Miracle-dz/UniFAR-FTUs huggingface dataset:
An Observational Cohort Feasibility Study to Identify Microvesicle and Micro-RNA Biomarkers of Acute Kidney Injury Following Pediatric Cardiac Surgery

Objectives: Micro-RNA, small noncoding RNA fragments involved in gene regulation, and microvesicles, membrane-bound particles less than 1 &mgr;m known to regulate cellular processes including responses to injury, may serve as disease-specific biomarkers of acute kidney injury. We evaluated the feasibility of measuring these signals as well as other known acute kidney injury biomarkers in a mixed pediatric cardiac surgery population. Design: Single center prospective cohort feasibility study. Setting: PICU. Patients: Twenty-four children (⩽ 17 yr) undergoing cardiac surgery with cardiopulmonary bypass without preexisting inflammatory state, acute kidney injury, or extracorporeal life support. Interventions: None. Measurements and Main Results: Acute kidney injury was defined according to modified Kidney Diseases Improving Global Outcomes criteria. Blood and urine samples were collected preoperatively and at 6–12 and 24 hours. Microvesicles derivation was assessed using flow cytometry and NanoSight analysis. Micro-RNAs were isolated from plasma and analyzed by microarray and quantitative real-time polymerase chain reaction. Data completeness for the primary outcomes was 100%. Patients with acute kidney injury (n = 14/24) were younger, underwent longer cardiopulmonary bypass, and required greater inotrope support. Acute kidney injury subjects had different fractional content of platelets and endothelial-derived microvesicles before surgery. Platelets and endothelial microvesicles levels were higher in acute kidney injury patients. A number of micro-RNA species were differentially expressed in acute kidney injury patients. Pathway analysis of candidate target genes in the kidney suggested that the most often affected pathways were phosphatase and tensin homolog and signal transducer and activator of transcription 3 signaling. Conclusions: Microvesicles and micro-RNAs expression patterns in pediatric cardiac surgery patients can be measured in children and potentially serve as tools for stratification of patients at risk of acute kidney injury.
Hyperstimulation of CaSR in human MSCs by biomimetic apatite inhibits endochondral ossification via temporal down-regulation of PTH1R

Significance Bone formation occurs through two distinct pathways, namely, endochondral ossification (EO) and intramembranous ossification (IMO). While significant effort has gone into understanding the role of various soluble signals in EO and IMO, the impact of the bone inorganic interface in triggering these ossification pathways has remained unexplored. Herein, we report the discovery that the bone-like mineral phase promotes formation of bone by mesenchymal stem/stromal cells (MSCs) exclusively via IMO even in the presence of soluble signals that promote the EO paradigm. Furthermore, we provide mechanistic insights into our observations and illustrate a previously unidentified role for extracellular calcium-sensing receptor (CaSR) in dictating the choice of ossification pathway in MSCs. These findings have significant implications for developing new strategies for bone repair and understanding bone homeostasis. In adult bone injuries, periosteum-derived mesenchymal stem/stromal cells (MSCs) form bone via endochondral ossification (EO), whereas those from bone marrow (BM)/endosteum form bone primarily through intramembranous ossification (IMO). We hypothesized that this phenomenon is influenced by the proximity of MSCs residing in the BM to the trabecular bone microenvironment. Herein, we investigated the impact of the bone mineral phase on human BM-derived MSCs’ choice of ossification pathway, using a biomimetic bone-like hydroxyapatite (BBHAp) interface. BBHAp induced hyperstimulation of extracellular calcium-sensing receptor (CaSR) and temporal down-regulation of parathyroid hormone 1 receptor (PTH1R), leading to inhibition of chondrogenic differentiation of MSCs even in the presence of chondroinductive factors, such as transforming growth factor-β1 (TGF-β1). Interestingly rescuing PTH1R expression using human PTH fragment (1–34) partially restored chondrogenesis in the BBHAp environment. In vivo studies in an ectopic site revealed that the BBHAp interface inhibits EO and strictly promotes IMO. Furthermore, CaSR knockdown (CaSR KD) disrupted the bone-forming potential of MSCs irrespective of the absence or presence of the BBHAp interface. Our findings confirm the expression of CaSR in human BM-derived MSCs and unravel a prominent role for the interplay between CaSR and PTH1R in regulating MSC fate and the choice of pathway for bone formation.
Taxonomic Resolution, Functional Traits, and the Influence of Species Groupings on Mapping Antarctic Seafloor Biodiversity

