Miracle-dz/UniFAR-FTUs huggingface dataset:
A case of G1013R FBN1 mutation: A potential genotype–phenotype correlation in severe Marfan syndrome

Marfan Syndrome (MFS) is an autosomal dominant connective tissue disorder with a wide range of severities. Ninety‐five percent of MFS probands have a mutation in the fibrillin‐1 gene (FBN1); however, there are a high number of unique mutations complicating attempts at establishing any phenotype–genotype correlations for this disease (Tiecke et al., European Journal of Human Genetics, 2001, 9, 13–21). One of the few extant genotype–phenotype correlations is in exon 24–32 which have been associated with a severe pediatric presentation of neonatal MFS with predominately cardiovascular symptoms. We present a 24‐year‐old male patient with a heterozygous de novo variant NM_000138. 4: c.3037G>A (p.G1013R) located in exon 25 of the FBN1 gene. The patient was found to have dysplastic mitral and tricuspid valves with dilated aortic root at 9 months of age. This is a notable case in that the location of this patient's mutation and his age of symptom onset would indicate a guarded prognosis. Further, this mutation, FBN1 G1013R, has been reported in the literature in four other unrelated patients all of whom presented at a young age with cardiac involvement and all of whom had relative longevity when compared to other patients with mutations in this exon 24–32 hot spot. These findings may represent a more specific genotype–phenotype correlation within this mutational hot spot.
HO-1 Interactors Involved in the Colonization of the Bone Niche: Role of ANXA2 in Prostate Cancer Progression

Background: Prostate cancer (PCa) dissemination shows a tendency to develop in the bone, where heme oxygenase 1 (HO-1) plays a critical role in bone remodeling. Previously by LC/ESI-MSMS, we screened for HO-1 interacting proteins and identified annexin 2 (ANXA2). The aim of this study was to analyze the relevance of ANXA2/HO-1 in PCa and bone metastasis. Methods: We assessed ANXA2 levels using a co-culture transwell system of PC3 cells (pre-treated or not with hemin, an HO-1 specific inducer) and the pre-osteoclastic Raw264.7 cell line. Results: Under co-culture conditions, ANXA2 mRNA levels were significantly modulated in both cell lines. Immunofluorescence analysis unveiled a clear ANXA2 reduction in cell membrane immunostaining for Raw264.7 under the same conditions. This effect was supported by the detection of a decrease in Ca2+ concentration in the conditioned medium. HO-1 induction in tumor cells prevented both, the ANXA2 intracellular relocation and the decrease in Ca2+ concentration. Further, secretome analysis revealed urokinase (uPA) as a key player in the communication between osteoclast progenitors and PC3 cells. To assess the clinical significance of ANXA2/HO-1, we performed a bioinformatics analysis and identified that low expression of each gene strongly associated with poor prognosis in PCa regardless of the clinico-pathological parameters assessed. Further, these genes appear to behave in a dependent manner. Conclusions: ANXA2/HO-1 rises as a critical axis in PCa.
Damaging de novo missense variants in EEF1A2 lead to a developmental and degenerative epileptic‐dyskinetic encephalopathy

Heterozygous de novo variants in the eukaryotic elongation factor EEF1A2 have previously been described in association with intellectual disability and epilepsy but never functionally validated. Here we report 14 new individuals with heterozygous EEF1A2 variants. We functionally validate multiple variants as protein‐damaging using heterologous expression and complementation analysis. Our findings allow us to confirm multiple variants as pathogenic and broaden the phenotypic spectrum to include dystonia/choreoathetosis, and in some cases a degenerative course with cerebral and cerebellar atrophy. Pathogenic variants appear to act via a haploinsufficiency mechanism, disrupting both the protein synthesis and integrated stress response functions of EEF1A2. Our studies provide evidence that EEF1A2 is highly intolerant to variation and that de novo pathogenic variants lead to an epileptic‐dyskinetic encephalopathy with both neurodevelopmental and neurodegenerative features. Developmental features may be driven by impaired synaptic protein synthesis during early brain development while progressive symptoms may be linked to an impaired ability to handle cytotoxic stressors.
A Literature Review on Psychosocial Support for Disaster Responders: Qualitative Synthesis with Recommended Actions for Protecting and Promoting the Mental Health of Responders

