Miracle-dz/UniFAR-FTUs huggingface dataset:
The Impact of Increased Allocation Priority for Children Awaiting Liver Transplant: A Liver Simulated Allocation Model (LSAM) Analysis

Objective: The aim of the study was to investigate the impact of prioritizing infants, children, adolescents, and the sickest adults (Status 1) for deceased donor livers. We compared outcomes under two “SharePeds” allocation schema, which prioritize children and Status 1 adults for national sharing and enhanced access to pediatric donors or all donors younger than 35 years, to outcomes under the allocation plan approved by the Organ Procurement and Transplant Network in December 2017 (Organ Procurement and Transplantation Network [OPTN] 12-2017). Methods: The 2017 Liver Simulated Allocation Model and Scientific Registry of Transplant Recipients data on all US liver transplant candidates and liver offers 7/2013 to 6/2016 were used to predict waitlist deaths, transplants, and post-transplant deaths under the OPTN 12-2017 and SharePeds schema. Results: Prioritizing national sharing of pediatric donor livers with children (SharePeds 1) would decrease waitlist deaths for infants (<2 years, P = 0.0003) and children (2–11 years, P = 0.001), with no significant change for adults (P = 0.13). Prioritizing national sharing of all younger than 35-year-old deceased donor livers with children and Status 1A adults (SharePeds 2) would decrease waitlist deaths for infants, children, and all Status 1A/B patients (P < 0.0001 for each). SharePeds 1 and 2 would increase the number of liver transplants done in infants, children, and adolescents compared to the OPTN-2017 schema (P < 0.00005 for all age groups). Both SharePeds schema would increase the percentage of pediatric livers transplanted into pediatric recipients. Conclusions: Waitlist deaths could be significantly decreased, and liver transplants increased, for children and the sickest adults, by prioritizing children for pediatric livers and with broader national sharing of deceased donor livers.
Communication about prognosis and end‐of‐life in pediatric organ failure and transplantation

Despite advancements in treatment and survival, pediatric organ failure and transplant populations continue to face significant risks of morbidity and mortality. Little scientific attention has been given to addressing the end‐of‐life care needs of this growing population of young people. This study characterized current practices, beliefs, and challenges specific to the disclosure of prognosis and end‐of‐life care topics among providers caring for pediatric organ failure and transplant populations.
Urinary steroid profiling: a powerful method for the diagnosis of abnormal steroidogenesis

In this review, we will focus on urinary steroid profiling by gas chromatography mass spectrometry (GC/MS) and summarize its contribution to the diagnosis of abnormal steroidogenesis; congenital enzyme deficiency of steroid synthesis and metabolism, adrenal carcinoma and other steroid related diseases. Mass spectrometry technique, such as GC/MS and liquid chromatography tandem mass spectrometry (LC-MS/MS), has become the main tool for steroid measurement and GC/MS is mainly used for urine sampling. We will discuss the pros and cons of urinary steroid profiling by GC/MS and LC-MS/MS. Although GC/MS analysis needs intricate pretreatment, time and expenses, sensitive and simultaneous measurement of whole pathway steroid measurements have improved the accuracy of diagnosis.
Role of postoperative adjuvant radiotherapy for locally advanced laryngeal cancer: a meta-analysis

Abstract Background: Studies have shown mixed results on the role of postoperative adjuvant radiotherapy (PORT) in surgically managed locally advanced laryngeal cancer. Objectives: The aim of this study is to review and investigate the role of PORT in patients with locally advanced laryngeal cancer using meta-analysis. Materials and methods: Relevant studies were searched using PubMed and eligible information has been extracted. Then, meta-analysis of hazard ratio (HR) was performed to evaluate the role of PORT in locally advanced laryngeal cancer. Results: This meta-analysis included 7 published studies containing 2007 patients. For overall survival (OS), patients of locally advanced laryngeal cancer who were treated with PORT have a combined hazard ratio (HR) of 0.67 with 95%CI (0.56, 0.79), compared to those who were not treated with PORT, which was significantly associated with better survival. PORT was also associated with a better disease-free survival (DFS) and local control rate (LCR) in patients with locally advanced laryngeal cancer. The pooled HR and 95%CI for DFS and LCR were 0.72 (0.53, 0.99) and 0.29 (0.09, 0.99), respectively. Conclusions and significance: This study suggested that PORT could improve the survival of patients with surgically managed locally advanced laryngeal cancer.
The OsmiR396–OsGRF8–OsF3H‐flavonoid pathway mediates resistance to the brown planthopper in rice (Oryza sativa)

