Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Features Distinguish Eosinophilic and Reflux-induced Esophagitis

Background and Objectives : Diagnosing eosinophilic esophagitis (EoE) depends on intraepithelial eosinophil count of ≥15 eosinophils per high-power field (HPF); however, differentiating EoE from gastroesophageal reflux disease (GERD) continues to be a challenge because no true “criterion standard” criteria exist. Identifying clinical and endoscopic characteristics that distinguish EoE could provide a more comprehensive diagnostic strategy than the present criteria. The aim of the study was to determine symptoms and signs that can be used to distinguish EoE from reflux esophagitis. Methods: Adult and pediatric patients with EoE were identified by present diagnostic guidelines including an esophageal biopsy finding of ≥15 eosinophils/HPF. Patients with GERD were age-matched one to one with patients with EoE. Clinical, endoscopic, and histologic information at the time of diagnosis was obtained from the medical record and compared between pairs by McNemar test. A conditional logistic regression model was created using 6 distinguishing disease characteristics. This model was used to create a nomogram to differentiate EoE from reflux-induced esophagitis. Results: Patients with EoE were 75% men and 68% had a history of atopy. Many aspects of EoE were statistically distinct from GERD when controlling for age. Male sex, dysphagia, history of food impaction, absence of pain/heartburn, linear furrowing, and white papules were the distinguishing variables used to create the logistic regression model and scoring system based on odds ratios. The area under the curve of the receiver-operator characteristic curve for this model was 0.858. Conclusions: EoE can be distinguished from GERD using a scoring system of clinical and endoscopic features. Prospective studies will be needed to validate this model.
Direct Anonymous Attestation With Optimal TPM Signing Efficiency

Direct Anonymous Attestation (DAA) is an anonymous signature scheme, which allows the Trusted Platform Module (TPM), a small chip embedded in a host computer, to attest to the state of the host system, while preserving the privacy of the user. DAA provides two signature modes: fully anonymous signatures and pseudonymous signatures. One main goal of designing DAA schemes is to reduce the TPM signing workload as much as possible, as the TPM has only limited resources. In an optimal DAA scheme, the signing workload on the TPM will be no more than that required for a normal signature like ECSchnorr. To date, no scheme has achieved the optimal signing efficiency for both signature modes. In this paper, we propose the first DAA scheme which achieves the optimal TPM signing efficiency for both signature modes. In this scheme, the TPM takes only a single exponentiation to generate a signature, and this single exponentiation can be pre-computed. Our scheme can be implemented using the existing TPM 2.0 commands, and thus is compatible with the TPM 2.0 specification. We benchmarked the TPM 2.0 commands needed for three DAA use cases on an Infineon TPM 2.0 chip, and also implemented the host signing and verification algorithm for our DAA scheme on a laptop with 1.80GHz Intel Core i7-8550U CPU. Our experimental results show that our DAA scheme obtains a total signing time of about 144 ms for either signature mode, while with pre-computation we can obtain a signing time of about 65 ms. Based on our benchmark results for the pseudonymous signature mode, our scheme is roughly $2\times $ (resp., $5\times $ ) faster than the existing DAA schemes supported by TPM 2.0 in terms of total (resp., online) signing efficiency.
Effects of long‐term microalgae supplementation on muscle microstructure, meat quality and fatty acid composition in growing pigs

We investigated the effects of long-term microalgae supplementation (7% in a piglet diet and 5% in a fattening diet) on muscle microstructure and meat quality, including fatty acid composition in female Landrace pigs (n = 31). The major effects were muscle-specific increases in n-3 and n-6 polyunsaturated fatty acids (PUFA) concentrations, resulting in increased accumulation of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Carcass traits and meat quality of longissimus thoracis muscle were not affected by the microalgae diet with the exception of reduced drip loss (p = 0.01) and increased protein proportion (p = 0.04). In addition, the microalgae diet resulted in a shift to a more oxidative myofibre type composition in semitendinosus but not longissimus thoracis muscle. In conclusion, microalgae supplementation offers a unique opportunity to enhance essential n-3 PUFA contents in pig meat. The results support small but coordinated changes in skeletal muscle phenotypic appearance and functionality.
Molecular insights into HSD10 disease: impact of SDR5C1 mutations on the human mitochondrial RNase P complex

SDR5C1 is an amino and fatty acid dehydrogenase/reductase, moonlighting as a component of human mitochondrial RNase P, which is the enzyme removing 5′-extensions of tRNAs, an early and crucial step in tRNA maturation. Moreover, a subcomplex of mitochondrial RNase P catalyzes the N1-methylation of purines at position 9, a modification found in most mitochondrial tRNAs and thought to stabilize their structure. Missense mutations in SDR5C1 cause a disease characterized by progressive neurodegeneration and cardiomyopathy, called HSD10 disease. We have investigated the effect of selected mutations on SDR5C1's functions. We show that pathogenic mutations impair SDR5C1-dependent dehydrogenation, tRNA processing and methylation. Some mutations disrupt the homotetramerization of SDR5C1 and/or impair its interaction with TRMT10C, the methyltransferase subunit of the mitochondrial RNase P complex. We propose that the structural and functional alterations of SDR5C1 impair mitochondrial RNA processing and modification, leading to the mitochondrial dysfunction observed in HSD10 patients.
The Roles of Dietary Glutamate in the Intestine