Little scientific evidence exists on ways to decrease the psychological stress experienced by disaster responders, or how to maintain and improve their mental health. In an effort to grasp the current state of research, we examined research papers, agency reports, the manuals of aid organisations, and educational materials, in both English and Japanese. Using MEDLINE, Ichushi-Web (Japanese search engine), Google Scholar, websites of the United Nations agencies, and the database of the Grants System for Japan’s Ministry of Health, Labour, and Welfare, 71 pertinent materials were identified, 49 of which were analysed. As a result, 55 actions were extracted that could potentially protect and improve the mental health of disaster responders, leading to specific recommendations. These include (1) during the pre-activity phase, enabling responders to anticipate stressful situations at a disaster site and preparing them to monitor their stress level; (2) during the activity phase, engaging in preventive measures against on-site stress; (3) using external professional support when the level of stress is excessive; and (4) after the disaster response, getting back to routines, sharing of experiences, and long-term follow-up. Our results highlighted the need to offer psychological support to disaster responders throughout the various phases of their duties.
Ocular axial length and straylight

Straylight refers to an optical phenomenon that takes places in the eye and leads to a deterioration of the retinal image. Past clinical findings suggest an increase of straylight with the eye's axial length, but the aetiology of the phenomenon was unclear. The purpose of this work is to demonstrate, through raytracing, simple geometrical optics, and the well‐established inverse‐angle square law for the angular distribution of straylight, why straylight increases when a myopic eye is corrected with spectacles.
Limbostomy: Longitudinal Intravital Microendoscopy in Murine Osteotomies

Bone healing involves the interplay of immune cells, mesenchymal cells, and vasculature over the time course of regeneration. Approaches to quantify the spatiotemporal aspects of bone healing at cellular resolution during long bone healing do not yet exist. Here, a novel technique termed Limbostomy is presented, which combines intravital microendoscopy with an osteotomy. This design allows a modular combination of an internal fixator plate with a gradient refractive index (GRIN) lens at various depths in the bone marrow and can be combined with a surgical osteotomy procedure. The field of view (FOV) covers a significant area of the fracture gap and allows monitoring cellular processes in vivo. The GRIN lens causes intrinsic optical aberrations which have to be corrected. The optical system was characterized and a postprocessing algorithm was developed. It corrects for wave front aberration‐induced image plane deformation and for background and noise signals, enabling us to observe subcellular processes. Exemplarily, we quantitatively and qualitatively analyze angiogenesis in bone regeneration. We make use of a transgenic reporter mouse strain with nucleargreen fluorescent protein and membrane‐bound tdTomato under the Cadherin‐5 promoter. We observe two phases of vascularization. First, rapid vessel sprouting pervades the FOV within 3–4 days after osteotomy. Second, the vessel network continues to be dynamically remodeled until the end of our observation time, 14 days after surgery. Limbostomy opens a unique set of opportunities and allows further insight on spatiotemporal aspects of bone marrow biology, for example, hematopoiesis, analysis of cellular niches, immunological memory, and vascularization in the bone marrow during health and disease. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.
SAKK38/07 study: integration of baseline metabolic heterogeneity and metabolic tumor volume in DLBCL prognostic model.

Several functional parameters from baseline (18)F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography have been proposed as promising biomarkers of treatment efficacy in diffuse large B-cell lymphoma (DLBCL). We tested their ability to predict outcome in 2 cohorts of DLBCL patients receiving conventional immunochemotherapy (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone [R-CHOP] regimen), either every 14 (R-CHOP14) or 21 days (R-CHOP21). Baseline PET analysis was performed in 141 patients with DLBCL treated with R-CHOP14 in the prospective SAKK38/07 study (NCT00544219) of the Swiss Group for Clinical Cancer Research (testing set). Reproducibility was examined in a validation set of 113 patients treated with R-CHOP21. In the SAKK38/07 cohort, progression-free survival (PFS) at 5 years was 83% for patients with low metabolic tumor volume (MTV) and 59% for those with high MTV (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.6-7.0; P = .0005), whereas overall survival (OS) was 91% and 64%, respectively (HR, 4.4; 95% CI, 1.9-10; P = .0001). MTV was the most powerful predictor of outcome also in the validation set. Elevated metabolic heterogeneity (MH) significantly predicted poorer outcomes in the subgroups of patients with elevated MTV. A model integrating MTV and MH identified high-risk patients with shorter PFS (testing set: HR, 5.6; 95% CI, 1.8-17; P < .0001; validation set: HR, 5.6; 95% CI, 1.7-18; P = .0002) and shorter OS (testing set: HR, 9.5; 95% CI, 1.7-52; P < .0001; validation set: HR, 7.6; 95% CI, 2.0-28; P = .0003). This finding was confirmed by an unsupervised regression tree analysis indicating that prognostic models based on MTV and MH may allow early identification of refractory patients who might benefit from treatment intensification. This trial was registered at www.clinicaltrials. gov as #NCT00544219.
Mortality Risk in Necrotizing Fasciitis: National Prevalence, Trend, and Burden.

