Miracle-dz/UniFAR-FTUs huggingface dataset:
Common motor patterns of asymmetrical and symmetrical bipedal gaits

Background Synergy modules have been used to describe activation of lower limb muscles during locomotion and hence to understand how the system controls movement. Walking and running have been shown shared synergy patterns suggesting common motor control of both symmetrical gaits. Unilateral skipping, an equivalent gait to the quadrupedal gallop in humans, has been defined as the third locomotion paradigm but the use by humans is limited due to its high metabolic cost. Synergies in skipping have been little investigated. In particular, to the best of our knowledge, the joint study of both trailing and leading limbs has never been addressed before. Research question How are organized muscle activation patterns in unilateral skipping? Are they organized in the same way that in symmetrical gaits? If yes, which are the muscle activation patterns in skipping that make it a different gait to walking or running? In the present research, we investigate if there are shared control strategies for all gaits in locomotion. Addressing these questions in terms of muscle synergies could suggest possible determinants of the scarce use of unilateral skipping in humans. Methods Electromyographic data of fourteen bilateral muscles were collected from volunteers while performing walking, running and unilateral skipping on a treadmill. Also, spatiotemporal gait parameters were computed from 3D kinematics. The modular composition and activation timing extracted by non-negative matrix factorization were analyzed to detect similarities and differences among symmetrical gaits and unilateral skipping. Results Synergy modules showed high similarity throughout the different gaits and between trailing and leading limbs during unilateral skipping. The synergy associated with the propulsion force operated by calf muscles was anticipated in bouncing gaits. Temporal features of synergies in the leading leg were very similar to those observed for running. The different role of trailing and leading legs in unilateral skipping was reflected by the different timing in two modules. Activation for weight acceptance was anticipated and extended in the trailing leg, preparing the body for landing impact after the flight phase. A different behaviour was detected in the leading leg, which only deals with a pendular weight transference. Significance The evidence gathered in this work supports the hypothesis of shared modules among symmetrical and asymmetrical gaits, suggesting a common motor control despite of the infrequent use of unilateral skipping in humans. Unilateral skipping results from phase-shifted activation of similar muscular groups used in symmetrical gaits, without the need for new muscular groups. The high and anticipated muscle activation in the trailing leg for landing could be the key distinctive event of unilateral skipping.
Future Pharmacists’ Opinions on the Facilitation of Self-Care with Over-the-Counter Products and Whether This Should Remain a Core Role

Background: The aim was to investigate pharmacy students’ views on the role of the pharmacist in facilitating self-care with over-the-counter (OTC) medicines, particularly in light of new roles, and establish personal practice. Methods: Final year pharmacy students at Queen’s University Belfast were invited to participate. Data were collected via a pre-piloted questionnaire, distributed at a compulsory class (only non-identifiable data were requested). Descriptive statistics were performed, and non-parametric tests were employed for inferential statistical analysis (responses by gender). Results: The response rate was 87.6% (78/89); 34.6% (27/78) males and 65.4% (51/78) females. Over a third [34.6% (27/78)] reported using OTC medicines about once a month. All appreciated the importance of an evidence-based approach to optimize patient care. Most [(96.2% (75/78)] deemed OTC consultations should remain a fundamental responsibility of pharmacists and 69.2% (54/78) thought OTC consultations have the potential to be as complex as independent pharmacist prescribing. Females felt more confident recommending OTC emergency contraception than males (p = 0.002 for levonorgestrel and p = 0.011 for ulipristal acetate). Many [61.5% (48/78)] considered more medicines should not be deregulated from prescription-only status. Conclusions: Data from this single institution suggests that enabling self-medication is an important part of practice but there were confidence issues around deregulations.
Does Methylphenidate Work in Children and Adolescents with Attention Deficit Hyperactivity Disorder?