Glutamate (Glu), either as one of the amino acids of protein or in free form, constitutes up to 8–10% of amino acid content in the human diet, with an intake of about 10–20 g/day in adults. In the intestine, postprandial luminal Glu concentrations can be of the order of mM and result in a high intra-mucosal Glu concentration. Glu absorbed from the intestinal lumen is for a large part metabolized by enterocytes in various pathways, including the production of energy to support intestinal motility and functions. Glu is the most important fuel for intestinal tissue, it is involved in gut protein metabolism and is the precursor of different important molecules produced within the intestinal mucosa (2-oxoglutarate, L-alanine, ornithine, arginine, proline, glutathione, γ-aminobutyric acid [GABA]). Studies in adult humans, pigs, piglets or preterm infants indicate that a large proportion of Glu is metabolized in the intestine, and that for the usual range of Glu dietary intake (bound Glu and free Glu including added Glu as a food additive in normal amounts up to 1 g/day), circulating Glu is tightly maintained at rather low concentrations. Systemic blood levels of Glu transiently rise when high doses monosodium glutamate (> 10–12 g), higher than normal human dietary consumption, are ingested and normalize within 2 h after the offset of consumption. Glu is also involved in oral and post oral nutrient chemosensing that involves gustatory nerves and both humoral and neural (vagal) gut-brain pathways with an impact on gut function and feeding behavior. Glu functions as a signaling molecule in the enteric nervous system and modulates neuroendocrine reflexes in the gastrointestinal tract. The oral taste sensation of Glu involves its binding to the oral umami taste receptors that triggers the cephalic phase response of digestion to prepare for food digestion. Glu is sensed again in the gut, inducing a visceral sensation that enhances additional gut digestive processes through the visceral sense (vago-vagal reflex).
Behavior of Healthcare Workers After Injuries From Sharp Instruments

Background Injuries with sharps are common occupational hazards for healthcare workers. Such injuries predispose the staff to dangerous infections such as hepatitis B, C and HIV. Objectives The present study was conducted to investigate the behaviors of healthcare workers in Kashan healthcare centers after needle sticks and injuries with sharps in 2012. Materials and Methods A cross-sectional study was conducted on 298 healthcare workers of medical centers governed by Kashan University of Medical Sciences. A questionnaire was used in this study. The first part included questions about demographic characteristics. The second part of the questionnaire consisted of 16 items related to the sharp instrument injuries. For data analysis, descriptive and analytical statistics (chi-square, ANOVA and Pearson correlation coefficient) SPSS version 16.0 software was used. Results From a total of 298 healthcare workers, 114 (38.3%) had a history of injury from needles and sharp instruments in the last six months. Most needle stick and sharp instrument injuries had occurred among the operating room nurses and midwifes; 32.5% of injuries from sharp instruments occurred in the morning shift. Needles were responsible for 46.5% of injuries. The most common actions taken after needle stick injuries were compression (27.2%) and washing the area with soap and water (15.8%). Only 44.6% of the injured personnel pursued follow-up measures after a needle stick or sharp instrument injury. Conclusions More than a half of the healthcare workers with needle stick or sharp instrument injury had refused follow-up for various reasons. The authorities should implement education programs along with protocols to be implemented after needle stick injuries or sharps.
Gallstone Disease and Type 2 Diabetes Risk: A Mendelian Randomization Study

The presence of gallstone disease (GSD) was reported to be positively associated with diabetes risk. Whether the association is causal remains unclear. We aim to examine the potential causal association between GSD and type 2 diabetes risk using a Mendelian randomization analysis. Observational study was conducted among 16,299 participants who were free of cancer, heart disease, stroke, and diabetes at baseline in the Dongfeng‐Tongji cohort study. GSD was diagnosed by experienced physicians by abdominal B‐type ultrasound inspection and type 2 diabetes was defined according to the criteria of the American Diabetes Association. Cox proportional hazard regression model was used to examine the association of GSD with type 2 diabetes risk. A genetic risk score (GRS) for GSD was constructed with eight single nucleotide polymorphisms that were derived from the previous genome‐wide association studies. The causal associations of the score for GSD with type 2 diabetes were tested among 7,000 participants in Mendelian randomization analysis. We documented 1,110 incident type 2 diabetes cases during 73,895 person‐years of follow‐up from 2008 to 2013 (median 4.6 years). Compared with participants without GSD, the multivariate‐adjusted hazard ratio of type 2 diabetes risk in those with GSD was 1.22 (95% confidence interval [CI], 1.03‐1.45, P = 0.02). Each 1 SD (0.23) increment in the weighted GRS was associated with a 17% increment of type 2 diabetes risk (odds ratio = 1.17, 95% CI, 0.90‐1.52) without statistical significance (P = 0.25). Conclusion: The present study supported a positive but not a causal association of GSD with type 2 diabetes risk. More studies are needed to verify our findings.
Use of generally recognized as safe or dietary compounds to inhibit buprenorphine metabolism: potential to improve buprenorphine oral bioavailability

