Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss-of-function variants in myocardin cause congenital megabladder in humans and mice

Myocardin (MYOCD) is the founding member of a class of transcriptional coactivators that bind the serum-response factor to activate gene expression programs critical in smooth muscle (SM) and cardiac muscle development. Insights into the molecular functions of MYOCD have been obtained from cell culture studies, and to date, knowledge about in vivo roles of MYOCD comes exclusively from experimental animals. Here, we defined an often lethal congenital human disease associated with inheritance of pathogenic MYOCD variants. This disease manifested as a massively dilated urinary bladder, or megabladder, with disrupted SM in its wall. We provided evidence that monoallelic loss-of-function variants in MYOCD caused congenital megabladder in males only, whereas biallelic variants were associated with disease in both sexes, with a phenotype additionally involving the cardiovascular system. These results were supported by cosegregation of MYOCD variants with the phenotype in 4 unrelated families by in vitro transactivation studies in which pathogenic variants resulted in abrogated SM gene expression and by the finding of megabladder in 2 distinct mouse models with reduced Myocd activity. In conclusion, we have demonstrated that variants in MYOCD result in human disease, and the collective findings highlight a vital role for MYOCD in mammalian organogenesis.
Hypothalamic–Pituitary and Adipose Tissue Responses to the Effect of Resistin in Sheep: The Integration of Leptin and Resistin Signaling Involving a Suppressor of Cytokine Signaling 3 and the Long Form of the Leptin Receptor

We hypothesized that resistin is engaged in the development of leptin central insensitivity/resistance in sheep, which is a unique animal model to explore reversible leptin resistance. Thirty Polish Longwool ewes, which were ovariectomized with estrogen replacement, were used. Treatments consisted of the intravenous injection of control (saline) or recombinant bovine resistin (rbresistin): control (Control; n = 10), a low dose of rbresistin (R1; 1.0 μg/kg body weight (BW); n = 10), and a high dose of rbresistin (R2; 10.0 μg/kg BW; n = 10). The studies were performed during short-day (SD) and long-day (LD) photoperiods. Leptin and resistin concentrations were determined. Expression levels of a suppressor of cytokine signaling (SOCS)-3 and the long form of the leptin receptor (LeptRb) were determined in selected brain regions, including in the anterior pituitary (AP), hypothalamic arcuate nucleus (ARC), preoptic area (POA), and ventro- and dorsomedial nuclei (VMH/DMH). The results indicate that resistin induced a consistent decrease in LeptRb (except in POA) and an increase in SOCS-3 expression during the LD photoperiod in all selected brain regions. In conclusion, the results demonstrate that the action of resistin appears to be strongly associated with photoperiod-driven changes in the leptin signaling pathway, which may underlie the phenomenon of central leptin resistance.
Comparable Investigation of Characteristics for Implant Intra-Body Communication Based on Galvanic and Capacitive Coupling

Implanted devices have important applications in biomedical monitoring, diagnosis and treatment, where intra-body communication (IBC) has a decent prospect in wireless implant communication technology by using the conductive properties of the human body to transmit a signal. Most of the investigations on implant IBC are focused on galvanic coupling type. Capacitive coupling IBC device seems hard to implant, because the ground electrode of it seemingly has to be exposed to air. Zhang et al. previously proposed an implantable capacitive coupling electrode, which can be totally implanted into the human body [1], but it lacks an overall characteristic investigation. In this paper, a comparable investigation of characteristics for implant intra-body communication based on galvanic and capacitive coupling is conducted. The human arm models are established by finite element method. Meanwhile, aiming to improve the accuracy of the model, electrode polarization impedance (EPI) is incorporated into the model, and the influences of electrode polarization impedance on simulation results are also analyzed. Subsequently, the corresponding measurements using porcine are conducted. We confirm good capacitive coupling communication performances can be achieved. Moreover, some important conclusions have been included by contrastive analysis, which can be used to optimize implant intra-body communication devices performance and provide some hints for practical IBC design. The conclusions also indicate that the implant IBC has promising prospect in healthcare and other related fields.
Utility of tissue Doppler imaging of systolic function to diagnose diastolic dysfunction in critically ill patients.

