Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolutionary rewiring of regulatory networks contributes to phenotypic differences between human and mouse orthologous genes

Abstract Mouse models have been engineered to reveal the biological mechanisms of human diseases based on an assumption. The assumption is that orthologous genes underlie conserved phenotypes across species. However, genetically modified mouse orthologs of human genes do not often recapitulate human disease phenotypes which might be due to the molecular evolution of phenotypic differences across species from the time of the last common ancestor. Here, we systematically investigated the evolutionary divergence of regulatory relationships between transcription factors (TFs) and target genes in functional modules, and found that the rewiring of gene regulatory networks (GRNs) contributes to the phenotypic discrepancies that occur between humans and mice. We confirmed that the rewired regulatory networks of orthologous genes contain a higher proportion of species-specific regulatory elements. Additionally, we verified that the divergence of target gene expression levels, which was triggered by network rewiring, could lead to phenotypic differences. Taken together, a careful consideration of evolutionary divergence in regulatory networks could be a novel strategy to understand the failure or success of mouse models to mimic human diseases. To help interpret mouse phenotypes in human disease studies, we provide quantitative comparisons of gene expression profiles on our website (http://sbi.postech.ac.kr/w/RN).
Family Planning Research in African Immigrant and Refugee Women: A Scoping Review

Introduction: African immigrants are a vulnerable population who are seldom seen in the literature, however, the scant research available reports that they experience increased challenges when making family planning decisions. A robust understanding of their specific family planning practices is imperative to providing appropriate, culturally congruent care. Considering this disparity, a scoping review was conducted to synthesize empirical knowledge and identify gaps in the literature around family planning in African immigrant populations in the United States. Methods: Guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) framework, EMBASE, Global Health Database, PsycINFO, CINAHL, and PubMed were searched for literature regarding family planning topics such as decision-making and health care access among African immigrant women in the United States in June 2020. Results: The small number of retrieved studies for the literature review clearly highlights a dearth of research. Available evidence indicates stark disparities in health care access, unmet individual needs, and unacknowledged preferences. Discussion: Ignoring cultural considerations for the growing African immigrant population perpetuates the divide in family planning practices.
Does isolation of the left atrial posterior wall using cryoballoon ablation improve clinical outcomes in patients with persistent atrial fibrillation? A prospective randomized controlled trial.

AIMS Posterior wall isolation (PWI) of the left atrium (LA) adjunct to pulmonary vein isolation (PVI) by radiofrequency catheter ablation has shown favourable outcomes in patients with persistent atrial fibrillation (PeAF). This study was sought to investigate the efficacy and safety of additional PWI by cryoballoon ablation (CBA) alone in patients with PeAF. METHODS AND RESULTS Patients who underwent de novo CBA for PeAF (n = 100) were randomly assigned (1 : 1) to the PVI only group and PVI combined with PWI (PVI+PWI) group. Procedural and clinical outcomes were prospectively compared over a 12-month follow-up. Baseline characteristics, including mean AF duration (56.2 ± 43.2 months) and LA size (48.2 ± 7.7 mm), were well-balanced between the groups. Successful PVI was achieved in all patients. In the PVI+PWI group, complete PWI by CBA was achieved in 31 (62%) patients. The LA indwelling and procedure times were significantly longer in the PVI+PWI group. The complication rates were not different between groups. During a mean follow-up of 457.9 ± 61.8 days, the recurrence rate of atrial tachyarrhythmia was significantly lower in the PVI+PWI group than in the PVI only group (24% vs. 46%; P = 0.035). The recurrence-free survival rate was significantly higher in the PVI+PWI group compared with the PVI only group, irrespective of complete PWI (log-rank P = 0.013). Multivariate analysis showed that adjunctive PWI [hazard ratio (HR) 0.255; P = 0.003] and LA size (HR 1.079; P = 0.014) were independent predictors of clinical recurrence. CONCLUSION Compared with PVI only, adjunctive PWI achieved exclusively by CBA resulted in better clinical outcomes without increasing complications in patients with PeAF.
Determinants of Emotional Intimate Partner Violence against Women and Girls with Children in Mexican Households: An Ecological Framework

