Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of trunk stabilization training robot on postural control and gait in patients with chronic stroke: a randomized controlled trial

Our study aimed to confirm the therapeutic effects of using a trunk stabilization training robot (3DBT-33) in patients with chronic stroke. A total of 38 patients with chronic stroke were randomly assigned to either an experimental or a control group. The robot group (n = 19) received 30 min of trunk stability robot training in addition to conventional physical therapy, while the control group (n = 19) received a similar conventional physical therapy as the robot group. All participants were assessed using the following: the Functional Ambulation Categories (FAC), timed up and go (TUG) test, Berg Balance Scale (BBS), Korean Modified Barthel Index (K-MBI), and Fugl-Meyer Assessment of Lower Extremity (FMA-LE). There were statistically significant improvements in all parameters at follow-up assessment after 4 weeks of intervention (P < 0.05). There were statistically significant differences in the FMA-LE, K-MBI, and BBS between the robot and control groups (P < 0.05). There was no significant difference in FAC (P = 0.935) and TUG (P = 0.442). Minimal detectable change was more significantly observed in the FMA-LE and BBS than in FAC, TUG, and K-MBI. The findings in the present study showed that trunk stabilization rehabilitation training using a rehabilitation robot in patients with chronic stroke was effective in improving the balance and functions in the lower extremities.
Alcohol Avoidance Training as a Mobile App for Problem Drinkers: Longitudinal Feasibility Study

Background Alcohol use is associated with an automatic tendency to approach alcohol, and the retraining of this tendency (cognitive bias modification [CBM]) shows therapeutic promise in clinical settings. To improve access to training and to enhance participant engagement, a mobile version of alcohol avoidance training was developed. Objective The aims of this pilot study were to assess (1) adherence to a mobile health (mHealth) app; (2) changes in weekly alcohol use from before to after training; and (3) user experience with regard to the mHealth app. Methods A self-selected nonclinical sample of 1082 participants, who were experiencing problems associated with alcohol, signed up to use the alcohol avoidance training app Breindebaas for 3 weeks with at least two training sessions per week. In each training session, 100 pictures (50 of alcoholic beverages and 50 of nonalcoholic beverages) were presented consecutively in a random order at the center of a touchscreen. Alcoholic beverages were swiped upward (away from the body), whereas nonalcoholic beverages were swiped downward (toward the body). During approach responses, the picture size increased to mimic an approach movement, and conversely, during avoidance responses, the picture size decreased to mimic avoidance. At baseline, we assessed sociodemographic characteristics, alcohol consumption, alcohol-related problems, use of other substances, self-efficacy, and craving. After 3 weeks, 37.89% (410/1082) of the participants (posttest responders) completed an online questionnaire evaluating adherence, alcohol consumption, and user satisfaction. Three months later, 19.03% (206/1082) of the participants (follow-up responders) filled in a follow-up questionnaire examining adherence and alcohol consumption. Results The 410 posttest responders were older, were more commonly female, and had a higher education as compared with posttest dropouts. Among those who completed the study, 79.0% (324/410) were considered adherent as they completed four or more sessions, whereas 58.0% (238/410) performed the advised six or more training sessions. The study identified a significant reduction in alcohol consumption of 7.8 units per week after 3 weeks (95% CI 6.2-9.4, P<.001; n=410) and another reduction of 6.2 units at 3 months for follow-up responders (95% CI 3.7-8.7, P<.001; n=206). Posttest responders provided positive feedback regarding the fast-working, simple, and user-friendly design of the app. Almost half of the posttest responders reported gaining more control over their alcohol use. The repetitious and nonpersonalized nature of the intervention was suggested as a point for improvement. Conclusions This is one of the first studies to employ alcohol avoidance training in a mobile app for problem drinkers. Preliminary findings suggest that a mobile CBM app fulfils a need for problem drinkers and may contribute to a reduction in alcohol use. Replicating these findings in a controlled study is warranted.
STUDY: THE CORRELATION BETWEEN HOMA-IR AND HEPATOCELLULAR CARCINOMA DEVELOPMENT IN HEPATITIS C PATIENTS

