Miracle-dz/UniFAR-FTUs huggingface dataset:
Demographic and socio-economic predictors of diet quality among adults in Bosnia and Herzegovina

Abstract Objective: To evaluate associations of demographic and socio-economic factors with diet quality among population subgroups in Bosnia and Herzegovina (B&H). Design: A cross-sectional analysis of 2017 B&H dietary survey data. Diet quality was assessed by the Prime Diet Quality Score (PDQS) utilizing data from two non-consecutive 24 h diet recalls. Socio-economic variables were extracted from the 2015 B&H Household Budget Survey. Homogeneity of means across population subgroups was evaluated using multivariable regression. Setting: B&H population survey. Participants: A population-based sample of 853 adults. Results: The mean PDQS was 15·8 (range 7–28 out of a possible 42 points). In general, Bosnian adults had low PDQS due to high intakes of refined grains, high-fat dairy and processed meats, and low intakes of whole grains, nuts and fish. The PDQS was significantly higher (P < 0·0001) among older individuals (17·0) compared with those in the youngest group (14·5), among individuals living in the central and northern regions (16·5) compared with those living in the south (15·1; P < 0·0001), and among people who are married/cohabitating (16·1) v. single (14·8; P = 0·02). In energy-adjusted models, socio-economic status (P = 0·04) and tertiles of household spending (P = 0·002) were inversely associated with the PDQS. Conclusions: Diet quality in this population was low. Young and middle-aged individuals, singles and those living in the south had significantly lower quality diets compared with other subgroups. Public health action is needed to promote higher consumption of whole grains, nuts and fish, and a higher variety of fruits and vegetables.
Cardiac neural crest contributes to cardiomyocytes in amniotes and heart regeneration in zebrafish

Cardiac neural crest cells contribute to important portions of the cardiovascular system including the aorticopulmonary septum and cardiac ganglion. Using replication incompetent avian retroviruses for precise high-resolution lineage analysis, we uncover a previously undescribed neural crest contribution to cardiomyocytes of the ventricles in Gallus gallus, supported by Wnt1-Cre lineage analysis in Mus musculus. To test the intriguing possibility that neural crest cells contribute to heart repair, we examined Danio rerio adult heart regeneration in the neural crest transgenic line, Tg(−4.9sox10:eGFP). Whereas the adult heart has few sox10+ cells in the apex, sox10 and other neural crest regulatory network genes are upregulated in the regenerating myocardium after resection. The results suggest that neural crest cells contribute to many cardiovascular structures including cardiomyocytes across vertebrates and to the regenerating heart of teleost fish. Thus, understanding molecular mechanisms that control the normal development of the neural crest into cardiomyocytes and reactivation of the neural crest program upon regeneration may open potential therapeutic approaches to repair heart damage in amniotes.
Characteristics of Natural Killer Cell Interaction with Trophoblast Cells During Pregnancy.

BACKGROUND Maternal natural killer cells (NK cells) are a prevailing leukocyte population in the uteroplacental bed. The contact interaction and/or cytokine production of these cells controls trophoblast differentiation, migration and invasion. OBJECTIVE To assess the impact of supernatants obtained during culturing of placentas from the first and third trimesters of healthy pregnancies on phenotype of trophoblast and NK cells and impact on adhesion and transmigration of NK cells through trophoblast cell layer. RESULTS We established that supernatants obtained from first trimester placentas increased the intensity of CD106, CD49e, CD95, CD49a, CD31, CD51/61, integrin β6, CD29 and VE-cadherin expression by trophoblast cells. The presence of supernatants obtained from the third trimester placentas resulted in increased intensity of CD106, CD51/61, CD49e, CD95, CD49a, CD31 and integrin β6 expression by trophoblast cells. Supernatants obtained from the first trimester placentas increased the intensity of CD11a, CD29, CD49d, CD58, KIR2DL3, CD119 and CD29 expression by NK cells. The presence of supernatants obtained from the third trimester placentas resulted in more intense KIR2DL3, CD119, CD29, CD49d, CD11a, CD29, CD49d and CD58 expression by NK cells. Migration of NK cells through trophoblast cells in the presence of first trimester placental supernatants was increased compared with the migration level in the presence of third trimester placental supernatants. This may be associated with increased expression of CD18 by NK cells. CONCLUSION Secretory products of the placenta increase receptor expression to ensure trophoblast adhesion to the matrix and increase the already sufficiently strong adhesion and migration potential of NK cells.
Tersect: a set theoretical utility for exploring sequence variant data

