Miracle-dz/UniFAR-FTUs huggingface dataset:
Interplay of Antibody and Cytokine Production Reveals CXCL13 as a Potential Novel Biomarker of Lethal SARS-CoV-2 Infection

The SARS-CoV-2 pandemic is continuing to impact the global population, and knowledge of the immune response to COVID-19 is still developing. This study assesses the interplay of different parts of the immune system during COVID-19 disease. ABSTRACT The SARS-CoV-2 pandemic is impacting the global population. This study was designed to assess the interplay of antibodies with the cytokine response in SARS-CoV-2 patients. We demonstrate that significant levels of anti-SARS-CoV-2 antibody to receptor binding domain (RBD), nucleocapsid, and spike S1 subunit of SARS-CoV-2 develop over the first 10 to 20 days of infection. The majority of patients produced antibodies against all three antigens (219/255 SARS-CoV-2+ patient specimens, 86%), suggesting a broad response to viral proteins. Antibody levels to SARS-CoV-2 antigens were different based on patient mortality, sex, blood type, and age. Analyses of these findings may help explain variation in immunity between these populations. To better understand the systemic immune response, we analyzed the levels of 20 cytokines by SARS-CoV-2 patients throughout infection. Cytokine analysis of SARS-CoV-2+ patients exhibited increases in proinflammatory markers (interleukin 6 [IL-6], IL-8, IL-18, and gamma interferon [IFN-γ]) and chemotactic markers (IP-10 and eotaxin) relative to healthy individuals. Patients who succumbed to infection produced decreased IL-2, IL-4, IL-12, RANTES, tumor necrosis factor alpha (TNF-α), GRO-α, and MIP-1α relative to patients who survived infection. We also observed that the chemokine CXCL13 was particularly elevated in patients who succumbed to infection. CXCL13 is involved in B cell activation, germinal center development, and antibody maturation, and we observed that CXCL13 levels in blood trended with anti-SARS-CoV-2 antibody levels. Furthermore, patients who succumbed to infection produced high CXCL13 and had a higher ratio of nucleocapsid to RBD antibodies. This study provides insights into SARS-CoV-2 immunity implicating the magnitude and specificity of response in relation to patient outcomes. IMPORTANCE The SARS-CoV-2 pandemic is continuing to impact the global population, and knowledge of the immune response to COVID-19 is still developing. This study assesses the interplay of different parts of the immune system during COVID-19 disease. We demonstrate that COVID-19 patients produce antibodies to three proteins of the COVID-19 virus (SARS-CoV-2) and identify many other immunological proteins that are involved during infection. The data suggest that one of these proteins (CXCL13) may be a novel biomarker for severe COVID-19 that can be readily measured in blood. This information combined with our broad-scale analysis of immune activity during COVID-19 provides new information on the immunological response throughout the course of disease and identifies a novel potential marker for assessing disease severity.
Effects of a Safety Letter on Metoclopramide Use in Korea: An Interrupted Time-Series Analysis

Background The Korean Ministry of Food and Drug Safety (MFDS) issued a safety letter regarding metoclopramide use and its adverse drug event of extrapyramidal disorder in October 2013. However, this safety letter had controversial effects on pharmacovigilance and management policies. The objective of this study was to estimate the impact of this government safety letter on the use of metoclopramide. Patients and Methods We conducted an interrupted time-series analysis using national claims data from January 2011 to December 2015 to assess the difference in metoclopramide utilization (ie, the total number of prescriptions per month, the average administration period per prescription per month, and the average dose per prescription per month) before and after the publication of the safety letter in October 2013. Results The number of prescriptions, the average administration period per prescription, and the average dose per prescription of metoclopramide decreased after the publication of the safety letter. Notably, the decrease in the average administration period per prescription after the safety letter was statistically significant. Conclusion Our results indicate that the changes in the number of prescriptions, dose, and the duration of prescription may have occurred as a result of the restrictions and recommendations in the safety letter. Further research is needed to optimize the use of metoclopramide and to identify the risk of adverse drug events since the safety letter was issued.
Ökosystem Darm

