Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic Advances for Huntington’s Disease

Huntington’s disease (HD) is a progressive neurological disease that is inherited in an autosomal fashion. The cause of disease pathology is an expansion of cytosine-adenine-guanine (CAG) repeats within the huntingtin gene (HTT) on chromosome 4 (4p16.3), which codes the huntingtin protein (mHTT). The common symptoms of HD include motor and cognitive impairment of psychiatric functions. Patients exhibit a representative phenotype of involuntary movement (chorea) of limbs, impaired cognition, and severe psychiatric disturbances (mood swings, depression, and personality changes). A variety of symptomatic treatments (which target glutamate and dopamine pathways, caspases, inhibition of aggregation, mitochondrial dysfunction, transcriptional dysregulation, and fetal neural transplants, etc.) are available and some are in the pipeline. Advancement in novel therapeutic approaches include targeting the mutant huntingtin (mHTT) protein and the HTT gene. New gene editing techniques will reduce the CAG repeats. More appropriate and readily tractable treatment goals, coupled with advances in analytical tools will help to assess the clinical outcomes of HD treatments. This will not only improve the quality of life and life span of HD patients, but it will also provide a beneficial role in other inherited and neurological disorders. In this review, we aim to discuss current therapeutic research approaches and their possible uses for HD.
Effects of Teaching Games on Decision Making and Skill Execution: A Systematic Review and Meta-Analysis

The question of how games should be taught is still a controversial subject. There has been a growing number of studies on teaching games and coaching sports since the first publication of Bunker and Thorpe on Teaching Games for Understanding (TGfU). In this sense, the present systematic review and meta-analysis aimed to systematically review the scientific literature about the effects of technical and tactical approach interventions on skill execution and decision making, and to examine the influence of the teacher/coach management style. A systematic literature search was carried out in accordance with PRISMA guidelines in Web of Science (WOS), PubMed (Medline), Scopus, and SportDiscus electronic databases. A total of seven and six studies were deemed to meet the inclusion criteria for decision making and skill execution, respectively. Meta-analysis results showed that tactical interventions achieved significant improvements in decision making (effect size = 0.89 with 95% confidence interval (CI) from 0.12 to 1.65), but they did not show significant improvements in skill execution (effect size = 0.89 with 95% CI from −0.45 to 2.23) compared to technical approaches. However, the heterogeneity of interventions was large and the quality of evidence was low according to GRADE. In conclusion, tactical approaches are recommended to teach games and sports in order to develop technique, understanding, tactical knowledge, and decision making, which are demanded in game play. These findings could be useful for teachers and coaches to improve these aspects of their players and students.
Obesity treatment: a role for occupational therapists?

Abstract Background Half of the Danish population is overweight or obese. Obesity can negatively impact health and daily life. The Danish National Board of Health´s guidelines for weight loss programmes to the Danish municipalities, recommends multidisciplinary teams, including occupational therapy, and interventions targeting diet, exercise, psychosocial coping, and everyday life. Aim To describe the structure and content of obesity programmes offered by the 98 municipalities in Denmark, including details such as the health professionals, programme recipients, dose, structure, content, and the role of occupational therapists. Method A quantitative content analysis was conducted on 234 published Danish municipal weight loss programmes. Programme descriptions were identified through internet searches using both sundhed.dk and Google.com. Results Various health professionals conducted the programmes, and five involved occupational therapists. Programmes targeted children, adolescent and adults. Dose, structure and content were heterogeneous. Conclusion The majority of the programmes were neither evidence-based, nor did they follow recommendations from Danish National Board of Health. Few programmes addressed the role of habits or social participation. Occupational therapists appear to be under-utilized as providers of the programmes. Significance Occupational therapists have a role to play in weight loss programmes, because of their training in activity analysis and their consideration of people, environments, and occupations. These components are included in the recommendations about psychosocial aspects and everyday life from the Danish National Board of Health.
The Strongest Size in Gradient Nanograined Metals.