Background: Necrotizing fasciitis (NF) is a fulminant, life-threating infection of fascia and subcutaneous tissue. Because of the low incidence, previous studies were statistically underpowered to assess factors associated with the risk of mortality. The aim of this study is to identify the risk factors associated with mortality in this select group of patients. Methods: A retrospective cross-sectional study was performed utilizing the Nationwide Readmissions Database, 2010-2014. The database captures 56.6% of all U.S. annual hospitalizations. Study population included inpatients admitted emergently with NF. Results: A total of 4,178 cases were included, of which 2,061(48.9%) patients had a history of diabetes mellitus (DM). The most common presentation was septicemia (39.5%) and 9.2% were admitted initially as cellulitis/abscess. Overall mortality risk was 12.6% with no substantial change in the annual trend. Mortality in patients with diabetes was substantially lower (8.5% vs. 16.5%, odds ratio [OR]: 0.44, 95% confidence interval [CI] = [0.34, 0.56], p < 0.001). Factors associated with a higher mortality risk included: older age, chronic liver diseases, disseminated intravascular coagulopathy, septic shock, pulmonary complications, acute renal failure, and not undergoing surgical intervention (p < 0.05 each). Patients who did not undergo surgical debridement were more likely to be ≥65 years of age and have multiple comorbidities. Hyperbaric oxygen therapy and intravenous immunoglobulin were used in 1.3% and 0.3% of the sample, respectively, with no reported use among patients who died. Conclusions: This study provides a new and updated perspective on the prevalence, trend, and outcomes of NF in the United States. Necrotizing fasciitis is associated with septicemia and lack of surgical intervention is associated with a higher mortality.
Ultrasound Assessment of the Abdominal Wall Muscles in Women with and without Primary Dysmenorrhea: A Cross-Sectional Study

Background: Primary dysmenorrhea (PD) is one of the most common gynecological disorders in women of reproductive age that may affect quality of life. It is believed that the underlying cause of PD may be the excessive production of prostaglandins (PGs), however, between 20%–25% of women with PD did not respond to pharmacological treatments, showing that nociceptive mechanisms underlying PD are still not understood. The purpose of this study was to measure and compare, through the use of ultrasound imaging, the thickness at rest of the abdominal wall, as well as the interrecti distance (IRD), in women with and without PD. Methods: A cross-sectional study has been performed using ultrasound imaging (USI) to measure the resting thickness of the external oblique (EO), internal oblique (IO), transversus abdominis (TrAb), rectus abdominis (RA), as well as the IRD in a sample of 39 women, 19 with PD and 20 without PD (median ± IR age: 20 ± 4 and 22.5 ± 7 years, respectively). Results: Findings of muscular thickness did not reveal statically significant differences (p < 0.05) in EO, IO, TrAb, RA, and the IRD between the PD group and control group. Conclusions: These findings suggest that the thickness of the abdominal wall is not associated with PD.
Milking time hygiene interventions on dairy farms reduce spore counts in raw milk.

