Miracle-dz/UniFAR-FTUs huggingface dataset:
Revisiting the infracardiac bursa using multimodal methods: topographic anatomy for surgery of the esophagogastric junction

In embryology, the infracardiac bursa (ICB) is a well‐known derivative separated from the omental bursa. During surgeries around the esophagogastric junction (EGJ), surgeons often encounter a closed space considered to be equivalent to the ICB, but the macroscopic anatomy in adults is hardly known. This study aimed to revisit the ICB using multimodal methods to show its development from the embryonic to adult stage and clarify its persistence and topographic anatomy. Histological sections of 79 embryos from Carnegie stage (CS) 16 to 23 and magnetic resonance (MR) images of 39 fetuses were examined to study the embryological development of the ICB. Horizontal sections around the EGJ obtained from three adult cadavers were examined to determine the topographic anatomy and histology of the ICB. Further, 32 laparoscopic surgical videos before (n = 16) and after (n = 16) the start of this study were reviewed to confirm its remaining rate and topographic anatomy in surgery. The ICB was formed in 1 out of 10 CS17 samples, and in 8 out of 10 CS18 samples. Further, it was observed in all CS19–23 except one CS23 sample and in 25 (64%) out of 39 fetus samples. Three‐dimensional reconstructed MR images of fetuses revealed that the ICB was located at the right alongside the esophagus and the cranial side of the diaphragmatic crus. In one adult cadaver, the caudal end of the ICB arose from the level of the esophageal hiatus and the cranial end reached up to the level of the pericardium. The inner surface cells of the space consisted of the mesothelium. In laparoscopic surgery, the ICB was identified in only 11 (69%) out of 16 surgeries before. However, subsequently we were able to identify the ICB reproducibly in 15 (94%) out of 16 surgeries. Thus, the ICB is the structure commonly remaining in almost all adults as a closed space located at the right alongside the esophagus and the cranial side of the diaphragmatic crus. It may be available as a useful landmark in surgery of the EGJ.
Does Public Health Insurance Coverage Lead to Better Health Outcomes? Evidence From Chinese Adults

This article examines the impacts of public health insurance on the health of adults through use of data from the China Health and Nutrition Survey. We use the endogenous treatment effects model to infer the causal effects of public health insurance on health. We find that public health insurance significantly improves the physical and mental health status of health insurance beneficiaries after controlling for other covariates. Among the 2 types of voluntary public health insurance, the Urban Resident Basic Medical Insurance has the greater impact in improving health than the New Cooperative Medical Scheme. Moreover, the health effect appears to be stronger for middle-aged individuals, the elderly, and those with lower incomes than for their counterparts. The positive health effects may result from few channels, including the increase of health care utilization, the improvement of health-related behaviors, and the fact that individuals with public health insurance are more likely to use higher level care providers. This study provides implications on reforming China’s health care system.
Predictive models of eukaryotic transcriptional regulation reveals changes in transcription factor roles and promoter usage between metabolic conditions

Abstract Transcription factors (TF) are central to transcriptional regulation, but they are often studied in relative isolation and without close control of the metabolic state of the cell. Here, we describe genome-wide binding (by ChIP-exo) of 15 yeast TFs in four chemostat conditions that cover a range of metabolic states. We integrate this data with transcriptomics and six additional recently mapped TFs to identify predictive models describing how TFs control gene expression in different metabolic conditions. Contributions by TFs to gene regulation are predicted to be mostly activating, additive and well approximated by assuming linear effects from TF binding signal. Notably, using TF binding peaks from peak finding algorithms gave distinctly worse predictions than simply summing the low-noise and high-resolution TF ChIP-exo reads on promoters. Finally, we discover indications of a novel functional role for three TFs; Gcn4, Ert1 and Sut1 during nitrogen limited aerobic fermentation. In only this condition, the three TFs have correlated binding to a large number of genes (enriched for glycolytic and translation processes) and a negative correlation to target gene transcript levels.
Molecular Grouping and Outcomes of Young Children with Newly Diagnosed Ependymoma Treated on the Multi-Institutional SJYC07 Trial.