Benthic marine biodiversity on the Antarctic continental shelf is high and unique, yet its distributional patterns are still relatively poorly understood. Some of the main issues are that biological data are sparse, and that many species are rare and seem only weakly related to environmental conditions. Grouping species by taxonomic or functional similarity has historically been used to compensate for missing species identification, to generate a more widespread distribution of data-points, and this practice can help to gain a better understanding of the distribution of biodiversity. However, there are few guidelines on how to group species, the implicit assumptions about species associations in the groups are difficult to validate, and the information loss associated with grouping species is unknown. Here, we analyse whether grouping benthic macrofaunal species by taxonomic or functional similarity preserves distributional patterns seen in species distributions, using a model-based approach called ‘species archetype model’ that groups species or other units based on the similarity in their responses to environmental factors. Using presence-absence data, the species archetype models identify twice as many assemblages when used on the highest taxonomic resolution data, than when applied to taxonomic data at lower resolution (e.g. class) or functional groups based on mobility, feeding type and body shape. Further, confidence in the predictions of either taxonomic or functional groups is far less than for predictions based on the highest taxonomic resolution data. Although using functional groups is often thought to accumulate species with similar environmental responses, our analysis shows that functional groups may insufficiently resolve assemblage structure for presence-absence data. Model-based approaches provide key information to understanding the regional distribution of Antarctic marine biodiversity, and care needs to be taken when using a-priori groupings of species to make statements about the distribution of biodiversity.
Relationship between high-sensitivity cardiac troponin T and the prognosis of elderly inpatients with non-acute coronary syndromes

Objective Low-level high-sensitivity cardiac troponin T (hs-cTnT) increases in elderly population. In this study, the relationship between hs-cTnT level and all-cause death of elderly inpatients with non-acute coronary syndrome (non-ACS) after discharge from the hospital was investigated. Materials and methods Non-ACS patients aged >65 years admitted in the General Practice Wards and Department of Geriatrics of Fuxing Hospital Affiliated to Capital Medical University were enrolled in the study. The patients were grouped according to the tertiles of hs-cTnT levels. Biochemical markers, hs-cTnT, and amino-terminal pro-brain natriuretic peptide were measured. The median follow-up period was 47 months, and all-cause deaths of the patients were observed. Results A total of 722 patients, including 473 males and 249 females, aged 65–98 (82.43±5.98) years were enrolled in the study. The level of hs-cTnT was found to be higher in males, and increased with age and comorbidities (P<0.01). Compared with low-level group, NT-proBNP level of patients in high-level group was higher, while hemoglobin (Hb), estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction (LVEF) levels were lower (P<0.001). The mortality rate increased significantly with increased hs-cTnT levels (P<0.001). The total number of deaths was 136 (18.8%), and of these, 108 (79.4%) were noncardiac deaths. Risk of all-cause deaths in the highest hs-cTnT level group was 7.3 times higher than that of the lowest hs-cTnT level group (95% CI: 4.29–12.51, P<0.001). After adjusting for gender, age, comorbidities, NT-proBNP, Hb, eGFR, and LVEF, hs-cTnT level still affected the patient’s survival time (HR: 3.01, 95% CI: 1.67–5.43, P<0.001). Conclusion These findings suggest that low-level hs-cTnT was increased in elderly inpatients without ACS. They further highlight that baseline hs-cTnT level was associated with increased risk of all-cause deaths among patients after their discharge, and most deaths were from non-cardiovascular diseases.
The Practice of Overlapping Colorectal Operations in a Tertiary Care Center Is Safe: A Model for Advancing Team-based Care.