Summary Multi‐functional microRNAs (miRNAs) are emerging as key modulators of plant–pathogen interactions. Although the involvement of some miRNAs in plant–insect interactions has been revealed, the underlying mechanisms are still elusive. The brown planthopper (BPH) is the most notorious rice (Oryza sativa)‐specific insect that causes severe yield losses each year and requires urgent biological control. To reveal the miRNAs involved in rice–BPH interactions, we performed miRNA sequencing and identified BPH‐responsive OsmiR396. Sequestering OsmiR396 by overexpressing target mimicry (MIM396) in three genetic backgrounds indicated that OsmiR396 negatively regulated BPH resistance. Overexpression of one BPH‐responsive target gene of OsmiR396, growth regulating factor 8 (OsGRF8), showed resistance to BPH. Furthermore, the flavonoid contents increased in both the OsmiR396‐sequestered and the OsGRF8 overexpressing plants. By analysing 39 natural rice varieties, the elevated flavonoid contents were found to correlate with enhanced BPH resistance. Artificial applications of flavonoids to wild type (WT) plants also increased resistance to BPH. A BPH‐responsive flavanone 3‐hydroxylase (OsF3H) gene in the flavonoid biosynthetic pathway was proved to be directly regulated by OsGRF8. A genetic functional analysis of OsF3H revealed its positive role in mediating both the flavonoid contents and BPH resistance. And analysis of the genetic correlation between OsmiR396 and OsF3H showed that down‐regulation of OsF3H complemented the BPH resistance characteristic and simultaneously decreased the flavonoid contents of the MIM396 plants. Thus, we revealed a new BPH resistance mechanism mediated by the OsmiR396–OsGRF8–OsF3H–flavonoid pathway. Our study suggests potential applications of miRNAs in BPH resistance breeding.
Relapse-associated AURKB blunts the glucocorticoid sensitivity of B cell acute lymphoblastic leukemia

Significance Understanding the mechanism of glucocorticoid-induced cell death and resistance on relapse is essential to improve treatment of leukemias. We used functional genomics, integrating gene regulation, gene misexpression on relapse, and genome-wide shRNA screen in B cell acute lymphoblastic leukemia (B-ALL). This revealed that glucocorticoids deploy select transcriptional cofactors to regulate effector genes that drive, and buffer genes that restrain, cell death. Aurora kinase B (AURKB), a negative regulator of the EHMT1/2 coregulator complex, was found to be overexpressed on relapse. Inhibitors of AURKB enhanced glucocorticoid regulation of effector genes while leaving key buffering genes unperturbed, resulting in potentiated glucocorticoid sensitivity in B-ALL cell lines and relapsed patient samples. This provides a potential therapy and deeper understanding of glucocorticoids in leukemia. Glucocorticoids (GCs) are used in combination chemotherapies as front-line treatment for B cell acute lymphoblastic leukemia (B-ALL). Although effective, many patients relapse and become resistant to chemotherapy and GCs in particular. Why these patients relapse is not clear. We took a comprehensive, functional genomics approach to identify sources of GC resistance. A genome-wide shRNA screen identified the transcriptional coactivators EHMT2, EHMT1, and CBX3 as important contributors to GC-induced cell death. This complex selectively supports GC-induced expression of genes contributing to cell death. A metaanalysis of gene expression data from B-ALL patient specimens revealed that Aurora kinase B (AURKB), which restrains GC signaling by phosphorylating EHMT1-2, is overexpressed in relapsed B-ALL, suggesting it as a potential contributor to relapse. Inhibition of AURKB enhanced GC-induced expression of cell death genes, resulting in potentiation of GC cytotoxicity in cell lines and relapsed B-ALL patient samples. This function for AURKB is distinct from its canonical role in the cell cycle. These results show the utility of functional genomics in understanding mechanisms of resistance and rapidly identifying combination chemotherapeutics.
A Scaffold- and Serum-Free Method to Mimic Human Stable Cartilage Validated by Secretome.