Background: Hepatocellular carcinoma (HCC) is the third most common cause of death from cancer worldwide which accounts for 80%-90% of primary liver cancer. It is characterized by a very poor prognosis. Outcome of HCC depends mainly on its early diagnosis. Serum αfetoprotein (AFP) is the marker that has been widely used for screening and diagnosis of HCCs. However, development of false-negative or false-positive rates with (AFP) was as high as 30%-40% for patients with small HCCs. Insulin resistance (IR) is found to occur early in the course of Hepatitis C (HCV) infection, independent of BMI (body mass index), stage of liver disease and presence or absence of diabetes. Recently, it has been observed the synergistic effect of IR and viral hepatitis in HCC development among HCV infected patients. Therefore, this study was done to investigate the correlation between HOMA-IR and HCC patients. Methods: Clinical and biochemical characteristics were investigated for 50 HCC patients related HCV and 50 normal controls. HCC patients were diagnosed by ultrasound assessment, abdominal triphasic CT and serum AFP. Homeostasis model assessment of IR (HOMA-IR) was investigated to all 100 participants. Results: Obese patients in HCC group showed significantly higher frequency of high HOMA-IR when compared to nonobese patients (P=0.001). HOMA-IR value increases as tumor size of HCC increases. Conclusion: Hepatocarcinogenisis may result from a combination of this direct viral effect and the influence of an array of metabolic factors resulting from virus-induced insulin resistance.
RNA polymerase II stalls on oxidative DNA damage via a torsion-latch mechanism involving lone pair–π and CH–π interactions

Significance DNA oxidative damage by reactive oxygen species represents a major challenge to genome integrity that contributes to the aging process as well as many human diseases. In particular, guanine is the most vulnerable of the nucleobases to oxidation and leads to transcription-blocking lesions: 5-guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp). The molecular mechanism of transcription stalling of these nonbulky but helix-distorting DNA lesions remains completely unknown. This work systematically investigates how these lesions affect transcription and provides structural snapshots of how Pol II is stalled by a nonbulky Gh lesion in a stepwise manner, revealing an unexpected mechanism of transcriptional stalling. Important insights are gained into understanding the mechanisms of lesion recognition, transcriptional stalling, transcriptional bypass, and mutagenesis of oxidative DNA lesions. Oxidation of guanine generates several types of DNA lesions, such as 8-oxoguanine (8OG), 5-guanidinohydantoin (Gh), and spiroiminodihydantoin (Sp). These guanine-derived oxidative DNA lesions interfere with both replication and transcription. However, the molecular mechanism of transcription processing of Gh and Sp remains unknown. In this study, by combining biochemical and structural analysis, we revealed distinct transcriptional processing of these chemically related oxidized lesions: 8OG allows both error-free and error-prone bypass, whereas Gh or Sp causes strong stalling and only allows slow error-prone incorporation of purines. Our structural studies provide snapshots of how polymerase II (Pol II) is stalled by a nonbulky Gh lesion in a stepwise manner, including the initial lesion encounter, ATP binding, ATP incorporation, jammed translocation, and arrested states. We show that while Gh can form hydrogen bonds with adenosine monophosphate (AMP) during incorporation, this base pair hydrogen bonding is not sufficient to hold an ATP substrate in the addition site and is not stable during Pol II translocation after the chemistry step. Intriguingly, we reveal a unique structural reconfiguration of the Gh lesion in which the hydantoin ring rotates ∼90° and is perpendicular to the upstream base pair planes. The perpendicular hydantoin ring of Gh is stabilized by noncanonical lone pair–π and CH–π interactions, as well as hydrogen bonds. As a result, the Gh lesion, as a functional mimic of a 1,2-intrastrand crosslink, occupies canonical −1 and +1 template positions and compromises the loading of the downstream template base. Furthermore, we suggest Gh and Sp lesions are potential targets of transcription-coupled repair.
Balancing Diets for Amino Acids: Nutritional, Environmental and Financial Implications