The present study evaluated the potential of five generally recognized as safe (GRAS) or dietary compounds (α‐mangostin, chrysin, ginger extract, pterostilbene and silybin) to inhibit oxidative (CYP) and conjugative (UGT) metabolism using pooled human intestinal and liver microsomes. Buprenorphine was chosen as the model substrate as it is extensively metabolized by CYPs to norbuprenorphine and by UGTs to buprenorphine glucuronide. Chrysin, ginger extract, α‐mangostin, pterostilbene and silybin were tested for their inhibition of the formation of norbuprenorphine or buprenorphine glucuronide in both intestinal and liver microsomes. Pterostilbene was the most potent inhibitor of norbuprenorphine formation in both intestinal and liver microsomes, with IC50 values of 1.3 and 0.8 μM, respectively, while α‐mangostin and silybin most potently inhibited buprenorphine glucuronide formation. The equipotent combination of pterostilbene and ginger extract additively inhibited both pathways in intestinal microsomes. Since pterostilbene and ginger extract showed potent CYP and/or UGT inhibition of buprenorphine metabolism, their equipotent combination was tested to assess the presence of synergistic inhibition. However, because the combination showed additive inhibition, it was not used while performing IVIVE analysis. Based on quantitative in vitro–in vivo extrapolation, pterostilbene (21 mg oral dose) appeared to be most effective in improving the mean predicted Foral and AUC∞PO of buprenorphine from 3 ± 2% and 340 ± 330 ng*min/ml to 75 ± 8% and 36,000 ± 25,000 ng*min/ml, respectively. At a 10‐fold lower dose of pterostilbene, the predicted buprenorphine Foral approximated sublingual bioavailability (~35%) and showed a 2–4 fold reduction in the variability around the predicted AUC∞PO of buprenorphine. These results demonstrate the feasibility of using various GRAS/dietary compounds to inhibit substantially the metabolism by CYP and UGT enzymes to achieve higher and less variable oral bioavailability. This inhibitor strategy may be useful for drugs suffering from low and variable oral bioavailability due to extensive presystemic oxidative and/or conjugative metabolism.
Peroxisome proliferator-activated receptors (PPARs) are potential drug targets for cancer therapy

Peroxisome-proliferator-activated receptors (PPARs) are nuclear hormone receptors including PPARα, PPARδ and PPARγ, which play an important role in regulating cancer cell proliferation, survival, apoptosis, and tumor growth. Activation of PPARs by endogenous or synthetic compounds regulates tumor progression in various tissues. Although each PPAR isotype suppresses or promotes tumor development depending on the specific tissues or ligands, the mechanism is still unclear. In this review, we summarized the regulative mechanism of PPARs on cancer progression.
Effect of Crusting Operations on the Physical Properties of Leather

Physical properties of leather form vital quality parameters that determine the performance characteristics in their areas of applications. However, the transformational processing of hide to leather involves a series of both chemical and physical/mechanical changes that affect these mechanical properties. Many researches have been published regarding the effect of processing on the mechanical properties of leather. However, the effect of entire crusting operations (post tanning) on the mechanical properties is not documented. This study reports the findings of the effect of crusting operations (retanning, dyeing and fatliquoring) on the mechanical properties of the final leather. Results have shown that retanning process improves tear and tensile strengths, distensions at crack and burst, and shrinkage temperature. An improvement in the organoleptic properties such as fullness was recorded in retanned crust leather. However, the uniformity coefficient and percentage elongation significantly decreased after retanning. Dyeing raises the elongation at break, distensions at crack and burst, shrinkage temperature and uniformity coefficient whereas both tensile and tear strengths decreased after dyeing. Similarly, fatliquored samples recorded higher elongation at break values, and distension values. Conversely, tensile and tear strengths, shrinkage temperature and uniformity coefficient decreased as a result of fatliquoring process. All the samples tested at tanning, retanning, dyeing and fatliquoring processes indicated no damage at 50,000 flexes. The study discussed these effects using transmission of fracture and damage mechanics in leather
Distribution, projections, and association with calbindin baskets of motor neurons, interneurons, and sensory neurons in guinea‐pig distal colon

