Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of NADPH Oxidase 4 (NOX4) Signaling Attenuates Tuberculous Pleural Fibrosis

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [NOX] enzymes serve several hemostatic and host defense functions in various lung diseases, but the role of NOX4 signaling in tuberculous pleurisy is not well understood. The role of NOX4 signaling in tuberculous pleural fibrosis was studied using invitro pleural mesothelial cell (PMC) experiments and a murine model of Mycobacterium bovis bacillus Calmette–Guérin (BCG) pleural infection. The production of NOX4 reactive oxygen species (NOX4–ROS) and the epithelial mesenchymal transition (EMT) in PMCs were both induced by heat-killed mycobacterium tuberculosis (HKMT). In cultured PMCs, HKMT-induced collagen-1 synthesis and EMT were blocked by pretreatment with small interfering RNA (siRNA) NOX4. Moreover, NOX4–ROS production and subsequent fibrosis were reduced by treatment with losartan and the toll-like receptor 4 (TLR4) inhibitor TAK-242. The HKMT-induced EMT and intracellular ROS production were mediated by NOX4 via the activation of extracellular signal-regulated kinase (ERK) signaling. Finally, in a BCG-induced pleurisy model, recruitment of inflammatory pleural cells, release of inflammatory cytokines, and thickened mesothelial fibrosis were attenuated by SiNOX4 compared to SiCon. Our study identified that HKMT-induced pleural fibrosis is mediated by NOX4–ERK–ROS via TLR4 and Angiotensin II receptor type1 (AT1R). There results suggest that NOX4 may be a novel therapeutic target for intervention in tuberculous pleural fibrosis.
A functional model for classifying metastatic lesions integrating scans and biomarkers

Perfusion computed tomography is an emerging functional imaging modality that uses physiological models to quantify characteristics pertaining to the passage of fluid through blood vessels. Perfusion characteristics provide physiological correlates for neovascularization induced by tumor angiogenesis and thus a quantitative basis for cancer detection, prognostication, and treatment monitoring. We consider a liver cancer study where patients underwent a dynamic computed tomography protocol to enable evaluation of multiple perfusion characteristics derived from interrogating the time-attenuation of the concentration of the intravenously administered contrast medium. The objective is to determine the effectiveness of using perfusion characteristics to identify and discriminate between regions of liver that contain malignant tissues from normal tissue. Each patient contributes multiple regions of interest which are spatially correlated due to the shared vasculature. We propose a multivariate functional data model to disclose the correlation over time and space as well as the correlation among multiple perfusion characteristics. We further propose a simultaneous classification approach that utilizes all the correlation information to predict class assignments for collections of regions. The proposed method outperforms conventional classification approaches in the presence of strong spatial correlation. The method offers maximal relative improvement in the presence of temporal sparsity wherein measurements are obtainable at only a few time points.
Fusarium Species and Mycotoxins Contaminating Veterinary Diets for Dogs and Cats

Veterinary diets are intended for diseased animals and may contain cereal grains, mainly maize and/or wheat. These, in turn, are often infected with pathogens of the Fusarium genus, which are able to produce numerous harmful mycotoxins. Forty-two samples of veterinary diets for dogs and cats were analyzed for the presence of Fusarium species and mycotoxins. Species were identified using molecular methods and the ergosterol and mycotoxins (fumonisin B1, deoxynivalenol, nivalenol and zearalenone) were quantified using HPLC methods. Two Fusarium species were identified: Fusarium proliferatum and Fusarium verticillioides. The highest concentrations of fumonisin B1, deoxynivalenol, nivalenol and zearalenone were 74.83, 2318.05, 190.90, and 45.84 ng/g, respectively. Only 9.5% of the samples were free from Fusarium mycotoxins. The acceptable limits of mycotoxin content in animal feed, specified by the EU regulations, were not exceeded in any of the samples tested. The mean mycotoxin content in veterinary diets for cats was lower than for dogs. Thus, it is recommended that veterinary diets are examined, since the mycotoxin contamination pose additional risk to animal health. The knowledge on Fusarium occurrence in veterinary diets is scarce and as far as we are aware this is the first report concerning the occurrence of Fusarium spp. and their important secondary metabolites—mycotoxins—in different types of veterinary diets for companion animals in Poland.
Mycobacterium avium paratuberculosis and 
Mycobacterium avium complex and related subspecies as causative agents of zoonotic and occupational diseases

