Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety Assessment of High-Purity, Synthetic Nicotinamide Riboside (NR-E) in a 90-Day Repeated Dose Oral Toxicity Study, With a 28-Day Recovery Arm

Nicotinamide riboside (NR) is a naturally occurring form of vitamin B3 shown to preferentially elevate the nicotinamide adenine dinucleotide (NAD+) metabolome compared to other vitamin B3 forms (nicotinic acid and nicotinamide). Although daily requirements of vitamin B3 are typically met through the diet, recent studies have shown that additional supplementation with NR may be an effective method to counter the age-related decline in NAD+ levels as NR bypasses the rate-limiting step in NAD+ biosynthesis. Furthermore, pharmaceutical applications of NR for age-related disorders have been proposed. In this study, the safety of a high-purity, nature-identical, synthetic NR (NR-E), manufactured under the guidelines of good manufacturing practices for dietary supplements (21 CFR 111) as well as for drugs (21 CFR 210), was investigated in a 90-day oral toxicity study in Sprague Dawley rats at 300, 500, and 1,200 mg/kg/d. There were no mortality or clinical observations attributable to the test substance at any dose. A small but statistically significant decrease in body weight was observed at day 92 in the 1,200 mg/kg/d NR-treated male rats only. In contrast to a previously published safety assessment using a different synthetic NR (NIAGEN), whose no-observed-adverse-effect-level (NOAEL) was reported to be 300 mg/kg/d, there were no adverse changes in clinical pathology parameters and no notable macroscopic or microscopic findings or treatment-related effects at similar doses. In the current study, the NOAEL for systemic toxicity of NR-E in Sprague-Dawley rats was conservatively determined to be 500 mg/kg/d for males (solely based on body weight) and 1,200 mg/kg/d for females.
Spinal cord stimulation for the treatment of neuropathic pain: expert opinion and 5-year outlook

ABSTRACT Introduction Spinal cord stimulation (SCS) is an effective treatment for chronic, intractable neuropathic pain. There have been relatively few high-level studies that suggest its unequivocal use. The decay of stimulation efficacy over time have opened opportunity for the entrance of new pulse trains and waveforms. Areas covered In this state-of-the-art review, we focused on many of the major studies published in the last 10 years that were considered level one evidence. A retrospective narrative approach was taken to conceptualize foundation studies as they pertain to current evidence. A special focus was taken on reported safety outcomes in comparison to foundation studies especially as they pertain to our 5-year outlook on the use of spinal cord stimulation. Expert opinion We find there are still significant limitations in the body of reviewed evidence and suggest that long-term data beyond 24 months are lacking in the literature. In addition, adverse event rates, device explantation rates and the sham effect looms as important concepts to address in the future in spite of the existing novel stimulation paradigms.
Prospective study to evaluate incidence and indicators for early detection of ethambutol toxicity

Aims To evaluate incidence of toxic optic neuropathy in patients receiving ethambutol (EMB) for 6 months and to identify its early indicators. Methods We included 50 patients on anti-tubercular therapy (ATT) including EMB (HRE regimen) based on total body weight for 6 months. Best-corrected visual acuity (ETDRS), colour vision (Ishihara pseudo-isochromatic plates), contrast sensitivity (Pelli-Robson chart), Humphrey visual field analysis (HVF 30-2 SITA FAST), pattern visual evoked response (VER) and spectral-domain optical coherence tomography (SDOCT) for ganglion cell inner plexiform layer (GCIPL) and retinal nerve fibre layer (RNFL) analysis were assessed at baseline and at 2, 4 and 6 months after starting ATT. Results Mean age of the patients was 36.5±14.7 years with male:female ratio of 2.5:1. Mean daily dosage of EMB was 17.5±1.3 mg/kg/day. No significant change was observed in visual acuity, contrast sensitivity, color vision and mean or pattern SD on HVF at 6 months. Significant increase in VER latency of >2 SD (>125 ms) was observed in 46% eyes on follow-up indicating subclinical toxicity. Significant loss of mean RNFL (from 100.79±16.05 μm to 89.96±13.79 μm) and GCIPL thickness (from 83.1±5.60 μm to 79.85±6.45 μm) was observed at 6 months (p=0.001 for both). Patients with subclinical toxicity had significantly greater damage in temporal RNFL quadrant, supero-nasal and infero-nasal GCIPL sectors compared with others. Conclusion The incidence of clinical EMB optic neuropathy was <2%, though subclinical damage in the form of increase in VER latency, and decrease in RNFL and GCIPL on OCT was seen in 46% eyes.
Visual Fixations and Motion Sensitivity: Protocol for an Exploratory Study