BACKGROUND This report documents the clinical characteristics, molecular grouping and outcome of young children with ependymoma treated prospectively on a clinical trial. METHODS Fifty-four children (aged ≤ 3 years) with newly diagnosed ependymoma were treated on the SJYC07 trial with maximal safe surgical resection, 4 cycles of systemic chemotherapy, consolidation therapy using focal conformal radiation therapy (RT) (5-mm clinical target volume), and 6 months of oral maintenance chemotherapy. Molecular groups were determined by tumor DNA methylation using Infinium Methylation EPIC BeadChip and profiled on DKFZ/German molecularneuropathology2.0 classifier. RESULTS One of the 54 study patients had metastases (CSF+) at diagnosis. Gross- or near-total resection was achieved in 48 (89%) patients prior to RT. At a median follow-up of 4.4 years (range, 0.2-10.3 years), 4-year progression-free survival (PFS) was 75.1% ± 7.2%, and overall survival was 92.6% ± 4.4%. The molecular groups showed no significant difference in PFS [4-year estimates: PF-EPN-A (42/54), 71.2% ± 8.3%; ST-EPN-RELA (8/54), 83.3% ± 17.0%; ST-EPN-YAP (4/54), 100%, p=0.22]. Subtotal resection prior to RT was associated with an inferior PFS compared to gross- or near-total resection (4-year PFS: 41.7% ± 22.5% vs. 79.0% ± 7.1%, p=0.024) as was PF-EPN-A group with 1q gain (p=0.05). Histopathologic grading was not associated with outcomes (classic vs anaplastic; p=0.89). CONCLUSIONS In this prospectively treated cohort of young children with ependymoma, ST-EPN-RELA tumors had a favorable outcome than reported from retrospective data. Histological grade did not impact outcome. PF-EPN-A with 1q gain, and sub-total resection were associated with inferior outcomes.
The carboxy‐terminus of the formin FMNL1ɣ bundles actin to potentiate adenocarcinoma migration

The formin family of proteins contributes to spatiotemporal control of actin cytoskeletal rearrangements during motile cell activities. The FMNL subfamily exhibits multiple mechanisms of linear actin filament formation and organization. Here we report novel actin‐modifying functions of FMNL1 in breast adenocarcinoma migration models. FMNL1 is required for efficient cell migration and its three isoforms exhibit distinct localization. Suppression of FMNL1 protein expression results in a significant impairment of cell adhesion, migration, and invasion. Overexpression of FMNL1ɣ, but not FMNL1β or FMNL1α, enhances cell adhesion independent of the FH2 domain and FMNL1ɣ rescues migration in cells depleted of all three endogenous isoforms. While FMNL1ɣ inhibits actin assembly in vitro, it facilitates bundling of filamentous actin independent of the FH2 domain. The unique interactions of FMNL1ɣ with filamentous actin provide a new understanding of formin domain functions and its effect on motility of diverse cell types suggest a broader role than previously realized.
MicroRNA-181c Inhibits Interleukin-6-mediated Beta Cell Apoptosis by Targeting TNF-α Expression

We have previously reported that long-term treatment of beta cells with interleukin-6 (IL-6) is pro-apoptotic. However, little is known about the regulatory mechanisms that are involved. Therefore, we investigated pro-apoptotic changes in mRNA expression in beta cells in response to IL-6 treatment. We analyzed a microarray with RNA from INS-1 beta cells treated with IL-6, and found that TNF-α mRNA was significantly upregulated. Inhibition of TNF-α expression by neutralizing antibodies significantly decreased annexin V staining in cells compared with those treated with a control antibody. We identified three microRNAs that were differentially expressed in INS-1 cells incubated with IL-6. In particular, miR-181c was significantly downregulated in IL-6-treated cells compared with control cells and the decrease of miR-181c was attenuated by STAT-3 signaling inhibition. TNF-α mRNA was a direct target of miR-181c and upregulation of miR-181c by mimics, inhibited IL-6-induced increase in TNF-α mRNA expression. Consequently, reduction of TNF-α mRNA caused by miR-181c mimics enhanced cell viability in IL-6 treated INS-1 cells. These results demonstrated that miR-181c regulation of TNF-α expression plays a role in IL-6-induced beta cell apoptosis.
Complete Genome Sequence of a Carrot Torradovirus 1 Isolate, Obtained from Angelica keiskei in Japan