Balancing for amino acids (AA) continues to focus on lysine (Lys) and methionine (Met), the two AA that are the most limiting for lactating dairy cows fed diets common to North America. Unless a deliberate attempt is made to increase their concentrations in metabolizable protein (MP), their concentrations in MP will always be lower than optimum and efficiency of use of MP for maintenance and milk production will be compromised. Recent efforts have focused on generating new dose-response plots for NRC (2001), as well as initial plots for CPM-Dairy (Cornell University, Ithaca, NY) and AMTS. Cattle (Agricultural Modeling and Training Systems, LLC, Lansing, NY), that relate changes in measured percentages and yields of milk protein to modelpredicted concentrations of Lys and Met in MP. The results indicate that the breakpoint estimates for the required concentrations of Lys and Met in MP for maximal content of milk protein for the NRC, CPM, and AMTS models were 6.80 and 2.29%, 7.46 and 2.57%, and 6.68 and 2.40%, respectively. The respective breakpoint estimates for maximal yield of milk protein were 7.10 and 2.52%, 7.51 and 2.30%, and 6.74 and 2.31%. The resulting optimal Lys:Met ratios in MP for the 3 models are considered to be 3.0:1, 2.9:1 and 2.8:1, respectively. Feeding strategies for getting close to achieving these concentrations of Lys and Met in MP include: 1) feeding high quality feeds and wellbalanced diets that are focused on maximizing rumen function and synthesis of microbial protein, 2) feeding adequate but not excessive amounts of rumen degradable protein (RDP), 3) preferential use of high Lys protein supplements over low Lys protein supplements whenever possible protein supplementation is needed, 4) feeding a rumenprotected Met supplement in the amounts needed to meet the optimal Lys:Met ratio in MP for the model that is being used, and 5) not overfeeding RUP. For successful AA balancing, it is important to express RDP and rumen undegradable protein (RUP) as percentages of dietary dry matter (DM) and to monitor and fine-tune their concentrations as needed to avoid over or under-feeding. The benefits of achieving higher concentrations of Lys and Met in MP that lead to increased dairy herd profitability include: 1) increased milk yields, 2) increased concentrations and yields of milk protein and fat, 3) reduced need for supplemental RUP for similar or greater component yields, 4) more predictable changes in milk and milk protein production to changes in RUP supply, 5) reduced N excretion per unit of milk or milk protein produced, and 6) improved health and reproduction. Increases in milk protein and fat concentrations of 0.1 to 0.25 percentage units for protein and 0.1 to 0.15 for fat and returns on investment of 2.0 to 3.5 are typical. Increases in milk yield are more common in early lactation cows than late lactation cows and can be rather significant if balancing for Lys and Met is started before calving. With high feed costs and low milk prices, an important benefit of AA balancing has been the opportunity to increase milk
Diagnosis of Non-Alcoholic Fatty Liver Disease (NAFLD) Is Independently Associated with Cardiovascular Risk in a Large Austrian Screening Cohort

Background: Many patients with non-alcoholic fatty liver disease (NAFLD) simultaneously suffer from cardiovascular (CV) disease and often carry multiple CV risk factors. Several CV risk factors are known to drive the progression of fibrosis in patients with NAFLD. Objectives: To investigate whether an established CV risk score, the Framingham risk score (FRS), is associated with the diagnosis of NAFLD and the degree of fibrosis in an Austrian screening cohort for colorectal cancer. Material and Methods: In total, 1965 asymptomatic subjects (59 ± 10 years, 52% females, BMI 27.2 ± 4.9 kg/m2) were included in this study. The diagnosis of NAFLD was present if (1) significantly increased echogenicity in relation to the renal parenchyma was present in ultrasound and (2) viral, autoimmune or hereditary liver disease and excess alcohol consumption were excluded. The FRS (ten-year risk of coronary heart disease) and NAFLD Fibrosis Score (NFS) were calculated for all patients. High CV risk was defined as the highest FRS quartile (>10%). Both univariable and multivariable logistic regression models were used to calculate associations of FRS with NAFLD and NFS. Results: Compared to patients without NAFLD (n = 990), patients with NAFLD (n = 975) were older (60 ± 9 vs. 58 ± 10 years; p < 0.001), had higher BMI (29.6 ± 4.9 vs. 24.9 ± 3.6 kg/m2; p < 0.001) and suffered from metabolic syndrome more frequently (33% vs. 7%; p < 0.001). Cardiovascular risk as assessed by FRS was higher in the NAFLD-group (8.7 ± 6.4 vs. 5.4 ± 5.2%; p < 0.001). A one-percentage-point increase of FRS was independently associated with NAFLD (OR 1.04, 95%CI 1.02–1.07; p < 0.001) after correction for relevant confounders in multivariable logistic regression. In patients with NAFLD, NFS correlated with FRS (r = 0.29; p < 0.001), and FRS was highest in patients with significant fibrosis (F3-4; 11.7 ± 5.4) compared to patients with intermediate results (10.9 ± 6.3) and those in which advanced fibrosis could be ruled-out (F0-2, 7.8 ± 5.9, p < 0.001). A one-point-increase of NFS was an independent predictor of high-risk FRS after correction for sex, age, and concomitant diagnosis of metabolic syndrome (OR 1.30, 95%CI 1.09–1.54; p = 0.003). Conclusion: The presence of NAFLD might independently improve prediction of long-term risk for CV disease and the diagnosis of NAFLD might be a clinically relevant piece in the puzzle of predicting long-term CV outcomes. Due to the significant overlap of advanced NAFLD and high CV risk, aggressive treatment of established CV risk factors could improve prognosis in these patients.
Conserved nuclear hormone receptors controlling a novel plastic trait target fast-evolving genes expressed in a single cell