Objective: Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder diagnosed in increasing proportions of children and adolescents. The psychostimulant methylphenidate has been considered the first-line pharmacological treatment for children and adolescents with ADHD for more than 60 years. Considering recent publications on methylphenidate for ADHD, we here give an overview of its effects in children and adolescents with ADHD, elicited by a well-disputed Cochrane review and narratively synthesise the evidence in the field. Method: We searched for systematic reviews and meta-analyses that investigated methylphenidate as an intervention for children and adolescence with ADHD compared with placebo or no treatment. We assessed the quality of the evidence using AMSTAR II. Results: We found 24 eligible systematic reviews and meta-analyses of which 11 were rated as high- quality evidence according to AMSTAR II. The evidence claiming that methylphenidate is beneficial in treating children and adolescents with ADHD was of very low certainty. The underreporting of adverse events in randomised clinical trials may impede an adequate depiction of the balance between benefits and harms. Conclusions: It appears that there is uncertain evidence on group-level to support the claim that methylphenidate is beneficial in treating children and adolescents with ADHD. Future randomised clinical trials and systematic reviews should include individual participant data, which would allow us to assess intervention effects across modifiers, like age, sex, ADHD subtypes, comorbidities, and dose.
Weight Loss Interventions for Hispanic Women in the United States: A Systematic Review

Background Obesity rates in Hispanic women residing in the United States (U.S.) are disproportionately high, increasing the risk of obesity-related disease and mortality. The effectiveness of interventions targeting weight loss in this population remains largely unknown. Purpose The purpose of this review was to systematically evaluate the evidence related to the effectiveness of weight loss interventions conducted among U.S. Hispanic women and provide guidance for future research. Methods Bibliographic databases (n = 10, from each database's inception to July 2, 2019) were searched using the PRISMA guidelines for systematic reviews. Randomized controlled trials (RCTs) and quasi-experimental studies with weight change outcomes were included. Results were described in a narrative synthesis. Results 5,423 articles were assessed for eligibility based on inclusion criteria; 15 studies were included in the final review. Nine trials were RCTs and six were quasi-experimental studies; all but six were pilot studies. Most studies recruited overweight or obese women with no existing medical conditions and did not follow participants beyond the intervention. All trials were delivered in-person. Intervention strategies and content and weight change outcomes were highly variable. Conclusions RCTs with statistically powered sample sizes are needed to robustly test the effects of weight loss interventions in this population.
Diagnostic Value of Fractional Exhaled Nitric Oxide and Small Airway Function in Differentiating Cough-Variant Asthma from Typical Asthma

Purpose To explore the diagnostic value of fractional exhaled nitric oxide (FeNO), small airway function, and a combined of both in differentiating cough-variant asthma (CVA) from typical asthma (TA). Methods A total of 206 asthma subjects, including 104 CVA and 102 TA, were tested for pulmonary function, bronchial provocation test and FeNO. The correlation between FeNO, small airway function and other pulmonary indicators was analyzed by single correlation and multiple regression analysis. The receiver operating characteristic (ROC) curve was established to evaluate the diagnostic efficiency of FeNO, small airway function, and their combination and to predict the optimal cut-off point. Results All the respiratory function parameters and small airway function indicators in TA group were significantly different from those in CVA group, and FeNO value was significantly higher than that in CVA group. In addition, the area under the ROC curve (AUC) was estimated to be 0.660 for FeNO, 0.895 for MMEF75%/25%, 0.873 for FEF50%, 0.898 for FEF25%, 0.695 for Fres, 0.650 for R5-R20, and 0.645 for X5. The optimal cut-off points of FeNO, MMEF75%/25%, FEF50%, FEF25%, Fres, R5-R20 and X5, were 48.50 ppb, 60.02%, 63.46%, 45.26%, 16.63 Hz, 0.38 kPa·L−1·s−1, and −1.32, respectively. And the AUC of FeNO combined with small airway function indexes FEF25%, Fres, R5-R20, and X5 were prior than single indicators. Conclusion FeNO and small airway function indexes might have great diagnostic value for differentiating CVA from TA. The combination of FeNO and FEF25%, Fres, R5-R20, and X5 provided a significantly better prediction than either alone.
Safety verification for polysorbate 20, pharmaceutical excipient for intramuscular administration, in Sprague-Dawley rats and New Zealand White rabbits