Background Motion sensitivity after vestibular disorders is associated with symptoms of nausea, dizziness, and imbalance in busy environments. Dizziness and imbalance are reported in places such as supermarkets and shopping malls which have unstable visual backgrounds; however, the mechanism of motion sensitivity is poorly understood. Objective The main aim of this exploratory observational study is to investigate visual fixations and postural sway in response to increasingly complex visual environments in healthy adults and adults with motion sensitivity. Methods A total of 20 healthy adults and 20 adults with motion sensitivity will be recruited for this study. Visual fixations, postural sway, and body kinematics will be measured with a mobile eye tracker device, force plate, and 3D motion capture system, respectively. Participants will be exposed to experimental tasks requiring visual fixation on letters, projected on a range of backgrounds on a large screen during quiet stance. Descriptive statistics (mean and standard deviation) will be calculated for each of the variables. One-way independent-measures analyses of variance will be performed to investigate the differences between groups for all variables. Results Data collection was started in May 2019 and was completed by February 2020. It was approved by Health and Disability Ethics Committees, Ministry of Health, New Zealand on November 2, 2018 (Ethics ref: 18/CEN/193). We are currently processing the data and will begin data analysis in July 2020. We expect the results to be available for publication by the end of 2020. The trial was funded by the Neurology Special Interest Group, Physiotherapy New Zealand, and the Eisdell Moore Centre in November 2018. Conclusions This study will provide a detailed investigation of visual fixations in response to increasingly complex visual environments. Investigating characteristics of visual fixations in healthy adults and those with motion sensitivity will provide insight into this disabling condition and may inform the development of new intervention strategies which explicitly cater to the needs of this population. Trial Registration Australian New Zealand Clinical Trials Registry, ACTRN12619000254190; https://tinyurl.com/yxbn7nks International Registered Report Identifier (IRRID) PRR1-10.2196/16805
Epidemiological studies regarding hypertensive disorders of pregnancy: A review

A hypertensive disorder of pregnancy (HDP) is defined as hypertension emerging after 20 weeks of gestation and resolving up to 12 weeks post‐partum, and occurs in about 5% of all pregnancies. Complications associated with HDP have poor prognoses, and maternal deaths attributable to HDP are predicted to exceed 70 000 per year worldwide. Understanding the pathogenesis and risk factors of hypertensive disorders of pregnancy is important, and they are often investigated in observational studies. Given that therapeutic interventions cannot be controlled in observed studies, it is necessary to interpret which factors correspond to exposure and which factors correspond to confounding and intermediate factors in each study. From the Babies and their parents' longitudinal observation in the Suzuki Memorial Hospital on Intrauterine period study, blood pressure in early pregnancy was not only predictive of a child's birthweight, but the trajectory was also associated with the birthweight. From the larger‐scale birth cohort studies currently conducted in Japan will provide the novel potential risk factors of hypertensive disorders of pregnancy and preventive strategies of them. In Japan, observational or intervention studies are just beginning to emerge. The continuation of both a distinctive cohort and a large cohort is needed, and the development of good quality intervention trials based on the results of observational studies is important.
Engagement of General Practice in an Australian Organised Bowel Cancer Screening Program: A Cross-Sectional Survey of Knowledge and Practice

