Miracle-dz/UniFAR-FTUs huggingface dataset:
Semi-automated speckle-tracking for quantitative right ventricular assessment in children and adolescents

Abstract Background: Assessment of right ventricular size and function is an important part of the clinical cardiac evaluation; however, these quantitative measures are challenging by echocardiography. Automated software could be useful in place of manual measurements and qualitative assessment. This study evaluates a semi-automated software by comparing automated to manual measures in normal children. Methods: Neonates to adolescents with normal echocardiograms were prospectively enrolled. Measurements were performed using manual techniques and semi-automated software (EchoInsight®, Epsilon Imaging, Ann Arbor, Michigan, United States of America). Right ventricular measurements included end-diastolic and end-systolic area, fractional area change, chamber dimensions, and tricuspid annular plane systolic excursion. Agreement between manual and semi-automated measures was compared. Results: Echocardiograms for 233 patients were included in the analysis. Intra- and inter-observer reliabilities for semi-automated measures were good with intraclass correlation coefficients all over 0.9 and 0.85, respectively. There was very strong correlation between manual and semi-automated methods for areas and dimensions (r = 0.93–0.99) and low bias (1.4–10.8%). For functional measures, tricuspid annular plane systolic excursion measures correlated well (r = 0.84), but fractional area change did not (r = 0.50). Both demonstrated significant bias (33.5–43.0%). The semi-automated method consistently underestimated fractional area change with a mean of 26.6% versus a manual mean of 36.1%. Conclusions: The semi-automated software is capable of generating quantitative right ventricular measures in children with good reliability. The software demonstrates very good correlation and low bias when compared to manual methods for right ventricular areas and dimensions. There is a significant difference between manual and semi-automated techniques for the functional measures.
Mutations associated with a 17-gene leukemia stem cell score and the score’s prognostic relevance in the context of the European LeukemiaNet classification of acute myeloid leukemia

Leukemia stem cells (LSC) are more resistant to standard chemotherapy and their persistence during remission can cause relapse, which is still one of the major clinical challenges in the treatment of acute myeloid leukemia (AML). A better understanding of the mutational patterns and the prognostic impact of molecular markers associated with stemness could lead to better clinical management and improve patients’ outcomes. We applied a previously described 17-gene expression score comprising genes differently expressed between LSC and leukemic bulk blasts, for 934 adult patients with de novo AML, and studied associations of the 17-gene LSC score with clinical data and mutation status of 81 genes recurrently mutated in cancer and leukemia. We found that patients with a high 17-gene score were older and had more mutations. The 17-gene score was found to have a prognostic impact in both younger (aged <60 years) and older (aged ≥60 years) patients with AML. We also analyzed the 17-gene LSC score in the context of the 2017 European LeukemiaNet genetic-risk classification and found that for younger patients the score refined the classification, and identified patients currently classified in the European LeukemiaNet Favorable-risk category who had a worse outcome.
Dairy fat intake and risk of type 2 diabetes in 3 cohorts of US men and women.

BACKGROUND Previous studies have examined dairy products with various fat contents in relation to type 2 diabetes (T2D) risk, although data regarding dairy fat intake per se are sparse. OBJECTIVES We aimed to evaluate the association between dairy fat intake and risk of T2D in 3 prospective cohorts. We also examined associations for isocalorically replacing dairy fat with other macronutrients. METHODS We prospectively followed 41,808 men in the Health Professionals Follow-Up Study (HPFS; 1986-2012), 65,929 women in the Nurses' Health Study (NHS; 1984-2012), and 89,565 women in the NHS II (1991-2013). Diet was assessed quadrennially using validated FFQs. Fat intake from dairy products and other relevant sources was expressed as percentage of total energy. Self-reported incident T2D cases were confirmed using validated supplementary questionnaires. Time-dependent Cox proportional hazards regression was used to estimate the HR for dairy fat intake and T2D risk. RESULTS During 4,219,457 person-years of follow-up, we documented 16,511 incident T2D cases. Dairy fat was not associated with risk of T2D when compared with calories from carbohydrates (HR for extreme quintiles: 0.98; 95% CI: 0.95, 1.02). Replacing 5% of calories from dairy fat with other sources of animal fat or carbohydrate from refined grains was associated with a 17% (HR: 1.17; 95% CI: 1.13, 1.21) and a 4% (HR: 1.04; 95% CI: 1.00, 1.08) higher risk of T2D, respectively. Conversely, a 5% calorie replacement with carbohydrate from whole grains was associated with a 7% lower risk of T2D (HR: 0.93; 95% CI: 0.88, 0.98). CONCLUSIONS Dairy fat intake was not associated with T2D risk in these cohort studies of US men and women when compared with calories from carbohydrate. Replacing dairy fat with carbohydrates from whole grains was associated with lower risk of T2D. Replacement with other animal fats or refined carbohydrates was associated with higher risk.
Bringing the social context into research using the common sense model