Conventional polycrystalline metals become stronger with decreasing grain size, yet softening starts to take over at nanometer regime, giving rise to the strongest size at which the predominate strengthening mechanism switches to softening. We show that this critical size for the onset of softening shifts from ~12 nm for homogeneous nanograined copper to ~7 nm for its gradient nanograined counterpart, and this strongest size decreases with increasing the grain size gradient. The decrease in the strongest size is prompted by mitigation of grain boundary-mediated softening processes accompanying by enhanced intragranular plastic deformations. We found the nanograins as small as 6 nm, mainly involving intergranular sliding in homogeneous structures, reveal anomalous plastic deformation in gradient systems, which is mediated by partial dislocations nucleation and motion. The results on extended dislocation slip and gradient stress and plasticity, stemming from the structure heterogeneity, shed light on an emerging class of heterogeneous nanostructured materials of improved strength-ductility synergy.
Improving the Tribological and Anticorrosion Performance of Waterborne Polyurethane Coating by the Synergistic Effect between Modified Graphene Oxide and Polytetrafluoroethylene

In this work, the effect of modified graphene oxide and polytetrafluoroethylene (PTFE) on the tribological and anticorrosion properties of waterborne polyurethane (WPU) was studied. The modified graphene oxide (MGO) was obtained by the surface functionalization modification of graphene oxide (GO) with isophorone diisocyanate (IPDI), and MGO/WPU composite coating and MGO-PTFE/WPU composite coating with different mass fractions of MGO were prepared. The tribological and electrochemical experiment results demonstrated that the tribological properties of the coating and the corrosion resistance of the worn coating were effectively enhanced under the synergistic effect of MGO and PTFE. Finally, a mechanism was proposed to explain the improvement in anticorrosion performance of the worn coating.
Feasibility and Acceptability of a Web-Based Dietary Intervention with Text Messages for Colorectal Cancer: A Randomized Pilot Trial

Background: Diet is associated with colorectal cancer survival. Yet, adherence to nutrition guidelines is low among colorectal cancer survivors. Methods: We conducted a pilot trial among colorectal cancer survivors to evaluate a 12-week remote dietary intervention. Participants received print materials and were randomized (1:1) to intervention (website, text messages) or wait-list control. Primary outcomes included feasibility and acceptability. We also explored change in diet from 0 to 12 and 24 weeks and change from 0 to 12 weeks in anthropometry and circulating biomarkers (Trial Registration: NCT02965521). Results: We randomized 50 colorectal cancer survivors (25 intervention, 25 control). Retention was 90% at 12 weeks and 84% at 24 weeks. Participants had a median age of 55 years and were 66% female, 70% non-Hispanic white, and 96% had a college degree. The intervention arm responded to a median 15 (71%) of 21 text messages that asked for a reply [interquartile range (IQR) = 8, 19] and visited the website a median of 13 (15%) days (IQR = 1, 33) of the 84 study days. Conclusions: We developed a Web-based dietary intervention for colorectal cancer survivors. Our pilot results suggest that colorectal cancer survivors may engage more with text messages than a study website. Research to improve tailoring of text messages, while maintaining scalability, is needed. Impact: Remote dietary interventions using text messages may be feasible for colorectal cancer survivors. See all articles in this CEBP Focus section, “Modernizing Population Science. ”
Intratumoral expression of IL-7 and IL-12 using an oncolytic virus increases systemic sensitivity to immune checkpoint blockade

