Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovering novel subsystems using comparative genomics

MOTIVATION Key problems for computational genomics include discovering novel pathways in genome data, and discovering functional interaction partners for genes to define new members of partially elucidated pathways. RESULTS We propose a novel method for the discovery of subsystems from annotated genomes. For each gene pair, a score measuring the likelihood that the two genes belong to a same subsystem is computed using genome context methods. Genes are then grouped based on these scores, and the resulting groups are filtered to keep only high-confidence groups. Since the method is based on genome context analysis, it relies solely on structural annotation of the genomes. The method can be used to discover new pathways, find missing genes from a known pathway, find new protein complexes or other kinds of functional groups and assign function to genes. We tested the accuracy of our method in Escherichia coli K-12. In one configuration of the system, we find that 31.6% of the candidate groups generated by our method match a known pathway or protein complex closely, and that we rediscover 31.2% of all known pathways and protein complexes of at least 4 genes. We believe that a significant proportion of the candidates that do not match any known group in E.coli K-12 corresponds to novel subsystems that may represent promising leads for future laboratory research. We discuss in-depth examples of these findings. AVAILABILITY Predicted subsystems are available at http://brg.ai.sri.com/pwy-discovery/journal.html. CONTACT lferrer@ai.sri.com SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Idea Generation and the Quality of the Best Idea

In a wide variety of settings, organizations generate a number of possible solutions to a problem---ideas---and then select a few for further development. We examine the effectiveness of two group structures for such tasks---the team structure, in which the group works together in time and space, and the hybrid structure, in which individuals first work independently and then work together. We define the performance of a group as the quality of the best ideas identified. Prior research has defined performance as the average quality of ideas or the number of ideas generated, ignoring what most organizations seek, a few great ideas. We build a theory that relates organizational phenomena to four different variables that govern the quality of the best ideas identified: (1) the average quality of ideas generated, (2) the number of ideas generated, (3) the variance in the quality of ideas generated, and (4) the ability of the group to discern the quality of the ideas. We test this theory with an experiment. We find that groups organized in the hybrid structure are able to generate more ideas, to generate better ideas, and to better discern the quality of the ideas they generate. Moreover, we find that the frequently recommended brainstorming technique of building on others' ideas is counterproductive; teams exhibiting such buildup neither create more ideas, nor are the ideas that build on previous ideas better.
Predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy.

OBJECTIVES Our objective was to evaluate in our clinic the perinatal outcomes of patients diagnosed with ICP based on pre-treatment maternal serum bile acid levels, attempt to identify the risk group and review the literature in light of this information. MATERIAL AND METHODS In total, 370 patients diagnosed with ICP were included in the study, divided into two groups based on the fasting total serum bile acid level before UDCA (Group 1: 10 ≥ 40 μmol/L, and Group 2: ≥ 40 μmol/L). The groups were examined for clinical characteristics and pregnancy outcomes. RESULTS It was found that preterm delivery and neonatal intensive care need increased at a serum bile acid cut-off value of 34 μmol/L. Regardless of serum bile acid, significantly higher rates of meconium-stained amniotic fluid and foetal distress were observed in patients whose diagnoses were made before 34 weeks of gestation. CONCLUSIONS Foetal complications over 40 μmol/L of serum bile acid were significantly increased. However, slightly lower levels cut-off values (34 μmol/L) were obtained in terms of preterm birth and neonatal intensive care need. The incidence of meconium-stained amniotic fluid and foetal distress was higher in patients whose diagnosis were made before 34 weeks of gestation.
Screening of underlying genetic biomarkers for ankylosing spondylitis

Genetic biomarkers for the diagnosis of ankylosing spondylitis (AS) remain unreported except for human leukocyte antigen B27 (HLA-B27). Therefore, the aim of the present study was to screen the differentially expressed genes (DEGs), and those that also possess differential single nucleotide polymorphism (SNP) loci in the whole blood of AS patients compared with healthy controls by integrating two mRNA expression profiles (GSE73754 and GSE25101) and SNP microarray data (GSE39428) collected from the Gene Expression Omnibus (GEO). Using the t-test, 1,056 and 1,073 DEGs were identified in the GSE73754 and GSE25101 datasets, respectively. Among them, 234 DEGs were found to be shared in both datasets, which were subsequently overlapped with 122 differential SNPs of genes in the GSE39428 dataset, resulting in identification of two common genes [eukaryotic translation elongation factor 1 epsilon 1 (EEF1E1) and serpin family A member 1 (SERPINA1)]. Their expression levels were significantly upregulated and the average expression log R ratios of SNP sites in these genes were significantly higher in AS patients than those in controls. Function enrichment analysis revealed that EEF1E1 was involved in AS by influencing the aminoacyl-tRNA biosynthesis, while SERPINA1 may be associated with AS by participating in platelet degranulation. However, only the genotype and allele frequencies of SNPs (rs7763907 and rs7751386) in EEF1E1 between AS and controls were significantly different between AS and the controls, but not SERPINA1. These findings suggest that EEF1E1 may be an underlying genetic biomarker for the diagnosis of AS.
Birth, School, Work, Death, and Resurrection: The Life Stages and Dynamics of Transposable Element Proliferation