Reviews of the literature on the common sense model (CSM) provide strong support for the value of the framework in understanding and predicting illness behavior. It is clear from these reviews, however, that there are gaps in the literature and aspects of the model that have been left relatively unexamined. Here, we focus on two such gaps. First is an inattention to social contextual factors, including relationships with both formal and informal care providers. The second gap discussed is the dearth of longitudinal research testing the model. In particular, we highlight the need for intensive longitudinal designs to facilitate examination of illness representation and behavior as processes that unfold dynamically overtime.
A Comparative Study of Computational Methods for Compressed Sensing Reconstruction of EMG Signal

Wearable devices offer a convenient means to monitor biosignals in real time at relatively low cost, and provide continuous monitoring without causing any discomfort. Among signals that contain critical information about human body status, electromyography (EMG) signal is particular useful in monitoring muscle functionality and activity during sport, fitness, or daily life. In particular surface electromyography (sEMG) has proven to be a suitable technique in several health monitoring applications, thanks to its non-invasiveness and ease to use. However, recording EMG signals from multiple channels yields a large amount of data that increases the power consumption of wireless transmission thus reducing the sensor lifetime. Compressed sensing (CS) is a promising data acquisition solution that takes advantage of the signal sparseness in a particular basis to significantly reduce the number of samples needed to reconstruct the signal. As a large variety of algorithms have been developed in recent years with this technique, it is of paramount importance to assess their performance in order to meet the stringent energy constraints imposed in the design of low-power wireless body area networks (WBANs) for sEMG monitoring. The aim of this paper is to present a comprehensive comparative study of computational methods for CS reconstruction of EMG signals, giving some useful guidelines in the design of efficient low-power WBANs. For this purpose, four of the most common reconstruction algorithms used in practical applications have been deeply analyzed and compared both in terms of accuracy and speed, and the sparseness of the signal has been estimated in three different bases. A wide range of experiments are performed on real-world EMG biosignals coming from two different datasets, giving rise to two different independent case studies.
Degradation of integral membrane proteins modified with the photosensitive degron module requires the cytosolic endoplasmic reticulum–associated degradation pathway

Protein quality mechanisms are fundamental for proteostasis of eukaryotic cells. Endoplasmic reticulum–associated degradation (ERAD) is a well-studied pathway that ensures quality control of secretory and endoplasmic reticulum (ER)–resident proteins. Different branches of ERAD are involved in degradation of malfolded secretory proteins, depending on the localization of the misfolded part, the ER lumen (ERAD-L), the ER membrane (ERAD-M), and the cytosol (ERAD-C). Here we report that modification of several ER transmembrane proteins with the photosensitive degron (psd) module resulted in light-dependent degradation of the membrane proteins via the ERAD-C pathway. We found dependency on the ubiquitylation machinery including the ubiquitin-activating enzyme Uba1, the ubiquitin-conjugating enzymes Ubc6 and Ubc7, and the ubiquitin–protein ligase Doa10. Moreover, we found involvement of the Cdc48 AAA-ATPase complex members Ufd1 and Npl4, as well as the proteasome, in degradation of Sec62-myc-psd. Thus, our work shows that ERAD-C substrates can be systematically generated via synthetic degron constructs, which facilitates future investigations of the ERAD-C pathway.
Agenesis of the putamen and globus pallidus caused by recessive mutations in the homeobox gene GSX2

Congenital malformations of the basal ganglia are rare. De Mori et al. describe a novel syndrome of severe dystonic tetraparesis and intellectual impairment, with hypo/agenesis of the basal ganglia. The syndrome is caused by recessive mutations in GSX2, a homeobox gene expressed in ganglionic eminences and essential for basal ganglia development.
The First Asian Kidney Transplantation Prediction Models for Long-term Patient and Allograft Survival