Human serum albumin (HSA) has been widely used as a pharmaceutical excipient in Botulinum toxin serotype A (BoNT/A) products that are indicated for use in therapeutics and cosmetics. However, HSA as a human-derived material has some concerns, such as the potential risk of transmission of infectious agents, an insufficient supply, and difficulty in maintaining a certain quality. For those reasons, newly developed BoNT/A products (CORETOX®, Medytox, Inc., Republic of Korea) contained polysorbate 20, a non-human-derived excipient, to replace the HSA. However, most safety studies of polysorbate 20 have been conducted with non-invasive routes of administration, and thus there are a few studies on the safety of polysorbate 20 when administered intramuscularly. To secure the in vivo safety profile of polysorbate 20, a four-week repeated intramuscular dose toxicity study (0.02, 0.1, and 0.4 mg/kg, one injection every two weeks for a total of three injections) was conducted in 66 Sprague-Dawley (SD) rats. An intradermal irritation study was further conducted with 18 New Zealand White (NZW) rabbits. The toxicological evaluation of HSA (0.06 and 0.12 mg/kg) was also carried out as a comparative substance. Systemic and local toxicities were not observed in any of the SD rats or NZW rabbits based on clinical signs, body weight, hematology, clinical biochemistry, macroscopic findings on necropsy, histopathology of the injection site, and allergic reactions. The current study suggested that intramuscular administration of polysorbate 20 was considered to be safe at a level similar to that of HSA, which has an in vivo safety profile accumulated over the years. This provided the basis for the in vivo safety profile of polysorbate 20 administered intramuscularly and the scientific reliability of the use of polysorbate 20 as an alternative to HSA, which is used as an excipient for various pharmaceuticals in terms of its safety.
Poor Lower Extremity Functioning Is Associated with Modest Increased Incidence of Probable Dementia

Lower extremity functioning in older adults provides a measure of poor physical performance and can predict negative health outcomes. The consequences of reduced lower extremity functioning on cognitive decline, measured as time-varying variables, have not been well documented in previous studies. We aimed to evaluate whether lower extremity functioning is associated with an increased incidence rate of probable dementia among older adults using data from the National Health and Aging Trends Study (NHATS). Participants (n = 6457) were followed for 8 years to examine the relationship between lower extremity functioning, as measured by the Short Physical Performance Battery (SPPB), and incident probable dementia. Using weighted data, a multivariable Poisson regression with generalized estimating equations (GEE) was used to calculate incidence rate ratios (IRR), adjusting for covariates and clustering. Participants with low SPPB scores (0–5) had a 5% increase in incident probable dementia when compared with those who had good SPPB scores (10–12) in the adjusted model (IRR = 1.05; 95% CI = 1.04–1.07). Lower extremity functioning is associated with a modest increase in incident probable dementia. The SPPB score may be helpful in identifying subjects at risk of dementia. Efforts aimed at improving physical functioning may lead to better cognitive outcomes.
ANMCO POSITION PAPER: Prognostic and therapeutic relevance of non-obstructive coronary atherosclerosis

Abstract Atherosclerosis often affects the coronary arterial tree. Frequently the disease does not translate in significant narrowing of the vessels, thus determining only a non-obstructive disease. This condition that is described as non-obstructive coronary artery disease (NobsCAD) should be distinguished from the absence of disease (i.e. smooth coronary arteries) as it carries a specific prognostic value. The detection and reporting of NobsCAD should prompt preventive measures that can be individualized upon the degree of the underlying burden of disease. The accompanying clinical condition, the other cardiovascular risk factors present, and the description of the severity and extent of NobsCAD should provide the framework for an individualized treatment that should also consider the best available scientific evidence and guidelines. The description of NobsCAD represents important information to be collected whenever a coronary angiogram (both invasive and non-invasive) is performed. Treating the patient according to the presence and extent of NobsCAD offers prognostic benefits well beyond those offered by considering only the traditional cardiovascular risk factors. In order to reach this goal, NobsCAD should not be confused with the absence of coronary atherosclerosis or even ignored when detected as if it was a trivial information to provide.
Effects of Variable Composite Attachment Shapes in Controlling Upper Molar Distalization with Aligners: A Nonlinear Finite Element Study