Die Analyse des menschlichen Mikrobioms hat ein neues Kapitel der Humanbiologie eröffnet. Die Zusammensetzung speziell des Darmmikrobioms wurde mit einer Vielzahl menschlicher Erkrankungen in Verbindung gebracht. Nach Abschluss einer beschreibenden Forschungsphase, wird nun nach Mitteln für therapeutische Eingriffe gesucht. Die hohe Komplexität des Darmmikrobioms und zu wenige Verlaufsstudien erweisen sich dabei als Barrieren, um Kausalzusammenhänge von bloßen Assoziationen zu trennen. Gezielte gesundheitsfördernde Veränderungen des Mikrobioms erweisen sich dabei als schwierig.
Gastrointestinal Stromal Tumor (GIST) Causing Obscure Gastrointestinal Bleeding: An Uncommon Way of Diagnosing An Uncommon Disease

Gastrointestinal stromal tumors (GISTs) are neoplasms that arise from the wall of the gastrointestinal tract or, rarely, from other intra-abdominal tissues. They are the most common mesenchymal tumors of the gastrointestinal tract and they should be considered in the differential diagnosis of obscure gastrointestinal bleeding. Computed tomography angiogram (CTA) can be utilized as an alternative imaging study when endoscopic and colonoscopy results are non-diagnostic. We report a case of a 59-year-old woman who presented with recurrent episodes of obscure overt gastrointestinal bleeding secondary to a gastrointestinal stromal tumor (GIST).
Design and Validation of a Diet Rich in Slowly Digestible Starch for Type 2 Diabetic Patients for Significant Improvement in Glycemic Profile

This study aimed at designing a—diet high in slowly digestible starch (SDS) by carefully selecting high-SDS starchy products and to validate its implementation, acceptance, and impact on the postprandial glycemic response in patients with type 2 diabetes (T2D). Starchy products were screened and classified as being either high (high-SDS) or low (low-SDS) in SDS (in vitro SDS method). A randomized controlled cross-over pilot study was performed: Eight patients with T2D consumed randomly a high-SDS or a low-SDS diet for one week each, while their glycemic profile was monitored for 6 days. Based on 250 food product SDS analyses and dietary recommendations for patients with T2D, the high-SDS and low-SDS diets were designed. The high-SDS diet significantly increased SDS intake and the SDS/carbohydrates proportion compared to the low-SDS diet (61.6 vs. 11.6 g/day and 30% vs. 6%; p < 0.0001, respectively). Increasing the SDS/carbohydrate proportion to 50% of the meal was significantly correlated with a 12% decrease in tAUC0–120 min and a 14% decrease in the glycemic peak value (p < 0.001 for both). A high-SDS diet can be easily designed by carefully selecting commercial starchy products and providing relevant recommendations for T2D to improve their glycemic profile.
MDM2-C Functions as an E3 Ubiquitin Ligase

Background Mouse double minute 2 (MDM2) is an E3 ubiquitin ligase that is over-expressed in many cancers and regulates target proteins through ubiquitination. Full-length MDM2 (MDM2-FL) is best known for targeting wild-type p53 for degradation by the proteasome, but the functions of the many splice variants of MDM2 are under-explored. The three well-studied alternative MDM2 isoforms are MDM2-A/ALT2, MDM2-B/ALT1, and MDM2-C/ALT3. MDM2-A and MDM2-B are capable of down-regulating MDM2-FL activity and have transforming activity in cancers with mutant p53. The MDM2 isoform MDM2-C is over-expressed in breast cancer and correlates with decreased survival in the context of mutant p53 expression. Therefore, MDM2-C requires further study to determine if it has biochemical activities similar to MDM2-FL. Hypothesis: We hypothesized that like MDM2-FL, the MDM2-C isoform (lacking exons 5–9 and containing a full C-terminal RING finger sequence) would maintain E3 ubiquitin ligase activity. Materials and Methods In order to explore the biochemical function of MDM2-C, we used an in vitro ubiquitination assay and a glutaraldehyde cross-linking assay. Results Here we report, for the first time, that MDM2-C has E3 auto-ubiquitin ligase activity, which can promote ubiquitination of wild-type p53 and mutant p53 R273H, and also can form a protein–protein interaction with p53 proteins. Conclusion This information strongly positions MDM2-C as a protein with biochemical activities that may explain the varied outcomes observed in patients with high-level expression of MDM2-C in the presence of wild-type p53 versus mutant p53.
Whole Grains and Consumer Understanding: Investigating Consumers’ Identification, Knowledge and Attitudes to Whole Grains