SUMMARY Comparing genomic features among a large panel of individuals across the same species is considered nowadays a core part of the bioinformatics analyses. This typically involves a series of complex theoretical expressions to compare, intersect, extract symmetric differences between individuals within a large set of genotypes. Several publically available tools are capable of performing such tasks, however, due to the sheer size of variants being queried, such tasks can be computationally expensive with a runtime ranging from few minutes up to several hours depending on the dataset size. This makes existing tools unsuitable for interactive data query or as part of genomic data visualization platforms such as genome browsers. Tersect is a lightweight, high-performance command-line utility which interprets and applies flexible set theoretical expressions to sets of sequence variant data. It can be used both for interactive data exploration and as part of a larger pipeline thanks to its highly optimized storage and indexing algorithms for variant data. AVAILABILITY AND IMPLEMENTATION Tersect was implemented in C and released under the MIT licence. Tersect is freely available at https://github.com/tomkurowski/tersect. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Efficacy and safety of interferon alpha therapy in children with chronic hepatitis B

Abstract Interferon-alpha (IFN-α) is currently the preferred antiviral treatment for children with chronic hepatitis B (CHB) aged >1-year-old. However, the evidence regarding the exact efficacy and safety in the real world is not sufficient. This study aimed to investigate the efficacy of IFN-α therapy in children with CHB and to provide a theoretical basis for practically identifying ideal antiviral therapies for CHB children. Clinical manifestations, baseline characteristics, related laboratory tests, and adverse events were retrospectively analyzed in children with CHB who visited the Children's Hospital of Fudan University, were treated with IFN-α and were followed up from January 2003 to October 2018. A total of 18 immune-active patients without advanced fibrosis were enrolled, and their average age at the start of treatment was 4.45 ± 2.75 years old. IFN α-2b was administered subcutaneously by body surface area (BSA) category, based on 3 MU/m2, for a median 48 weeks. Before treatment, the alanine aminotransferase (ALT) range was 81 to 409 U/L (median 158 U/L). The median hepatitis B virus (HBV)-DNA load was 9.89 × 107 IU/mL, and the HBV-DNA load varied from 3.10 × 104 to 4.56 × 108 IU/mL. The ALT levels of 17 children became normal at an average of 12 weeks during treatment, and those of 1 child became normal at 6 weeks after IFN-α withdrawal. Sixteen (88.9%, 16/18) children became HBV-DNA negative (<103 IU/mL) at an average of 24 weeks during treatment, while 1 became negative at 96 weeks after IFN-α withdrawal and 1 remained HBV-DNA positive. HBV e antigen (HBeAg) seroconversion occurred in 13 of 14 (92.9%, 13/14) HBeAg-positive patients at an average of 12 weeks during treatment. HBV s antigen (HBsAg) loss or seroconversion occurred in 4 (22.2%, 4/18) patients at an average of 21 weeks during treatment. Only mild flu-like symptoms and transient neutropenia appeared in some children at the early treatment stage. No severe abnormal results were observed in other laboratory parameters. The antiviral monotherapy of 48 weeks of IFN-α was well tolerated and good responded, which was associated with higher rates of HBeAg seroconversion and HBsAg clearance in the children in this study than in previously reported adults and pediatric patients.
Molecular affinity rulers: systematic evaluation of DNA aptamers for their applicabilities in ELISA

