Miracle-dz/UniFAR-FTUs huggingface dataset:
Original Research: Long-Term Efficacy and Safety of Periarticular Hyaluronic Acid in Acute Ankle Sprain

Abstract The objectives of this study were to determine the long-term efficacy and safety of periarticular hyaluronic acid (HA) injections in acute lateral ankle sprain. A randomized, controlled, prospective trial in a primary sports medicine and emergency practice involved 158 competitive athletes who suffered an acute grade 1 or 2 lateral ankle sprain, and who were randomly assigned within 48 hours of injury. Patients were randomly assigned at baseline to periarticular injection with HA + standard of care (rest, ice, elevation, and compression [RICE]) or placebo injection (PL) + standard of care (RICE) treatment at baseline assessment and day 4 after injury. Follow-up was at 30, 90, and 712 days after treatment. Assessments at baseline and days 4, 8, 30, 90, and 712 included visual analogue scale (VAS) (0-10 cm) pain on weight bearing and walking 20 m, patient global assessment of ankle injury (5-point categorical scale), patient satisfaction with treatment (5-point categorical scale), time to return to pain-free and disability-free sport, recurrent ankle sprain, total number of days missing from primary sport activity, and adverse events (AEs). Time to intervention was 39 ± 4 hours with no difference between groups. A significant reduction in VAS pain on both weight bearing and walking was observed at all follow-up assessments for HA compared with PL (P < 0.001). Time to pain-free and disability-free return to sport was 11 (± 8) versus 17 (± 8) days for HA and PL, respectively (P < 0.05). At 24 months, in the PL versus HA group, there were 2 versus 0 lower limb fractures, 16 versus 7 second ankle sprains (P < 0.05), 3 versus 1 third ankle sprains, and a significantly greater number of days missing primary sport activity (41 vs 21; P < 0.002). Significantly greater patient satisfaction was also observed for HA versus PL at all follow-up assessments. No serious AEs were recorded throughout follow-up. Periarticular HA treatment for acute ankle sprain was highly satisfactory in the short and long term versus PL. This was associated with reduced pain, more rapid return to sport, fewer recurrent ankle sprains, fewer missed days from sport, and with few associated AEs to 24 months.
Lack of a Clinically Significant Pharmacokinetic Interaction between Etravirine and Raltegravir Using an Original Approach Based on Drug Metabolism, Protein Binding, and Penetration in Seminal Fluid: A Pharmacokinetic Substudy of the ANRS‐163 ETRAL Study

The ANRS163‐ETRAL study showed that etravirine 200 mg/raltegravir 400 mg twice‐daily dual therapy was highly effective in the treatment of human immunodeficiency virus (HIV)‐infected patients older than 45 years, with virologic and therapeutic success rates at week 48 of 99.4% and 94.5%, respectively. The objective of this study was to determine whether a clinically significant pharmacokinetic interaction between etravirine and raltegravir exists by assessing steady‐state total and unbound etravirine, raltegravir, and inactive raltegravir‐glucuronide concentrations 12 hours after last intake (C12h) in blood plasma (BP) and seminal plasma (SP).
Developmental Impairments in a Rat Model of Methyl Donor Deficiency: Effects of a Late Maternal Supplementation with Folic Acid

Vitamins B9 (folate) and B12 act as methyl donors in the one-carbon metabolism which influences epigenetic mechanisms. We previously showed that an embryofetal deficiency of vitamins B9 and B12 in the rat increased brain expression of let-7a and miR-34a microRNAs involved in the developmental control of gene expression. This was reversed by the maternal supply with folic acid (3 mg/kg/day) during the last third of gestation, resulting in a significant reduction of associated birth defects. Since the postnatal brain is subject to intensive developmental processes, we tested whether further folate supplementation during lactation could bring additional benefits. Vitamin deficiency resulted in weaned pups (21 days) in growth retardation, delayed ossification, brain atrophy and cognitive deficits, along with unchanged brain level of let-7a and decreased expression of miR-34a and miR-23a. Whereas maternal folic acid supplementation helped restore the levels of affected microRNAs, it led to a reduction of structural and functional defects taking place during the perinatal/postnatal periods, such as learning/memory capacities. Our data suggest that a gestational B-vitamin deficiency could affect the temporal control of the microRNA regulation required for normal development. Moreover, they also point out that the continuation of folate supplementation after birth may help to ameliorate neurological symptoms commonly associated with developmental deficiencies in folate and B12.
An analysis of undergraduate ophthalmology training in Canada.