The complete genome sequence of the first Japanese isolate of carrot torradovirus 1 (CaTV1-J), which infects Angelica keiskei, was determined. This is the first report of a CaTV1 isolate obtained from A. keiskei. ABSTRACT The complete genome sequence of the first Japanese isolate of carrot torradovirus 1 (CaTV1-J), which infects Angelica keiskei, was determined. This is the first report of a CaTV1 isolate obtained from A. keiskei.
Post-harvest quality and quantification of betalains, phenolic compounds and antioxidant activity in fruits of three cultivars of prickly pear (Opuntia ficus-indica L. Mill)

Postharvest quality, quantification of betalains, phenolic compounds, and antioxidant activity of peel, pulp, and juice of fruits of three prickly pears (Opuntia ficus-indica L. Mill.) cultivars of Colegio de Postgraduados in México, were measured. The red and orange cultivars showed outstanding features of postharvest quality (size, texture, TSS and pulp and juice content) highest content of betalains and phenolic compounds. Therefore, highest antioxidant activity. In general, the highest content of bioactive compounds was detected in the peel, besides the content in pulp and juice did not show statistically significant differences. Phenolic content is very high in comparison with other fruits. Antioxidant activity was measured by three assays:FRAP, ABTS, and DPPH. Three cultivars showed a high correlation between antioxidant activity and phenolic compounds. The methodologies used in this work are a very useful tool for the quantification of bioactive compounds in O. ficus-indica fruit tissues.
Oxidative stress in lung cancer patients is associated with altered serum markers of lipid metabolism

In lung cancer (LC), alterations in redox balance are extensively observed and are a consequence of disease as well as co-occurrent with smoking. We previously demonstrated that metabolic disturbances such as trace element status and carbohydrate metabolism alterations are linked with redox status. The aim of this study was to evaluate relationships between the serum parameters of lipid metabolism and redox balance in LC patients. Serum parameters of lipid metabolism, i.e. total cholesterol (T-C), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), triglycerides (TG), T-C:HDL-C ratio, non-HDL-C, apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B) and Apo-B:Apo-A1 ratio, as well as systemic redox status, i.e. total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), vitamin E (VE), vitamin C (VC), malonyldialdehyde (MDA), conjugated dienes (CD), and 4-hydroxynonenal (4-HNE) were determined in 92 LC patients and 82 control subjects (CS). LC women had significantly lower T-C and LDL-C, and higher TG, while HDL-C, Apo-A1 and Apo-B were significantly decreased in LC patients regardless of sex, when compared to CS. LC men had alterations in the systemic total redox balance such as lower TAS and higher OSI than CS men. LC women had lower VC, but VE was decreased in LC patients, regardless of sex. We observed higher lipid peroxidation in LC patients expressed via higher 4-HNE and CD. Systemic redox disturbances were associated with serum lipid alterations: TOS and OSI were positively correlated with T-C:HDL-C ratio and Apo-B:Apo-A1 ratio and negatively with HDL-C. The parameters of lipid peroxidation CD and MDA were significantly associated with variables reflecting lipid disturbances. The observed correlations were strengthened by general overweight/obesity, abdominal obesity, hypertriglyceridemia and non-smoking status. In conclusion, parameters related to lipid alterations are associated with oxidative stress in LC patients. The largest contribution from lipid parameters was revealed for T-C:HDL-C ratio, HDL-C and Apo-B:Apo-A1 ratio, while the largest contribution from redox status was revealed for OSI and VE. Overweight, obesity, hypertriglyceridemia and non-smoking status intensified these relationships.
Clinical Features of Chronic Graft-Versus-Host Disease Following Haploidentical Transplantation Combined with Infusion of a Cord Blood.

Our previous studies demonstrated promising outcomes after haploidentical donor transplant combined with unrelated umbilical cord blood (haplo-cord- hematopoietic stem cell transplantation [HSCT]) for hematological disorders. However, clinical profiling regarding chronic graft-versus-host disease (cGVHD) has not yet been fully described under this protocol. This study analyzed the clinical characteristics of cGVHD among 300 patients with hematological malignancies who received haplo-cord-HSCT between January 2012 and July 2016 at our center. During the follow-up, the 5-year cumulative incidence of cGVHD based on the National Institutes of Health (NIH) consensus criteria was 32.2% (95% confidence interval [CI], 28.7-35.7); the 5-year cumulative incidence of moderate to severe cGVHD was 11.4% (95% CI, 9.4-13.4). After the multivariate analysis, the GVHD overall survival (GOS) was associated with relapse, thrombocytopenia, bronchiolitis obliterans syndrome, and steroid-refractory cGVHD. The infused CD34+ cells (≥3.46 × 106/kg) from haploidentical grafts were a protective factor affecting GOS. This study proposed a nomogram for predicting GOS using the aforementioned five variables. The concordance index was 0.877 (95% CI, 0.859-0.895) for the accuracy evaluation of the nomogram. Our results suggested that the 5-year cumulative incidence of NIH-defined cGVHD after haplo-cord-HSCT was 32.2%, and this nomogram may help clinicians select reasonable treatment strategies.
The Challenge of Managing Undernutrition in Older People with Frailty