Transposable elements (TEs) can be maintained in sexually reproducing species even if they are harmful. However, the evolutionary strategies that TEs employ during proliferation can modulate their impact. In this review, I outline the different life stages of a TE lineage, from birth to proliferation to extinction. Through their interactions with the host, TEs can exploit diverse strategies that range from long-term coexistence to recurrent movement across species boundaries by horizontal transfer. TEs can also engage in a poorly understood phenomenon of TE resurrection, where TE lineages can apparently go extinct, only to proliferate again. By determining how this is possible, we may obtain new insights into the evolutionary dynamics of TEs and how they shape the genomes of their hosts.
Critical success factors for ERP implementation in a Fortis hospital: an empirical investigation

Purpose – The purpose of this paper is to examine the success of enterprise resource planning (ERP) implementation based on five identified items, i.e. top management commitment (TMC), user involvement (UI), business process reengineering (BPR), project management (PM) and ERP teamwork and composition (TWC) factors at Fortis hospital, Bangalore, India. It also tests a number of hypotheses and examines the hypothetical relationships among critical success items and success of ERP implementation. Design/methodology/approach – Empirical data were collected via a survey questionnaire/interview technique. A structured interview was planned and conducted with key executives of Fortis hospital who were familiar with success of ERP implementation progress as well as examination of company documentation supported by literature. Findings – A significant relationship was found between TMC, UI, BPR, PM and ERP TWC with success of ERP implementation at Fortis hospital. Originality/value – The value of this paper is th.
Group Treatment of Fecal Incontinence: A Description of an Interdisciplinary Intervention.

INTRODUCTION Approximately 5% of children in the United States have chronic fecal incontinence. Unfortunately, standard medical management of fecal incontinence fails in 20-60% of cases. A combined medical-behavioral model is often recommended in these cases. The purpose of this pilot study was to describe an interdisciplinary group-based treatment for fecal incontinence in school-aged children, and to present a description of changes in treatment adherence rates that impact clinical effectiveness. METHOD Poop Group employed a developmentally appropriate model of care in which caregivers and children participated in separate but simultaneously held therapy groups. This interdisciplinary 6-week protocol is designed to increase appropriate stooling, decrease soiling events, and increase medication adherence pre- to post-treatment. Group sessions focus on (1) the GI system, (2) medication, (3) toilet sitting posture, (4) hydration, (5) fiber, and (6) behavior contracts. In addition, participant families consult with an Advanced Nurse Practitioner privately at each session discussing symptoms and making medication modifications as needed. RESULTS Nineteen families completed the 6-week protocol. Appropriate stool frequency was improved (p ≤ 0.01), and soiling was reduced (p ≤ .00). Medication adherence was also improved (p ≤ 0.04). Treatment results were maintained at one-month follow-up. DISCUSSION Poop Group may be an effective interdisciplinary treatment option for families of children who fail traditional outpatient treatment. The developmentally targeted interventions and the interdisciplinary focus of treatment likely account for treatment successes.
Analysis of the physical development of youth and the state of its health.

OBJECTIVE Introduction: The sharp deterioration in the physical development of the younger generation is worrying. The morbidity of youth has increased by 29.9% compared with the last century. More than 33% of boys and girls, among first-year students with chronic diseases. The aim: Assessing the state of the students' body by examining the results of a survey among the second- and third-year students of the university using a specially designed questionnaire. PATIENTS AND METHODS Materials and methods: The material on the assessment of the state of health and the characteristics of the organism has been processed by studying the results of a survey of young men and women aged 20-23, obtained on the basis of using the developed questionnaire. RESULTS Results: Physical development has been studied in accordance with the state of health of the students, as well as a thorough study of a number of criteria: diseases of the musculoskeletal system were 37.1%, 49.7% and 43.45 among boys aged 20, 22 and 23 and respectively 33.3 %, 38.6% and 47.7% among girls in their 20s, 22s and 23s. The morbidity of eye was 18.0%, 3.8% and 9.9% among boys aged 20, 22 and 23 years and 17.7%, 17.1% and 7.7% among girls aged 20, 22 and 23 years. CONCLUSION Conclusions: In the structure of morbidities are diseases of the musculoskeletal system, diseases of the nervous system and the organ of vision. Correlation of the characteristics of the level of students' health and their physical development have indicators on the level of educational adaptation and the number of diseases.
Additive and Interactive Effects of Victimization on Adolescent Aggression Across Social Settings