OBJECTIVE To investigate the adequacy of undergraduate ophthalmology education in Canada in comparison with the International Council of Ophthalmology (ICO) guidelines. DESIGN Cross-sectional survey. PARTICIPANTS First-year residents who had graduated from Canadian medical schools. METHODS Eligible residents were invited to participate in an online survey in 2007. Data were categorized by demographic variables, and basic statistics were done. RESULTS Responses were obtained from 386 of the 1425 individuals (27.0%) contacted. The majority (64.0%) stated they had "too little" or "no exposure" to ophthalmology in medical school. The majority (76.2%) of respondents stated that they had had 1 week or less of overall exposure to ophthalmology. Sufficient exposure to several ICO core subspecialty areas was reported, including lens/cataract (81.1%) and cornea/external diseases (81.6%); however, some areas did not receive adequate time allocation, such as vitreoretinal disease (41.9%). Similarly, competency was obtained in certain ICO examination skills, including assessment of visual acuity (83.3%) and pupillary reflexes (90.7%) but was not achieved for other skills, such as fundoscopy (52.3%), slit-lamp examination (44.8%), and intraocular pressure assessment (19.9%). When asked whether sufficient ophthalmology knowledge and skills had been obtained during medical school, only 42.9% and 25.9% agreed, respectively. CONCLUSIONS Undergraduate ophthalmology training in Canada contains gaps in certain key areas. Developing a national, standardized curriculum could ensure that medical students acquire competency in the ophthalmology knowledge and skills required for future clinical practice.
Antimicrobial Potential of Single Metabolites of Curcuma longa Assessed in the Total Extract by Thin-Layer Chromatography-Based Bioautography and Image Analysis

Curcuma longa from Zingiberaceae belongs to the major spices consumed around the world, known from its cholagogue, anti-inflammatory, and antimicrobial properties. Lack of data on the activity of single components of turmeric extract encouraged the authors to apply TLC (thin-layer chromatography) based bioautography studies to reveal its antimicrobial constituents and construct a universal platform for the bioactivity assessment of crude extracts, with help of a freeware ImageJ software. This optimized chromatographic bioassay performed on diethyl ether and methanol extracts of Curcuma longa was successfully applied on the total extract and revealed the antimicrobial potential of single components against a variety of Gram-positive strains, with no need for their isolation from the mixture. The obtained results were further confronted with a classic microdilution antimicrobial assay on the isolates, purified from the crude extracts by centrifugal partition chromatography in the following solvent system: heptane-chloroform-methanol-water (5:6:3:2) (v/v/v/v).
Cathodic-leading pulses are more effective than anodic-leading pulses in intracortical microstimulation of the auditory cortex

Objective. Intracortical microstimulation (ICMS) is widely used in neuroscientific research. Earlier work from our lab showed the possibility to combine ICMS with neuronal recordings on the same shank of multi-electrode arrays and consequently inside the same cortical column in vivo. The standard stimulus pulse shape for ICMS is a symmetric, biphasic current pulse. Here, we investigated the role of the leading-phase polarity (cathodic- versus anodic-leading) of such single ICMS pulses on the activation of the cortical network. Approach. Local field potentials (LFPs) and multi-unit responses were recorded in the primary auditory cortex (A1) of adult guinea pigs (n = 15) under ketamine/xylazine anesthesia using linear multi-electrode arrays. Physiological responses of A1 were recorded during acoustic stimulation and ICMS. For the ICMS, the leading-phase polarity, the stimulated electrode and the stimulation current where varied systematically on any one of the 16 electrodes while recording at the same time with the 15 remaining electrodes. Main results. Cathodic-leading ICMS consistently led to higher response amplitudes. In superficial cortical layers and for a given current amplitude, cathodic-leading and anodic-leading ICMS showed comparable activation patterns, while in deep layers only cathodic-leading ICMS reliably generated local neuronal activity. ICMS had a significantly smaller dynamic range than acoustic stimulation regardless of leading-phase polarity. Significance. The present study provides in vivo evidence for a differential neuronal activation mechanism of the different leading-phase polarities, with cathodic-leading stimulation being more effective, and suggests that the waveform of the stimulus should be considered systematically for cortical neuroprosthesis development.
A New Self-Powered Sensor Using the Radial Field Piezoelectric Diaphragm in d33 Mode for Detecting Underwater Disturbances

