Miracle-dz/UniFAR-FTUs huggingface dataset:
Distribution and phenotypes of hemifacial microsomia and its association with other anomalies

Objective To investigate the distribution and phenotypes of hemifacial microsomia (HFM) and its association with other anomalies. Methods This study included 249 Korean patients with HFM, whose charts, photographs, radiographs, and/or computed tomography scans acquired during 1998–2018 were available from Seoul National University Hospital and Dental Hospital. Prevalence according to sex, side involvement, degree of mandibular deformity, compensatory growth of the mandibular body, and Angle's classification, and its association with other anomalies were statistically analyzed. Results Prevalence was not different between male and female patients (55.0% vs. 45.0%, p > 0.05). Unilateral HFM (UHFM) was more prevalent than bilateral HFM (BHFM) (86.3% vs. 13.7%, p < 0.001). Although distribution of the Pruzansky–Kaban types differed significantly in patients with UHFM (I, 53.0%; IIa, 18.6%; IIb, 24.7%; III, 3.7%; p < 0.001), no difference was observed in occurrence between the right and left sides (52.6% vs. 47.4%, p > 0.05). Among patients with BHFM, prevalence of different Pruzansky–Kaban types on the right and left sides was greater than that of the same type on both sides (67.6% vs. 32.4%, p < 0.05). Despite hypoplasia of the condyle/ramus complex, compensatory growth of the mandibular body on the ipsilateral side occurred in 35 patients (14.1%). Class I and II molar relationships were more prevalent than Class III molar relationships (93.2% vs. 6.8%, p < 0.001). Forty-eight patients (19.3%) had other anomalies, with 50.0% and 14.4% in the BHFM and UHFM groups (p < 0.001). Conclusions Patients with HFM require individualized diagnosis and treatment planning because of diverse phenotypes and associations with other anomalies.
Multistep peripherin-2/rds self-assembly drives membrane curvature for outer segment disk architecture and photoreceptor viability

Significance Rod and cone photoreceptors are sensory neurons that underlie vertebrate vision. Rods and cones each use specialized membranous organelles, called outer segments (OSs), to transduce photons into cellular signals. This report investigates the molecular basis for normal OS structure. It demonstrates that peripherin-2/rds (P/rds), a photoreceptor-specific protein associated with a broad range of inherited retinal diseases, shapes membranes to help build the distinctive architecture of photoreceptor OSs. More specifically, it reveals the normal function of P/rds as a curvature-generating protein that is essential for high-fidelity organelle formation, and advances understanding of how sight-robbing genetic defects impair P/rds function to negatively affect OS structure. Rod and cone photoreceptor outer segment (OS) structural integrity is essential for normal vision; disruptions contribute to a broad variety of retinal ciliopathies. OSs possess many hundreds of stacked membranous disks, which capture photons and scaffold the phototransduction cascade. Although the molecular basis of OS structure remains unresolved, recent studies suggest that the photoreceptor-specific tetraspanin, peripherin-2/rds (P/rds), may contribute to the highly curved rim domains at disk edges. Here, we demonstrate that tetrameric P/rds self-assembly is required for generating high-curvature membranes in cellulo, implicating the noncovalent tetramer as a minimal unit of function. P/rds activity was promoted by disulfide-mediated tetramer polymerization, which transformed localized regions of curvature into high-curvature tubules of extended lengths. Transmission electron microscopy visualization of P/rds purified from OS membranes revealed disulfide-linked tetramer chains up to 100 nm long, suggesting that chains maintain membrane curvature continuity over extended distances. We tested this idea in Xenopus laevis photoreceptors, and found that transgenic expression of nonchain-forming P/rds generated abundant high-curvature OS membranes, which were improperly but specifically organized as ectopic incisures and disk rims. These striking phenotypes demonstrate the importance of P/rds tetramer chain formation for the continuity of rim formation during disk morphogenesis. Overall, this study advances understanding of the normal structure and function of P/rds for OS architecture and biogenesis, and clarifies how pathogenic loss-of-function mutations in P/rds cause photoreceptor structural defects to trigger progressive retinal degenerations. It also introduces the possibility that other tetraspanins may generate or sense membrane curvature in support of diverse biological functions.
Coagulopathy and transfusion ratios in pediatric trauma