Background: Understanding factors causing variation in family physicians/general practitioners (GPs) screening knowledge, understanding and support of organised population-based colorectal cancer (CRC) programs can direct interventions that maximise the influence of a CRC screening recommendation from a GP. This study aims to assess contextual factors that influence knowledge and quality improvement (QI) practice directed to CRC screening in Australian general practice. Methods: A convenience sample of anonymous general practice staff from all Australian states and territories completed a web-based survey. Multivariate analyses assessed the association between CRC screening knowledge and QI-CRC practice scores and patient, organisational and environmental-level contextual factors. Results: Of 1,013 survey starts, 918 respondents (90.6%) completed the survey. Respondents less likely to recommend FOBT screening had lower knowledge and QI practice scores directed to CRC screening. Controlling for individual and practice characteristics, respondents’ rating of the Australian National Bowel Cancer Screening Program (NBCSP) support for preventive care, attending external education, and sufficient practice resources to implement QI practice (generally) were the strongest factors associated with QI practice directed towards CRC screening. Knowledge scores were less amenable to the influence of contextual factors explored. Conclusion: More active engagement of family medicine/general practice to improve screening promotion could be achieved through better QI resourcing without changing the fundamental design of population-based CRC screening programs.
Isolation and characterization of antimicrobial proteins produced by a potential probiotic strain of human Lactobacillus rhamnosus 231 and its effect on selected human pathogens and food spoilage organisms

Abstract Objective: To study in vitro properties of potential probiotics and the antimicrobial activity of Lactobacillus rhamnosus 231 isolated from human faeces. Methods and Results: Lact. rhamnosus 231 isolated from human faeces tolerated bile salt (4%), phenol (0.5%), and NaCl (4%) and retained viability at low pH (2.5). The cell-free culture (CFC) filtrate and extracellular protein concentrate (EPC) of Lact. rhamnosus 231 contained antimicrobial substances active against Pseudomonas aeruginosa, Escherichia coli, Enterobacter aerogenes, Staphylococcus aureus, Salmonella spp. , Helicobacter pylori, Campylobacter jejuni, Bacillus cereus, Bacillus megaterium, and Listeria monocytogenes. EPC contained a mixture of low molecular weight antimicrobial proteins, produced during log and stationary phases of growth against the test organisms. Thermostability of the antimicrobial proteins and their sensitivity to proteinase K was observed to be test organism specific. The antimicrobial activity was observed in the pH range 4.5–9 except against Ps. aeruginosa and Ent. aerogenes. These antimicrobial proteins are low molecular weight (4 kDa) anionic peptides as determined by tricine-SDS-PAGE and 2D gel. Periodic acid-Schiff's (PAS) staining of gel confirmed the presence of carbohydrate moiety with low molecular weight peptides. The antimicrobial activity of the partially purified protein was determined against Staph. aureus 74B, H. pylori 33, H. pylori 17874, and C. jejuni CJE 33566. Conclusion: Human Lact. rhamnosus 231 exhibits in vitro properties of potential probiotic. CFC filtrate and EPC of Lact. rhamnosus 231 exhibit antimicrobial activity against potential human pathogens and food spoilage organisms. Antimicrobial proteins in EPC were partially purified and characterized. In vitro properties of potential probiotic and antimicrobial properties of Lact. rhamnosus 231 could be useful as food additive against human pathogens and removal of food contaminants in the target environment.
Increased Levels of Runt-Related Transcription Factor 2 Are Associated With Poor Survival of Patients With Idiopathic Pulmonary Arterial Hypertension

Runt-related transcription factor 2 (RUNX2) plays a pivotal role in the pathogenesis of pulmonary arterial hypertension (PAH); yet, whether circulating levels of RUNX2 can predict survival of patients with idiopathic PAH (IPAH) is still unclear. The present study aimed to investigate the correlation between circulating levels of RUNX2 and survival of patients with IPAH. Blood samples were collected from 46 incident patients with IPAH and 30 healthy controls in Shanghai Pulmonary Hospital. Levels of RUNX2 were measured using ELISA. Linear regression and cox proportional hazards analysis were performed to assess the prognostic value of RUNX2 levels in predicting survival using the Kaplan–Meier method. Nonsurvivors had significantly shorter 6MWD, higher levels of NT-proBNP, increased mRAP, mPAP, mPAWP, PVR, and decreased CO as well as CI, compared with survivors (p < .05). Plasma levels of RUNX2 were significantly higher in nonsurvival and survival patients with IPAH compared with controls (p ≤ .001), and higher in nonsurvivors than in survivors (p = .001). RUNX2 levels served as an independent predictor of survival in these patients (p < .001). RUNX2 levels ≥41.5 ng/ml had a sensitivity of 80.0% and a specificity of 74.2% by ROC analysis. Patients with a RUNX2 level <41.5 ng/ml and/or mRAP <3.5 mmHg had a significantly better prognosis than those with a higher RUNX2 level in all subjects as well as in male or female patients (p < .05). The level of circulating RUNX2 is an independent predictor for survival and it is correlated with the clinical severity of IPAH.
Multimedia intervention for specific phobias: A clinical and experimental study.