Whole grains may assist in reducing risk of non-communicable disease, but consumption is limited in many countries. In Australia, the reasons for poor consumption are not well understood. The aim of this study was to investigate consumers’ knowledge, attitudes and identification of whole grains, incorporating an exploration of factors influencing consumption, promotion and provision. An online semi-structured questionnaire was used to gather responses from 735 participants (61% complete responses). Although 92% of respondents consumed grains, only 8% reported an intake consistent with age and gender recommendations. Refined pasta and rice were the most frequently purchased grain foods followed by wholemeal/whole grain bread. Of whole grain foods, bread and breakfast cereals were consumed more frequently. However, overall, participants did not prioritise consumption of whole grains. Despite this, 93% of participants had seen food packaging information drawing attention to whole grain content, with a high proportion describing whole grain as less processed (72%) or high in dietary fibre (67%). Two-thirds were aware of health benefits but stated that if they had further information, they would be more likely to swap to whole grain. Further education, increasing exposure, accessibility and extensive promotion of whole grain health benefits are required to facilitate whole grain consumption. Furthermore, removing the negative stigma associated with carbohydrate foods, including grains, will be necessary to improve consumption.
Functional androdioecy in the rare endemic tree Tapiscia sinensis

Tapiscia sinensis, a rare endemic woody plant with both male and hermaphrodite individuals, is distributed in southern China. Whether T. sinensis is functionally androdioecious is unknown. In this study, we compare the male fitness between male and hermaphrodite individuals and perform pollination experiments in different habitats, identify the ability of actual siring of pollen from hermaphrodites and males under natural pollination, and discuss the evolution and maintenance of androdioecy in T. sinensis. Research suggests that flowers and fruits grow synchronously on hermaphrodite plants of T. sinensis from April to June. The males of T. sinensis had more than twice the genetic contribution of hermaphrodites through their male function and the fruit set from male pollination and cross-pollination was the highest in all of the treatments, whereas that from self-pollination was the lowest. Additionally, paternity analysis showed that the hermaphroditic pollen could result in siring success under natural pollination. The results showed that T. sinensis is a functionally androdioecious tree, that male individuals might evolve from a hermaphroditic ancestor and that the synchronous growth of flowers and fruit in hermaphrodites might facilitate the evolution and maintenance of androdioecy in T. sinensis.
Knowledge, Perception, and Application of Pharmacogenomics Among Hospital Pharmacists in Saudi Arabia

Introduction The accelerated transformation in the healthcare system supported by the Saudi Vision 2030 makes the present the best time to start the real application of pharmacogenomics in Saudi Arabia. The current study aimed to assess the knowledge, perception and the application status of pharmacogenomics among pharmacists in the hospital settings in Saudi Arabia. Methods This cross-sectional observational survey was conducted among 206 qualified pharmacists working in Saudi hospitals. A self-administered questionnaire was sent to all participants. Results Only 30% of the pharmacists had received any type of formal training on PGx. Of these, only nine participants had actually put the knowledge into practice. Participants showed a moderate to low level of knowledge when responded to the pharmacogenomic knowledge indicators used in the study. The low knowledge and the availability of the pharmacogenetic test are the main barriers for the low adoption of the pharmacogenomics in the clinical practice. Approximately 83% felt the need to know more about pharmacogenomics. Participants show positive perception with high motivation levels to incorporate this technology in practice. For example, 76% stated that pharmacogenetic testing should be applied to pharmacy practice. Around 38% of participants reported that the Saudi government and the Saudi FDA had been promoting the pharmacogenomics. However, 50% of the total participants reported that their hospital management is unaware of the pharmacogenomics importance in clinical practice. Discussion This study emphasizes on two needs which can help promote the use and implementation of pharmacogenomics. One is the need to update the pharmacy education and training programs with pharmacogenomic-related areas to raise the pharmacist’s knowledge and practical skill to apply pharmacogenomics in the clinical practice effectively. Another need is to increase the awareness of the decision and policy-makers with the importance of pharmacogenomics for the patient benefit and safety. This preliminary evaluation will provide future insight into the best approach to applying pharmacogenomics in the Saudi healthcare system.
Crude glycerin in meat goat diets: intake, performance and carcass traits