BACKGROUND Coagulopathy has been associated with poor outcomes in adult and pediatric trauma. Previous clinical trials have shown benefits with balanced transfusion ratios in trauma resuscitation in adults, but smaller retrospective studies have not established the same in pediatrics. We constructed a pediatric trauma database at a Level I trauma center for analysis. METHODS The institutional trauma registry was queried for all pediatric trauma activations from 2008 to 2018. Patient identifiers were used to identify laboratory data from the electronic data warehouse. RESULTS There were 2,769 pediatric patients with trauma identified, with 1,492 arriving direct from the scene. Of those with complete transport data available, 81% arrived within 60 minutes from time of injury. Fifty-two patients were transfused in the first 24 hours, with 25 receiving greater than an estimated 40 mL/kg of blood products. No significant difference in ratios of red cell to plasma transfused at 24 hours was observed between patients surviving to discharge (1.4; 95% confidence interval, 1.0–1.6) and deceased (1.7; 95% confidence interval, 1.4–1.9) (p = 0.087). Among direct admissions, an abnormal prothrombin time or partial thromboplastin time taken within 2 hours of arrival was significantly associated with in-hospital mortality (p = 0.003 and <0.001), but no significant associations were seen for abnormal fibrinogen or platelet counts. Red cell to plasma transfusion ratios were not significantly associated with length of stay or ventilator days (p = 0.74 and 0.28). CONCLUSION There was no significant difference between transfusion ratios of surviving and deceased patients at 3- and 24-hour time points, including in a weight-adjusted highly transfused subgroup. Coagulopathy remains an important issue in pediatric trauma and may guide future multicenter studies in optimizing transfusion ratios in pediatric trauma. LEVEL OF EVIDENCE Retrospective comparative study, level III.
The association of potassium intake with bone mineral density and the prevalence of osteoporosis among older Korean adults

BACKGROUND/OBJECTIVES Osteoporosis is characterized by low bone mass and results in vulnerability to fracture. Calcium and vitamin D are known to play an important role in bone health. Recently, potassium has been identified as another important factor in skeletal health. We examined the link between potassium intake and bone health among the Korean older adult population. SUBJECTS/METHODS This retrospective, cross-sectional study included 8,732 men and postmenopausal women over 50 years old who completed the Korean National Health and Nutrition Survey (KNHANES) between 2008 and 2011. Potassium consumption was evaluated using a 24-hour recall method. Bone mineral density (BMD) was measured at three sites (total hip, femur neck, and lumbar spine) by dual-energy X-ray absorptiometry (DEXA). Multinomial logistic regression was used to examine the link between potassium intake and prevalence of osteoporosis and osteopenia, after controlling for potential confounding variables. RESULTS The BMD of the total femur and Ward's triangle were significantly different according to the potassium intake among men (P = 0.031 and P = 0.010, respectively). Women in the top tertile for potassium intake showed higher BMD than those in the bottom tertile at all measurement sites (all P < 0.05). Daily potassium intake was significantly related to a decreased risk of osteoporosis at the lumbar spine in postmenopausal women (odds ratios: 0.68, 95% confidence interval: 0.48-0.96, P trend = 0.031). However, the dietary potassium level was not related to the risk of osteoporosis in men. CONCLUSION Current findings indicate that higher dietary potassium levels have a favorable effect on bone health and preventing osteoporosis in older Korean women.
Genomewide Mapping of Selection Signatures and Genes for Extreme Feather Pecking in Two Divergently Selected Laying Hen Lines