BACKGROUND Exposure is the treatment of choice for specific phobias. We present an experimental and clinical study on the efficacy of the progressive multimedia exposure procedure for specific phobias. METHOD The sample size consisted of 36 individuals, 7 men and 29 women (mean age: 29 years old), with different types of specific phobias. A combined between-groups (3x4) with repeated measures design was used, including several follow-ups up to 3 years. Participants were assigned to different groups: Experimental (10), Waiting List (12), and Control (14). As an evaluation method, a Behavioural Avoidance Test (BAT) with subjective anxiety and heart rate was used for images and videos, plus general and specific anxiety questionnaires for each phobia. The intervention was carried out in four phases of multimedia exposure: photographs, videos, simulated stimuli, and real stimulation. RESULTS Anxiety and avoidance were significantly reduced in the experimental group, with a very large effect size (between d = 1.37 and 5.37). There were no significant changes in either the Control Group or the Waiting List Group. CONCLUSIONS The treatment had a clinically significant impact on the daily life of the participants. This multimedia procedure was shown to be effective and to use few resources, thus allowing it to always be adapted to the individual characteristics of the participants.
Inhibitory Effects of Green Tea Polyphenols on Glucan Synthesis and Cellular Adherence of Cariogenic Streptococci

Inhibitory effects of green tea polyphenols on glucan synthesis by glucosyltransferases of Streptococcus mutatis MT8148 and Streptococcus sohrinus 6715DP and on sucrose-dependent adherence of the bacterial cells were examined in vitro. The glucan synthesis by the bacterial glucosyltransf erase was strongly inhibited by (−)-epicatechin gallate (ECg) and (−)-epigallocatechin gallate (EGCg), the main components of the tea polyphenols. It was also demonstrated that ECg and EGCg interfered with the sucrose-dependent adherence of those bacterial cells at much smaller concentrations than those which were needed to inhibit the growth of the bacteria.
His‐bundle pacing: A novel treatment for left bundle branch block‐mediated cardiomyopathy

Chronic left bundle branch block (LBBB) can lead to LBBB‐mediated cardiomyopathy from left ventricular dysynchrony. His‐bundle pacing (HBP) results in direct electrical synchrony using the native His‐Purkinje system, providing a novel treatment for this cardiomyopathy.
TP53 Arg72Pro and XPD Lys751Gln Gene Polymorphisms and Risk of Lung Cancer in Bangladeshi Patients

Background: Tumor suppressor gene (TP53) is considered as the most frequently mutated gene in almost all forms of human cancer. Moreover, genetic variations in the XPD gene affect the DNA repair capacity increasing cancer susceptibility. Polymorphisms within these genes can play a major role in determining individual lung cancer susceptibility. However, several studies have investigated this possibility; but reported conflicting results. Therefore, the objective of this study was to investigate the role of TP53 Arg72Pro and XPD Lys751Gln gene polymorphisms on lung cancer susceptibility in the Bangladeshi population. Materials and Methods: Study subjects comprised of 180 lung cancer patients and 200 healthy volunteers. Genetic polymorphism of TP53 was determined by multiplex PCR-based method, while XPD genotypes were analyzed using Polymerase Chain Reaction-based Restriction Fragment Length Polymorphism (PCR-RFLP) method. Lung cancer risk was estimated as odds ratio (OR) and 95% confidence interval (CI). Results: From the results, no significant association between TP53 Arg72Pro polymorphism and lung cancer risk was observed. Whereas, patients with homozygous mutant variants (Gln/Gln) of XPD at codon 751 were found significantly associated with lung cancer risk when compared to the control (OR=3.58; 95% CI=1.58-8.09; p=0.002). Lung cancer risk was found significantly higher with Gln/Gln variants of XPD among smokers (OR=4.03; 95% CI=1.11-14.63; p=0.026). Significant increased risk of lung cancer was found with Arg/Pro genotypes of TP53, Lys/Gln and Gln/Gln variants of XPD in individuals with family history of cancer (OR=3.44; 95% CI=1.36-8.72; p=0.011; OR=3.17; 95% CI=1.20-8.39; p=0.024; OR=16.35; 95% CI=0.92-289.5; p=0.007, respectively). Conclusion: The findings indicated that homozygous mutant variants (Gln/Gln) of XPD were associated with increased lung cancer risk, whereas TP53 Arg72Pro polymorphism was not associated with risk of lung cancer among Bangladeshi patients.
Towards a dialogic construction grammar: Ad hoc routines and resonance activation