OBJECTIVE Determine the safety of overlapping surgery in a tertiary care colorectal surgery practice. SUMMARY Although overlapping surgery is common in academic centers, reports on outcomes of this practice are limited. The primary aim of this study was to investigate the safety of overlapping surgery in a dedicated tertiary care academic colorectal practice by comparing groups of patients who did or did not have their surgery performed in an overlapping fashion. METHODS Retrospective review of 1270 colorectal patients undergoing inpatient colorectal surgery at our institution. Eligible participants were all patients undergoing elective inpatient colorectal surgery by one of the colorectal surgeons at the Mayo Clinic Rochester between January 1, 2012 and December 31, 2015. Patients under the age of 18 or who underwent an emergent procedure were excluded. Data were abstracted using the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) database. Additionally, each subject's chart was reviewed and further abstracted. The safety of overlapping surgery on outcomes was assessed using multiple multivariable models. RESULTS One thousand two hundred seventy patients were included in the study cohort of whom 50.7% were female and the average age was 55.4 years. Overlapping surgery occurred in 576 patients (45%). There were no significant differences in demographic, surgical indications, procedures, or operative complexity between patients undergoing overlapping surgery and those who did not. Overall adverse events were significantly less likely in patients undergoing overlapping surgery compared with those who did not (18.4% vs 23.6%, P = 0.02). We found that overlapping surgery was associated with significantly less adverse events compared with patients not undergoing overlapping surgery using a model that controlled for the effect of the individual surgeon (OR 0.7, 95% CI 0.6 - 0.96; P = .02) and a multivariable propensity score (OR 0.7, 95% CI 0.5- 0.9; P = 01). CONCLUSIONS Overlapping surgery in a tertiary care colorectal practice is safe and not associated with adverse patient outcomes.
Bevacizumab Diminishes Inflammation in an Acute Endotoxin-Induced Uveitis Model

Introduction: Uveitis is an eye disease characterized by inflammation of the uvea and an early and exhaustive diagnosis is essential for its treatment. The aim of our study is to assess the potential toxicity and anti-inflammatory efficacy of Bevacizumab in an experimental uveitis model by subcutaneously injecting lipopolysaccharide into Lewis rats and to clarify its mechanism. Material and Methods: Blood–aqueous barrier integrity was assessed 24 h after endotoxin-induced uveitis (EIU) by analyzing two parameters: cell count and protein concentration in aqueous humors. Histopathology of all eye structures was also studied. Enzyme-linked immunosorbent analyses of the aqueous humor samples were performed in order to calculate the diverse chemokine and cytokine protein levels and oxidative stress-related markers were also evaluated. Results: The aqueous humor’s cellular content significantly increased in the group treated with only Bevacizumab, but it had no effect on retina histopathological grading. Nevertheless, the inflammation noted in ocular structures when administering Bevacizumab with endotoxin was mostly prevented since aqueous humor cell content considerably lowered, and concomitantly with a sharp drop in uveal, vitreous, and retina histopathological grading. The values of the multi-faceted cytokine IL-2 also significantly decreased (p < 0.05 vs. endotoxin group), and the protective IL-6 and IL-10 cytokines values rose with related anti-oxidant system recovery (p < 0.05 vs. endotoxin group). Concurrently, some related M1 macrophage chemokines substantially increased, e.g., GRO/KC, a chemokine that also displays any kind of protective role. Conclusion: All these results revealed that 24 h after being administered, Bevacizumab treatment in EIU significantly prevented inflammation in various eye structures and correct results in efficacy vs. toxicity balance were obtained.
Efficient Algorithms for Adaptive Influence Maximization

Given a social network G, the influence maximization (IM) problem seeks a set S of k seed nodes in G to maximize the expected number of nodes activated via an influence cascade starting from S. Although a lot of algorithms have been proposed for IM, most of them only work under the non-adaptive setting, i.e., when all k seed nodes are selected before we observe how they influence other users. In this paper, we study the adaptive IM problem, where we select the k seed nodes in batches of equal size b, such that the choice of the i-th batch can be made after the influence results of the first i - 1 batches are observed. We propose the first practical algorithms for adaptive IM with an approximation guarantee of 1 − exp(ξ − 1) for b = 1 and 1 − exp(ξ − 1 + 1/e) for b > 1, where ξ is any number in (0, 1). Our approach is based on a novel AdaptGreedy framework instantiated by non-adaptive IM algorithms, and its performance can be substantially improved if the non-adaptive IM algorithm has a small expected approximation error. However, no current non-adaptive IM algorithms provide such a desired property. Therefore, we further propose a non-adaptive IM algorithm called EPIC, which not only has the same worst-case performance bounds with that of the state-of-the-art non-adaptive IM algorithms, but also has a reduced expected approximation error. We also provide a theoretical analysis to quantify the performance gain brought by instantiating AdaptGreedy using EPIC, compared with a naive approach using the existing IM algorithms. Finally, we use real social networks to evaluate the performance of our approach through extensive experiments, and the experimental experiments strongly corroborate the superiorities of our approach.
Mycotoxin contamination of sorghum and its contribution to human dietary exposure in four sub-Saharan countries