The purpose of this paper is to identify the risk factors for emotional intimate partner violence (IPV) against women and girls with children in Mexico from an ecological perspective. To that end, we generate a dataset with 35,004 observations and 42 covariates, to which we apply an additive probit model estimated with a boosting algorithm to overcome high-dimensionality and simultaneously perform variable selection and model choice. The dataset integrates 10 information sources, allowing us to properly characterize the four levels of the ecological approach, which is the first contribution of this paper. In addition, there are three key contributions. First, we identify a number of factors significantly linked to emotional IPV against women with children: age, age at sexual initiation, age at marriage (or cohabitation), autonomy regarding professional issues, social support networks, division of housework, the community’s Gini index, women’s economic participation in the municipality, and the prevalence of crime against males in the region. Second, we discuss some risk factors whose effects have not been examined or have been underexplored for Mexico; these include women’s decision-making autonomy, social support networks, distribution of housework, the community’s economic inequality, and criminality. Third, we identify specific risk subgroups that are generally overlooked: women who had their first sexual intercourse during childhood and women who got married (or moved in together with a partner) late in life. The main results suggest that strategies aiming to promote women’s social and economic empowerment and reduce criminality should also incorporate a gender component regarding emotional violence against women with children in the context of intimate relationships.
Green synthesis of selenium nanoparticles and evaluate their effect on the expression of ERG3, ERG11 and FKS1 antifungal resistance genes in Candida albicans and Candida glabrata

Drug resistance in Candida species has been considerably increased in the last decades. Given the opposition to antifungal agents, toxicity and interactions of the antimicrobial drugs, identifying new antifungal agents seems essential. This study assessed the antifungal effects of nanoparticles (NPs) on the standard strains of Candida albicans and Candida glabrata and determined the expression genes, including ERG3, ERG11 and FKS1. Selenium nanoparticles (Se‐NPs) were biosynthesized with a standard strain of C. albicans and approved by several methods including, ultraviolet‐visible spectrophotometer, X‐ray diffraction technique, Fourier‐transform infrared analysis, field‐emission scanning electron microscopy and EDX diagram. The antifungal susceptibility testing performed the minimum inhibitory concentrations (MICs) using the CLSI M27‐A3 and M27‐S4 broth microdilution method. The expression of the desired genes was examined by the real‐time PCR assay between untreated and treated by antifungal drugs and Se‐NPs. The MICs of itraconazole, amphotericin B and anidulafungin against C. albicans and C. glabrata were 64, 16 and 4 µg ml−1. In comparison, reduced the MIC values for samples treated with Se‐NPs to 1 and 0·5 µg ml−1. The results obtained from real‐time PCR and analysis of the ∆∆Cq values showed that the expression of ERG3, ERG11 and FKS1 genes was significantly down‐regulated in Se‐NPs concentrations (P < 0·05). This study's evidence implies biosafety Se‐NPs have favourable effects on the reducing expression of ERG3, ERG11 and FKS1 antifungal resistance genes in C. albicans and C. glabrata.
Effect of a novel 90-second “Gear” exercise programme on markers of inflammation and cardiorespiratory fitness measurements in person at risk of cardiovascular disease

ABSTRACT The study compared the effect of the novel “Gear” exercise programmes on inflammatory markers and cardiorespiratory fitness measurements. The participants mean age was 38 ± 5.74 years, with a mean body mass of 83 ± 16.93kg. Participants were randomly assigned to either the “Gear” exercise programme repeated at different times during the day (GEP-DT): cycled for 90 seconds, repeated three times per day, three days per week; the “Gear” exercise programme repeated at one point in time (GEP-OT): cycled for 90 seconds followed by four minutes and 30 seconds rest, repeated three times at one point in time, three days per week; moderate-intensity continuous exercise group (MICE): cycled for 30 minutes at 55–69% of HRmax or the control group (CTRL): did not exercise. The GEP-DT demonstrated a moderate increase in load at ventilation threshold (VT-L) (MD = 8.18 ± 12.30, % Δ = 14.53, d = 0.77, d (95% CI): (−0.17, 1.64)). The GEP-OT group demonstrated a large effect size for VT-L (MD = 11.79 ± 18.77, % Δ = 18.86, d = 0.81, d (95% CI): (−0.02, 1.63)). The GEP-DT and GEP-OT raised the VT-L, which prevented premature fatigue and improved the efficiency of the cardiorespiratory system.
A Feasible Alternative Strategy Targeting Furin Disrupts SARS-CoV-2 Infection Cycle