Many older people with frailty are at risk of malnutrition and poor health, yet there is evidence that improving nutrition and weight loss can reduce frailty. This will become more important as the number of older people with frailty increases worldwide in future. Identifying those at risk is challenging due to the difficulty of reaching and screening those older people most at risk, the large number of nutritional assessment tools used, and the lack of consensus on the criteria to make a diagnosis of malnutrition. The management of older people with or at risk of malnutrition should be multi-modal and multi-disciplinary, and all care staff have an important role in delivering appropriate nutritional advice and support. This paper will highlight a number of practical approaches that clinicians can take to manage malnutrition in older people with frailty in community and acute settings, including environmental changes to enhance mealtime experience, food fortification and supplementation.
The etiological contribution of GABAergic plasticity to the pathogenesis of neuropathic pain

Neuropathic pain developing after peripheral or central nerve injury is the result of pathological changes generated through complex mechanisms. Disruption in the homeostasis of excitatory and inhibitory neurons within the central nervous system is a crucial factor in the formation of hyperalgesia or allodynia occurring with neuropathic pain. The central GABAergic pathway has received attention for its extensive distribution and function in neural circuits, including the generation and development of neuropathic pain. GABAergic inhibitory changes that occur in the interneurons along descending modulatory and nociceptive pathways in the central nervous system are believed to generate neuronal plasticity, such as synaptic plasticity or functional plasticity of the related genes or proteins, that is the foundation of persistent neuropathic pain. The primary GABAergic plasticity observed in neuropathic pain includes GABAergic synapse homo- and heterosynaptic plasticity, decreased synthesis of GABA, down-expression of glutamic acid decarboxylase and GABA transporter, abnormal expression of NKCC1 or KCC2, and disturbed function of GABA receptors. In this review, we describe possible mechanisms associated with GABAergic plasticity, such as central sensitization and GABAergic interneuron apoptosis, and the epigenetic etiologies of GABAergic plasticity in neuropathic pain. Moreover, we summarize potential therapeutic targets of GABAergic plasticity that may allow for successful relief of hyperalgesia from nerve injury. Finally, we compare the effects of the GABAergic system in neuropathic pain to other types of chronic pain to understand the contribution of GABAergic plasticity to neuropathic pain.
Vascular Tissue Specific miRNA Profiles Reveal Novel Correlations with Risk Factors in Coronary Artery Disease

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Non-coding RNAs have already been linked to CVD development and progression. While microRNAs (miRs) have been well studied in blood samples, there is little data on tissue-specific miRs in cardiovascular relevant tissues and their relation to cardiovascular risk factors. Tissue-specific miRs derived from Arteria mammaria interna (IMA) from 192 coronary artery disease (CAD) patients undergoing coronary artery bypass grafting (CABG) were analyzed. The aims of the study were 1) to establish a reference atlas which can be utilized for identification of novel diagnostic biomarkers and potential therapeutic targets, and 2) to relate these miRs to cardiovascular risk factors. Overall, 393 individual miRs showed sufficient expression levels and passed quality control for further analysis. We identified 17 miRs–miR-10b-3p, miR-10-5p, miR-17-3p, miR-21-5p, miR-151a-5p, miR-181a-5p, miR-185-5p, miR-194-5p, miR-199a-3p, miR-199b-3p, miR-212-3p, miR-363-3p, miR-548d-5p, miR-744-5p, miR-3117-3p, miR-5683 and miR-5701–significantly correlated with cardiovascular risk factors (correlation coefficient >0.2 in both directions, p-value (p < 0.006, false discovery rate (FDR) <0.05). Of particular interest, miR-5701 was positively correlated with hypertension, hypercholesterolemia, and diabetes. In addition, we found that miR-629-5p and miR-98-5p were significantly correlated with acute myocardial infarction. We provide a first atlas of miR profiles in IMA samples from CAD patients. In perspective, these miRs might play an important role in improved risk assessment, mechanistic disease understanding and local therapy of CAD.
Atomic insight into prion disorder: An intricate detail gained by 0.5 μs molecular dynamics simulation of preventive G127V and deleterious D178V mutation in prion protein