ABSTRACT This research aimed at evaluating the safety, and the type, level and prevalence of mycotoxins in grain sorghum of four sub-Saharan African (SSA) countries (Burkina Faso, Ethiopia, Mali and Sudan). A multi-analyte LC-MS/MS method for quantification of 23 mycotoxins (nivalenol, deoxynivalenol, fusarenon X, neosolaniol, 3-acetyl deoxynivalenol, 15-acetyl deoxynivalenol, diacetoxyscirpenol, roquefortine C, HT-2 toxin, alternariol, T-2 toxin, FB1, FB2, FB3, zearalenone, aflatoxin G1, aflatoxin G2, aflatoxin B1, aflatoxin B2, sterigmatocystin, OTA, altenuene, alternariol monomethylether) was applied to different sorghum matrices. Of the 1533 analysed samples, 33% were contaminated with at least one of the following mycotoxins: aflatoxins, fumonisins, sterigmatocystin, Alternaria toxins, OTA and zearalenone. Country of origin, colour, source and collection period of sorghum samples significantly influenced the type, level and prevalence of mycotoxins. Sterigmatocystin (15%), fumonisins (17%) and aflatoxins (13%) were the most prevalent. FB1 (274 ± 585 µg/kg) had the highest mean concentration followed by FB2 (214 ± 308 µg/kg) while diacetoxyscirpenol (8.12 ± 19.2 µg/kg) and HT-2 (11.9 ± 0.00 µg/kg) had the lowest concentrations. Neosolaniol, fusarenon-X, 3-acetyl deoxynivalenol, 15-acetyl deoxynivalenol, T-2 toxin, nivalenol and roquefortine C were not detected in any of the samples. Sudan had the lowest prevalence and mean concentration of all mycotoxins. Pink sorghum had the highest concentrations of fumonisins and aflatoxins. Mycotoxins from Aspergillus spp. and Alternaria spp. are the mycotoxins of concern in SSA grain sorghum with regard to prevalence, concentration and possible health risk from exposure. Based on the performed risk characterisation, daily consumption of sorghum containing aflatoxins, alternariol, alternariol monomethyl ether, sterigmatocystin and OTA could result in exceeding the established health-based guidance values for these toxins.
Association of risk factors with temporomandibular disorders in the Northern Finland Birth Cohort 1966

Abstract Objective: To investigate the association between risk factors and pain-related symptoms and clinical signs of temporomandibular disorders (TMD) in Northern Finland Birth Cohort (NFBC) 1966. Material and methods: A total of 1962 subjects (1050 women, 912 men) attended the follow-up study. The questionnaires included the subjects’ background information concerning living conditions and general health, socioeconomic factors, and dental health. The clinical examination was performed using the modified protocol of Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) presented at the International Association for Dental Research (IADR) Conference in 2010. Cross-tabulation, a chi-square test and Fisher’s exact test were used to analyze differences between groups. Results: Female gender showed statistically significant association with symptoms and signs of TMD, while marital status, living conditions, and socioeconomic group showed no association. A strong association was found between self-reported health condition as well as general health problems [i.e. depression, migraine, fibromyalgia (FM), gastrointestinal diseases] and TMD pain-related symptoms and pain on palpation in the masticatory muscles and TMJs. Conclusion: In conclusion, general health problems and female gender had a strong association with pain-related symptoms and clinical signs of TMD. These findings are important to take into account when diagnosing and treating TMD patients. Conversely to earlier presented results, no statistically significant association was shown here between marital status, living conditions or socioeconomic group and pain-related symptoms and clinical signs of TMD.
Intranasal Oxytocin Does Not Modulate Responses to Alcohol in Social Drinkers