Since its emergence in December 2019, COVID-19 has remained a global economic and health threat. Although RNA and DNA vector-based vaccines induced antibody response and immunological memory have proven highly effective against hospitalization and mortality, their long-term efficacy remains unknown against continuously evolving SARS-CoV-2 variants. ABSTRACT The COVID-19 causing coronavirus (SARS-CoV-2) remains a public health threat worldwide. SARS-CoV-2 enters human lung cells via its spike glycoprotein binding to angiotensin-converting enzyme 2 (ACE2). Notably, the cleavage of the spike by the host cell protease furin in virus-producing cells is critical for subsequent spike-driven entry into lung cells. Thus, effective targeted therapies blocking the spike cleavage and activation in viral producing cells may provide an alternate strategy to break the viral transmission cycle and to overcome disease pathology. Here we engineered and described an antibody-based targeted strategy, which directly competes with the furin mediated proteolytic activation of the spike in virus-producing cells. The described approach involves engineering competitive furin substrate residues in the IgG1 Fc-extended flexible linker domain of SARS-CoV-2 spike targeting antibodies. Considering the site of spike furin cleavage and SARS-CoV-2 egress remains uncertain, the experimental strategy pursued here revealed novel mechanistic insights into proteolytic processing of the spike protein, which suggest that processing does not occur in the constitutive secretory pathway. Furthermore, our results show blockade of furin-mediated cleavage of the spike protein for membrane fusion activation and virus host-cell entry function. These findings provide an alternate insight of targeting applicability to SARS-CoV-2 and the future coronaviridae family members, exploiting the host protease system to gain cellular entry and subsequent chain of infections. IMPORTANCE Since its emergence in December 2019, COVID-19 has remained a global economic and health threat. Although RNA and DNA vector-based vaccines induced antibody response and immunological memory have proven highly effective against hospitalization and mortality, their long-term efficacy remains unknown against continuously evolving SARS-CoV-2 variants. As host cell-enriched furin-mediated cleavage of SARS-CoV-2 spike protein is critical for viral entry and chain of the infection cycle, the solution described here of an antibody Fc-conjugated furin competing peptide is significant. In a scenario where spike mutational drifts do not interfere with the Fc-conjugated antibody's epitope, the proposed furin competing strategy confers a broad-spectrum targeting design to impede the production of efficiently transmissible SARS-CoV-2 viral particles. In addition, the proposed approach is plug-and-play against other potentially deadly viruses that exploit secretory pathway independent host protease machinery to gain cellular entry and subsequent transmissions to host cells.
The Impact of Antimicrobial Stewardship in Children in Low- and Middle-income Countries

Background: Antimicrobial stewardship (AMS) is central to the World Health Organisation Global Action Plan against antimicrobial resistance (AMR). If antibiotics are used without restraint, morbidity and mortality from AMR will continue to increase. In resource-rich settings, AMS can safely reduce antibiotic consumption. However, for children in low- and middle-income countries (LMIC), the impact of different AMS interventions is unknown. Aim: To determine the impact of different AMS interventions on antibiotic use and clinical and microbiologic outcomes in children in LMIC. Methods: MEDLINE, Embase and PubMed were searched for studies of AMS interventions in pediatric population in LMIC settings. Controlled trials, controlled before-and-after studies and interrupted time series studies were included. Outcomes assessed were antibiotic use, multidrug-resistant organism (MDRO) rates, clinical outcomes and cost. Results: Of 1462 studies, 34 met inclusion criteria including a total population of >5,000,000 in 17 countries. Twenty were in inpatients, 2 in ED, 10 in OPD and 2 in both. Seven studies were randomized controlled trials. All types of interventions reported a positive impact on antibiotic prescribing. AMS bundles with education, and clinical decision tools appeared more effective than guidelines alone. AMS interventions resulted in significantly decreased clinical infections (4/4 studies) and clinical failure (2/2) and reduced MDRO colonization rate (4/4). There was no concomitant increase in mortality (4/4 studies) or length of stay (2/2). Conclusion: Multiple effective strategies exist to reduce antibiotic consumption in LMIC. However, marked heterogeneity limit conclusions regarding the most effective approach, particularly regarding clinical outcomes. Overall, AMS strategies are important tools in the reduction of MDRO-related morbidity in children in LMIC.
Deficiency of ribosomal proteins reshapes the transcriptional and translational landscape in human cells