Mycobacterium avium complex (MAC) and Mycobacterium avium paratuberculosis (MAP) cause zoonotic infections transmitted by birds and livestock herds. These pathogens have remained as serious economic and health threats in most areas of the world. As zoonotic diseases, the risk of development of occupational disease and even death outcome necessitate implementation of control strategies to prevent its spread. Zoonotic MAP infections include Crohn’s disease, inflammatory bowel disease, ulcerative colitis, sarcoidosis, diabetes mellitus, and immune‐related diseases (such as Hashimoto’s thyroiditis). Paratuberculosis has classified as type B epidemic zoonotic disease according to world health organization which is transmitted to human through consumption of dairy and meat products. In addition, MAC causes pulmonary manifestations and lymphadenitis in normal hosts and human immunodeficiency virus (HIV) progression (by serotypes 1, 4, and 8). Furthermore, other subspecies have caused respiratory abscesses, neck lymph nodes, and disseminated osteomyelitis in children and ulcers. However, the data over the occupational relatedness of these subspecies is rare. These agents can cause occupational infections in susceptible herd breeders. Several molecular methods have been recognized as proper strategies for tracking the infection. In this study, some zoonotic aspects, worldwide prevalence and control strategies regarding infections due to MAP and MAC and related subspecies has been reviewed.
Implementation of Korean Clinical Imaging Guidelines: A Mobile App-Based Decision Support System

Objective The aims of this study were to develop a mobile app-based clinical decision support system (CDSS) for implementation of Korean clinical imaging guidelines (K-CIGs) and to assess future developments therein. Materials and Methods K-CIGs were implemented in the form of a web-based application (http://cdss.or.kr/). The app containing K-CIGs consists of 53 information databases, including 10 medical subspecialties and 119 guidelines, developed by the Korean Society of Radiology (KSR) between 2015 and 2017. An email survey consisting of 18 questions on the implementation of K-CIGs and the mobile app-based CDSS was distributed to 43 members of the guideline working group (expert members of the KSR and Korean Academy of Oral and Maxillofacial Radiology) and 23 members of the consultant group (clinical experts belonging to related medical societies) to gauge opinion on the future developmental direction of K-CIGs. Results The web-based mobile app can be downloaded from the Google Play Store. Detailed information on the grade of recommendation, evidence level, and radiation dose for each imaging modality in the K-CIGs can be accessed via the home page and side menus. In total, 32 of the 66 experts contacted completed the survey (response rate, 45%). Twenty-four of the 32 respondents were from the working group and eight were from the consulting group. Most (93.8%) of the respondents agreed on the need for ongoing development and implementation of K-CIGs. Conclusion This study describes the mobile app-based CDSS designed for implementation of K-CIGs in Korea. The results will allow physicians to have easy access to the K-CIGs and encourage appropriate use of imaging modalities.
The Beneficial and Adverse Effects of Raloxifene in Menopausal Women: A Mini Review

Objectives The present mini review aimed to summarize the existing knowledge regarding the beneficial and adverse effects of raloxifene in menopausal women. Methods This study is a review of relevant publications about the effects of raloxifene on sleep disorder, depression, venous thromboembolism, the plasma concentration of lipoprotein, breast cancer, and cognitive function among menopausal women. Results Raloxifene showed no significant effect on depression and sleep disorder. Verbal memory improved with administration of 60 mg/day of raloxifene while a mild cognitive impairment risk reduction by 33% was observed with administration of 120 mg/day of raloxifene. Raloxifene was associated with a 50% decrease in the need for prolapse surgery. The result of a meta-analysis showed a significant decline in the plasma concentration of lipoprotein in the raloxifene group compared to placebo (standardized mean difference, −0.43; 10 trials). A network meta-analysis showed that raloxifene significantly decreased the risk of breast cancer (relative risk, 0.572; 95% confidence interval, 0.327–0.881; P = 0.01). In terms of adverse effects of raloxifene, the odds ratio (OR) was observed to be 1.54 (P = 0.006), indicating 54% increase in the risk of deep vein thrombosis (DVT) while the OR for pulmonary embolism (PE) was 1.05, suggesting a 91% increase in the risk of PE alone (P = 0.03). Conclusions Raloxifene had no significant effect on depression and sleep disorder but decreased the concentration of lipoprotein. Raloxifene administration was associated with an increased risk of DVT and PE and a decreased risk of breast cancer and pelvic organ prolapse in postmenopausal women.
Serum Neuron-Specific Enolase Level as Predictor of Neurologic Outcome after Aortic Surgery

