Miracle-dz/UniFAR-FTUs huggingface dataset:
The C. elegans model in toxicity testing

Caenorhabditis elegans is a small nematode that can be maintained at low cost and handled using standard in vitro techniques. Unlike toxicity testing using cell cultures, C. elegans toxicity assays provide data from a whole animal with intact and metabolically active digestive, reproductive, endocrine, sensory and neuromuscular systems. Toxicity ranking screens in C. elegans have repeatedly been shown to be as predictive of rat LD50 ranking as mouse LD50 ranking. Additionally, many instances of conservation of mode of toxic action have been noted between C. elegans and mammals. These consistent correlations make the case for inclusion of C. elegans assays in early safety testing and as one component in tiered or integrated toxicity testing strategies, but do not indicate that nematodes alone can replace data from mammals for hazard evaluation. As with cell cultures, good C. elegans culture practice (GCeCP) is essential for reliable results. This article reviews C. elegans use in various toxicity assays, the C. elegans model's strengths and limitations for use in predictive toxicology, and GCeCP. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Journal of Applied Toxicology published by John Wiley & Sons Ltd.
Risk factors for unrecognized invasive carcinoma in patients with vulvar high-grade squamous intraepithelial lesion at vulvoscopy-directed biopsy

Objective To evaluate the prevalence and risk factors for unrecognized invasive carcinoma in a series of patients undergoing surgical excision after an office biopsy of vulvar high-grade squamous intraepithelial lesion (VHSIL). Methods Two hundred and sixteen consecutive patients treated in a tertiary-level referral center for vulvar disease in north-western Italy were recruited. Patients' records were reviewed by trained personnel. Factors showing a statistically significant (p<0.05) association with detection of stromal invasion at excisional surgery in univariate analysis were further examined in a backward stepwise multiple logistic regression model. Results The median patient age was 50 years (range, 19–88). More than 25% patients with VHSIL at biopsy had associated cervical/vaginal intraepithelial neoplasia, and more than 35% had a multifocal lesion. Invasive carcinoma was detected in surgical specimens from 24 patients (11%). The depth of stromal invasion varied between 0.1 mm and 3.0 mm with a median of 0.5 mm. In multivariate analysis, the risk of invasive carcinoma detection was greater for patients in the highest tertile of age (p=0.008), for patients with a lesion ≥20 mm in size (p=0.013) and with clitoral involvement (p<0.001), and for patients presenting with a nodular lesion (p=0.078). Conclusion Our study suggests that patient age, lesion size, clitoral involvement and nodular appearance in patients with VHSIL at vulvoscopy-directed biopsy are independently associated with the risk of unrecognized invasive carcinoma.
Promoter CpG island methylation in ion transport mechanisms and associated dietary intakes jointly influence the risk of clear-cell renal cell cancer.

Background Sodium intake, but not potassium or fluid intake, has been associated with higher renal cell cancer (RCC) risk. However, risk factors may differ by molecular subtypes of the tumour. In renal physiology, electrolyte and water homeostasis is facilitated by ion transport mechanisms (ITM). Aberrant regulation of ITM genes, for example by promoter CpG island methylation, may modify associations between sodium, potassium and fluid intake and RCC risk. Methods We identified ARHGDIG , ATP1A1 , SCNN1B and SLC8A3 as ITM genes exhibiting RCC-specific promoter methylation and down-regulation. Methylation-specific polymerase chain reaction (PCR) was used to analyse promoter CpG island methylation in tumour DNA of 453 RCC cases from the Netherlands Cohort Study ( n = 120 852) after 20.3 years of follow-up. Diet was measured at baseline using food-frequency questionnaires. Cox regression analyses were restricted to clear-cell (cc)RCC ( n = 306) and stratified by tumours with no, low (1 gene) and high (≥ 2 genes) methylation. Results Sodium intake (high vs low) increased ccRCC risk particularly in tumours with a high methylation index: hazard ratio (HR) [95% confidence interval (CI)]: 2.04 (1.16-3.58), whereas heterogeneity across the methylation index was not significant ( P -heterogeneity = 0.26). Potassium intake was differentially associated with ccRCC risk ( P -heterogeneity = 0.008); the risk for high (vs low) potassium intake was low for unmethylated tumours [HR (95% CI): 0.60 (0.36-1.01)], but high for tumours with a high methylation index [HR (95% CI): 1.60 (0.96-2.65)]. Risks similarly differed for fluid intake, though not significantly ( P -heterogeneity = 0.54). Conclusions Our findings suggest for the first time that dietary intakes are differentially associated with ccRCC risk according to molecular subtypes defined by ITM gene-specific promoter methylation.
in older women : a randomised controlled trial