Considering that children and adolescents can face multiple exposures to violence due to their involvement in different socialization domains, this study aimed to analyze additive and interactive effects of physical and verbal victimization by parents, peers, and schoolteachers on adolescent aggression across social settings. With regard to parent–child and teacher–adolescent relationships, physical and verbal forms of aggression were differentiated, whereas aggression by and toward peers was assessed by a composite measure of overt and indirect aggression. Data were drawn from three large secondary school surveys of ninth-grade students within one federal German state conducted in the years 2013, 2015, and 2017. Based on a sample of 8,458 adolescents (mean age = 14.9 years), results provided evidence for additive as well as interactive effects of victimization across settings. Controlling for a range of risk factors associated with victimization and aggression, victimization by parents, peers, and teachers was uniquely related to adolescent aggression across social settings. In addition, three significant interaction effects were identified between different combinations of victimization: Students exposed to earlier parent-to-child physical aggression perpetrated more physical aggression toward parents within the last 12 months if they were also recently victimized by peers. Furthermore, parent-to-child physical aggression exacerbated the positive relationship between teacher-to-adolescent physical aggression and adolescent-to-teacher physical aggression. In contrast, exposure to teacher-to-adolescent verbal aggression reduced the positive link between peer-to-adolescent aggression and aggression toward peers. Findings suggest that intervention should be particularly sensitive toward multiple exposure to violence across socialization contexts, as well as toward the interdependence of cross-setting victimization.
Saccharomyces cerevisiae Cdc42p GTPase Is Involved in Preventing the Recurrence of Bud Emergence during the Cell Cycle

ABSTRACT The Saccharomyces cerevisiae Cdc42p GTPase interacts with multiple regulators and downstream effectors through an ∼25-amino-acid effector domain. Four effector domain mutations, Y32K, F37A, D38E, and Y40C, were introduced into Cdc42p and characterized for their effects on these interactions. Each mutant protein showed differential interactions with a number of downstream effectors and regulators and various levels of functionality. Specifically, Cdc42D38Ep showed reduced interactions with the Cla4p p21-activated protein kinase and the Bem3p GTPase-activating protein and cdc42D38E was the only mutant allele able to complement the Δcdc42 null mutant. However, the mutant protein was only partially functional, as indicated by a temperature-dependent multibudded phenotype seen in conjunction with defects in both septin ring localization and activation of the Swe1p-dependent morphogenetic checkpoint. Further analysis of this mutant suggested that the multiple buds emerged consecutively with a premature termination of bud enlargement preceding the appearance of the next bud. Cortical actin, the septin ring, Cla4p-green fluorescent protein (GFP), and GFP-Cdc24p all predominantly localized to one bud at a time per multibudded cell. These data suggest that Cdc42D38Ep triggers a morphogenetic defect post-bud emergence, leading to cessation of bud growth and reorganization of the budding machinery to another random budding site, indicating that Cdc42p is involved in prevention of the initiation of supernumerary buds during the cell cycle.
Alternations between physical and cognitive tasks in repetitive work – effect of cognitive task difficulty on fatigue development in women

Abstract In a context of job rotation, this study determined the extent to which the difficulty of a cognitive task (CT) interspersed between bouts of repetitive, low-intensity work (pipetting) influences recovery from fatigue. Fifteen participants performed three experimental sessions, each comprising 10 repeats of a 7 min + 3 min combination of pipetting and CT. The CT was easy, moderate or hard. Surface electromyography (EMG amplitude of the forearm extensor and trapezius muscles) and self-reports was used to assess fatigability. Perceived fatigue and trapezius EMG amplitude increased during sessions. CT difficulty influenced fatigue development only little, besides forearm extensor EMG increasing more in CT3 than in CT1 and CT2. During CT bouts, fatigability recovered, and to a similar extent irrespective of CT. Thus, CT difficulty influenced recovery of perceived as well as performance fatigability to a minor extent, and may not be a critical issue in job rotation comprising alternating physical and cognitive tasks. Practitioner summary: Alternations between physical and cognitive tasks may be an attractive option for job rotation. In this study on women, we show that the difficulty of the cognitive task influences recovery from fatigue only little and we conclude that cognitive difficulty, within reasonable limits, may be a minor issue in job rotation.
Engagement in care among youth living with parenterally-acquired HIV infection in Romania

ABSTRACT Transition from adolescent to adult care can be challenging for youth living with HIV. We conducted a cohort study of youth born between 1985 and 1993 and infected with HIV parenterally, followed by the same medical team from age 15 years or first clinic visit until age 25 years or 30 November 2016. A longitudinal continuum-of-care was constructed, categorizing individuals’ status for each month of follow-up as: engaged in care (EIC); not in care (NIC: no clinic visits within past year); lost-to-follow-up (LTFU: NIC and did not return to clinic); or died. Five hundred and forty-five individuals (52% male) were followed for 4775 person-years. At age 15, 92% were EIC, decreasing to 84% at age 20 and 74% at age 25. Of those EIC, HIV outcomes improved with age: 79% and 52% had a CD4 ≥200 cells/µl and VL <400 cps/ml at age 15; increasing to 86% and 73% at age 20 and 87% and 80% at age 25. We conclude that youth infected during early childhood tended to disengage from care, even when followed by the same medical team for a lengthy period of time. For those that did engage in care, HIV-related outcomes improved from adolescence through adulthood.
Incidence and human papillomavirus (HPV) type distribution of genital warts in a multinational cohort of men: the HPV in men study.