Abstract Human ribosomes have long been thought to be uniform factories with little regulatory function. Accumulating evidence emphasizes the heterogeneity of ribosomal protein (RP) expression in specific cellular functions and development. However, a systematic understanding of functional relevance of RPs is lacking. Here, we surveyed translational and transcriptional changes after individual knockdown of 75 RPs, 44 from the large subunit (60S) and 31 from the small subunit (40S), by Ribo-seq and RNA-seq analyses. Deficiency of individual RPs altered specific subsets of genes transcriptionally and translationally. RP genes were under cotranslational regulation upon ribosomal stress, and deficiency of the 60S RPs and the 40S RPs had opposite effects. RP deficiency altered the expression of genes related to eight major functional classes, including the cell cycle, cellular metabolism, signal transduction and development. 60S RP deficiency led to greater inhibitory effects on cell growth than did 40S RP deficiency, through P53 signaling. Particularly, we showed that eS8/RPS8 deficiency stimulated apoptosis while eL13/RPL13 or eL18/RPL18 deficiency promoted senescence. We also validated the phenotypic impacts of uL5/RPL11 and eL15/RPL15 deficiency on retina development and angiogenesis, respectively. Overall, our study provides a valuable resource for and novel insights into ribosome regulation in cellular activities, development and diseases.
High Level Mobility Training in Ambulatory Patients with Acquired Non-Progressive Central Neurological Injury: a Feasibility Study

ABSTRACT The purpose of this study was to test the feasibility and safety of High-Level Mobility (HLM) training on adults with Acquired Brain Injury (ABI). Our hypotheses were that HLM training would be feasible and safe. This study was a pilot randomized control trial with a Simple Skill Group (SSG) and a Complex Skill Group (CSG). Both groups received 12 sessions over 8 weeks and completed 4 testing sessions over 16 weeks. The SSG focused on locomotion, while CSG focused on the acquisition of running. Feasibility was assessed in terms of process, resources, management, and scientific metrics, including safety. Among the 41 participants meeting inclusion criteria, 28 consented (CSG, n = 13, SSG, n = 15), 20 completed the assigned protocol and 8 withdrew (CSG n = 4, SSG n = 4). Adherence rate to assigned protocol was 100%. There were two Adverse Events (AEs), 1 over 142 SSG sessions and 1 over 120 CSG sessions. The AE Odd Ratio (OR) (CSG:SSG) was 1.18 (95% CI: 0.07, 19.15). The data support our hypotheses that HLM training is feasible and safe on ambulatory adults with ABI.
Aspirin use in patients with diagnosed diabetes in the United States and China: Nationally representative analysis

Background The epidemiological data on the use of aspirin in diabetic patients is very limited. The main purpose of this study is to examine the current status of aspirin use in the United States (US) and China in large representative populations. Methods Data came from the National Health and Nutrition Examination Survey (NHANES) and China Hypertension Survey (CHS), two nationally representative cross-sectional studies. Results The percentage of aspirin use was 73.8% in US diabetic patients with ASCVD, and the percentage of aspirin use in diabetic patients with high ASCVD risk was marginally higher in men (p = .052), 54.5% in men and 37.1% in women. The percentages of aspirin use in diabetic patients with intermediate and low ASCVD risk were 55.1% and 35.0%, respectively. In China, the percentage of aspirin use in diabetic patients with ASCVD was 53.5%, and were 14.3%, 9.7%, and 3.2% among diabetic patients with high, intermediate, and low ASCVD risk, respectively. Conclusions In summary, the percentage of aspirin use in primary prevention in US diabetic patients in men was higher than in women, and this percentage for primary and secondary prevention in US patients was higher than that in Chinese patients.
Significance-Quest Theory