Objective: To test the effect of a 16-week multi-modal exercise program on neurocognitive and physical functioning and brain-derived neurotrophic factor (BDNF). Design: A single-blinded, parallel-group randomised controlled trial. Settings: University campus and community based halls. Subjects: Forty-nine women aged 65 and 75 years, with no cognitive impairment and not undertaking more than one hour of formal exercise training per week. Methods: The intervention group attended a 60-minute multi-modal class twice each week which included cardiovascular, strength, and motor fitness training. The primary outcome was neurocognitive functioning and secondary outcomes were physical functioning and plasma levels of BDNF. Results: Twenty-five participants were randomised to the intervention group and 24 to the control group. One control participant withdrew before follow-up data collection. The intervention group performed significantly better than the control group at follow-up (when controlled for baseline) in the Trail Making Test A and B, the California Older Adult Stroop Test (Word, Interference and Total scores), Controlled Oral Word Association Test and the Timed Up-and-Go Test , Six-Minute Walk Test, One–Legged Stance Test and plasma BDNF. Conclusion: This multi-modal exercise program resulted in neurocognitive and physical performance improvements and increased levels of plasma BDNF, in older women, when compared to controls. This RCT provides evidence that a multimodal exercise intervention can achieve larger effect sizes than those generally resulting from single modality interventions. Increases in BDNF levels imply neurogenesis may be a component of the mechanism underpinning the cognitive improvements associated with multimodal exercise. Trial Registration: Australian and New Zealand Clinical Trial Registration Number: ANZCTR12612000451808
Evaluating the nutritional value of date pits and demonstrating their application in laying hen diets

This experiment was carried out to study the feeding value of ground date pits (DP) (Phoenix dactylifera L.) with and without enzyme supplementation on laying hens' performance. Apparent metabolizable energy value of DP was determined by the total collection method using 10 adult Leghorn cockerels. After that, a total number of 144 Lohmann 50-week-old LSL-Lite hens were randomly allocated into six groups consisting of four replicates of six birds, based on a 3 × 2 factorial arrangement of the treatments. Six iso-caloric and iso-nitrogenous experimental diets including I-corn-soya bean meal-based control, II-corn-soya bean meal oil-based control and III- corn-soya bean meal-based diet (180 g/kg DP) were formulated. Each of the diets was supplemented with two levels of an enzyme (0.0 and 0.07 g/kg Natozim Plus). The experiment lasted 10 weeks after 7 days of adaptation. The results revealed that there was no significant difference in feed intake, feed conversion ratio, egg production, egg mass, eggshell weight, eggshell thickness and Haugh unit among the treatments. Dietary inclusion of DP significantly decreased body weight gain (BWG), egg weight and yolk colour score. On the other hand, corn-soya bean meal-based control diet with vegetable oil significantly increased egg weight and BWG of birds in comparison with other treatments. The serum biochemical metabolites were not affected by DP and enzyme supplementation. Thus, DP can be used as alternative feedstuff in laying hen diets, up to 18% of the diet with little effect on the performance of hens, including egg weight, and also, it had an adverse effect on yolk colour. Eventually, in terms of performance, the results failed to demonstrate any positive effect of Natozim Plus on either the controls or 18% DP diets.
Site-specific glycosylation regulates the form and function of the intermediate filament cytoskeleton

Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction. Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy. Despite this pathophysiological significance, how cells regulate IF structure, dynamics, and function remains poorly understood. Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration. In addition, we show that the intracellular pathogen Chlamydia trachomatis, which remodels the host IF cytoskeleton during infection, requires specific vimentin glycosylation sites and O-GlcNAc transferase activity to maintain its replicative niche. Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.
Reduction of the Harmonic Series Influences Musical Enjoyment With Cochlear Implants.

OBJECTIVE Cochlear implantation is associated with poor music perception and enjoyment. Reducing music complexity has been shown to enhance music enjoyment in cochlear implant (CI) recipients. In this study, we assess the impact of harmonic series reduction on music enjoyment. STUDY DESIGN Prospective analysis of music enjoyment in normal-hearing (NH) individuals and CI recipients. SETTING Single tertiary academic medical center. PATIENTS NH adults (N = 20) and CI users (N = 8) rated the Happy Birthday song on three validated enjoyment modalities-musicality, pleasantness, and naturalness. INTERVENTION Subjective rating of music excerpts. MAIN OUTCOME MEASURES Participants listened to seven different instruments play the melody, each with five levels of harmonic reduction (Full, F3+F2+F1+F0, F2+F1+F0, F1+F0, F0). NH participants listened to the segments both with and without CI simulation. Linear mixed effect models (LME) and likelihood ratio tests were used to assess the impact of harmonic reduction on enjoyment. RESULTS NH listeners without simulation rated segments with the first four harmonics (F3+F2+F1+F0) most pleasant and natural (p <0.001, p = 0.004). NH listeners with simulation rated the first harmonic alone (F0) most pleasant and natural (p <0.001, p = 0.003). Their ratings demonstrated a positive linear relationship between harmonic reduction and both pleasantness (slope estimate = 0.030, SE = 0.004, p <0.001, LME) and naturalness (slope estimate = 0.012, SE = 0.003, p = 0.003, LME). CI recipients also found the first harmonic alone (F0) to be most pleasant (p = 0.003), with a positive linear relationship between harmonic reduction and pleasantness (slope estimate = 0.029, SE = 0.008, p <0.001, LME). CONCLUSION Harmonic series reduction increases music enjoyment in CI and NH individuals with or without CI simulation. Therefore, minimization of the harmonics may be a useful strategy for enhancing musical enjoyment among both NH and CI listeners.
Factorial Invariance of Self-efficacy in Physical Health Care Scale for Men and Women University Students

The present study analyses the psychometric properties of the Selfefficacy in Physical Health Care Scale. The overall sample consisted of 2006 subjects: 902 women and 1104 men, with a mean age of 18.53 years (SD= 1.52) and 18.84 years (SD= 1.55) respectively. The Factorial Psychometric analysis showed that a three-factorial structure (nutrition, physical health and hydration) was viable and adequate for both populations (men and woman) according to the established psychometric requirements when the informers are the students themselves. The results showed that factor structure, factor loadings and intercepts of the instrument could be considered invariant across groups; however, there are differences between groups in favor of men for the means of the nutrition and physical health factors.
EFFECT OF SUPPLIER MANAGEMENT PRACTICES ON SUPPLY CHAIN PERFORMANCE AMONG STATE CORPORATIONS IN KENYA: CASE STUDY OF THE KENYA MEDICAL SUPPLIES AUTHORITY

