealed that all the three substrates could bind well at the active site. However, profenofos exhibit a stronger binding affinity to MPH in comparison to the other two substrates. Therefore, our findings provide molecular insight on the binding of different OP pesticides which could help us design the enzyme for OP pesticides degradation.
Changes in plasma alpha‐1 acid glycoprotein following hemorrhagic trauma: Possible role in dose differences of ALM drug therapy in rat and pig resuscitation

The binding of drugs to plasma proteins is an important consideration in drug development. We have reported that the dose of adenosine, lidocaine, and magnesium (ALM) fluid therapy for resuscitation from hemorrhagic shock is nearly 3‐times higher for pigs than rats. Since lidocaine strongly binds to serum alpha‐1‐acid glycoprotein (AGP), the aim of the study was to investigate the effect of hemorrhagic shock on levels of AGP in rats and pigs.
Changes in self‐reported suicidal ideation during treatment with electroconvulsive therapy: A retrospective cohort study

Suicidal ideation (SI) is common in patients with depressive symptoms, who are the most common recipients of electroconvulsive therapy (ECT). We sought to quantify changes in self‐reported SI occurring during treatment with ECT, and to identify factors associated with persistence of SI in patients beginning treatment with SI.
Resource Discovery in Ad hoc Networks

Much of the current research in mobile networking investigates how to support a mobile user within an established infrastructure of routers and servers. Ad hoc networks come into play when no such established infrastructure exits. This paper presents a two-stage protocol to solve the resource discovery problem in ad hoc networks: how hosts discover what resources are available in the network and how they discover how to use the resources. This protocol does not require any established servers or other infrastructure. It only requires routing capabilities in the network.