Even though the motivation to feel worthy, to be respected, and to matter to others has been identified for centuries by scholars, the antecedents, consequences, and conditions of its activation have not been systematically analyzed or integrated. The purpose of this article is to offer such an integration. We feature a motivational construct, the quest for significance, defined as the need to have social worth. This need is typically fulfilled by a sense of measuring up to the values one shares with significant others. Our significance-quest theory (SQT) assumes that the need for significance is universal, whereas the means of satisfying it depend on the sociocultural context in which one’s values are embedded. Those means are identified in a narrative supported and validated by one’s network, or reference group. The quest for significance is activated by significance loss and/or the opportunity for significance gain. It motivates behavior that aims to affirm, realize, and/or show commitment to an important value. The SQT is consistent with large bodies of prior research and supported by novel studies in multiple laboratory and field settings. It transcends prior understandings and offers guidance for further study of this essential human motivation.
Neurocognitive Profiles in Patients With Persisting Cognitive Symptoms Associated With COVID-19

Abstract Objective A subset of individuals with coronavirus disease 2019 (COVID-19) appears to develop persisting cognitive and medical symptoms. Research in the acute stages of illness, generally utilizing cognitive screening measures or case reports, suggests presence of deficits in attention and executive function. This observational study investigated cognitive functioning among individuals with persistent cognitive complaints about 5.5 months after COVID-19 infection. Methods Patients with polymerase chain reaction confirmed COVID-19 and persistent cognitive complaints underwent comprehensive in-person neuropsychological evaluations. Patients with prior neurological disorders were excluded. When diagnosed, 40% required hospitalization, 15% were in an intensive care unit, 10% needed mechanical ventilation, and 10% experienced delirium. Results This sample was predominately women (90%), White non-Hispanic (70%), with average education of 15 years. Mild cognitive deficits were seen on tests involving attention and processing speed or executive function. Seventy percent of patients were diagnosed with a mood disorder prior to COVID-19 infection. At the time of testing, 35%–40% endorsed moderate to severe mood symptoms and 85% noted significant fatigue as measured by the Fatigue Severity Scale. Conclusions The pattern of cognitive deficits, although mild, is consistent with prior research at the acute stage of the illness. These findings suggest that psychological factors and other persisting symptoms (e.g., sleep, fatigue) may play a significant role in subjective cognitive complaints in patients with persisting complaints post COVID-19 who did not require intensive treatment. These patients would likely benefit from resources to manage persisting or new mood symptoms and compensatory strategies for the cognitive inefficiencies they experience.
Intrinsic Sources and Functional Impacts of Asymmetry at Electrical Synapses

Abstract Electrical synapses couple inhibitory neurons across the brain, underlying a variety of functions that are modifiable by activity. Despite recent advances, many functions and contributions of electrical synapses within neural circuitry remain underappreciated. Among these are the sources and impacts of electrical synapse asymmetry. Using multi-compartmental models of neurons coupled through dendritic electrical synapses, we investigated intrinsic factors that contribute to effective synaptic asymmetry and that result in modulation of spike timing and synchrony between coupled cells. We show that electrical synapse location along a dendrite, input resistance, internal dendritic resistance, or directional conduction of the electrical synapse itself each alter asymmetry as measured by coupling between cell somas. Conversely, we note that asymmetrical gap junction (GJ) conductance can be masked by each of these properties. Furthermore, we show that asymmetry modulates spike timing and latency of coupled cells by up to tens of milliseconds, depending on direction of conduction or dendritic location of the electrical synapse. Coordination of rhythmic activity between two cells also depends on asymmetry. These simulations illustrate that causes of asymmetry are diverse, may not be apparent in somatic measurements of electrical coupling, influence dendritic processing, and produce a variety of outcomes on spiking and synchrony of coupled cells. Our findings highlight aspects of electrical synapses that should always be included in experimental demonstrations of coupling, and when assembling simulated networks containing electrical synapses.