Spore-forming bacteria, such as Paenibacillus spp. and Bacillus spp. , can survive HTST pasteurization in spore form and affect the quality of dairy products (e.g., spoilage in fluid milk). With the demand for higher quality finished products that have longer shelf lives and that can be distributed further and to new markets, dairy processors are becoming interested in obtaining low-spore raw milk supplies. One method to reduce spores in the dairy system will require disrupting the transmission of spores from environmental locations, where they are often found at high concentrations (e.g., manure, bedding), into bulk tank raw milk. Previous research has suggested that cow hygiene factors (e.g., udder hygiene, level of spores in milk from individual cows) are important for the transmission of spores into bulk tank raw milk, suggesting that one potential strategy to reduce spores in bulk tank milk should target cow hygiene in the parlor. To that end, we conducted a study on 5 New York dairy farms over a 15-mo period to evaluate the effect of a combination of intervention strategies, applied together, on the levels of aerobic spores in bulk tank raw milk. The combination of interventions included (1) training milking staff to focus on teat-end cleaning during milking preparation, and (2) implementing changes in laundered towel preparation (i.e., use of detergent, chlorine bleach, and drying). Study design involved collecting bulk tank raw milk samples for a week before and a week after initiating the combination of interventions (i.e., training on the importance of teat-end cleaning and towel treatment). Observations on teat-end condition, udder hygiene scores, and number of kickoffs during milking were also collected for 24 h before and after implementation of the interventions. A total of 355 bulk tank raw milk samples were collected with mean mesophilic and thermophilic spore counts of 2.1 and 2.4 cfu/mL, respectively, before interventions were applied, and 1.6 and 1.5 cfu/mL, respectively, after the interventions were applied. These reductions represent decreases of 37 and 40% in bulk tank raw milk mesophilic spores and thermophilic spores, respectively. Importantly, spore reductions were observed during each of the 3 visits once the interventions were applied, and the largest reduction in spores was recorded for the first sampling after training the milking staff. Further, when a higher proportion of very rough teat ends was observed, bulk tank milk thermophilic spore counts were significantly higher. The intervention strategies tested here represent easy-to-execute cleaning strategies (e.g., focusing on teat-end hygiene and towel washing procedures) that can reduce bulk tank raw milk spore levels. Future studies should validate the effect of on-farm interventions for reduced spore raw milk on corresponding processed product quality and will need to verify the effects of these small changes on product shelf life.
Disappearance of middle ear effusion in acute otitis media monitored daily with tympanometry

Background: Disappearance of middle ear effusion is one of the most important outcomes in the treatment of acute otitis media (AOM). Aim: To evaluate the duration of effusion in AOM treated by antimicrobials and to find factors influencing it. Methods: Parents of 90 children with AOM monitored daily the disappearance of effusion with tympanometry. The children were randomly allocated to be treated with either oral amoxicillin or cefuroxime‐axetil for 10 d. Daily monitoring lasted for 14 d or until the tympanogram was normal (curve A or C) in both ears. Pneumatic otoscopy was carried out every 2 wk. Results: Normal tympanograms were obtained after a median time of 7.5 d (range 1–58 d) among 75 successfully monitored patients. In two‐thirds (69%) of them, effusion resolved in 14 d. The median duration of effusion did not differ significantly between the two treatment groups (8 vs 7 days, p=0.7). The children who had unilateral AOM cured more rapidly than those with bilateral AOM (5 vs 19 d, p<0.001). In logistic regression analysis adjusted for age, bilaterality explained treatment failure at 2 wk with an odds ratio of 28.1 (95% CI 4.6–169.5, p<0.001).
The Rice Basic Helix–Loop–Helix 79 (OsbHLH079) Determines Leaf Angle and Grain Shape

Changes in plant architecture, such as leaf size, leaf shape, leaf angle, plant height, and floral organs, have been major factors in improving the yield of cereal crops. Moreover, changes in grain size and weight can also increase yield. Therefore, screens for additional factors affecting plant architecture and grain morphology may enable additional improvements in yield. Among the basic Helix-Loop-Helix (bHLH) transcription factors in rice (Oryza sativa), we found an enhancer-trap T-DNA insertion mutant of OsbHLH079 (termed osbhlh079-D). The osbhlh079-D mutant showed a wide leaf angle phenotype and produced long grains, similar to the phenotypes of mutants with increased brassinosteroid (BR) levels or enhanced BR signaling. Reverse transcription-quantitative PCR analysis showed that BR signaling-associated genes are largely upregulated in osbhlh079-D, but BR biosynthesis-associated genes are not upregulated, compared with its parental japonica cultivar ‘Dongjin’. Consistent with this, osbhlh079-D was hypersensitive to BR treatment. Scanning electron microscopy revealed that the expansion of cell size in the adaxial side of the lamina joint was responsible for the increase in leaf angle in osbhlh079-D. The expression of cell-elongation-associated genes encoding expansins and xyloglucan endotransglycosylases/hydrolases increased in the lamina joints of leaves in osbhlh079-D. The regulatory function of OsbHLH079 was further confirmed by analyzing 35S::OsbHLH079 overexpression and 35S::RNAi-OsbHLH079 gene silencing lines. The 35S::OsbHLH079 plants showed similar phenotypes to osbhlh079-D, and the 35S::RNAi-OsbHLH079 plants displayed opposite phenotypes to osbhlh079-D. Taking these observations together, we propose that OsbHLH079 functions as a positive regulator of BR signaling in rice.
US-guided Microwave ablation of Low-risk Papillary thyroid Microcarcinoma: Longer-term results of a Prospective study.