Simple Summary Feather pecking is a behavior frequently occurring in commercial layer flocks. It often leads to skin injuries and cannibalism. Besides economic losses, severe animal welfare problems cannot be ignored. Previous research has shown that the trait is heritable. Thus breeding against feather pecking is possible, but phenotyping in a commercial environment is economically unfeasible at the moment because of the lack of proper techniques. Therefore, understanding the genetic background of the trait is mandatory to establish a genomic breeding program. This would require genotypic information of the hens, which is feasible under practical conditions. In the present study, we used different methods to identify regions in the genome that influence feather pecking and extreme feather pecking. We found one trait associated with the genomic region. The use of genotypic information from this region in terms of selection against the undesired behavior may help to improve animal welfare in layer flocks. Abstract Feather pecking (FP) is a longstanding serious problem in commercial flocks of laying hens. It is a highly polygenic trait and the genetic background is still not completely understood. In order to find genomic regions influencing FP, selection signatures between laying hen lines divergently selected for high and low feather pecking were mapped using the intra-population iHS and the inter-population FST approach. In addition, the existence of an extreme subgroup of FP hens (EFP) across both selected lines has been demonstrated by fitting a mixture of negative binomial distributions to the data and calculating the posterior probability of belonging to the extreme subgroup (pEFP) for each hen. A genomewide association study (GWAS) was performed for the traits pEFP and FP delivered (FPD) with a subsequent post GWAS analysis. Mapping of selection signatures revealed no clear regions under selection. GWAS revealed a region on Chromosome 1, where the existence of a QTL influencing FP is likely. The candidate genes found in this region are a part of the GABAergic system, which has already been linked to FP in previous studies. Despite the polygenic nature of FP, selection on these candidate genes may reduce FP.
The stress polarity signaling (SPS) pathway serves as a marker and a target in the leaky gut barrier: implications in aging and cancer

Using patient-derived organoids the authors show how a specialized polarity pathway protects our gut barrier from stress-induced collapse. Findings highlight both diagnostic and therapeutic potential of the pathway for treating gut barrier dysfunction in aging, cancer, and dysbiosis. The gut barrier separates trillions of microbes from the largest immune system in the body; when compromised, a “leaky” gut barrier fuels systemic inflammation, which hastens the progression of chronic diseases. Strategies to detect and repair the leaky gut barrier remain urgent and unmet needs. Recently, a stress-polarity signaling (SPS) pathway has been described in which the metabolic sensor, AMP-kinase acts via its effector, GIV (also known as Girdin) to augment epithelial polarity exclusively under energetic stress and suppresses tumor formation. Using murine and human colon-derived organoids, and enteroid-derived monolayers (EDMs) that are exposed to stressors, we reveal that the SPS-pathway is active in the intestinal epithelium and requires a catalytically active AMP-kinase. Its pharmacologic augmentation resists stress-induced collapse of the epithelium when challenged with microbes or microbial products. In addition, the SPS-pathway is suppressed in the aging gut, and its reactivation in enteroid-derived monolayers reverses aging-associated inflammation and loss of barrier function. It is also silenced during progression of colorectal cancers. These findings reveal the importance of the SPS-pathway in the gut and highlights its therapeutic potential for treating gut barrier dysfunction in aging, cancer, and dysbiosis.
Diaphragm thickening assessed by ultrasonography is lower than healthy adults in patients with chronic obstructive pulmonary disease

Ultrasound imaging has been widely used for imaging of the diaphragm thickness (Tdi) and thickening. Few studies assessed the Tdi using ultrasonography in patients with chronic obstructive pulmonary disease (COPD). We measured the Tdi and thickening in patients with COPD compared with healthy younger and healthy older adults to reveal the influence of ageing and/or COPD.
Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies

Background: Angiopoietin-2 (Ang-2), as one of the ligands of endothelial receptor Tie2, is known to be significant for vessel maturation and stabilization after birth. Previous studies showed the relationship between Ang-2 level and the risk of mortality in patients with acute respiratory distress syndrome (ARDS). However, the link between circulating Ang-2 and the risk of mortality in patients with ARDS varied in different investigations. Results: We performed a systematic review and meta-analysis of all available cohort studies regarding the association between baseline circulating Ang-2 and mortality in patients with ARDS. Among the 10 eligible studies, pooled odds ratio (OR) showed that high Ang-2 level contributed to ARDS mortality [OR = 1.56, 95% confidence interval (CI): 1.30–1.89, I2 = 76.2%]. Stratified analysis revealed that higher circulating Ang-2 was related to a 30% higher risk in the high-quality scores group (OR = 1.68, 95% CI: 1.33–2.68, I2 = 62.4%). The I2 of the bad compliance group decreased from 76.2% to 8.5%, which suggested that compliance is a significant source of heterogeneity. This association may be blunted by potential bias, although the results was not meaningfully changed by omitting only one study at a time. Further subgroup analysis and meta-regression support that compliance of patients also affects the results significantly, compared with the publication year, follow-up duration, the samples, or population characteristics. Conclusion: Participants with higher baseline Ang-2 were at a higher risk for future risk of mortality in patients with ARDS. Higher circulating Ang-2 levels could independently predict the risk of mortality in patients with ARDS. However, further large scale prospective cohorts or even interventional studies are warranted to evaluate the diagnostic power of Ang-2 and its causative role on ARDS outcome. The reviews of this paper are available via the supplemental material section.
Liver Iron Retention Estimated from Utilization of Oral and Intravenous Radioiron in Various Anemias and Hemochromatosis in Humans

Patients with hereditary hemochromatosis and non-transfusion-dependent hereditary anemia develop predominantly liver iron-overload. We present a unique method allowing quantification of liver iron retention in humans during first-pass of 59Fe-labeled iron through the portal system, using standard ferrokinetic techniques measuring red cell iron uptake after oral and intravenous 59Fe administration. We present data from patients with iron deficiency (ID; N = 47), hereditary hemochromatosis (HH; N = 121) and non-transfusion-dependent hereditary anemia (HA; N = 40). Mean mucosal iron uptake and mucosal iron transfer (±SD) were elevated in patients with HH (59 ± 18%, 80 ± 15% respectively), HA (65 ± 17%, 74 ± 18%) and ID (84 ± 14%, 94 ± 6%) compared to healthy controls (43 ± 19%, 64 ± 18%) (p < 0.05) resulting in increased iron retention after 14 days compared to healthy controls in all groups (p < 0.01). The fraction of retained iron utilized for red cell production was 0.37 ± 0.17 in untreated HA, 0.55 ± 0.20 in untreated HH and 0.99 ± 0.22 in ID (p < 0.01). Interestingly, compared to red blood cell iron utilization after oral iron administration, red blood cell iron utilization was higher after injection of transferrin-bound iron in HA and HH. Liver iron retention was considerably higher in HH and HA compared to ID. We hypothesize that albumin serves as a scavenger of absorbed Fe(II) for delivering albumin-bound Fe(III) to hepatocytes.
Genome-Wide Characterization and Expression Profiling of GASA Genes during Different Stages of Seed Development in Grapevine (Vitis vinifera L.) Predict Their Involvement in Seed Development

Members of the plant-specific GASA (gibberellic acid-stimulated Arabidopsis) gene family have multiple potential roles in plant growth and development, particularly in flower induction and seed development. However, limited information is available about the functions of these genes in fruit plants, particularly in grapes. We identified 14 GASA genes in grapevine (Vitis vinifera L.) and performed comprehensive bioinformatics and expression analyses. In the bioinformatics analysis, the locations of genes on chromosomes, physiochemical properties of proteins, protein structure, and subcellular positions were described. We evaluated GASA proteins in terms of domain structure, exon-intron distribution, motif arrangements, promoter analysis, phylogenetic, and evolutionary history. According to the results, the GASA domain is conserved in all proteins and the proteins are divided into three well-conserved subgroups. Synteny analysis proposed that segmental and tandem duplication have played a role in the expansion of the GASA gene family in grapes, and duplicated gene pairs have negative selection pressure. Most of the proteins were predicted to be in the extracellular region, chloroplasts, and the vacuole. In silico promoter analysis suggested that the GASA genes may influence different hormone signaling pathways and stress-related mechanisms. Additionally, we performed a comparison of the expression between seedless (Thompson seedless) and seeded (Red globe) cultivars in different plant parts, including the ovule during different stages of development. Furthermore, some genes were differentially expressed in different tissues, signifying their role in grapevine growth and development. Several genes (VvGASA2 and 7) showed different expression levels in later phases of seed development in Red globe and Thompson seedless, suggesting their involvement in seed development. Our study presents the first genome-wide identification and expression profiling of grapevine GASA genes and provides the basis for functional characterization of GASA genes in grapes. We surmise that this information may provide new potential resources for the molecular breeding of grapes.
Developing sustainable capacity-building in mental health research: implementation outcomes of training of trainers in systematic reviewing