Oncolytic vaccinia virus encoding IL-7 and IL-12 facilitates immune checkpoint blockade in treatment-resistant solid tumors. A virus with benefits Oncolytic viruses, which kill cancer cells, have received increasing attention in recent years as the field has advanced toward biological and immune-based approaches to fighting cancer. To help further these viruses’ cancer-fighting potential, Nakao et al. engineered an oncolytic vaccinia virus to deliver two cytokines that help stimulate antitumor immune responses. The authors successfully tested this approach in multiple immunocompetent mouse models, showing promising results in directly treated tumors and in distant tumors of the same type, as well as protection from rechallenge with tumor cells. The treatment was particularly effective in combination with immune checkpoint inhibitors, even in tumors unresponsive to checkpoint inhibitors alone. The immune status of the tumor microenvironment is a key indicator in determining the antitumor effectiveness of immunotherapies. Data support the role of activation and expansion of tumor-infiltrating lymphocytes (TILs) in increasing the benefit of immunotherapies in patients with solid tumors. We found that intratumoral injection of a tumor-selective oncolytic vaccinia virus encoding interleukin-7 (IL-7) and IL-12 into tumor-bearing immunocompetent mice activated the inflammatory immune status of previously poorly immunogenic tumors and resulted in complete tumor regression, even in distant tumor deposits. Mice achieving complete tumor regression resisted rechallenge with the same tumor cells, suggesting establishment of long-term tumor-specific immune memory. Combining this virotherapy with anti–programmed cell death-1 (PD-1) or anti–cytotoxic T lymphocyte antigen 4 (CTLA4) antibody further increased the antitumor activity as compared to virotherapy alone, in tumor models unresponsive to either of the checkpoint inhibitor monotherapies. These findings suggest that administration of an oncolytic vaccinia virus carrying genes encoding for IL-7 and IL-12 has antitumor activity in both directly injected and distant noninjected tumors through immune status changes rendering tumors sensitive to immune checkpoint blockade. The benefit of intratumoral IL-7 and IL-12 expression was also observed in humanized mice bearing human cancer cells. These data support further investigation in patients with non-inflamed solid tumors.
Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms

Oxidative stress is a key player of the inflammatory cascade responsible for the initiation of ulcerative colitis (UC). Although the short chain quinone idebenone is considered a potent antioxidant and a mitochondrial electron donor, emerging evidence suggests that idebenone also displays anti-inflammatory activity. This study evaluated the impact of idebenone in the widely used dextran sodium sulphate (DSS)-induced mouse model of acute colitis. Acute colitis was induced in C57BL/6J mice via continuous exposure to 2.5% DSS over 7 days. Idebenone was co-administered orally at a dose of 200 mg/kg body weight. Idebenone significantly prevented body weight loss and improved the disease activity index (DAI), colon length, and histopathological score. Consistent with its reported antioxidant function, idebenone significantly reduced the colonic levels of malondialdehyde (MDA) and nitric oxide (NO), and increased the expression of the redox factor NAD(P)H (nicotinamide adenine dinucleotide phosphate) dehydrogenase quinone-1 (NQO-1) in DSS-exposed mice. Immunohistochemistry revealed a significantly increased expression of tight junction proteins, which protect and maintain paracellular intestinal permeability. In support of an anti-inflammatory activity, idebenone significantly attenuated the elevated levels of pro-inflammatory cytokines in colon tissue. These results suggest that idebenone could represent a promising therapeutic strategy to interfere with disease pathology in UC by simultaneously inducing antioxidative and anti-inflammatory pathways.
Variation in Ultrasound Diagnostic Thresholds for Carotid Stenosis in the United States

Supplemental Digital Content is available in the text. Background: Individuals with carotid stenosis enter surveillance or are considered for surgery on the basis of disease severity assessed by ultrasound. However, there is variation in the ultrasound diagnostic thresholds used to determine disease severity. Our objective was to describe this variation and its potential impact on patients. Methods: To describe the variation in carotid ultrasound diagnostic thresholds, we examined testing protocols from 338 accredited vascular testing centers in the United States. To determine the potential impact of this variation, we applied the range of thresholds to carotid ultrasound parameters from 2 groups: a population-based sample ≥65 years of age in the Cardiovascular Health Study (n=4791), and a cohort of patients who underwent surgery for asymptomatic carotid stenosis in the Vascular Quality Initiative registry (n=28 483). Results: Internal carotid artery peak systolic velocity was used by all centers to assess disease severity, with 60 distinct thresholds in use. The peak systolic velocity threshold for moderate (≥50%) stenosis ranged from 110 to 245 cm/s (median, 125; 5th and 95th percentile, 125 and 150), and the threshold for severe (≥70%) stenosis ranged from 175 to 340 cm/s (median, 230; 5th and 95th percentile, 230 and 275). In the population-based sample, the 5th percentile threshold would assign a diagnosis of moderate carotid stenosis to twice as many individuals as the 95th percentile threshold (7.9% versus 3.9%; relative risk, 2.01 [CI, 1.70–2.38]). In the surgical cohort, 1 in 10 (9.8%) patients had peak systolic velocity values that warranted the diagnosis of severe carotid stenosis at centers in the 5th percentile, but not in the 95th. Conclusions: The diagnostic threshold for carotid stenosis varies considerably. Whether or not a person is said to have moderate stenosis and enters surveillance, and whether or not they have severe stenosis and are candidates for surgery, can depend on which center performs their ultrasound.
Analyzing snapshot diversity patterns with the Neutral Theory can show functional groups' effects on community assembly.