BACKGROUND Data on the natural history of human papillomavirus (HPV)-related genital warts (GWs) in men are sparse. We described the distribution of HPV types in incident GWs and estimated GW incidence and time from type-specific incident HPV infections to GW detection in a multinational cohort of men aged 18-70 years. METHODS Participants included 2487 men examined for GWs and tested for HPV every 6 months and followed up for a median of 17.9 months. Samples were taken from 112 men with incident GWs to test for HPV DNA by polymerase chain reaction. RESULTS Incidence of GWs was 2.35 cases per 1000 person-years, with highest incidence among men aged 18-30 years (3.43 cases per 1000 person-years). HPV 6 (43.8%), HPV 11 (10.7%), and HPV 16 (9.8%) were the genotypes most commonly detected in GWs. The 24-month cumulative incidence of GWs among men with incident HPV 6/11 infections was 14.6% (95% confidence interval [CI], 7.5%-21.1%). Median time to GW detection was 17.1 months (95% CI, 12.4-19.3 months), with shortest time to detection among men with incident infections with HPV 6/11 only (6.2 months; 95% CI, 5.6-24.2 months). CONCLUSIONS HPV 6/11 plays an important role in GW development, with the highest incidence and shortest time to detection among men with incident HPV 6/11 infection.
Susceptibility effects of GABA receptor subunit alpha-2 (GABRA2) variants and parental monitoring on externalizing behavior trajectories: Risk and protection conveyed by the minor allele

Abstract Understanding factors increasing susceptibility to social contexts and predicting psychopathology can help identify targets for prevention. Persistently high externalizing behavior in adolescence is predictive of psychopathology in adulthood. Parental monitoring predicts low externalizing behavior, yet youth likely vary in the degree to which they are affected by parents. Genetic variants of GABA receptor subunit alpha-2 (GABRA2) may increase susceptibility to parental monitoring, thus impacting externalizing trajectories. We had several objectives: (a) to determine whether GABRA2 (rs279827, rs279826, rs279858) moderates the relationship between a component of parental monitoring, parental knowledge, and externalizing trajectories; (b) to test the form of this interaction to assess whether GABRA2 variants reflect risk (diathesis–stress) or susceptibility (differential susceptibility) factors; and (c) to clarify GABRA2 associations on the development of problem behavior. This prospective study (N = 504) identified three externalizing trajectory classes (i.e., low, decreasing, and high) across adolescence. A GABRA2 × Parental Monitoring effect on class membership was observed, such that A-carriers were largely unaffected by parental monitoring, whereas class membership for those with the GG genotype was affected by parental monitoring. Findings support differential susceptibility in GABRA2.
Molding Helmet Therapy for Deformational Brachycephaly.

BACKGROUND Molding helmet therapy is used for the treatment of infants with deformational brachycephaly (DB). There is a lack of rigorous outcome measures of helmet therapy in patients with DB using 3-dimensional (3D) imaging, with most reports rely on either subjective or 2-dimensional analyses. Furthermore, the longitudinal assessment of head shape improvement over the course of helmet therapy has not been documented. Our goal was to assess the outcome of molding helmet therapy using 3D surface imaging, and to document the pace of improvement during treatment. METHODS The head shape of 18 infants with DB who underwent orthotic molding helmet therapy was assessed. The 3D scans were obtained before treatment, during treatment, and at the end of treatment. First, we applied shape analysis techniques based on template deformation to obtain average (composite) heads of the 18 patients at the 3 time points of treatment (pretreatment, during, and posttreatment). In addition, we used 3D curvature analysis to quantify the degree of flatness at the same time points. RESULTS Molding helmet therapy started at 6.7 ± 0.9 months of age and lasted for 4.3 ± 0.8 months. The overall difference in the occipital contour between pretreatment and end of treatment was 6.3 ± 1.7 mm. Curvature analysis revealed that 15% of the back of the head had prehelmet marked flatness (mean curvature <5/m), which decreased to 9% at 2.5 months into treatment and 7% at the end of treatment. CONCLUSION Over 65% of the head shape improvement occurred during the 2.5 months of molding helmet therapy.