BACKGROUND Diastolic dysfunction might be associated with increased mortality in severe sepsis and septic shock. In 2016 new American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) guidelines were published. They simplify our approach to diastolic dysfunction recognition, but they were not validated in critical care settings. The aim of the study was to assess the applicability of systolic tissue Doppler imaging of left ventricle in patients with and without diastolic dysfunction classified on the basis of the new guidelines. METHODS Two echocardiographers analyzed transthoracic echocardiography (TTE) exa-minations and assigned patients according to ASE/EASCVI guidelines to three groups: patients with systolic dysfunction and diastolic dysfunction, patients with normal systolic function and diastolic dysfunction, and patients with normal systolic and diastolic function. RESULTS We performed 593 examinations in 320 patients and 390 examinations in 200 patients were included in the study. In 264 examinations with ejection fraction (EF) < 55% systolic and diastolic dysfunction was diagnosed (group 1). In 114 examinations with EF ≥ 55% normal systolic and diastolic function was diagnosed (group 2). In 12 examinations with EF ≥ 55% normal systolic and abnormal diastolic dysfunction was diagnosed (group 3). After analyzing mean systolic tissue Doppler of the mitral annulus we found a statistically significant difference between group 1 and 2 (P < 0.0001) and between group 2 and 3 (P < 0.0001). The difference in values of means in group 1 vs. 3 was not statistically significant (P = 0.853). CONCLUSION Systolic tissue Doppler analysis of mitral annulus might help to diagnose diastolic dysfunction especially in patients with preserved ejection fraction.
Complete Genome Sequence of Herpes Simplex Virus 1 Strain MacIntyre

Herpes simplex virus type 1 (HSV-1) strain MacIntyre has a severe defect in the anterograde spread after replication in the nucleus. To better understand and identify the genetic determinants that lead to the unique phenotypes of the MacIntyre strain, we sequenced its genome with PacBio single-molecule real-time sequencing technology and resolved the complete sequence. ABSTRACT Herpes simplex virus type 1 (HSV-1) strain MacIntyre has a severe defect in the anterograde spread after replication in the nucleus. To better understand and identify the genetic determinants that lead to the unique phenotypes of the MacIntyre strain, we sequenced its genome with PacBio single-molecule real-time sequencing technology and resolved the complete sequence.
How effective is teamwork really? The relationship between teamwork and performance in healthcare teams: a systematic review and meta-analysis

Objectives To investigate the relationship between teamwork and clinical performance and potential moderating variables of this relationship. Design Systematic review and meta-analysis. Data source PubMed was searched in June 2018 without a limit on the date of publication. Additional literature was selected through a manual backward search of relevant reviews, manual backward and forward search of studies included in the meta-analysis and contacting of selected authors via email. Eligibility criteria Studies were included if they reported a relationship between a teamwork process (eg, coordination, non-technical skills) and a performance measure (eg, checklist based expert rating, errors) in an acute care setting. Data extraction and synthesis Moderator variables (ie, professional composition, team familiarity, average team size, task type, patient realism and type of performance measure) were coded and random-effect models were estimated. Two investigators independently extracted information on study characteristics in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results The review identified 2002 articles of which 31 were included in the meta-analysis comprising 1390 teams. The sample-sized weighted mean correlation was r =0.28 (corresponding to an OR of 2.8), indicating that teamwork is positively related to performance. The test of moderators was not significant, suggesting that the examined factors did not influence the average effect of teamwork on performance. Conclusion Teamwork has a medium-sized effect on performance. The analysis of moderators illustrated that teamwork relates to performance regardless of characteristics of the team or task. Therefore, healthcare organisations should recognise the value of teamwork and emphasise approaches that maintain and improve teamwork for the benefit of their patients.
Development of a High-Throughput Screening-Compatible Assay for Discovery of GPR3 Inverse Agonists Using a cAMP Biosensor

While G-protein-coupled receptors (GPCRs) represent the largest class of cell surface proteins, there are ≥100 orphan GPCRs whose endogenous ligands are unknown. Accordingly, these could prove to be potential therapeutic targets for the pharmaceutical intervention of various diseases. Constitutively active orphan GPCRs are activated without ligands; thus, inverse agonists may be very useful pharmacological tools for inhibiting constitutive activity. However, in general, inverse agonist screening is considered more difficult to perform with high quality than antagonist screening, particularly due to the narrow assay window. We developed a high-throughput screening (HTS)-compatible assay to identify inverse agonists of GPR3. GPR3 is expressed in the central nervous system (CNS) and is known to be related to Alzheimer’s disease and other CNS diseases. The GPR3 inducible cell line was established using T-REx 293 cells that stably expressed the tetracycline repressor protein, and the cAMP biosensor, GloSensor, was stably co-expressed. After optimization of the induction level of GPR3 and assay conditions, the GloSensor assay showed an approximately 20-fold signal-to-background ratio and high sensitivity. Using the HTS method, we successfully screened a library of hundreds of thousands of compounds for the inhibition of constitutive activity with good quality and excellent reproducibility. Finally, 35 compounds were identified as GPR3 selective inverse agonists. This inverse agonist screening approach using GloSensor in combination with the inducible expression of orphan GPCR indicates universal applicability to the search for inverse agonists of constitutively active orphan GPCRs.
The Association between Air Pollution and Sleep Duration: A Cohort Study of Freshmen at a University in Beijing, China