Environment shapes development through a phenomenon called developmental plasticity. Deciphering its genetic basis has potential to shed light on the origin of novel traits and adaptation to environmental change. However, molecular studies are scarce, and little is known about molecular mechanisms associated with plasticity. We investigated the gene regulatory network controlling predatory vs. non-predatory dimorphism in the nematode Pristionchus pacificus and found that it consists of genes of extremely different age classes. We isolated mutants in the conserved nuclear hormone receptor nhr-1 with previously unseen phenotypic effects. They disrupt mouth-form determination and result in animals combining features of both wild-type morphs. In contrast, mutants in another conserved nuclear hormone receptor nhr-40 display altered morph ratios, but no intermediate morphology. Despite divergent modes of control, NHR-1 and NHR-40 share transcriptional targets, which encode extracellular proteins that have no orthologs in Caenorhabditis elegans and result from lineage-specific expansions. An array of transcriptional reporters revealed co-expression of all tested targets in the same pharyngeal gland cell. Major morphological changes in this gland cell accompanied the evolution of teeth and predation, linking rapid gene turnover with morphological innovations. Thus, the origin of feeding plasticity involved novelty at the level of genes, cells and behavior.
Later School Start Time: The Impact of Sleep on Academic Performance and Health in the Adolescent Population

The crucial role of sleep in physical and mental health is well known, especially during the developmental period. In recent years, there has been a growing interest in examining the relationship between sleep patterns and school performance in adolescents. At this stage of life, several environmental and biological factors may affect both circadian and homeostatic regulation of sleep. A large part of this population does not experience adequate sleep, leading to chronic sleep restriction and/or disrupted sleep–wake cycles. Studies investigating the effects of different sleep–wake schedules on academic achievement showed that impaired sleep quality and quantity are associated with decreased learning ability and compromised daytime functioning. This review focuses on the most recent studies that evaluated the effects of modified school start time on sleep patterns and related outcomes. Moreover, based on the available empirical evidence, we intend to propose a direction for future studies targeted to implement prevention or treatment programs by modifying sleep timing.
Radiation history of Asian Asarum (sect. Heterotropa, Aristolochiaceae) resolved using a phylogenomic approach based on double-digested RAD-seq data.

BACKGROUND AND AIMS The genus Asarum sect. Heterotropa (Aristolochiaceae) likely experienced rapid diversification into 62 species centred on the Japanese Archipelago and Taiwan, providing an ideal model for studying island adaptive radiation. However, resolving the phylogeny of this plant group using Sanger sequencing-based approaches has been challenging. To uncover the radiation history of Heterotropa, we employed a phylogenomic approach using double-digested RAD-seq (ddRAD-seq) to yield a sufficient number of phylogenetic signals and compared its utility with that of the Sanger sequencing-based approach. METHODS We first compared the performance of phylogenetic analysis based on the plastid matK and trnL-F regions and nuclear ribosomal ITS and phylogenomic analysis based on ddRAD-seq using a reduced set of the plant materials (83 plant accessions consisting of 52 species, 1 subspecies and 5 varieties). We also conducted more thorough phylogenomic analyses including the reconstruction of biogeographic history using comprehensive samples of 135 plant accessions consisting of 55 species, 1 subspecies, 8 varieties of Heterotropa, and 6 outgroup species. KEY RESULTS Phylogenomic analyses of Heterotropa based on ddRAD-seq were superior to Sanger sequencing-based approaches and resulted in a fully resolved phylogenetic tree with strong support for 72.0-84.8% (depending on the tree-reconstruction methods) of the branches. We clarified the history of Heterotropa radiation and found that A. forbesii, the only deciduous Heterotropa species native to mainland China, is sister to the evergreen species (core Heterotropa) mostly distributed across the Japanese Archipelago and Taiwan. CONCLUSIONS The core Heterotropa group was divided into nine subclades, each of which had a narrow geographic distribution. Moreover, most estimated dispersal events (22 out of 24) were between adjacent areas, indicating that the range expansion has been geographically restricted throughout the radiation history. The findings enhance our understanding of the remarkable diversification of plant lineages in the Japanese Archipelago and Taiwan.
Human Vaccines & Immunotherapeutics: news