BACKGROUND Preclinical and clinical evidence suggest that the neuropeptide oxytocin may be of value in treating alcohol use disorder, by either reducing the rewarding effects of alcohol or reducing negative affect induced by alcohol withdrawal. However, the effect of a single dose of oxytocin on subjective and psychomotor responses to alcohol in social drinkers is not known. METHODS This study examined the effect of intranasal oxytocin on subjective, behavioral, and physiological responses to a moderate dose of alcohol (0.8 g/kg) in young adult social drinkers. Participants (N = 35) completed 2 study sessions at which they consumed beverages containing alcohol (ALC; N = 20) or placebo (NoALC; N = 15) in combination with intranasal oxytocin (40 IU with a 20 IU booster) or placebo. They received oxytocin at one session and placebo at the other session (order counterbalanced) 20 minutes before consuming beverages. Subjective mood and drug effects ratings, heart rate and blood pressure, and 4 behavioral tasks (flanker task, digit span, go/no-go, and pursuit rotor) were the primary outcome measures. RESULTS ALC produced its expected subjective and behavioral effects; including feeling intoxicated and impaired performance on the digit span and go/no-go tasks. Oxytocin alone had no significant subjective or physiological effects, and it did not affect responses to alcohol on any measure. CONCLUSIONS We can conclude that, under these conditions, a single dose of intranasal oxytocin does not alter the effects of acute alcohol in healthy young adult social drinkers. Further research is needed to determine whether oxytocin alters responses to alcohol under different conditions, and to determine its potential as an aid in treatment for substance use disorders.
Identification and Characterization of Flavonoid Biosynthetic Enzyme Genes in Salvia miltiorrhiza (Lamiaceae)

Flavonoids are a class of important secondary metabolites with a broad spectrum of pharmacological functions. Salvia miltiorrhiza Bunge (Danshen) is a well-known traditional Chinese medicinal herb with a broad diversity of flavonoids. However, flavonoid biosynthetic enzyme genes have not been systematically and comprehensively analyzed in S. miltiorrhiza. Through genome-wide prediction and molecular cloning, twenty six flavonoid biosynthesis-related gene candidates were identified, of which twenty are novel. They belong to nine families potentially encoding chalcone synthase (CHS), chalcone isomerase (CHI), flavone synthase (FNS), flavanone 3-hydroxylase (F3H), flavonoid 3′-hydroxylase (F3′H), flavonoid 3′,5′-hydroxylase (F3′5′H), flavonol synthase (FLS), dihydroflavonol 4-reductase (DFR), and anthocyanidin synthase (ANS), respectively. Analysis of intron/exon structures, features of deduced proteins and phylogenetic relationships revealed the conservation and divergence of S. miltiorrhiza flavonoid biosynthesis-related proteins and their homologs from other plant species. These genes showed tissue-specific expression patterns and differentially responded to MeJA treatment. Through comprehensive and systematic analysis, fourteen genes most likely to encode flavonoid biosynthetic enzymes were identified. The results provide valuable information for understanding the biosynthetic pathway of flavonoids in medicinal plants.
Non-Operative Management of Type 2 ERCP-Related Retroperitoneal Duodenal Perforations: A 9-Year Experience From a Single Center

Background No consensus exists on treatment of endoscopic retrograde cholangiopancreatography (ERCP) -related, retroperitoneal duodenal perforations. The aim of this study is to determine the incidence of post-ERCP retroperitoneal periampullary (type 2) duodenal perforations and the clinical outcome of non-surgical management. Methods Patients who underwent ERCP in our institution during the period from January 1, 2009 to December 31, 2017 were included. Any cases of retroperitoneal periampullary duodenal (type 2) perforation were identified. Relevant data (patient characteristics, indications, radiographic findings, time to diagnosis and surgery, surgical procedures, hospital stay and outcome) were retrospectively collected and reviewed. Results were compared to those from the existing literature. Results There were 24 patients with retroperitoneal type 2 duodenal perforation following 4,196 ERCPs were identified (24/4196, 0.57%) over the 9-year period. ERCP indications were: choledocholithiasis, obstructive jaundice and ampullectomy (ampullary adenoma). Diagnosis (aided by CT scan) was established within the first 12 h in the majority of patients (21/24, 87.5%) and intraprocedural in 3/24, (12.5%). Twelve patients (50%) with deteriorating clinical course were managed with CT-guided percutaneous drainage. Surgical intervention was required in two (8.3%). Overall mortality was 4.2%, 1/24 (one patient died after surgery). Conclusions Retroperitoneal duodenal perforation is a rare and severe ERCP complication. However, conservative management is feasible in the majority of cases.