Abstract Many nucleic acid aptamers that bind to target molecules have been reported as antibody alternatives. However, while the affinities of aptamers vary widely, little is known about the relationship between the affinities and their applicabilities for practical use. Here, we developed molecular affinity rulers: a series of DNA aptamers with different affinities that bind to the same area of target molecules, to measure the aptamer and its device applicabilities. For the ruler preparation, we used high-affinity DNA aptamers containing a hydrophobic unnatural base (Ds) as the fifth base. By replacing Ds bases with A bases in Ds-DNA aptamers targeting VEGF165 and interferon-γ, we prepared two sets of DNA aptamers with dissociation constants (KD) ranging from 10−12 to 10−8 M. Using these molecular affinity rulers, we evaluated the sensitivity of DNA aptamers in ELISA (enzyme-linked immunosorbent assay), which showed the clear relationship between aptamer affinities and their detection sensitivities. In sandwich-type ELISA using combinations of aptamers and antibodies, aptamers with KD values lower than ∼10−9 M were required for sufficient sensitivities (limit of detection (LOD) < 10 pM) and signal intensities, but optimizations improved the lower-affinity aptamers’ applicabilities. These aptamer affinity rulers could be useful for evaluating and improving aptamer applicabilities.
The crystal structure of human microsomal triglyceride transfer protein

Significance This study provides a structure for microsomal triglyceride transfer protein, a key protein in lipid metabolism and transport. Microsomal triglyceride transfer protein is linked to a human disease state, abetalipoproteinemia. The structure helps us to understand how this protein functions and gives a rationale for how previously reported mutations result in loss of function of the protein and hence, cause disease. The structure also provides a means for rational drug design to treat cardiovascular disease, hypercholesterolemia, and obesity. Microsomal triglyceride transfer protein is composed of 2 subunits. The β-subunit, protein disulfide isomerase (PDI), also acts independently as a protein folding catalyst. The structure that we present here gives insights into how PDI functions in protein folding. Microsomal triglyceride transfer protein (MTP) plays an essential role in lipid metabolism, especially in the biogenesis of very low-density lipoproteins and chylomicrons via the transfer of neutral lipids and the assembly of apoB-containing lipoproteins. Our understanding of the molecular mechanisms of MTP has been hindered by a lack of structural information of this heterodimeric complex comprising an MTPα subunit and a protein disulfide isomerase (PDI) β-subunit. The structure of MTP presented here gives important insights into the potential mechanisms of action of this essential lipid transfer molecule, structure-based rationale for previously reported disease-causing mutations, and a means for rational drug design against cardiovascular disease and obesity. In contrast to the previously reported structure of lipovitellin, which has a funnel-like lipid-binding cavity, the lipid-binding site is encompassed in a β-sandwich formed by 2 β-sheets from the C-terminal domain of MTPα. The lipid-binding cavity of MTPα is large enough to accommodate a single lipid. PDI independently has a major role in oxidative protein folding in the endoplasmic reticulum. Comparison of the mechanism of MTPα binding by PDI with previously published structures gives insights into large protein substrate binding by PDI and suggests that the previous structures of human PDI represent the “substrate-bound” and “free” states rather than differences arising from redox state.
Convolutional Neural Networks for Character-level Classification

Optical character recognition (OCR) automatically recognizes text in an image. OCR is still a challenging problem in computer vision. A successful solution to OCR has important device applications, such as text-to-speech conversion and automatic document classification. In this work, we analyze character recognition performance using the current state-of-the-art deep-learning structures. One is the AlexNet structure, another is the LeNet structure, and the other one is the SPNet structure. For this, we have built our own dataset that contains digits and upper- and lowercase characters. We experiment in the presence of salt-and-pepper noise or Gaussian noise, and report the performance comparison in terms of recognition error. Experimental results indicate by five-fold cross-validation that the SPNet structure (our approach) outperforms AlexNet and LeNet in recognition error.
Myenteric networks of interstitial cells of Cajal are reduced in horses with inflammatory bowel disease.