The newly emerged coronavirus SARS-CoV-2 that causes COVID-19 disease has spread around the world, infecting >300,000 people and killing >82,000 in virtually every country. Only 2% of the affected population are people <20 years of age, while the severe form of the disease is experienced by the elderly and subjects with comorbidities. Several vaccine candidates are likely to emerge soon. Sanofi plans to utilize a platform, which provided partial protection against the related ‘SARS’ virus in a preclinical challenge study. It could enter clinical trials in 2021, the company said. Another candidate comes from the Trimer-Tag technology (Clover Biopharmaceuticals), in which covalently trimerized fusion proteins are recombinantly expressed in mammalian cell culture. It has been employed for the development of vaccines against other enveloped RNA viruses, such HIV and influenza. The vaccine will be formulated with the AS03 adjuvant (GSK). A fourth candidate, a ‘molecular clamp’ vaccine developed at the University of Queensland, utilizes purified viral fusion proteins stabilized in a pre-fusion conformation, thus exposing neutralizing epitopes, and also is formulated with ASO3 adjuvant. Efforts to develop vaccine against COVID-19 might be accelerated by the fact that the viral genome has been fully sequenced and the structure has been determined for its spike protein, which the virus uses for cell entry.
Repeated cobalt and chromium ion measurements in patients with bilateral large-diameter head metal-on-metal ReCap-M2A-Magnum total hip replacement

Background and purpose — Whole-blood (WB) chromium (Cr) and cobalt (Co) measurements are vital in the follow-up of metal-on-metal total hip replacement (MoM THR) patients. We examined whether there is a substantial change in repeated WB, Co, and Cr levels in patients with bilateral ReCap-M2A-Magnum THR. We also specified the number of patients exceeding the safe upper limit (SUL) of WB Co and Cr in the repeated measurement. Patients and methods — We identified 141 patients with bilateral ReCap-M2A-Magnum THR operated in our institution. 61 patients had repeated WB metal ion measurements with bilateral MoM implants still in situ in the second measurement. The mean time elapsing from the first measurement (initial measurement) to the second (control measurement) was 1.9 years (SD = 0.6, range 0.2–3.5). We used earlier established SUL levels for bilateral implants by Van Der Straeten et al. (2013). Results — The median (range) Co and Cr values decreased in the repeated measurement from 2.7 (0.6–25) to 2.1 (0.5–21) and 2.6 (0.8–14) to 2.1 (0.5–18) respectively. In 13% of the patients Co levels exceeded the SUL in the initial measurement and the proportion remained constant, at 13%, in the repeated measurement. In 5% of the patients, Cr levels were above SUL in the initial measurement and an equal 5% in the control measurement. Interpretation — Repeated WB metal ion levels did not increase in patients with bilateral ReCap-M2A-Magnum THR with a mean 1.9-year measurement interval. Long-term development of WB metal ion levels is still unclear in these patients.
Effects of risperidone on blood levels of interleukin-6 in schizophrenia

Abstract Background: To evaluate the association between risperidone use and interleukin-6 (IL-6) levels by conducting a meta-analysis of controlled before-and-after studies. Methods: Studies were identified through a systematic search of PubMed and Embase. The mean and standardized differences were extracted to calculate the standardized mean differences. IL-6 levels were compared in patients with schizophrenia before and after risperidone treatment. Results: Ten studies were included in the final meta-analysis. The primary findings from our study suggest that there was a significant decrease in serum IL-6 levels after risperidone treatment (P = .021). A subgroup analysis revealed the sources of heterogeneity. The sensitivity analysis indicated that the results were stable, and no publication bias was observed. Conclusions: The present meta-analysis provides evidence that risperidone can significantly reduce IL-6 levels in schizophrenia. IL-6 is a potential biomarker of the pathophysiology and clinical processes of schizophrenia.