IMPACT STATEMENT Promising adult stem cell sources for cartilage regeneration include adipose stem/stromal cells (ASCs) from subcutaneous adipose tissue. Our main objective was the development of a reproducible and easy-to-handle scaffold- and serum-free method to obtain stable cartilage from induced ASC spheroids. In addition to targeted protein profiling and biomechanical analysis, we provide the first characterization of the secretome composition for ASC spheroids, providing a useful tool to monitor in vitro chondrogenesis and a noninvasive quality control of tissue-engineered constructs. Furthermore, our secretome analysis revealed a potential novel biomarker-thrombospondin-1 (TSP-1), known by its antiangiogenic properties and recently described as an antihypertrophic protein.
Revealing the functions of novel mutations in RAB3GAP1 in Martsolf and Warburg micro syndromes

Purpose: Martsolf (MS) and Warburg micro syndromes (WARBM) are rare autosomal recessive inherited allelic disorders, which share similar clinical features including microcephaly, intellectual disability, brain malformations, ocular abnormalities, and spasticity. Here, we revealed the functions of novel mutations in RAB3GAP1 in a Turkish female patient with MS and two siblings with WARBM. We also present a review of MS patients as well as all reported RAB3GAP1 pathogenic mutations in the literature. Methods: We present a female with MS phenotype and two siblings with WARBM having more severe phenotypes. We utilized whole‐exome sequencing to identify the molecular basis of these syndromes and confirmed suspected variants by Sanger sequencing. Quantitative (q) RT‐PCR analysis was carried out to reveal the functions of novel splice site mutation detected in MS patient. Results: We found a novel homozygous c.2607‐1G>C splice site mutation in intron 22 of RAB3GAP1 in MS patient and a novel homozygous c. 2187_2188delinsCT, p.(Met729_Lys730delinsIleTer) mutation in exon 19 of RAB3GAP1 in the WARBM patients. We showed exon skipping in MS patient by Sanger sequencing and gel electrophoresis. qRT‐PCR analysis demonstrated the reduced expression of RAB3GAP1 in the patient with the c.2607‐1G>C splice site mutation compared to a healthy control individual. Conclusion: Here, we have studied two novel RAB3GAP1 mutations in two different phenotypes; a MS associated novel splice site mutation, and a WARBM1 associated novel deletion–insertion mutation. Our findings suggest that this splice site mutation is responsible for milder phenotype and the deletion–insertion mutation presented here is associated with severe phenotype.
Unveiling Genomic Diversity among Members of the Species Bifidobacterium pseudolongum, a Widely Distributed Gut Commensal of the Animal Kingdom

Currently, little information exists on the genetics of the B. pseudolongum taxon due to the limited number of sequenced genomes belonging to this species. In order to survey genome variability within this species and explore how members of this taxon evolved as commensals of the animal gut, we isolated and decoded the genomes of 51 newly isolated strains. Comparative genomics coupled with growth profiles on different carbohydrates has further provided insights concerning the genotype and phenotype of members of the B. pseudolongum taxon. ABSTRACT Bifidobacteria are commensals of the animal gut and are commonly found in mammals, birds, and social insects. Specifically, strains of Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium longum, and Bifidobacterium pseudolongum are widely distributed in the mammalian gut. In this context, we investigated the genetic variability and metabolic abilities of the B. pseudolongum taxon, whose genomic characterization has so far not received much attention. Phylogenomic analysis of the genome sequences of 60 B. pseudolongum strains revealed that B. pseudolongum subsp. globosum and B. pseudolongum subsp. pseudolongum may actually represent two distinct bifidobacterial species. Furthermore, our analysis highlighted metabolic differences between members of these two subspecies. Moreover, comparative analyses of genetic strategies to prevent invasion of foreign DNA revealed that the B. pseudolongum subsp. globosum group exhibits greater genome plasticity. In fact, the obtained findings indicate that B. pseudolongum subsp. globosum is more adaptable to different ecological niches such as the mammalian and avian gut than is B. pseudolongum subsp. pseudolongum. IMPORTANCE Currently, little information exists on the genetics of the B. pseudolongum taxon due to the limited number of sequenced genomes belonging to this species. In order to survey genome variability within this species and explore how members of this taxon evolved as commensals of the animal gut, we isolated and decoded the genomes of 51 newly isolated strains. Comparative genomics coupled with growth profiles on different carbohydrates has further provided insights concerning the genotype and phenotype of members of the B. pseudolongum taxon.
Equally interchangeable? - How sex and gender affect transplantation.