In this study we are looking into two contradicting mutations found in prion protein (PrP) viz G127V and D178V, that are reportedly protective and pathogenic, respectively. Despite significant advances in comprehension of the role of pathogenic mutations, the role of protective mutation in amyloid fold inhibition still lacks a substantial basis. To understand the structural basis of protective mutation, molecular dynamics simulation coupled with protein‐protein docking and molecular mechanics/Poisson‐Boltzmann surface area analysis was used to understand the instant structural variability brought about by these mutations alone and in combination on PrP and prion‐prion complex. Atomic‐scale investigations successfully revealed that the binding pattern of prion‐prion varies differentially in protective and pathogenic mutations with secondary structure showing distinct contrasting patterns, which could supposedly be a critical factor for differential prion behavior in protective and pathogenic mutations. Considering the reported role of an amyloid fold in prion‐prion binding, the contrasting pattern has given us a lead in comprehending the role of these mutations and has been used in this study to look for small molecules that can inhibit amyloid fold for prion‐prion interaction in pathogenic mutant carrying PrP.
Disaggregating the predictive effects of impaired psychosocial functioning on future DSM-5 eating disorder onset in high-risk female adolescents.

OBJECTIVE Impaired psychosocial functioning previously emerged as the only risk factor to predict future onset of each of the four Diagnostic and Statistical Manual of Mental Disorder (5th ed.) (DSM-5) eating disorders. The goal of this follow-up report was to refine understanding of this newly identified risk factor. METHOD Combining data from women at risk for eating disorders because of body image concerns (N = 1,153, mean age = 18.5 years, SD = 4.2), we investigated which subdomain(s) and individual item(s) of psychosocial functioning (friends, family, school, and work) at baseline predicted onset of any eating disorder, using Cox regression (CRA) and classification tree analysis (CTA). RESULTS Psychosocial impairment with friends, family, and at school, but not at work, significantly increased risk for disorder onset over 3-year follow-up in univariate models. A one-unit increase in each domain raw score was associated with a 107, 22, and 43% increased hazard of eating disorder onset, respectively. Multivariate CRA found friends functioning, with a 92% increased hazard of disorder onset, contributed the strongest unique effect. CTA suggested that loneliness was the most potent risk factor with a threefold increased onset risk (eating disorder incidence for high vs. low scorers was 27 and 8%). Three friends functioning items and one school functioning item produced additional CTA branches. DISCUSSION Results refine understanding of the relation of psychosocial impairment to future onset of eating disorders, suggesting that peer functioning is the most critical. Data imply it would be useful to target young women with impaired psychosocial functioning in prevention programs.
Lipid Mini-On: mining and ontology tool for enrichment analysis of lipidomic data

SUMMARY Here we introduce Lipid Mini-On, an open-source tool that performs lipid enrichment analyses and visualizations of lipidomics data. Lipid Mini-On uses a text-mining process to bin individual lipid names into multiple lipid ontology groups based on the classification (e.g., LipidMaps) and other characteristics, such as chain length. Lipid Mini-On provides users with the capability to conduct enrichment analysis of the lipid ontology terms using a Shiny app with options of five statistical approaches. Lipid classes can be added to customize the user's database and remain updated as new lipid classes are discovered. Visualization of results is available for all classification options (e.g., lipid subclass and individual fatty acid chains). Results are also visualized through an editable network of relationships between the individual lipids and their associated lipid ontology terms. The utility of the tool is demonstrated using biological (e.g, human lung endothelial cells) and environmental (e.g., peat soil) samples. AVAILABILITY Rodin (R package: https://github.com/PNNL-Comp-Mass-Spec/Rodin), Lipid Mini-On Shiny app (https://github.com/PNNL-Comp-Mass-Spec/LipidMiniOn) and Lipid Mini-On online tool (https://omicstools.pnnl.gov/shiny/lipid-mini-on/). SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.