Background: Rising levels of air pollution in Beijing, China have become a serious environmental issue affecting human health, and young adults are experiencing high rates of insufficient sleep duration or a lack of sleep. Gaps in previous research remain regarding the relationship between air pollution and sleep duration among young adults. The purpose of this study is to assess the associations between air pollution and sleep duration among college students living in Beijing, China. Methods: We conducted follow-up health surveys on 16,889 freshman students enrolled at Tsinghua University over a five-year study period (2013–2018). Sleep duration was measured using the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI), which has been validated in China to measure sleep duration. Corresponding levels of the average hourly air quality index (AQI), PM2.5 (µg/m3), PM10 (µg/m3), and NO2 (µg/m3) were gathered from data provided by the Beijing Municipal Ecological Environment Bureau in a closed site at Tsinghua University. Multilevel mixed-effects linear regression models were used to analyze the data. Results: One standard deviation increase in air pollution concentration in AQI, PM2.5, PM10, and NO2 was associated with a reduction in daily hours of sleep by 0.68 (95% confidence interval (CI) = 0.63, 0.73), 0.55 (95% CI = 0.51, 0.59), 0.70 (95% CI = 0.64, 0.76), and 0.51 (95% CI = 0.47, 0.54), respectively. Conclusions: Air pollution was associated with a reduction in sleep duration among freshman students living in Beijing, China. Replication of this study is warranted among various populations within China.
Deciphering the Patterns of Genetic Admixture and Diversity in the Ecuadorian Creole Chicken

Simple Summary In Ecuador, the production of Ecuadorian Creole chicken is of crucial importance in the economy and for the nutrition of families. These chickens represent a focal point in scientific research for three main reasons: (1) they are an unknown genetic resource derived from 500 years of environmental and human selection and represent an important reservoir of genetic variability and adaptability; (2) Ecuadorian Creole chicken production is normally familiar, in a marginal dimension, and it is an important source of economic input for medium–low income communities; and (3) being a local genetic resource, it is available to local communities without intermediary international enterprises and represents the starting point for food sovereignty. We aimed to measure the level of genetic diversity and its phylogenetic position compared with other outgroup breeds using information from microsatellite and mitochondrial markers. Our results showed that these chicken populations represent a great reservoir of genetic variability; however, the genetic fragmentation owing to the high geographical diversity of the country could compromise the conservation status and, therefore, the establishment of an official breeding program is needed for the conservation and valuation of these avian populations, with this genetic characterization being a first step. Abstract Latin American Creole chickens are generally not characterized; this is the case in Ecuador, where the lack of scientific information is contributing to their extinction. Here, we developed a characterization of the genetic resources of Ecuadorian chickens located in three continental agroecosystems (Pacific coastal, Andean, and Amazonian). Blood samples of 234 unrelated animals were collected in six provinces across Ecuador: Bolívar, Chimborazo, Cotopaxi, Guayas, Morona Santiago, and Tungurahua, in order to perform a genetic characterization and population structure assessment using the AVIANDIV project microsatellites panel (30 loci) and D-loop sequences of mitochondrial DNA and comparing with reference data from other breeds or genetic lines. The results indicate that Ecuadorian Creole chickens are the result of the admixture of different genetic groups that occurred during the last five centuries. While the influence of South Spanish breeds is demonstrated in the colonial age, genetic relationships with other breeds (Leghorn, Spanish fighter cock) cannot be discarded. The geographical configuration of the country and extreme climate variability have influenced the genetic isolation of groups constituting a homogeneous genetic status into the whole population. This is not only a source of genetic variation, but also a critical point because genetic drift produces a loss of genetic variants.
Executive Functioning in Pediatric Solid Organ Transplant Recipients: A Meta-analytic Review

Background. Examining executive functioning (EF) posttransplant has become increasingly prevalent, as EF deficits are associated with poor disease-related outcomes and psychosocial functioning. The purpose of the current meta-analysis was to compare overall and domain-specific EF between healthy youth and those with a kidney, heart, or liver transplant, and identify moderating variables related to EF differences between these 2 groups. Methods. A literature search of PsycINFO, Pubmed, and Medline was conducted for eligible articles published until January 2019. Twenty studies met eligibility criteria and were included in the present meta-analysis. Results. Results from the random-effects model indicated a significant standardized mean difference in overall EF skills with transplant recipients demonstrating worse EF (g = 0.40; 95% confidence interval [CI], 0.29-0.50) than healthy youth. Specifically, transplanted youth had worse working memory (g = 0.33; 95% CI, 0.01-0.66), processing speed (g = 0.41; 95% CI, 0.19-0.62), attentional control (g = 0.53; 95% CI, 0.33-0.73), and metacognitive skills (g = 0.36; 95% CI, 0.18-0.54). Assessment type and time since transplantation were not significant moderators. Conclusions. Pediatric solid organ transplant recipients demonstrate worse overall EF skills and deficits in working memory, processing speed, attentional control, and metacognitive skills. Many children who have undergone solid organ transplantation will require additional support in medical and academic settings because of deficits in various EF domains.
Gastrointestinal Symptoms in Infants of Mothers with a Psychiatric History and the Role of Depression and Bonding.