Abstract Background This study aimed to evaluate the significance of serum neuron-specific enolase (NSE) level as a predictor of neurologic injury in thoracic aortic surgery. Methods We neurologically assessed 60 consecutive patients who underwent thoracic aortic surgery for thoracic aortic aneurysm (n = 26) and aortic dissection (n = 34). Using moderate hypothermic circulatory arrest with antegrade cerebral perfusion, total arch replacement and hemiarch replacement were performed in 37 and 23 patients, respectively. Serum NSE levels in venous blood samples drawn before surgery and at 1 day after surgery were measured. Severity of neurologic injury was categorized as either uncomplicated (n = 48), temporary neurologic dysfunction (TND, n = 5), or permanent neurologic dysfunction (PND, n = 7). The extent of stroke was estimated on computed tomography or magnetic resonance imaging. Results The NSE level significantly differed among the three groups (PND > TND > uncomplicated) on the first postoperative day. Receiver-operating characteristic curve analysis showed that the cutoff value of NSE level was 34.14 ng/mL for neurologic injury (sensitivity, 0.769; specificity, 0.851) and 43.56 ng/mL for PND (sensitivity, 1.000; specificity, 0.963). The NSE level significantly correlated with the extent of stroke (r = 0.61, p < 0.001). Conclusion Serum NSE level is a significant predictor of adverse neurologic outcomes and extent of stroke after thoracic aortic surgery.
SleepOMICS: How Big Data Can Revolutionize Sleep Science

Sleep disorders have reached epidemic proportions worldwide, affecting the youth as well as the elderly, crossing the entire lifespan in both developed and developing countries. “Real-life” behavioral (sensor-based), molecular, digital, and epidemiological big data represent a source of an impressive wealth of information that can be exploited in order to advance the field of sleep research. It can be anticipated that big data will have a profound impact, potentially enabling the dissection of differences and oscillations in sleep dynamics and architecture at the individual level (“sleepOMICS”), thus paving the way for a targeted, “one-size-does-not-fit-all” management of sleep disorders (“precision sleep medicine”).
HDAC8 Inhibitor WK2-16 Therapeutically Targets Lipopolysaccharide-Induced Mouse Model of Neuroinflammation and Microglial Activation

Glial activation and neuroinflammatory processes play important roles in the pathogenesis of brain abscess and neurodegenerative diseases. Activated glial cells can secrete various proinflammatory cytokines and neurotoxic mediators, which contribute to the exacerbation of neuronal cell death. The inhibition of glial activation has been shown to alleviate neurodegenerative conditions. The present study was to investigate the specific HDAC8 inhibitor WK2-16, especially its effects on the neuroinflammatory responses through glial inactivation. WK2-16 significantly reduced the gelatinolytic activity of MMP-9, and expression of COX-2/iNOS proteins in striatal lipopolysaccharide (LPS)-induced neuroinflammation in C57BL/6 mice. The treatment of WK2-16 markedly improved neurobehavioral deficits. Immunofluorescent staining revealed that WK2-16 reduced LPS-stimulated astrogliosis and microglial activation in situ. Consistently, cellular studies revealed that WK2-16 significantly suppressed LPS-induced mouse microglia BV-2 cell proliferation. WK2-16 was proven to concentration-dependently induce the levels of acetylated SMC3 in microglial BV-2 cells. It also reduced the expression of COX-2/iNOS proteins and TNF-α production in LPS-activated microglial BV-2 cells. The signaling studies demonstrated that WK2-16 markedly inhibited LPS-activated STAT-1/-3 and Akt activation, but not NF-κB or MAPK signaling. In summary, the HDAC8 inhibitor WK2-16 exhibited neuroprotective effects through its anti-neuroinflammation and glial inactivation properties, especially in microglia in vitro and in vivo.
Phylogeny and evolution of infectious bursal disease virus circulating in Turkish broiler flocks