This experiment aimed to evaluate the effect of including glycerin in kid goats diet on intake, performance and carcass traits. Twenty intact male kid goats Boer crossbred were used, with body weight of 25.06±4.15kg and 8.00±0.66 months old, allocated in block design, with four treatments and five replicates. The treatments consisted on including dry matter basis (DM) of the diet of four levels of glycerin: zero, five, 10 and 15%, in replacing corn. It was not reported influence (P>0.05) of level of glycerin on intake of forage and feed conversion of animals. The concentrate and total DM intake were affected (P 0.05) of level of glycerin on weight gain, carcass yield and percentage of cooling losses. However, the hot and cold carcass weight was lower (P<0.05) to the animals feed with 15% of glycerin. The inclusion up to 15% of glycerin in the diet of kid goats Boer crossbred, although did not affect feed conversion and performance, compromised the intake and carcass weight.
Antioxidative Activity of Proanthocyanidins Isolated from Barley Bran.

大麦糠由来のプロアントシアニジン(2量体及び3量体)について,幾つかの生体モデル系における抗酸化性試験を行った. また,その作用をカテキンと比較した. (1) プロアントシアニジンのt-BuOOHによって誘導された赤血球膜ゴーストの脂質酸化に対する抑制能を測定した結果,その作用はプロデルフィニジンがプロシアニジンよりも大きい傾向を示した. また,その作用は(-)-ECG及び(-)-EGCGに匹敵した. (2) プロアントシアニジンの酵素反応支配下におけるラリト肝ミクロソームの脂質酸化に対する抑制能を測定した結果,赤血球膜ゴーストに対する抑制能の結果と同様にプロデルフィニジンがプロシアニジンと比較し,その作用が大きい傾向を示した. また,その作用は(-)-ECG及び(-)-EGCGに匹敵した. (3) プロアントシアニジンのCu2+で触媒されたLDLの酸化に対する抑制能を測定した結果,化学構造による酸化抑制能に傾向が見られなかったが,比較的カテキンよりその作用が大きいことがわかった.
Two Cases of Intrafamilial Transmission of Community-Acquired Methicillin-Resistant Staphylococcus aureus Producing Both PVL and TSST-1 Causing Fatal Necrotizing Pneumonia and Sepsis

Introduction Staphylococcus aureus produces numerous toxins, such as toxic shock syndrome toxin 1 (TSST-1) and Panton–Valentine leukocidin (PVL). We isolated community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strains producing both TSST-1 and PVL isolated from severe necrotizing pneumonia cases in a Nepali family. Detection of these CA-MRSA strains is rare in the world, and infection with these strains can take a rapidly progressive and lethal course. In this study, we traced the clinical course of this case and conducted a genetic analysis of the isolated strains. Case Report We described 2 familial cases (a 20-year-old male and 61-year-old female) of severe necrotizing pneumonia caused by CA-MRSA with the TSST-1 and PVL genes. A 20-year-old Nepalese male was admitted to our hospital after a 3-day history of high fever and coughing. Despite resuscitation efforts, he died of multiple organ failure. A 61-year-old Nepalese female was admitted to our hospital with a complaint of high fever and dyspnea for 1 day. She was the grandmother of the male subject and mostly stayed at his residence in Japan. We administered intravenous antibiotics, including anti-MRSA antibiotics, and she improved in 2 weeks. The sequence type of the isolates was ST22/SCCmec type IVa, and the spa type was t005. The virulence genes detected were as follows: PVL gene (lukSF-pv), TSST-1 gene (tst-1), sec, seg, sei, sel, sem, sen, seo, and seu. ST22 was not the dominant CA-MRSA clone type in Japan. Some of the reports demonstrated that PVL-/TSST-1-positive ST22-MRSA strains are prevalent in Nepal. Therefore, the MRSA strains were thought to be acquired from Nepal. Conclusion These cases highlight the emergence of TSST-1- and PVL-positive CA-MRSA infection and its association with life-threatening community-acquired necrotizing pneumonia. Clinicians should note the possibility of introducing MRSA strains from abroad and be aware of this illness to initiate appropriate treatment.
Induced Pluripotent Stem Cell Modeling of Best Disease and Autosomal Recessive Bestrophinopathy