Organ transplantation as an option to overcome end-stage diseases is common in countries with advanced healthcare systems and is increasingly provided in emerging and developing countries. A review of the literature points to sex- and gender-based inequity in the field with differences reported at each step of the transplant process, including access to a transplantation waiting list, access to transplantation once waitlisted as well as outcome after transplantation. In this review, we summarize the data regarding sex- and gender-based disparity in adult and pediatric kidney, liver, lung, heart and hematopoietic stem-cell transplantation and argue that there are not only biological but also psychological and socio-economic issues that contribute to disparity in the outcome, as well as an inequitable access to transplantation for women and girls. Because the demand for organs has always exceeded the supply, the transplant community has long recognized the need to ensure equity and efficiency of the organ allocation system. In the spirit of equity and equality, the authors call for recognition of these inequities and the development of policies that have the potential to ensure that girls and women have equitable access to transplantation.
From Siloed Applications to National Digital Health Ecosystems: A Strategic Perspective for African Countries

Substantial investment in digital solutions for improved health services has occurred in recent years in Africa. Digital Health provides for proven, beneficial applications in many different areas of health systems. It supports the transformation of healthcare delivery, and its potential is seemingly boundless. However, the deployed systems are in silos, and interoperability and integration are largely missing. There is no timely information for easy and quick decision making; there is no ability to track service levels across the whole health sector. What is missing is an integrated information system across all healthcare facilities nationwide. Such a Digital Health Ecosystem, the holistic application of information and communications technologies, services and applications, will support health systems and improve healthcare delivery, coordination and integration across providers. Based on global experience in resource-constraint contexts, core steps necessary to develop and implement such an ecosystem are explored, and four fundamental building blocks and their elements are developed. The results presented are succinctly integrated into six statements on lessons learned and recommendations.
Exercise Supervision Is Important for Cardiometabolic Health Improvements: A 16-Week Randomized Controlled Trial.

Hunter, JR, Gordon, BA, Bird, SR, and Benson, AC. Exercise supervision is important for cardiometabolic health improvements: a 16-week randomized controlled trial. J Strength Cond Res XX(X): 000-000, 2019-Exercise supervision enhances health and fitness improvements in clinical populations compared with unsupervised or home-based exercise, but effects of supervision type are unknown in healthy employees. Eighty-five Australian university employees (62 females; mean ± SD 43.2 ± 9.8 years) were randomized to personal (1:1; SUP, n = 28), nonpersonal (typical gym-based; NPS, n = 28) supervision or unsupervised control (CON, n = 29) exercise groups. Subjects received a 16-week individually tailored, moderate-to-high intensity aerobic and resistance exercise program completed at an onsite exercise facility (SUP and NPS) or without access to a specific exercise facility (CON). Repeated-measures ANOVA analyzed changes to cardiometabolic outcomes. Mean ± SD increases to V[Combining Dot Above]O2 peak were greater (p < 0.01) with SUP (+10.4 ± 11.1%) vs. CON (+3.8 ± 8.9%) but not different to NPS (+8.6 ± 8.2%). Compared to CON (+1.7 ± 7.7%), upper-body strength increases were greater with SUP (+12.8 ± 8.4%; p < 0.001) and NPS (+8.4 ± 7.3%; p < 0.05). Lower-body strength increases were greater with SUP (+26.3 ± 12.7%) vs. NPS (+15.0 ± 14.6%; p < 0.05) and CON (+4.1 ± 12.4%; p < 0.001), and NPS vs. CON (p < 0.01). Body fat reductions were greater with SUP (-2.2 ± 2.2%) vs. NPS (-0.6 ± 1.9%; p < 0.05) and CON (-0.7 ± 1.9%; p < 0.05). Access to an onsite exercise facility with personal or nonpersonal exercise supervision was important for improving several cardiometabolic outcomes, with greater improvements to lower-body strength and body composition from personal 1:1 exercise supervision.
Disordered eating among Australian adolescents: Prevalence, functioning, and help received