ABSTRACT The emergence of new infectious bursal disease virus (IBDV) variants can threaten poultry health and production all over the world causing significant economic losses. Therefore, this study was performed to determine IBDV molecular epidemilogy, VP2 gene variation, and corresponding pathological lesions in IBDV infected chickens in Turkey. For this, 1855 bursa of Fabricius samples were collected from 371 vaccinated broiler flocks. Atrophia and haemorrhages were seen in the bursa Fabricius of very virulent IBDV (vvIBDV) infected chickens. Partial VP2 gene was sequenced and phylogenetic, recombination, and evolutionary analyses were performed. 1548 (83.5%) out of 1855 of bursa of Fabricius samples were IBDV positive and 1525 of those could be sequenced. The recombination analysis did not detect occurrence of any recombination event among the Turkish strains. Among 1525 sequenced samples, 1380 of them were found to be classical strains. Among 1380 classical strains, 1317 were similar to IBDV 2512, 11 to Faragher 52/70, 40 to 228 E, and 12 to Lukert strain. Out of 1525 reverse transcriptase ploymerase chain reaction positive samples, 144 of them were found to be similar to vvIBDV‐VP2 gene reported to GenBank previously. The phylogenetic tree performed on a broad sequence dataset demonstrated grouping of vvIBDV Turkish strains in three different clusters, including sequences collected also from Iraq and Kuwait (Cluster 1), Indian (Cluster 2), and a distinct Turkish‐only cluster (Cluster 3). The evolutionary rate estimation on branches/clades including Turkish strain mirrored the expected one for RNA viruses and no significant differences were found among different considered branches. In conclusion, results of this study indicate that vvIBDV strains similar to those circulating in various countries in the Middle East are present and undergoing evolution in chickens from Turkish broiler flocks. This point needs to be taken into account in planning adequate control strategies.
Impact of Fermentable Fibres on the Colonic Microbiota Metabolism of Dietary Polyphenols Rutin and Quercetin

Dietary fibre and polyphenols are both metabolised to short-chain fatty acids (SCFAs) and phenolic acids (PA) by the colonic microbiota. These may alter microbiota growth/diversity, but their interaction is not understood. Interactions between rutin and raftiline, ispaghula or pectin were investigated in human faecal batch cultures (healthy participants; 19–33 years, 4 males, 6 females, BMI 18.4–27.4) after a low (poly)phenol diet three days prior to study. Phenolic acids were measured by gas chromatography-mass spectrometry and SCFAs by gas chromatography-flame ionisation after 2, 4, 6, and 24 h. Rutin fermentation produced Phenyl acetic acid (PAA), 4-Hydroxy benzoic acid (4-OHBA), 3-Hydroxy phenyl acetic acid (3-OHPAA), 4-Hydroxy phenyl acetic acid (4-OHPAA), 3,4-Dihydroxy phenyl acetic acid (3,4-diOHPAA), 3-Hydroxy phenyl propionic acid (3-OHPPA), and 4-Hydroxy phenyl propionic acid (4-OHPPA). 3,4-DiOHPAA and 3-OHPAA were predominant at 6 h (1.9 ± 1.8 µg/mL, 2.9 ± 2.5 µg/mL, and 0.05 ± 0.0 µg/mL, respectively) and 24 h (5.5 ± 3.3 µg/mL, 3.1 ± 4.2 µg/mL, and 1.2 ± 1.6 µg/mL). Production of all PA except 3-OHPPA and 4-OHPPA was reduced by at least one fibre. Inhibition of PA was highest for rutin (8-fold, p < 0.01), then pectin (5-fold, p < 0.01), and ispaghula (2-fold, p = 0.03). Neither rutin nor quercetin had a detectable impact on SCFA production. These interactions should be considered when assessing dietary polyphenols and potential health benefits.
Current Trends in Fabrication of Biomaterials for Bone and Cartilage Regeneration: Materials Modifications and Biophysical Stimulations