BACKGROUND Papillary thyroid microcarcinoma (PTMC) has become a main cause of the extremely high incidence of thyroid carcinoma. This study aimed to evaluate the longer-term effectiveness of ultrasound (US)-guided microwave ablation (MWA) for treatment of low-risk PTMC with a large population. METHODS This prospective study was approved by ethics committee of our institution. MWA was performed under US-guidance for 119 unifocal PTMC patients without clinically cervical or distant metastasis. The target ablation zone exceeded the tumour edge judged by contrast-enhanced US to avoid marginal residue and recurrence. US and thyroid function evaluation were followed at 1, 3, 6 and 12 months after treatment and every 6-12 months thereafter. Any adverse event associated with MWA was evaluated. RESULTS The follow-up duration after MWA was 37.2±20.9 months (range, 12-101 months). Tumour volume decreased significantly from 1.87±1.03 ml immediately after MWA to 0.01±0.04 ml at the final evaluation (p <0.001), with a mean volume reduction ratio of 99.4±2.2% and 107 cases (93.9%) got complete remission. A patient was detected with cervical lymph node metastasis at 26-month follow-up and underwent one additional MWA treatment successfully. No distant metastasis was observed. All the acquired histological pathology results confirmed the absence of residual or recurrent tumuor cells after MWA. No delayed complications associated with MWA were encountered for all patients. CONCLUSIONS Percutaneous MWA is technically feasible for complete PTMC destruction and showed well longer-term effectiveness, thus it seems to be an effective nonsurgical therapy to complement the current recommendation for selected low-risk PTMC patients.
Circulating and tissue microRNAs as a potential diagnostic biomarker in patients with thrombotic events

Venous and arterial thrombosis are conditions that have a considerable burden if left untreated. The hypoxia‐induced by the occluded vessel can disrupt the circulation of any organ, the cornerstone of treating thrombosis is rapid diagnosis and appropriate treatment. Diagnosis of thrombosis may be made by using laboratory tests or imaging techniques in individuals who have clinical manifestations of a thrombotic event. The use of serum micro ribonucleic acids (RNAs) has recently been applied to the diagnosis of thrombosis. These small RNA molecules are emerging as new diagnostic markers but have had very limited applications in vascular disease. Most of the articles provided various microRNAs with different levels of accuracy. However, there remains a lack of an appropriate panel of the most specific microRNA in the literature. The purpose of the present review was to summarize the existing data on the use of microRNAs as a diagnostic biomarker for venous thrombosis.
Coworker Trust and Knowledge Sharing among Public Sector Employees in Kenya

This study investigates the association between coworker trust and knowledge sharing among public sector employees with additional consideration of team-member exchange (TMX). It also accounts for the use of supportive technology as a determinant of coworker trust. The study aims to develop a framework to help organizations understand the complex associations among coworker trust, exchange, and knowledge sharing and recognizes the roles of supportive technology and task interdependence in those associations. A cross-sectional survey of 255 employees at three Kenyan public organizations was analyzed. A hierarchical regression analysis tested five hypotheses in eight models to estimate direct, moderating, and mediating relationships. Coworker trust was positively related to knowledge sharing and TMX. Supportive technology significantly moderated the relationships; however, task interdependence was not statistically significant. The results imply that organizations might increase knowledge sharing by focusing on building trustful bonds among workers.