OBJECTIVE To estimate the prevalence of disordered eating (DE) among Australian adolescents and examine associations with clinical mental health problems, problems with functioning, and help received. METHOD We analyzed data from the Young Minds Matter survey (n = 2,298, 13-17 years). We derived an index of DE severity with four levels: (1) no DE; (2) subclinical DE; (3) suspected eating disorder; and (4) lifetime eating disorder diagnosis. RESULTS In 2013-2014, 31.6% (95%CI 35.5-39.9) of Australian adolescents experienced DE, comprising 25.7% (95%CI 23.9-37.6) with subclinical DE, 11.0% (95%CI 9.7-12.6) with a suspected eating disorder, and 0.9% (95%CI 0.6-1.3) with a lifetime eating disorder diagnosis. DE was more common among girls (41.4%, 95%CI 37.9-44.4) than boys (34.0%, 95%CI 31.1-37.0; p = .002). Adolescents with DE, compared to those without, were more likely to experience clinical mental health problems and problems with functioning. Most adolescents with DE reported help-seeking in the past year, commonly self-help; around 40% used school-based, primary care or specialist services (i.e., formal services). In multivariate analyses, the use of more specialized and intensive services was associated with more severe DE, greater problems with functioning, female gender, and 12-month mental disorder or subthreshold mental disorder symptoms. DISCUSSION The implementation of mental health promotion and prevention efforts for DE, and screening for DE in school and primary care settings, may facilitate detection and appropriate help-seeking among adolescents with DE.
Enabled homolog shown to be a potential biomarker and prognostic indicator for breast cancer by bioinformatics analysis.

BACKGROUND Human enabled homolog (ENAH; also known as human ortholog of mammalian enabled, hMENA) is a member of the enabled/vasodilator-stimulated phosphor protein family that regulates fibroblast movement and nervous system development. The ENAH over-expression promotes breast cancer (BC) cell invasion and metastasis. METHODS We studied ENAH mRNA expression in various tumors and normal tissues using the ONCOMINE database, and in an array of cancer cell lines using Cancer Cell Line Encyclopedia data. We also investigated the prognostic value of ENAH expression in patients with BC using Kaplan-Meier plots. RESULTS Compared with normal tissues, ENAH expression levels were markedly elevated in BC. We identified a correlation between low ENAH and superior relapse-free survival (RFS) of patients with BC; specifically, those with ER(-), HER-2(+), Grade 3 and wild-type TP53 subtypes. Additionally, a correlation was detected between low ENAH and prolonged overall survival of patients with luminal B disease. CONCLUSION ENAH is a potential biomarker and important prognostic factor in BC.
Usability Analysis of Contending Electronic Health Record Systems

In this paper, we report measured usability of two leading EHR systems during procurement. A total of 18 users participated in paired-usability testing of three scenarios: ordering and managing medications by an outpatient physician, medicine administration by an inpatient nurse and scheduling of appointments by nursing staff. Data for audio, screen capture, satisfaction rating, task success and errors made was collected during testing. We found a clear difference between the systems for percentage of successfully completed tasks, two different satisfaction measures and perceived learnability when looking at the results over all scenarios. We conclude that usability should be evaluated during procurement and the difference in usability between systems could be revealed even with fewer measures than were used in our study.
Aerosolized Bexarotene Inhibits Lung Tumorigenesis without Increasing Plasma Triglyceride and Cholesterol Levels in Mice

Prior studies have shown the retinoid X receptor (RXR) agonist bexarotene has preventive efficacy in rodent models of mammary and lung tumorigenesis albeit causing hypertriglyceridemia and hypercholesterolemia. We reasoned that bexarotene delivered by inhalation may provide sufficient dose directly to the respiratory tract to achieve efficacy while avoiding these side effects. In this study, the chemopreventive activity of aerosolized bexarotene was investigated in the benzo(a)pyrene [B(a)P]-induced mouse lung tumor model as assessed by tumor multiplicity and tumor load. Aerosolized bexarotene significantly decreased tumor multiplicity and tumor load by 43% and 74%, respectively. Our data showed that bexarotene can both inhibit proliferation and promote apoptosis in vivo. Our data also show that aerosolized bexarotene did not increase plasma total cholesterol and triglyceride level compared with diet group. These results indicate that aerosolization may be a safe and effective route of administering bexarotene for chemoprevention of lung cancer. Cancer Prev Res; 4(2); 270–6. ©2010 AACR.