OBJECTIVES Gastroesophageal reflux (GER), excessive crying, and constipation are common gastrointestinal symptoms in infancy of multifactorial origin in which psychosocial stress factors play an important role. The aims of this observational study were to investigate the presence of gastrointestinal symptoms in infants of mothers with or without a history of a psychiatric disorder, their association with maternal depressive symptoms, and the possible mediating role of bonding. METHODS 101 mothers with a history of a psychiatric disorder ("PD mothers") and 60 control mothers were included. Infant gastrointestinal symptoms, maternal depressive symptoms, and mother-infant bonding were assessed using validated questionnaires and diagnostic criteria at 1.5 month postpartum. RESULTS The mean total score on the Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) reported in infants of PD mothers (13.4 SD 5.4) was significantly higher than in infants of control mothers (10.8 SD 5.4; P = .003). No significant differences were found in the presence of excessive crying (modified Wessel's criteria and subjective experience) and constipation (ROME IV criteria) between both groups. Infant GER was associated with maternal depressive symptoms (P = 0.027) and bonding problems (P = <0.001). Constipation was related to maternal depressive symptoms (P = 0.045), and excessive crying (Wessel and subjective criteria) was associated with bonding problems (respectively P = 0.022 and P = 0.002). The effect of maternal depressive symptomatology on infant GER symptoms and excessive crying was mediated by bonding problems. CONCLUSION Maternal psychiatric history is associated with infant gastrointestinal symptoms, in which mother-infant bonding is a mediating factor.
Cutaneous Ultrasound for Tumor Thickness Measurement in Squamous Cell Carcinoma: The Effect of Neoadjuvant Intralesional Methotrexate in 40 Patients.

BACKGROUND Intralesional methotrexate (il-MTX) has been used as neoadjuvant therapy for cutaneous squamous cell carcinoma (cSCC) but studies on its effects on tumor thickness are lacking. OBJECTIVE The objective of this study was to evaluate il-MTX response with ultrasound examination. METHODS The authors conducted a prospective study in 40 patients with histologically confirmed cSCC. Neodjuvant il-MTX therapy was administered before surgery. Ultrasound evaluation was performed before the first infiltration and before surgical treatment. RESULTS Response to neoadjuvant treatment was observed in 92.5% of patients, both clinically and sonographically. There was a good correlation between both types of measurements, with r = 0.892 for the minor diameter and r = 0.944 for the major diameter (p < .001). The authors found an ultrasound overestimation compared to the clinical measurements in 92.5% of patients (mean overestimation: 1.08 mm). There was a good correlation between ultrasound and histological measurements in tumor thickness with r = 0.932 (p < .01), with an ultrasound overestimation in 97.5% of cases (mean overestimation: 0.90 mm). CONCLUSION Neoadjuvant il-MTX can reduce not only surface tumor dimensions but also tumor thickness. Ultrasound improves treatment response control with greater accuracy than clinical assessment alone.
Nuclei deformation reveals pressure distributions in 3D cell clusters

Measuring pressures within complex multi-cellular environments is critical for studying mechanobiology as these forces trigger diverse biological responses, however, these studies are difficult as a deeply embedded yet well-calibrated probe is required. In this manuscript, we use endogenous cell nuclei as pressure sensors by introducing a fluorescent protein localized to the nucleus and confocal microscopy to measure the individual nuclear volumes in 3D multi-cellular aggregates. We calibrate this measurement of nuclear volume to pressure by quantifying the nuclear volume change as a function of osmotic pressure in isolated 2D culture. Using this technique, we find that in multicellular structures, the nuclear compressive mechanical stresses are on the order of MPa, increase with cell number in the cluster, and that the distribution of stresses is homogenous in spherical cell clusters, but highly asymmetric in oblong clusters. This approach may facilitate quantitative mechanical measurements in complex and extended biological structures both in vitro and in vivo.
Electron Microscopy of Argyria Treated With Picosecond Alexandrite Laser.

instability may result in graft failure. Donor site morbidity is another significant adverse effect associated with skin grafting. Secondary intention healing is another option, but it may take several weeks before a sufficiently granulated wound bed is formed. In this case, the use of a porcine transitional cell epithelium biosynthetic xenograft resulted in efficient granulation with minimal wound care requirements and good aesthetic outcome. Biologic xenografts, therefore,may serve as a useful adjunct to managing granulating surgical wounds.