The aim of engineering of biomaterials is to fabricate implantable biocompatible scaffold that would accelerate regeneration of the tissue and ideally protect the wound against biodevice-related infections, which may cause prolonged inflammation and biomaterial failure. To obtain antimicrobial and highly biocompatible scaffolds promoting cell adhesion and growth, materials scientists are still searching for novel modifications of biomaterials. This review presents current trends in the field of engineering of biomaterials concerning application of various modifications and biophysical stimulation of scaffolds to obtain implants allowing for fast regeneration process of bone and cartilage as well as providing long-lasting antimicrobial protection at the site of injury. The article describes metal ion and plasma modifications of biomaterials as well as post-surgery external stimulations of implants with ultrasound and magnetic field, providing accelerated regeneration process. Finally, the review summarizes recent findings concerning the use of piezoelectric biomaterials in regenerative medicine.
Acute IgA-Dominant Glomerulonephritis Associated with Syphilis Infection in a Pregnant Teenager: A New Disease Association

Chronic kidney disease (CKD) is increasingly recognized as a risk factor in pregnancy; the differential diagnosis between CKD and preeclampsia (PE) may be of pivotal importance for pregnancy management and for early treatment of CKD. Acknowledging this connection may be useful also in a wider context, such as in the case reported in this paper, which for the first time describes an association between syphilis infection and IgA-dominant glomerulonephritis. A 16-year-old woman, referred to a general hospital due to a seizure, was found to be unknowingly pregnant. Based on hypertension and nephrotic proteinuria, she was initially diagnosed with PE. Immunological tests, as well as hepatitis and HIV tests showed negative results. However, secondary syphilis was diagnosed. In discordance with the PE diagnosis, urinalysis showed glomerular microhematuria with cellular casts. Proteinuria and hypertension did not remit after delivery, which was made via caesarean section, due to uncontrolled hypertension, at an estimated gestational age of 29 weeks. A male baby, weighing 1.1 kg (6.5 centile) was born. The baby was hospitalized in the neonatal intensive care unit, where he developed subependymal hemorrhage and thrombocytopenia, and neonatal syphilis was diagnosed. The mother underwent a kidney biopsy one week after delivery, leading to the diagnosis of IgA-dominant postinfectious glomerulonephritis. Mother and child were treated with support and antibiotic therapy, and were discharged in good clinical conditions four weeks later. Four months after delivery, the mother was normotensive without therapy, with normal kidney function and without hematuria or proteinuria. In conclusion, this case suggests that IgA-dominant postinfectious glomerulonephritis should be added to the spectrum of syphilis-associated glomerulonephritides, and underlines the need for a careful differential diagnosis with CKD in all cases of presumed PE. While diagnosis relies on kidney biopsy, urinary sediment, a simple and inexpensive test, can be the first step in distinguishing PE from other nephropathies.
Accelerated progression of IDH mutant glioma after first recurrence.

BACKGROUND Isocitrate dehydrogenase (IDH) mutant gliomas are a distinct subtype, reflected in the World Health Organization (WHO) 2016 revised diagnostic criteria. To inform IDH-targeting trial design, we sought to characterize outcomes exclusively within IDH mutant gliomas. METHODS We retrospectively analyzed 275 IDH mutant glioma patients treated at our institution. Progression was determined using low-grade glioma criteria from Response Assessment in Neuro-Oncology. We calculated survival statistics with the Kaplan-Meier method, and survival proportions were correlated with molecular, histologic, and clinical factors. RESULTS During a median follow-up of 6.4 years, 44 deaths (7.6%) and 149 first progression (PFS1) events (54.1%) were observed. Median PFS1 was 5.7 years (95% CI: 4.7-6.4) and OS was 18.7 years (95% CI: 12.2 y-not reached). Consistent with prior studies, we observed an association of grade, molecular diagnosis, and treatment with PFS1. Following the first progressive episode, 79 second progression events occurred during a median follow-up period of 4.1 years. Median PFS following an initial progressive event (PFS2) was accelerated at 3.1 years (95% CI: 2.1-4.1). PFS2 was a surrogate prognostic marker, identifying patients with poorer overall survival. CONCLUSION We report outcomes in a large cohort of IDH mutant glioma, providing a well-characterized historical control population for future clinical trial design. Notably, the interval between first and second recurrence (PFS2, 3.0 y) is shorter than time from diagnosis to first recurrence (PFS1, 5.7 y), evidence that these tumors clinically degenerate from an indolent course to an accelerated malignant phase. Thus, PFS2 represents a relevant outcome for trials investigating drug efficacy at recurrence.