A central question of community ecology is to understand how the interplay between processes of the Neutral Theory (e.g., immigration and ecological drift) and niche-based processes (e.g., environmental filtering, intra- and interspecific density-dependence) shape species diversity in competitive communities. The articulation between these two categories of mechanisms can be studied through the lens of the intermediate organizational level of "functional groups" (FGs), defined as clusters of species with similar traits. Indeed, FGs stress ecological differences among species and are thus likely to unravel non-neutral interactions within communities. Here we presented a novel approach to explore how FGs affect species coexistence by comparing species and functional diversity patterns. Our framework considers the Neutral Theory as a mechanistic null hypothesis. It assesses how much the functional diversity deviates from species diversity in communities, and compares this deviation, called the "average functional deviation", to a neutral baseline. We showed that the average functional deviation can indicate reduced negative density-dependence or environmental filtering among FGs. We validated our framework using simulations illustrating the two situations. We further analyzed tropical tree communities in Western Ghats, India. Our analysis of the average functional deviation revealed environmental filtering between deciduous and evergreen FGs along a broad rainfall gradient. By contrast, we did not find clear evidence for reduced density-dependence among FGs. We predict that applying our approach to new case studies where environmental gradients are milder and FGs are more clearly associated to resource partitioning should reveal the missing pattern of reduced density-dependence among FGs.
A novel peptide exerts potent immunosuppression by blocking the two-site interaction of NFAT with calcineurin

The calcineurin/nuclear factor of activated T cell (CN/NFAT) signaling pathway plays a critical role in the immune response. Therefore, inhibition of the CN/NFAT pathway is an important target for inflammatory disease. The conserved PXIXIT and LXVP motifs of CN substrates and targeting proteins have been recognized. Based on the affinity ability and inhibitory effect of these docking sequences on CN, we designed a bioactive peptide (named pep3) against the CN/NFAT interaction, which has two binding sites derived from the RCAN1-PXIXIT motif and the NFATc1-LXVP motif. The shortest linker between the two binding sites in pep3 is derived from A238L, a physiological binding partner of CN. Microscale thermophoresis revealed that pep3 has two docking sites on CN. Pep3 also has the most potent inhibitory effect on CN. It is suggested that pep3 contains an NFATc1-LXVP–substrate recognition motif and RCAN1-PXIXIT–mediated anchoring to CN. Expression of this peptide significantly suppresses CN/NFAT signaling. Cell-permeable 11-arginine–modified pep3 (11R-pep3) blocks the NFAT downstream signaling pathway. Intranasal administration of the 11R-pep3 peptide inhibits airway inflammation in an ovalbumin-induced asthma model. Our results suggest that pep3 is promising as an immunosuppressive agent and can be used in topical remedies.
Characterization of METTL16 as a cytoplasmic RNA binding protein