BACKGROUND Inflammatory bowel disease (IBD) is a well-recognised but poorly understood disease complex in the horse. Clinical signs may vary but often include weight loss, diarrhoea and colic. The effect this disease process may have on the gastrointestinal pacemaker cells (the interstitial cells of Cajal), enteric neurons and glial cells has not been previously evaluated in the horse. OBJECTIVES To compare the density of the interstitial cells of Cajal (ICC), enteric neurons and glial cells in horses with IBD to those of normal horses using immunohistochemical markers. STUDY DESIGN Retrospective, quantitative immunohistochemical study. METHODS Ileal samples were collected during post mortem examinations from 14 horses with a clinical and histopathological diagnosis of IBD and from 8 normal controls. All horses were Standardbreds 1-15 years of age. Six of the IBD cases had eosinophilic gastroenteritis while the remaining eight had granulomatous enteritis. Tissue sections were labelled with anti-CD117 (c-Kit), anti-TMEM16 (TMEM16), anti-protein gene product (PGP9.5) and anti-glial fibrillary acidic protein (GFAP) using standard immunohistochemical labelling techniques. Image analysis was performed to quantify the presence of ICC (CD117, TMEM16) as well as neuronal (PGP9.5) and enteroglial (GFAP) networks. RESULTS Interstitial cells of Cajal networks were significantly reduced in the myenteric plexus region in IBD horses compared with the controls for both markers (P<0.05). There was no significant difference in the density of the neuronal or glial cell markers between the two groups (P>0.05). MAIN LIMITATIONS The number of horses included in the study. CONCLUSIONS Disruption to ICC networks may contribute to the clinical signs of colic in some horses with IBD. Further studies are needed to establish the pathophysiological mechanisms involved and the functional effects of the reduced ICC networks. This article is protected by copyright. All rights reserved.
A Novel Therapeutic Induces DEPTOR Degradation in Multiple Myeloma Cells with Resulting Tumor Cytotoxicity

Prior work indicates DEPTOR expression in multiple myeloma cells could be a therapeutic target. DEPTOR binds to mTOR via its PDZ domain and inhibits mTOR kinase activity. We previously identified a drug, which prevented mTOR–DEPTOR binding (NSC126405) and induced multiple myeloma cytotoxicity. We now report on a related therapeutic, drug 3g, which induces proteasomal degradation of DEPTOR. DEPTOR degradation followed drug 3g binding to its PDZ domain and was not due to caspase activation or enhanced mTOR phosphorylation of DEPTOR. Drug 3g enhanced mTOR activity, and engaged the IRS-1/PI3K/AKT feedback loop with reduced phosphorylation of AKT on T308. Activation of TORC1, in part, mediated multiple myeloma cytotoxicity. Drug 3g was more effective than NSC126405 in preventing binding of recombinant DEPTOR to mTOR, preventing binding of DEPTOR to mTOR inside multiple myeloma cells, in activating mTOR and inducing apoptosis in multiple myeloma cells. In vivo, drug 3g injected daily abrogated DEPTOR expression in xenograft tumors and induced an antitumor effect although modest weight loss was seen. Every-other-day treatment, however, was equally effective without weight loss. Drug 3g also reduced DEPTOR expression in normal tissues. Although no potential toxicity was identified in hematopoietic or hepatic function, moderate cardiac enlargement and glomerular mesangial hypertrophy was seen. DEPTOR protected multiple myeloma cells against bortezomib suggesting anti-DEPTOR drugs could synergize with proteasome inhibitors (PI). Indeed, combinations of drug NSC126405 + bortezomib were synergistic. In contrast, drug 3g was not and was even antagonistic. This antagonism was probably due to prevention of proteasomal DEPTOR degradation.
Temporary Fixation of Reduction with Fabric Adhesive Bandage in the Surgical Treatment of Pediatric Supracondylar Humerus Fractures