This research project was set to determine the effect of supplier management practices on supply chain performance among State Corporations in Kenya. Managing suppliers is a large part of the job of supply chain professionals. Suppliers are key stakeholders in any firm‟s supply chain since they form a key component of the upstream supply chain partners. Most researchers have looked at supplier management in one dimension, that is, the focus has been on individual aspects of supplier management, for example; supplier relations management, supplier evaluation and supplier selection. This study sought to determine the effect of supplier management practices on supply chain performance of state corporations in Kenya. A census study was conducted and questionnaires were used to obtain data in a bid to answer the following research questions; What is the effect of supplier identification practices on supply chain performance among state corporations? ; What is the effect of supplier evaluation and selection practices on supply chain performance among state corporations? ; What is the effect of supplier performance measurement practices on supply chain performance among state corporations? ; What is the effect of supplier relationship management practices on supply chain performance among state corporations? A total 24 KEMSA employees were surveyed yielding a response rate of 85.7%. The study revealed that supply chain performance was significantly influenced by supplier selection and supplier performance measurement. The study recommended: proper protection of public institution from false information offered by suppliers, augmenting of supplier performance measurement and supplier relationship management practices as well as setting structure to minimize political interference during supplier identification and selection.
Variants in the SP110 gene are associated with genetic susceptibility to tuberculosis in West Africa

The sst1 locus has been identified in a mouse model to control resistance and susceptibility of Mycobacterium tuberculosis infection. Subsequent studies have now identified Ipr1 (intracellular pathogen resistance 1) to be the gene responsible. Ipr1 is encoded within the sst1 locus and is expressed in the tuberculosis lung lesions and macrophages of sst1-resistant, but not sst1-susceptible mice. We have therefore examined the closest human homologue of Ipr1, SP110, for its ability to control susceptibility to M. tuberculosis infection in humans. In a study of families from The Gambia we have identified three polymorphisms that are associated with disease. On examination of additional families from Guinea-Bissau and the Republic of Guinea, two of these associations were independently replicated. These variants are in strong linkage disequilibrium with each other and lie within a 31-kb block of low haplotypic diversity, suggesting that a polymorphism within this region has a role in genetic susceptibility to tuberculosis in humans.
Reconstructing Ancestral Haplotypes with a Dictionary Model

We propose a dictionary model for haplotypes. According to the model, a haplotype is constructed by randomly concatenating haplotype segments from a given dictionary of segments. A haplotype block is defined as a set of haplotype segments that begin and end with the same pair of markers. In this framework, haplotype blocks can overlap, and the model provides a setting for testing the accuracy of simpler models invoking only nonoverlapping blocks. Each haplotype segment in a dictionary has an assigned probability and alternate spellings that account for genotyping errors and mutation. The model also allows for missing data, unphased genotypes, and prior distribution of parameters. Likelihood evaluations rely on forward and backward recurrences similar to the ones encountered in hidden Markov models. Parameter estimation is carried out with an EM algorithm. The search for the optimal dictionary is particularly difficult because of the variable dimension of the model space. We define a minimum description length criteria to evaluate each dictionary and use a combination of greedy search and careful initialization to select a best dictionary for a given dataset. Application of the model to simulated data gives encouraging results. In a real dataset, we are able to reconstruct a parsimonious dictionary that captures patterns of linkage disequilibrium well.
SGX-Step: A Practical Attack Framework for Precise Enclave Execution Control

Protected module architectures such as Intel SGX hold the promise of protecting sensitive computations from a potentially compromised operating system. Recent research convincingly demonstrated, however, that SGX's strengthened adversary model also gives rise to to a new class of powerful, low-noise side-channel attacks leveraging first-rate control over hardware. These attacks commonly rely on frequent enclave preemptions to obtain fine-grained side-channel observations. A maximal temporal resolution is achieved when the victim state is measured after every instruction. Current state-of-the-art enclave execution control schemes, however, do not generally achieve such instruction-level granularity. This paper presents SGX-Step, an open-source Linux kernel framework that allows an untrusted host process to configure APIC timer interrupts and track page table entries directly from user space. We contribute and evaluate an improved approach to single-step enclaved execution at instruction-level granularity, and we show how SGX-Step enables several new or improved attacks. Finally, we discuss its implications for the design of effective defense mechanisms.
Autofluorescence for the diagnosis of visceral pleural invasion in non-small-cell lung cancer