Normal gut function relies on the activity of the enteric nervous system (ENS) found within the wall of the gastrointestinal tract. The structural and functional organization of the ENS has been extensively studied in the guinea pig small intestine, but less is known about colonic circuitry. Given that there are significant differences between these regions in function, observed motor patterns and pathology, it would be valuable to have a better understanding of the colonic ENS. Furthermore, disorders of colonic motor function, such as irritable bowel syndrome, are much more common. We have recently reported specialized basket‐like structures, immunoreactive for calbindin, that likely underlie synaptic inputs to specific types of calretinin‐immunoreactive neurons in the guinea‐pig colon. Based on detailed immunohistochemical analysis, we postulated the recipient neurons may be excitatory motor neurons and ascending interneurons. In the present study, we combined retrograde tracing and immunohistochemistry to examine the projections of circular muscle motor neurons, myenteric interneurons, and putative sensory neurons. We focused on neurons with immunoreactivity for calbindin, calretinin and nitric oxide synthase and their relationship with calbindin baskets. Retrograde tracing using indocarbocyanine dye (DiI) revealed that many of the nerve cell bodies surrounded by calbindin baskets belong to motor neurons and ascending interneurons. Unique functional classes of myenteric neurons were identified based on morphology, neuronal markers and polarity of projection. We provide evidence for three groups of ascending motor neurons based on immunoreactivity and association with calbindin baskets, a finding that may have significant functional implications.
Locating blood vessels in retinal images by piece-wise threshold probing of a matched filter response

We describe an automated method to locate and outline blood vessels in images of the ocular fundus. Such a tool should prove useful to eye care specialists for purposes of patient screening, treatment evaluation, and clinical study. Our method differs from previously known methods in that it uses local and global vessel features cooperatively to segment the vessel network. We evaluate our method using hand-labeled ground truth segmentations of 20 images. A plot of the operating characteristic shows that our method reduces false positives by as much as 15 times over basic thresholding of a matched filter response (MFR), at up to a 75% true positive rate. For a baseline, we also compared the ground truth against a second hand-labeling, yielding a 90% true positive and a 4% false positive detection rate, on average. These numbers suggest there is still room for a 15% true positive rate improvement, with the same false positive rate, over our method. We are making all our images and hand labelings publicly available for interested researchers to use in evaluating related methods.
Increased Expression of Herpes Virus-Encoded hsv1-miR-H18 and hsv2-miR-H9-5p in Cancer-Containing Prostate Tissue Compared to That in Benign Prostate Hyperplasia Tissue

Purpose: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. Methods: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. Results: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001). Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9). Conclusions: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections.
Learning Latent Representations for Style Control and Transfer in End-to-end Speech Synthesis

In this paper, we introduce the Variational Autoencoder (VAE) to an end-to-end speech synthesis model, to learn the latent representation of speaking styles in an unsupervised manner. The style representation learned through VAE shows good properties such as disentangling, scaling, and combination, which makes it easy for style control. Style transfer can be achieved in this framework by first inferring style representation through the recognition network of VAE, then feeding it into TTS network to guide the style in synthesizing speech. To avoid Kullback-Leibler (KL) divergence collapse in training, several techniques are adopted. Finally, the proposed model shows good performance of style control and outperforms Global Style Token (GST) model in ABX preference tests on style transfer.
PARENTS 2 Study: a qualitative study of the views of healthcare professionals and stakeholders on parental engagement in the perinatal mortality review—from ‘bottom of the pile’ to joint learning

Objective Engaging bereaved parents in the review process that examines their care before and after a perinatal death might help parents deal with their grief more effectively and drive improvements in patient safety. The objective of this study is to explore whether healthcare professionals would accept or support parent engagement in the perinatal mortality review process. Design Qualitative focus group interviews. Transcripts were analysed with an inductive thematic approach. Setting Two geographically distinct tertiary maternity hospitals in the UK. Participants Five focus groups were conducted with clinical staff including midwives, obstetricians, neonatologists, nursing staff and chaplaincy services. Results Twenty-seven healthcare professionals unanimously agreed that parents’ involvement in the perinatal mortality review process is useful and necessary. Six key themes emerged including: parental engagement; need for formal follow-up; critical structure of perinatal mortality review meeting; coordination and streamlining of care; advocacy for parents including role of the bereavement care lead; and requirement for training and support for staff to enable parental engagement. Conclusions Healthcare professionals strongly advocated engaging bereaved parents in the perinatal mortality review: empowering parents to ask questions, providing feedback on care, helping generate lessons and providing them with the opportunity to discuss a summary of the review conclusions with their primary healthcare professional contact. The participants agreed it is time to move on from ‘a group of doctors reviewing notes’ to active learning and improvement together with parents, to enable better care and prevention of perinatal death.