Purpose To understand the pathophysiology of Best disease (BD) and autosomal recessive bestrophinopathy (ARB) by establishing an in vitro model using human induced pluripotent stem cell (iPSC). Materials and Methods Human iPSC lines were generated from mononuclear cells in peripheral blood of one ARB patient, one autosomal dominant BD patient, and two normal controls. Immunocytochemistry and reverse transcriptase polymerase chain reaction in iPSC lines were conducted to demonstrate the pluripotent markers. After the differentiation of iPSC into functional retinal pigment epithelium (RPE), morphological characteristics of the RPE were evaluated using confocal microscopy and immunocytochemistry. The rates of fluid flow across iPSC-RPE monolayer were measured to compare apical to basal fluid transports by RPE. RNA sequencing was performed on iPSC-RPE to identify the differences in gene expression profiles, and specific gene sets were tested using Gene Set Enrichment Analysis. Results Morphological characteristics, gene expression, and epithelial integrity of ARB iPSC were comparable to those of BD patient or normal control. Fluid transport from apical to basal was significantly decreased in ARB iPSC-RPE compared with BD iPSC-RPE or control iPSC-RPE. Gene Set Enrichment Analysis confirmed that ARB iPSC-RPE exhibited significant enrichments of epithelial-mesenchymal transition gene set and TNF-α signaling via NF-κB gene set compared to control iPSC-RPE or BD iPSC-RPE. Conclusion A human iPSC model of ARB showed a functional deficiency rather than anatomical defects. ARB may be caused by RPE dysfunction following BEST1 mutation.
Effect of Roux-en-Y Bariatric Bypass Surgery on Subclinical Atherosclerosis and Oxidative Stress Markers in Leukocytes of Obese Patients: A One-Year Follow-Up Study

Little is known about the mechanisms underlying the cardioprotective effect of Roux en-Y gastric bypass (RYGB) surgery. Therefore, the aim of the present study was to investigate whether weight loss associated with RYGB improves the oxidative status of leukocytes and ameliorates subclinical atherosclerotic markers. This is an interventional study of 57 obese subjects who underwent RYGB surgery. We determined biochemical parameters and qualitative analysis of cholesterol, leukocyte and systemic oxidative stress markers —superoxide production, glutathione peroxidase 1 (GPX1), superoxide dismutase (SOD) activity and protein carbonylation—, soluble cellular adhesion molecules —sICAM-1 and sP-selectin—, myeloperoxidase (MPO) and leukocyte-endothelium cell interactions—rolling flux, velocity and adhesion. RYGB induced an improvement in metabolic parameters, including hsCRP and leukocyte count (p < 0.001, for both). This was associated with an amelioration in oxidative stress, since superoxide production and protein carbonylation were reduced (p < 0.05 and p < 0.01, respectively) and antioxidant systems were enhanced (GPX1; p < 0.05 and SOD; p < 0.01). In addition, a significant reduction of the following parameters was observed one year after RYGB: MPO and sICAM (p < 0.05, for both), sPselectin and pattern B of LDL particles (p < 0.001, for both), and rolling flux and adhesion of leukocytes (p < 0.05 and p < 0.01, respectively). Our results suggest that patients undergoing RYGB benefit from an amelioration of the prooxidant status of leukocytes, metabolic outcomes, and subclinical markers of atherosclerosis.
Treatment of Synchronous Liver Metastases from Gastric Cancer: A Single-Center Study

Objective The therapeutic effects of surgical resection in gastric cancer with liver metastasis remain largely unclear. We sought to examine surgical resection combined with chemotherapy for survival benefit in cases of synchronous liver metastases from gastric cancer (LMGC), and to identify factors affecting patient prognosis. Methods Patients diagnosed with synchronous LMGC between January 2010 and December 2015 were enrolled in this study. The effects of gastrectomy and metastasectomy combined with chemotherapy (surgical resection group) and palliative chemotherapy (palliative chemotherapy group) on survival were comparatively assessed. Results Of the 132 included cases, 57 (43.2%) and 75 (56.8%) were treated with surgical resection/chemotherapy and palliative chemotherapy, respectively. Overall survival (OS) was markedly prolonged in the surgical resection group compared with the palliative chemotherapy group (33.6 vs 12.4 months, P<0.001). In patients who underwent surgical resection, R0 resection resulted in prolonged OS in comparison with the non-R0 resection subgroup (45.1 vs 13.5 months, P<0.001). Surgical resection (hazard ratio [HR]=0.453; 95% confidence interval [CI] 0.276–0.813; P=0.009) and solitary liver metastasis (HR=0.540; 95% CI 0.315–0.796; P =0.043) were independent predictors of OS. Conclusion Patients with synchronous LMGC might benefit from radical surgical resection combined with appropriate chemotherapy. Additional well-designed prospective studies are required to verify the above findings.