This paper presents a new sensor based on a radial field bulk piezoelectric diaphragm to provide energy-efficient and high-performance situational sensing for autonomous underwater vehicles (AUVs). This sensor is self-powered, does not need an external power supply, and works efficiently in d33 mode by using inter-circulating electrodes to release the radial in-plane poling. Finite element analysis was conducted to estimate the sensor behavior. Sensor prototypes were fabricated by microfabrication technology. The dynamic behaviors of the piezoelectric diaphragm were examined by the impedance spectrum. By imitating the underwater disturbance and generating the oscillatory flow velocities with a vibrating sphere, the performance of the sensor in detecting the oscillatory flow was tested. Experimental results show that the sensitivity of the sensor is up to 1.16 mV/(mm/s), and the detectable oscillatory flow velocity is as low as 4 mm/s. Further, this sensor can work well under a disturbance with low frequency. The present work provides a good application prospect for the underwater sensing of AUVs.
Shape analysis of moss (Bryophyta) sporophytes: Insights into land plant evolution.

PREMISE OF THE STUDY The alternation of generations life cycle represents a key feature of land-plant evolution and has resulted in a diverse array of sporophyte forms and modifications in all groups of land plants. We test the hypothesis that evolution of sporangium (capsule) shape of the mosses-the second most diverse land-plant lineage-has been driven by differing physiological demands of life in diverse habitats. This study provides an important conceptual framework for analyzing the evolution of a single, homologous character in a continuous framework across a deep expanse of time, across all branches of the tree of life. METHODS We reconstruct ancestral sporangium shape and ancestral habitat on the largest phylogeny of mosses to date, and use phylogenetic generalized least squares regression to test the association between habitat and sporangium shape. In addition, we examine the association between shifts in sporangium shape and species diversification. RESULTS We demonstrate that sporangium shape is convergent, under natural selection, and associated with habitat type, and that many shifts in speciation rate are associated with shifts in sporangium shape. CONCLUSIONS Our results suggest that natural selection in different microhabitats results in the diversity of sporangium shape found in mosses, and that many increasing shifts in speciation rate result in changes in sporangium shape across their 480 million year history. Our framework provides a way to examine if diversification shifts in other land plants are also associated with massive changes in sporophyte form, among other morphological traits.
The Digital Education to Limit Salt in the Home Program Improved Salt-Related Knowledge, Attitudes, and Behaviors in Parents

Background Currently, Australian children and adults are eating too much salt, increasing their risk of cardiovascular-related conditions. Web-based programs provide an avenue to engage the parents of primary schoolchildren in salt-specific messages, which may positively impact their own salt-related knowledge, attitudes, and behaviors (KABs). Objective This pilot study aimed to determine whether parents’ salt-related KABs improved following participation in the Digital Education to LImit Salt in the Home (DELISH) Web-based education program. Methods The DELISH program was a 5-week, home-delivered, Web-based intervention, with a pre- and posttest design, targeting schoolchildren aged 7 to 10 years and their parents. Parents received weekly Web-based educational newsletters and text messages and completed online pre- and postprogram surveys assessing salt-related KABs. Upon completion of the program, all parents were also invited to complete an online evaluation survey. Changes in KABs outcomes were assessed using McNemar tests and paired t tests. Results Of the 80 parents that commenced the program, 73 parents (mean age 41.0, SD 7.0 years; 86% (63/73) females) completed both pre- and postsurveys. Overall, mean score for salt-related knowledge improved (+3.6 [standard error (SE) 0.41] points), and mean behavior score also improved (+4.5 [SE 0.61] points), indicating a higher frequency of engaging in behaviors to reduce salt in the diet, and mean attitude score decreased (−0.7 [SE 0.19] points), representing lower importance of using salt to enhance the taste of food (all P<.001). Following participation, the proportion of parents aware of the daily salt intake recommendation increased from 40% (29/73) to 74% (54/73) (P<.001), and awareness of bread as the main source of salt increased from 58% (42/73) to 95% (69/73) (P<.001). The proportion of parents who agreed that salt should be used in cooking to enhance the flavor of food decreased from 30% (22/73) to 11% (8/73) (P=.002) and the proportion who agreed that sodium information displayed on food labels was difficult to understand decreased from 52% (38/73) to 32% (23/73) (P=.009). There was a reduction in the proportion of parents who reported adding salt during cooking (55% [40/73] vs 41% [30/73]; P=.03) and at the table (32% [23/73] vs 18% [13/73]; P=.002). Of the 16 parents who completed the evaluation survey, 75% (12/16) enjoyed the program, and all parents found the newsletters to be useful. Almost all parents (15/16, 94%) agreed that the DELISH program would be useful to other parents. Conclusions The improvement in salt-related KABs in the DELISH program indicates the potential for online technology, to disseminate simple salt reduction education messages to families with primary school–aged children. Future work should seek to improve the quality of data collected by including a larger sample size and a control group to integrate the program within the school setting to enable wider dissemination.
SYP22 and VAMP727 regulate BRI1 plasma membrane targeting to control plant growth in Arabidopsis.