Supplemental Digital Content is available in the text. Background. Several kidney transplantation (KT) prediction models for patient and graft outcomes have been developed based on Caucasian populations. However, KT in Asian countries differs due to patient characteristics and practices. To date, there has been no equation developed for predicting outcomes among Asian KT recipients. Methods. We developed equations for predicting 5- and 10-year patient survival (PS) and death-censored graft survival (DCGS) based on 6662 patients in the Thai Transplant Registry. The cohort was divided into training and validation data sets. We identified factors significantly associated with outcomes by Cox regression. In the validation data set, we also compared our models with another model based on KT in the United States. Results. Variables included for developing the DCGS and PS models were recipient and donor age, background kidney disease, dialysis vintage, donor hepatitis C virus status, cardiovascular diseases, panel reactive antibody, donor types, donor creatinine, ischemic time, and immunosuppression regimens. The C statistics of our model in the validation data set were 0.69 (0.66–0.71) and 0.64 (0.59–0.68) for DCGS and PS. Our model performed better when compared with a model based on US patients. Compared with tacrolimus, KT recipients aged ≤44 years receiving cyclosporine A had a higher risk of graft loss (adjusted hazard ratio = 1.26; P = 0.046). The risk of death was higher in recipients aged >44 years and taking cyclosporine A (adjusted hazard ratio = 1.44; P = 0.011). Conclusions. Our prediction model is the first based on an Asian population, can be used immediately after transplantation. The model can be accessed at www.nephrochula. com/ktmodels.
The Significance of Thiol/Disulfide Homeostasis and Ischemia-modified Albumin Levels in Assessing Oxidative Stress in Obese Children and Adolescents

Objective: There is an association between obesity and several inflammatory and oxidative markers in children. In this study, we analyzed thiol/disulfide homeostasis and serum ischemia-modified albumin (IMA) levels for the first time in order to clarify and determine the oxidant/antioxidant balance in metabolically healthy and unhealthy children. Methods: This study included obese children and healthy volunteers between 4-18 years of age. The obese patients were divided into two groups: metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Biochemical parameters including thiol/disulfide homeostasis, and IMA concentrations were analyzed. Results: There were 301 recruits of whom 168 (55.8%) were females. The obese children numbered 196 (MHO n=58 and MUO n=138) and healthy controls numbered 105. No statistically significant difference could be found in ages and genders of the patients among all groups (p>0.05, for all). Native thiol (SH), total thiol (SH+SS), and native thiol/total thiol (SH/SH+SS) ratio were statistically significantly lower in the MUO group than the control group (p<0.001, p=0.005, and p=0.005; respectively). Disulfide (SS), disulfide/native thiol (SS/SH), disulfide/total thiol (SS/SH+SS) and IMA levels were statistically significantly higher in the MUO group than the control group (p=0.002, p<0.001, p<0.001, and p=0.001, respectively). Conclusion: Chronic inflammation due to oxidative stress induced by impaired metabolic parameters in MUO children caused impairment in thiol redox homeostasis. Our data suggested that the degree of oxidant imbalance in obese children worsened as obesity and metabolic abnormalities increased. It is hypothesized that thiol/disulfide homeostasis and high serum IMA levels may be reliable indicators of oxidant-antioxidant status in MUO children.
Pharmacokinetics, bioavailability and urinary excretion of scopolin and its metabolite scopoletin in Sprague-Dawley rats by LC-MS/MS.

The aim of this study is to investigate the pharmacokinetics, bioavailability and urinary excretion of scopolin and its metabolite scopoletin in rat. A LC-MS/MS method for simultaneous determination of scopolin and scopoletin in rat biomatrices was developed and validated over the rage of 5.0-2000 ng/mL. Chromatographic separation was carried out on a Hypersil GOLD C18 column with acetonitrile and 0.1% formic acid in water as mobile phase with gradient elution. Detection was performed in the positive ionization and selected reaction monitoring mode. The intra- and inter- batch precision and accuracy, extraction recovery and matrix effect, stability of scopolin and scopoletin were well within the acceptable limits of variation. There was no gender-related difference in pharmacokinetic profiles of scopolin. There were significant differences in AUC, Tmax and Cl/F of scopoletin between the male and female rats (p < 0.05). The bioavailability of scopolin was exceptionally low. The maximal excretion rates were 7.61 μg/h and 7.15 μg/h for scopolin and 31.68 μg/h and 25.58 μg/h for scopoletin in male and female rats, respectively. The LC-MS/MS method was successfully applied to the pharmacokinetic, bioavailability and urinary excretion studies of scopolin and its metabolite scopoletin following single administration of scopolin to rats.
Transferable Mechanisms of Quinolone Resistance from 1998 Onward