The objective of the present study is to describe the stress and displacement patterns created by clear aligners and composite attachments bonded with the acid-etch technique on the labial surface of the maxillary first upper molar during its distalization. Maxillary molar distalization is a clinical orthodontics procedure used to move the first maxillary molar distally. The procedure is useful in patients with some Class II malocclusion allowing the first molar to move into a Class I relationship and the correction of associated malocclusion features. Three finite element models were designed to simulate the alveolar bone, molar tooth, periodontal ligament, aligner, and composite attachments. The first model had no composite attachment, the second model had a vertical rectangular attachment, and the third model had a newly designed attachment. A loading method was developed that mimicked the aligner's molar distal movement. PDL was set as a viscoelastic material with a nonlinear mechanical response. von Mises and maximum principal stresses and tooth displacement patterns were analyzed using dedicated software. All the configurations showed some form of clockwise rotation in addition to the distal movement. The crown portion of the tooth showed maximum displacement in all three models; however, in the absence of attachment, the root apex moved in the opposite direction which was compatible with uncontrolled tipping movement. Simulations with attachments exhibited the best performance regarding the movement patterns. The third group, with the newly designed attachment, exhibited the best performance concerning stress distribution (principal stress and von Mises stresses) and higher stresses in the periodontal ligament and tooth. Incorporating a vertical rectangular attachment in a clear aligner resulted in the reduction of mesiodistal tipping tendency during molar distalization. The third model was the most efficient considering both displacement pattern and stress distribution. The level of stress generated by the third model needs to be further investigated in future studies.
Comparative Evaluation of Two Glass Polyalkenoate Cements: An In Vivo Pilot Study Using a Sheep Model

Poly(methyl methacrylate) (PMMA) is used to manage bone loss in revision total knee arthroplasty (rTKA). However, the application of PMMA has been associated with complications such as volumetric shrinkage, necrosis, wear debris, and loosening. Glass polyalkenoate cements (GPCs) have potential bone cementation applications. Unlike PMMA, GPC does not undergo volumetric shrinkage, adheres chemically to bone, and does not undergo an exothermic setting reaction. In this study, two different compositions of GPCs (GPCA and GPCB), based on the patented glass system SiO2-CaO-SrO-P2O5-Ta2O5, were investigated. Working and setting times, pH, ion release, compressive strength, and cytotoxicity of each composition were assessed, and based on the results of these tests, three sets of samples from GPCA were implanted into the distal femur and proximal tibia of three sheep (alongside PMMA as control). Clinical CT scans and micro-CT images obtained at 0, 6, and 12 weeks revealed the varied radiological responses of sheep bone to GPCA. One GPCA sample (implanted in the sheep for 12 weeks) was characterized with no bone resorption. Furthermore, a continuous bone–cement interface was observed in the CT images of this sample. The other implanted GPCA showed a thin radiolucent border at six weeks, indicating some bone resorption occurred. The third sample showed extensive bone resorption at both six and 12 weeks. Possible speculative factors that might be involved in the varied response can be: excessive Zn2+ ion release, low pH, mixing variability, and difficulty in inserting the samples into different parts of the sheep bone.
Inhibition of the lncRNA Coded within Transglutaminase 2 Gene Impacts Several Relevant Networks in MCF-7 Breast Cancer Cells