Abstract In this paper, we take a Construction Grammar approach to Du Bois' concept of resonance activation. We suggest that the structural mapping relations between juxtaposed utterances in discourse, described in terms of diagraphs in dialogic syntax, can acquire the status of ad hoc constructions or locally entrenched form-meaning pairings within the boundaries of an ongoing conversation. We argue that the local emergence of these ad hoc constructions involves the same cognitive mechanism described for the abstraction of conventional grammatical constructions from usage patterns. Accordingly, we propose to broaden the scope of Construction Grammar to include not only symbolic units that are conventionalized in a larger speech community, but also a dimension of online syntax, i.e. the emergence of grammatical patterns at the micro-level of a single conversation. Drawing on dialogic data from political talk shows and parliamentary debates, we illustrate the spectrum of these ad hoc constructional routines and show their local productivity, which we take as an indication of their (micro-)entrenchment within a given conversation.
Learning From Worked Examples, Erroneous Examples, and Problem Solving: Toward Adaptive Selection of Learning Activities

Problem solving, worked examples, and erroneous examples have proven to be effective learning activities in Intelligent Tutoring Systems (ITSs). However, it is generally unknown how to select learning activities adaptively in ITSs to maximize learning. In the previous work of A. Shareghi Najar and A. Mitrovic, alternating worked examples with problem solving (AEP) was found to be superior to learning only from worked examples or only from problem solving. In our first study, we investigated whether the addition of erroneous examples further improves learning in comparison to AEP. The results indicated that erroneous examples prepared students better for problem solving in comparison to worked examples. Explaining and correcting erroneous examples also led to improved debugging and problem-solving skills. In the second study, we introduced a novel strategy that adaptively decided what learning activity (a worked example, a 1-error erroneous example, a 2-error erroneous example, or a problem to be solved) is appropriate for a student based on his/her performance. We found the adaptive strategy resulted in comparative learning improvement in comparison to the fixed sequence of worked/erroneous examples and problem solving, but with a significantly lower number of learning activities.
An integrated model of exercise support for people affected by cancer: consensus through scoping

Abstract Introduction Exercise support for people with cancer is a national priority. The purpose of this study was to identify the success factors necessary to create a model of exercise support for people affected by cancer in a large city in the north of England. Method Two groups of participants were recruited; people affected by cancer (n = 26) and professional stakeholders (n = 14) contributing to either focus groups or semi-structured interviews. Data were analysed using framework analysis. Results Results from this study suggest that the promotion of exercise is not a priority in routine cancer care. Patients identified a lack of support and difficulty attaining information as a barrier to becoming active, emphasising a gulf between the patients’ needs and the health professionals’ priorities. People affected by cancer and professionals agreed that exercise was beneficial to cancer patients both during and after treatment. For an exercise pathway to be successful, key factors were identified including accessibility; tailored support; social interaction; affordability; competence of exercise delivery staff. Conclusions There was consensus on the importance of exercise and critical factors required to develop a sustainable, accessible and effective service. Evidence to inform the development of an exercise pathway for people affected by cancer is provided. Implications for rehabilitation Exercise should be an included component of a cancer treatment plan, discussed and initiated from diagnosis. Health professionals have a responsibility to provide clear, consistent evidence-based advice on exercise. Exercise professionals must be appropriately trained in cancer rehabilitation according to National Institute for Health and care Excellence (2014). Individual assessments of exercise needs, preferences and cancer limitations will result in a bespoke plan of recommendations and support. The option of group activities has the advantage of increased social interaction, peer support and shared experiences. Available exercise/physical activity services should be accessible and affordable but may involve a modest contribution.