While the description of resistance to quinolones is almost as old as these antimicrobial agents themselves, transferable mechanisms of quinolone resistance (TMQR) remained absent from the scenario for more than 36 years, appearing first as sporadic events and afterward as epidemics. In 1998, the first TMQR was soundly described, that is, QnrA. SUMMARY While the description of resistance to quinolones is almost as old as these antimicrobial agents themselves, transferable mechanisms of quinolone resistance (TMQR) remained absent from the scenario for more than 36 years, appearing first as sporadic events and afterward as epidemics. In 1998, the first TMQR was soundly described, that is, QnrA. The presence of QnrA was almost anecdotal for years, but in the middle of the first decade of the 21st century, there was an explosion of TMQR descriptions, which definitively changed the epidemiology of quinolone resistance. Currently, 3 different clinically relevant mechanisms of quinolone resistance are encoded within mobile elements: (i) target protection, which is mediated by 7 different families of Qnr (QnrA, QnrB, QnrC, QnrD, QnrE, QnrS, and QnrVC), which overall account for more than 100 recognized alleles; (ii) antibiotic efflux, which is mediated by 2 main transferable efflux pumps (QepA and OqxAB), which together account for more than 30 alleles, and a series of other efflux pumps (e.g., QacBIII), which at present have been sporadically described; and (iii) antibiotic modification, which is mediated by the enzymes AAC(6′)Ib-cr, from which different alleles have been claimed, as well as CrpP, a newly described phosphorylase.
Geochemical and Metagenomic Characterization of Jinata Onsen, a Proterozoic-Analog Hot Spring, Reveals Novel Microbial Diversity including Iron-Tolerant Phototrophs and Thermophilic Lithotrophs

Hydrothermal systems, including terrestrial hot springs, contain diverse geochemical conditions that vary over short spatial scales due to progressive interactions between reducing hydrothermal fluids, the oxygenated atmosphere, and, in some cases, seawater. At Jinata Onsen on Shikinejima Island, Japan, an intertidal, anoxic, iron-rich hot spring mixes with the oxygenated atmosphere and seawater over short spatial scales, creating diverse chemical potentials and redox pairs over a distance of ~10 m. We characterized geochemical conditions along the outflow of Jinata Onsen as well as the microbial communities present in biofilms, mats, and mineral crusts along its traverse using 16S rRNA gene amplicon and genome-resolved shotgun metagenomic sequencing. Microbial communities significantly changed downstream as temperatures and dissolved iron concentrations decreased and dissolved oxygen increased. Biomass was more limited near the spring source than downstream, and primary productivity appeared to be fueled by the oxidation of ferrous iron and molecular hydrogen by members of Zetaproteobacteria and Aquificae. The microbial community downstream was dominated by oxygenic Cyanobacteria. Cyanobacteria are abundant and active even at ferrous iron concentrations of ~150 μM, which challenges the idea that iron toxicity limited cyanobacterial expansion in Precambrian oceans. Several novel lineages of Bacteria are also present at Jinata Onsen, including previously uncharacterized members of the phyla Chloroflexi and Calditrichaeota, positioning Jinata Onsen as a valuable site for the future characterization of these clades.
Preoperative Sedative-hypnotic Medication Use and Adverse Postoperative Outcomes