Brassinosteroids (BRs) are a group of bioactive steroid molecules that act as plant hormones. Brassinosteroid signaling is monitored by the plasma membrane (PM)-bound receptor BRASSINOSTEROID INSENSITIVE1 (BRI1), a leucine-rich repeat (LRR) receptor-like kinase (RLK) (Belkhadir & Jaillais, 2015). Binding of BRs to the extracellular domain of BRI1 initiates an intracellular signal cascade response which is rapidly transmitted to the nucleus ultimately resulting in transcription of BR-responsive genes (Jaillais & Vert, 2016). Brassinosteroid responsive genes ultimately help to control various aspects of plant growth and development, including root development, cell division, vascular patterning, organ boundary development, stress response and pathogen defense (Nakashita et al., 2003; Yamamoto et al., 2007; Gonzalez-Garcia et al., 2011; Gendron et al., 2012; Bekh-Ochir et al., 2013). This article is protected by copyright. All rights reserved.
Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos

Spotting off-targets from gene editing Unintended genomic modifications limit the potential therapeutic use of gene-editing tools. Available methods to find off-targets generally do not work in vivo or detect single-nucleotide changes. Three papers in this issue report new methods for monitoring gene-editing tools in vivo (see the Perspective by Kempton and Qi). Wienert et al. followed the recruitment of a DNA repair protein to DNA breaks induced by CRISPR-Cas9, enabling unbiased detection of off-target editing in cellular and animal models. Zuo et al. identified off-targets without the interference of natural genetic heterogeneity by injecting base editors into one blastomere of a two-cell mouse embryo and leaving the other genetically identical blastomere unedited. Jin et al. performed whole-genome sequencing on individual, genome-edited rice plants to identify unintended mutations. Cytosine, but not adenine, base editors induced numerous single-nucleotide variants in both mouse and rice. Science, this issue p. 286, p. 289, p. 292; see also p. 234 Cytosine base editing in mouse embryos generates numerous off-target single-nucleotide variants. Genome editing holds promise for correcting pathogenic mutations. However, it is difficult to determine off-target effects of editing due to single-nucleotide polymorphism in individuals. Here we developed a method named GOTI (genome-wide off-target analysis by two-cell embryo injection) to detect off-target mutations by editing one blastomere of two-cell mouse embryos using either CRISPR-Cas9 or base editors. Comparison of the whole-genome sequences of progeny cells of edited and nonedited blastomeres at embryonic day 14.5 showed that off-target single-nucleotide variants (SNVs) were rare in embryos edited by CRISPR-Cas9 or adenine base editor, with a frequency close to the spontaneous mutation rate. By contrast, cytosine base editing induced SNVs at more than 20-fold higher frequencies, requiring a solution to address its fidelity.
Sequence analysis of the complete mitochondrial genome of Youxian sheldrake

Abstract Youxian sheldrake is excellent native breeds in Hunan province in China. The complete mitochondrial (mt) genome sequence plays an important role in the accurate determination of phylogenetic relationships among metazoans. This is the first study to determine the complete mitochondrial genome sequence of Youxian sheldrake using PCR-based amplification and Sanger sequencing. The characteristic of the entire mitochondrial genome was analyzed in detail, the total length of the mitogenome is 16,605 bp, with the base composition of 29.21% A, 22.18% T, 32.84% C, 15.77% G in the Youxian sheldrake. It contained 2 ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA genes and a major non-coding control region (D-loop region). The complete mitochondrial genome sequence of Youxian sheldrake provided an important data for further study of the phylogenetics of poultry, and available data for the genetics and breeding.
PREVALENCE OF OBSTRUCTIVE SLEEP APNEA DETERMINED BY THE WATCHPAT IN NONOBESE JAPANESE PATIENTS WITH POOR GLUCOSE CONTROL AND TYPE 2 DIABETES.