mRNA modification by N6-methyladenosine (m6A) is involved in many post-transcriptional regulation processes including mRNA stability, splicing and promotion of translation. Accordingly, the recently identified mRNA methylation complex containing METTL3, METTL14, and WTAP has been the subject of intense study. However, METTL16 (METT10D) has also been identified as an RNA m6A methyltransferase that can methylate both coding and noncoding RNAs, but its biological role remains unclear. While global studies have identified many potential RNA targets of METTL16, only a handful, including the long noncoding RNA MALAT1, the snRNA U6, as well as the mRNA MAT2A have been verified and/or studied to any great extent. In this study we identified/verified METTL16 targets by immunoprecipitation of both endogenous as well as exogenous FLAG-tagged protein. Interestingly, exogenously overexpressed METTL16 differed from the endogenous protein in its relative affinity for RNA targets which prompted us to investigate METTL16's localization within the cell. Surprisingly, biochemical fractionation revealed that a majority of METTL16 protein resides in the cytoplasm of a number of cells. Furthermore, siRNA knockdown of METTL16 resulted in expression changes of a few mRNA targets suggesting that METTL16 may play a role in regulating gene expression. Thus, while METTL16 has been reported to be a nuclear protein, our findings suggest that METTL16 is also a cytoplasmic methyltransferase that may alter its RNA binding preferences depending on its cellular localization. Future studies will seek to confirm differences between cytoplasmic and nuclear RNA targets in addition to exploring the physiological role of METTL16 through long-term knockdown.
Seasonality and Small Spatial-Scale Variation of Chlorophyll a Fluorescence in Bryophyte Syntrichia ruralis [Hedw.] in Semi-Arid Sandy Grassland, Hungary

Bryophytes face challenges due to global climate change which is leading to in-depth research in monitoring and studying their photosynthetic activity. The aim of this preliminary experiment was to study the seasonal variation trend in the chlorophyll a fluorescence parameters, Fv/Fm (ratio of variable to maximum fluorescence), photochemical fluorescence quenching (qP), photochemical quantum yield of photosystem II (ΦPS II), fluorescence quenching (qN), and non-photochemical quenching (NPQ), in the moss cushions of Syntrichia ruralis [Hedw. ] collected from semi-arid sandy dunes for two slopes i.e., north-east (NE) and south-west (SW) direction. Our results showed a seasonal and small-spatial scale variation trend in all chlorophyll fluorescence parameters. These variations are due to different seasonal conditions referring to different degrees of environmental stress. ΦPS II and qP values were maximum in winter and in spring seasons while Fv/Fm, NPQ and qN were maximum in summer. Based on the different exposition of dunes, the SW slope showed increased values of the effective quantum yield of PS II and qP in comparison to the NE slope due to the optimal microclimate conditions for their expansion. These results may refer to the future changing in diversification and coverage of the Syntrichia species in semi-arid sandy grassland due to more effective metabolism in the beneficial microclimatic conditions.
Population Spatial Frequency Tuning in Human Early Visual Cortex.

Neurons within early visual cortex are selective for basic image statistics, including spatial frequency. However, these neurons are thought to act as band-pass filters, with the window of spatial frequency sensitivity varying across the visual field and across visual areas. Although a handful of previous fMRI studies have examined human spatial frequency sensitivity using conventional designs and analysis methods, these measurements are time-consuming and fail to capture the precision of spatial frequency tuning (bandwidth). In this study, we introduce a model-driven approach to fMRI analyses that allows for fast and efficient estimation of population spatial frequency tuning (pSFT) for individual voxels. BOLD responses within early visual cortex were acquired while subjects viewed a series of full-field stimuli that swept through a large range of spatial frequency content. Each stimulus was generated by band-pass filtering white noise with a central frequency that changed periodically between a minimum of 0.5 cpd and a maximum of 12 cpd. To estimate the underlying frequency tuning of each voxel, we assumed a log-Gaussian pSFT and optimized the parameters of this function by comparing our model output against the measured BOLD time series. Consistent with previous studies, our results show that an increase in eccentricity within each visual area is accompanied by a drop in the peak spatial frequency of the pSFT. Moreover, we found that pSFT bandwidth depends upon eccentricity, and is correlated with the pSFT peak; populations with lower peaks possess broader bandwidths in logarithmic scale, whereas in linear scale this relationship is reversed.