Supplemental Digital Content is available in the text Objective: To determine the association between preoperative benzodiazepine and nonbenzodiazepine receptor agonist (“Z-drugs”) use and adverse outcomes after surgery. Background: Prescriptions for benzodiazepines and Z-drugs have increased over the past decade. Despite this, the association of preoperative benzodiazepines and Z-drug receipt with adverse outcomes after surgery is unknown. Methods: Using the Optum Clinformatics Datamart, we performed a retrospective cohort study of adults 18 years or older who underwent any of 10 common surgical procedures between 2010 and 2015. The principal exposure was one or more filled prescriptions for a benzodiazepine or Z-drug in the 90 days before surgery. The primary outcome was any emergency department visit or hospital admission for either (1) a drug related adverse medical event or overdose or (2) a traumatic injury in the 30 days after surgery. Results: Of 785,346 patients meeting inclusion criteria, 94,887 (12.1%) filled a preoperative prescription for a benzodiazepine or Z-drug. From multivariable logistic regression, benzodiazepine or Z-drug use was associated with an increased odds of an adverse postoperative event [odds ratio 1.13; 95% confidence interval: 1.08–1.18). In a separate regression, coprescription of benzodiazepines or Z-drugs with opioids was associated with a 1.45 odds of an adverse postoperative event (95% confidence interval: 1.37–1.53). Conclusions: Preoperative benzodiazepines and Z-drug use is common and associated with increased odds of adverse outcomes after surgery, particularly when coprescribed with opioids. Counseling on appropriate benzodiazepine and Z-drug use in advance of elective surgery may potentially increase the safety of surgical care.
Incidence and Risks for Non Alcoholic Fatty Liver Disease and Steatohepatitis Post Liver Transplant: Systematic Review and Meta-analysis.

BACKGROUND The true incidence and unique risk factors for recurrent and de novo nonalcoholic fatty liver (NAFLD) and nonalcoholic steatohepatitis (NASH) post liver transplant (LT) remain poorly characterized. We aimed to identify the incidence and risk factors for recurrent and de novo NAFLD/NASH post-LT. METHODS MEDLINE via PubMed, Embase, Scopus and CINAHL were searched for studies from 2000- 2018. Risk of bias was adjudicated using the Newcastle-Ottawa Scale. RESULTS Seventeen studies representing 2,378 patients were included. All were retrospective analyses of patients with post-LT liver biopsies, with the exception of two studies that used imaging for outcome assessment. Seven studies evaluated recurrent, three de novo, and seven included both. In studies at generally high or moderate risk of bias, mean 1, 3 and ≥5-year incidence rates may be: 59%, 57 %, and 82% for recurrent NAFLD; 67%, 40%, and 78% for de novo NAFLD; Mean 1, 3 and ≥5-year incidence rates may be: 53%, 57.4%, and 38% for recurrent NASH; 13%, 16%, and 17% for de novo NASH. Multivariate analysis demonstrated that post-LT BMI (summarized OR 1.27) and hyperlipidemia were the most consistent predictors of outcomes. CONCLUSIONS There is low confidence in the incidence of recurrent and de novo NAFLD and NASH after LT due to study heterogeneity. Recurrent and de novo NAFLD may occur in over half of recipients as soon as 1 year after LT. NASH recurs in most patients after LT, while de novo NASH occurs rarely. NAFLD/NASH after LT are associated with metabolic risk factors.
Size Dependency of Circulation and Biodistribution of Biomimetic Nanoparticles: Red Blood Cell Membrane-Coated Nanoparticles

Recently, biomimetic nanoparticles, especially cell membrane-cloaked nanoparticles, have attracted increasing attention in biomedical applications, including antitumor therapy, detoxification, and immune modulation, by imitating the structure and the function of biological systems such as long circulation life in the blood. However, the circulation time of cell membrane-cloaked nanoparticles is far less than that of the original cells, greatly limiting their biomedical applications, while the underlying reasons are seldom demonstrated. In this study, the influence of particle size on the circulation and the biodistribution of red blood cell membrane-coated nanoparticles (RBC-NPs) as model biomimetic nanoparticles were investigated. Differently sized RBC-NPs (80, 120, 160, and 200 nm) were prepared by fusing RBC membranes on poly(lactic-co-glycolic acid) nanoparticles. It was shown that the particle size did not change the cellular uptake of these biomimetic nanoparticles by macrophage cells in vitro and their immunogenic responses in vivo. However, their circulation life in vivo decreased with the particle size, while their accumulation in the liver increased with the particle size, which might be related to their size-dependent filtration through hepatic sinusoids. These findings will provide experimental evidence for the design and the optimization of biomimetic nanoparticles.