OBJECTIVES This study was conducted to evaluate the accuracy of autofluorescence as a mode of diagnosis for visceral pleural invasion of non-small-cell lung cancer compared with white-light by means of clinical questions to several thoracic surgeons. METHODS Eight independent thoracic surgeons evaluated visceral pleural invasion in 25 cases of non-small-cell lung cancer attached to the visceral pleura on lung windows of preoperative computed tomography images. At the first study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using conventional white-light images, the surgeons diagnosed visceral pleural invasion based on information in preoperative computed tomography images, histological types and videos recorded with white-light mode using a thoracoscope. At the second study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using autofluorescence, the same surgeons diagnosed visceral pleural invasion based on information in 2 videos recorded in white-light mode and in autofluorescence mode using the thoracoscope. RESULTS The overall average sensitivity, specificity and accuracy of visceral pleural invasion diagnosis by white-light versus autofluorescence mode were 64.6% vs 83.3%, 53.9% vs 73.7% and 56.5% vs 76.0%, respectively. CONCLUSIONS The sensitivity, specificity and accuracy of visceral pleural invasion diagnosis was improved through the additional use of the autofluorescence mode compared with the white-light mode alone.
CO2 laser polishing of microfluidic channels fabricated by femtosecond laser assisted carving

In this study, we investigate the effects of CO2 laser polishing on microscopic structures fabricated by femtosecond laser assisted carving (FLAC). FLAC is the peripheral laser irradiation of 2.5D structures suitable for low repetition rate lasers and is first used to define the microwell structures in fused silica followed by chemical etching. Subsequently, the bottom surface of patterned microwells is irradiated with a pulsed CO2 laser. The surfaces were characterized using an atomic force microscope (AFM) and scanning electron microscope (SEM) in terms of roughness and high quality optical imaging before and after the CO2 laser treatment. The AFM measurements show that the surface roughness improves more than threefold after CO2 laser polishing, which promises good channel quality for applications that require optical imaging. In order to demonstrate the ability of this method to produce low surface roughness systems, we have fabricated a microfluidic channel. The channel is filled with polystyrene bead-laden fluid and imaged with transmission mode microscopy. The high quality optical images prove CO2 laser processing as a practical method to reduce the surface roughness of microfluidic channels fabricated by femtosecond laser irradiation. We further compared the traditional and laser-based glass micromachining approaches, which includes FLAC followed by the CO2 polishing technique.
Metabolic network segmentation: A probabilistic graphical modeling approach to identify the sites and sequential order of metabolic regulation from non-targeted metabolomics data

In recent years, the number of large-scale metabolomics studies on various cellular processes in different organisms has increased drastically. However, it remains a major challenge to perform a systematic identification of mechanistic regulatory events that mediate the observed changes in metabolite levels, due to complex interdependencies within metabolic networks. We present the metabolic network segmentation (MNS) algorithm, a probabilistic graphical modeling approach that enables genome-scale, automated prediction of regulated metabolic reactions from differential or serial metabolomics data. The algorithm sections the metabolic network into modules of metabolites with consistent changes. Metabolic reactions that connect different modules are the most likely sites of metabolic regulation. In contrast to most state-of-the-art methods, the MNS algorithm is independent of arbitrary pathway definitions, and its probabilistic nature facilitates assessments of noisy and incomplete measurements. With serial (i.e., time-resolved) data, the MNS algorithm also indicates the sequential order of metabolic regulation. We demonstrated the power and flexibility of the MNS algorithm with three, realistic case studies with bacterial and human cells. Thus, this approach enables the identification of mechanistic regulatory events from large-scale metabolomics data, and contributes to the understanding of metabolic processes and their interplay with cellular signaling and regulation processes.