Long non-coding RNAs are nucleotide molecules that regulate transcription in numerous cellular processes and are related to the occurrence of many diseases, including cancer. In this regard, we recently discovered a polyadenylated long non-coding RNA (named TG2-lncRNA) encoded within the first intron of the Transglutaminase type 2 gene (TGM2), which is related to tumour proliferation in human cancer cell lines. To better characterize this new biological player, we investigated the effects of its suppression in MCF-7 breast cancer cells, using siRNA treatment and RNA-sequencing. In this way, we found modifications in several networks associated to biological functions relevant for tumorigenesis (apoptosis, chronic inflammation, angiogenesis, immunomodulation, cell mobility, and epithelial–mesenchymal transition) that were originally attributed only to Transglutaminase type 2 protein but that could be regulated also by TG2-lncRNA. Moreover, our experiments strongly suggest the ability of TG2-lncRNA to directly interact with important transcription factors, such as RXRα and TP53, paving the way for several regulatory loops that can potentially influence the phenotypic behaviour of MCF-7 cells. These considerations imply the need to further investigate the relative relevance of the TG2 protein itself and/or other gene products as key regulators in the organization of breast cancer program.
Neurovascular imaging with QUTE-CE MRI in APOE4 rats reveals early vascular abnormalities

Cerebrovascular abnormality is linked to Alzheimer’s disease and related dementias (ADRDs). ApoE-Ɛ4 (APOE4) is known to play a critical role in neurovascular dysfunction, however current medical imaging technologies are limited in quantification. This cross-sectional study tested the feasibility of a recently established imaging modality, quantitative ultra-short time-to-echo contrast-enhanced magnetic resonance imaging (QUTE-CE MRI), to identify small vessel abnormality early in development of human APOE4 knock-in female rat (TGRA8960) animal model. At 8 months, 48.3% of the brain volume was found to have significant signal increase (75/173 anatomically segmented regions; q<0.05 for multiple comparisons). Notably, vascular abnormality was detected in the tri-synaptic circuit, cerebellum, and amygdala, all of which are known to functionally decline throughout AD pathology and have implications in learning and memory. The detected abnormality quantified with QUTE-CE MRI is likely a result of hyper-vascularization, but may also be partly, or wholly, due to contributions from blood-brain-barrier leakage. Further exploration with histological validation is warranted to verify the pathological cause. Regardless, these results indicate that QUTE-CE MRI can detect neurovascular dysfunction with high sensitivity with APOE4 and may be helpful to provide new insights into health and disease.
Association of Red Blood Cell Distribution Width Levels with Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD)

Objective The aim of this study was to evaluate the diagnostic and prognostic value of red blood cell distribution width (RDW) in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). Methods We retrospectively reviewed 213 CTD-ILD patients and 97 CTD patients without ILD from February 2017 to February 2020. Hospital and office records were used as data sources. CTD-ILD patients were followed up. Results Patients with CTD-ILD had significantly higher RDW than those with CTD without ILD (p < 0.001). The area under the receiver operating characteristic curve (AUROC) of RDW for discriminating CTD-ILD from CTD without ILD was 0.64 (95% CI: 0.57-0.70, p < 0.001). The cutoff value of RDW for discriminating CTD-ILD from CTD without ILD was 13.95% with their corresponding specificity (55.9%) and sensitivity (70.1%). Correlation analyses showed that the increased RDW was significantly correlated with decreased DLCO%predicted (r = −0.211, p = 0.002). Cox multiple regression analysis indicated that RDW (HR = 1.495, p < 0.001) was an independent factor in the survival of CTD-ILD. The best cutoff value of RDW to predict the survival of patients with CTD-ILD was 14.05% (AUC = 0.78, 95% CI: 0.72-0.84, p < 0.001). The log-rank test showed a significant difference in survival between the two groups (RDW > 14.05% and RDW < 14.05%). Conclusion RDW was higher in CTD-ILD patients and had a negative correlation with DLCO%predicted. RDW may be an important serum biomarker for severity and prognosis of patients with CTD-ILD.
Experimental Models to Study Skin Wound Healing with a Focus on Angiogenesis

A large number of models are now available for the investigation of skin wound healing. These can be used to study the processes that take place in a phase-specific manner under both physiological and pathological conditions. Most models focus on wound closure, which is a crucial parameter for wound healing. However, vascular supply plays an equally important role and corresponding models for selective or parallel investigation of microcirculation regeneration and angiogenesis are also described. In this review article, we therefore focus on the different levels of investigation of skin wound healing (in vivo to in virtuo) and the investigation of angiogenesis and its parameters.