ABSTRACT Less than 1% of biomedical research papers originate in Africa. Locally relevant mental health research, including synthesis of existing evidence, is essential for developing interventions and strengthening health systems, but institutions may lack the capacity to deliver training on systematic reviewing for publication in international journals. This paper describes the development and implementation of a training-of-trainers (ToT) course on systematic reviewing. The ToT prepared junior faculty (‘trainers’) from universities in Ethiopia, Malawi, and Zimbabwe to lead a five-day systematic reviewing workshop. Using an evaluation framework based on implementation science outcomes, the feasibility of the ToT was assessed by tracking the number of workshops the trainers subsequently conducted and the number of trainers and trainees who participated; acceptability was assessed through post-workshop surveys on trainee perspectives; impact was evaluated through trainee scores on a 15-item multiple choice test on systematic reviewing concepts; and sustainability was assessed based on whether the workshop was integrated into university curricula. Twelve trainers (86% of those trained) facilitated a total of seven workshops in their home countries (total 103 trainees). The first workshop run in each country was evaluated, and there was a significant improvement in mean knowledge scores between pre- and post-tests among trainees (MD= 3.07, t= 5.90, 95% CI 2.02–4.11). In two of the three countries, there are efforts to integrate the systematic review workshop into university curricula. The cost of the workshop led by the international trainer was $1480 per participant, whereas the trainer-led workshops cost approximately $240 per participant. Overall, ToT is relatively new to research capacity building, although it has been used widely in clinical settings. Our findings suggest ToT is a promising, low-cost way to develop both technical skills of individuals and the pedagogical capacity of universities, and to promote sustainability of research capacity building programs that often have time-limited grant funding.
Short term association between ozone and mortality: global two stage time series study in 406 locations in 20 countries

Abstract Objective To assess short term mortality risks and excess mortality associated with exposure to ozone in several cities worldwide. Design Two stage time series analysis. Setting 406 cities in 20 countries, with overlapping periods between 1985 and 2015, collected from the database of Multi-City Multi-Country Collaborative Research Network. Population Deaths for all causes or for external causes only registered in each city within the study period. Main outcome measures Daily total mortality (all or non-external causes only). Results A total of 45 165 171 deaths were analysed in the 406 cities. On average, a 10 µg/m3 increase in ozone during the current and previous day was associated with an overall relative risk of mortality of 1.0018 (95% confidence interval 1.0012 to 1.0024). Some heterogeneity was found across countries, with estimates ranging from greater than 1.0020 in the United Kingdom, South Africa, Estonia, and Canada to less than 1.0008 in Mexico and Spain. Short term excess mortality in association with exposure to ozone higher than maximum background levels (70 µg/m3) was 0.26% (95% confidence interval 0.24% to 0.28%), corresponding to 8203 annual excess deaths (95% confidence interval 3525 to 12 840) across the 406 cities studied. The excess remained at 0.20% (0.18% to 0.22%) when restricting to days above the WHO guideline (100 µg/m3), corresponding to 6262 annual excess deaths (1413 to 11 065). Above more lenient thresholds for air quality standards in Europe, America, and China, excess mortality was 0.14%, 0.09%, and 0.05%, respectively. Conclusions Results suggest that ozone related mortality could be potentially reduced under stricter air quality standards. These findings have relevance for the implementation of efficient clean air interventions and mitigation strategies designed within national and international climate policies.