Background and objectives: Supracondylar humerus fractures are common in children and can be surgically treated. However, the general surgical procedures involving reduction and fixation might lead to reduction loss, failure to direct the Kirschner (K)-wire toward the desired position, prolonged surgery, or chondral damage. This study aimed to show that temporary fixation of closed reduction with a fabric adhesive bandage in pediatric supracondylar humerus fractures could maintain reduction so that surgical treatment can be easily performed by a single physician. Materials and Methods: Forty-six patients with Gartland type 3 supracondylar humerus fractures who underwent surgical treatment between May 2017 and June 2018 were retrospectively evaluated. Fluoroscopy-guided reduction and fixation were performed from the distal third of the forearm to the proximal third of the humerus using a fabric adhesive bandage. Two crossed pins were applied on the fracture line by first inserting a lateral-entry K-wire and then inserting another K-wire close to the anterior aspect of the medial epicondyle and diverging from the ulnar nerve tunnel. A tourniquet was not applied in any patient and no patients required open reduction. Results: The study included 32 boys (69.6%) and 14 girls (30.4%) (mean age, 7.1; range, 2–16 years). The mean hospital stay and follow-up duration were 4.3 ± 3.9 days and 48.1 ± 14.3 weeks, respectively. Heterotopic ossification was detected in one patient, and ulnar nerve neuropraxia was detected in another patient. Functional (according to Flynn criteria) and cosmetic outcomes were excellent in 95.6%, moderate in 2.2%, and poor in 2.2% of patients. The mean duration of fixation of the closed reduction with a fabric adhesive bandage was 8.1 ± 3.9 min, and the mean duration of pinning was 7.9 ± 1.4 min. Conclusions: Temporary preoperative fixation of supracondylar humerus fractures that require surgical treatment with a fabric adhesive bandage may be significantly convenient in practice.
Impact of Stressful Climates on Provider Perceptions of Integrated Behavioral Health Services in Pediatric Primary Care: An Exploratory Study.

OBJECTIVE Pediatric primary care providers (PCPs) work in challenging environments and are increasingly called to implement complex interventions, such as behavioral health (BH) service integration. We explore how perceived stressful practice climates (1) change over time in and (2) influence provider perceptions of collaborative care versus usual care, 2 models of integrated BH care. METHODS Secondary exploratory analysis using hierarchical linear modeling was performed on an 18-month cluster-randomized trial of 8 pediatric primary care practices to Doctor-Office Collaborative Care (DOCC), where an on-site care manager delivered BH services in coordination with PCPs, or Enhanced Usual Care (EUC), where a care manager facilitated referrals to local BH providers. Various indicators of PCP perceptions of BH services, including satisfaction with practice, burdens and beliefs regarding psychosocial problems, and effectiveness in treating behavioral problems, were assessed as outcomes. Moderators were 2 domains of stressful climates, role conflict and role overload. RESULTS Role conflict and role overload stayed stable in both conditions. Role conflict strengthened the positive effect of DOCC on PCP perceived effectiveness in treating behavioral problems (β [SE], 0.04 [0.02]; p = 0.04) and improvement in managing oppositional/aggressive behavior (0.02 [0.01]; p = 0.02). Role overload strengthened the positive effect of DOCC on PCP-perceived improvement in managing attention-deficit hyperactivity disorder (0.03 [0.01]; p = 0.01). Stressful climates did not influence perceptions for EUC providers. CONCLUSIONS Providers experiencing more stressful practice climates developed more positive perceptions of collaborative care. This may encourage stressed providers to make effective practice changes and promote practice integration of BH services.
Exploring Energy Expenditure and Body Movement of Exergaming in Children of Different Weight Status.

PURPOSE This study examined differences in energy expenditure and bodily movement among children of different weight status during exergames that varied in mode and intensity. METHODS Fifty-seven 8- to 12-year-old children including overweight/obesity (n = 28) and normal weight (n = 29) played three 10-minute interval Xbox One exergames (Fruit Ninja, Kung-Fu, and Shape Up) categorized based on predominantly upper-, whole-, or lower-limb movement, respectively. The authors measured bodily movement through accelerometry and obtained energy expenditure and metabolic equivalent (MET) via indirect calorimetry. RESULTS Energy expended during gameplay was the highest in Shape Up (P < .01) and higher in Kung-Fu than Fruit Ninja (P < .01). Absolute energy expenditure was significantly higher in overweight/obese children (P < .01), but not when controlling for body mass across 3 exergames (P > .05). Based on the MET cut-points, overweight/obese children spent more time at light intensity (<3 METs) for Fruit Ninja (P < .05) and Shape Up (P < .01), but less time at vigorous intensity (≥6 METs) for Kung-Fu (P < .01) and Shape Up (P < .01). Lower-limb movements during Shape Up were less in overweight/obese children (P = .03). CONCLUSION Although children in both groups expended similar energy relative to their body mass during gameplay, overweight/obese children spent more time at light intensity but less time at vigorous intensity with fewer movements especially while playing a lower limb-controlled exergame.