OBJECTIVE Diagnosing obstructive sleep apnea (OSA) usually involves high cost, patient inconvenience, and the need for examination at a specialized center. This study employed a portable, wearable, diagnostic device (WatchPAT) to investigate the prevalence of OSA in nonobese Japanese patients with type 2 diabetes. METHODS Patients with type 2 diabetes were tested for OSA over one night using the WatchPAT. Logistic regression analysis was used to estimate the odds ratios (ORs) of risk factors for OSA in nonobese subjects. RESULTS A total of 200 eligible patients with type 2 diabetes were studied (64.5% men; aged 60.1 ± 13.6 years; body mass index [BMI], 26.3 ± 5.2 kg/m2). When OSA was defined as apnea-hypopnea index ≥5/hour, its prevalence was 80.5%. The prevalence of OSA in subjects with a BMI <20 kg/m2, ≥20 and <25 kg/m2, ≥25 and <30 kg/m2, and ≥30 kg/m2 was 38.9%, 73.5%, 86.5%, and 97.5%, respectively. The severity of OSA increased in proportion to BMI, especially when the BMI was >25 kg/m2. The prevalence of OSA was also high (66.3%) in normal-weight subjects (BMI <25 kg/m2). Furthermore, the serum triglyceride level (OR, 1.01; 95% confidence interval, 1.00 to 1.02; P = .042) was significantly related to OSA. CONCLUSION A high prevalence of OSA was observed in this nonobese population of Japanese patients with type 2 diabetes. The triglyceride level was associated with OSA among nonobese patients. ABBREVIATIONS AHI = apnea-hypopnea Index; BMI = body mass index; CI = confidence interval; ESS = Epworth Sleepiness Scale; HbA1c = glycated hemoglobin; OR = odds ratio; OSA = obstructive sleep apnea; PAT = peripheral arterial tone; T2D = type 2 diabetes; TG = triglyceride.
Virtual reality videos used in undergraduate palliative and oncology medical teaching: results of a pilot study

Background Virtual reality (VR) immersive environments have been shown to be effective in medical teaching. Our university hospital received funding from our deanery, Health Education in Wales, to film teaching videos with a 360-degree camera. Aims To evaluate whether VR is an effective and acceptable teaching environment. VR headsets were set up for medical students who rotated through Velindre Cancer Hospital’s Palliative Care department. Methods Students were asked to put on a VR headset and experience a pre-recorded 27 min presentation on nausea and vomiting in palliative care settings. They subsequently viewed a radiotherapy treatment experience from a patient’s point of view. Results Of the 72 medical students who participated, 70 found the experience comfortable, with two students stating they felt the experience uncomfortable (1=headset too tight; 1=blurry visuals). Numerical scoring on ability to concentrate in VR from 0 to 10 (0=worst, 10=best) scored an average of 8.44 (range, 7–10). Asked whether this format suited their learning style, average score was 8.31 (range 6–10). 97.2 % (n=70) students stated that they would recommend this form of learning to a colleague, with one student saying he/she would not recommend and another stating he/she was unsure. Students left anonymous free-text feedback comments which helped frame future needs in this emerging area. Discussion This study suggests that there is room for exploring new ways of delivering teaching and expanding it more widely in palliative care and oncology, but also provides feedback on areas that need further careful attention. Comments from students included: “Might have been the novelty factor but I learnt more from this 20 min VR thing than I have from many lectures”. Summary The project has proved sufficiently popular in medical student feedback, that the VR experience is now available on YouTube and has been permanently introduced into routine teaching. Further 360-degree teaching environments have been filmed. Of note is that our 360-degree videos have been viewed in Africa, so this format of teaching could prove valuable due to its global reach.