Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Muscle Synergy Extraction Method Used for Motor Function Evaluation of Stroke Patients: A Pilot Study

In this paper, we present a novel muscle synergy extraction method based on multivariate curve resolution–alternating least squares (MCR-ALS) to overcome the limitation of the nonnegative matrix factorization (NMF) method for extracting non-sparse muscle synergy, and we study its potential application for evaluating motor function of stroke survivors. Nonnegative matrix factorization (NMF) is the most widely used method for muscle synergy extraction. However, NMF is susceptible to components’ sparseness and usually provides inferior reliability, which significantly limits the promotion of muscle synergy. In this study, MCR-ALS was employed to extract muscle synergy from electromyography (EMG) data. Its performance was compared with two other matrix factorization algorithms, NMF and self-modeling mixture analysis (SMMA). Simulated data sets were utilized to explore the influences of the sparseness and noise on the extracted synergies. As a result, the synergies estimated by MCR-ALS were the most similar to true synergies as compared with SMMA and NMF. MCR-ALS was used to analyze the muscle synergy characteristics of upper limb movements performed by healthy (n = 11) and stroke (n = 5) subjects. The repeatability and intra-subject consistency were used to evaluate the performance of MCR-ALS. As a result, MCR-ALS provided much higher repeatability and intra-subject consistency as compared with NMF, which were important for the reliability of the motor function evaluation. The stroke subjects had lower intra-subject consistency and seemingly had more synergies as compared with the healthy subjects. Thus, MCR-ALS is a promising muscle synergy analysis method for motor function evaluation of stroke patients.
Inequalities in Periodontal Disease According to Insurance Schemes in Thailand

Few studies have considered the effects of insurance on periodontal disease. We aimed to investigate the association between insurance schemes and periodontal disease among adults, using Thailand’s National Oral Health Survey (2017) data. A modified Community Periodontal Index was used to measure periodontal disease. Insurance schemes were categorized into the Universal Coverage Scheme (UCS), Civil Servant Medical Benefit Scheme (CSMBS), Social Security Scheme (SSS), and “others”. Poisson regression was applied to estimate the prevalence ratios (PRs) of insurance schemes for periodontal disease, with adjustment for age, gender, residential location, education attainment, and income. The data of 4534 participants (mean age, 39.6 ± 2.9 years; 2194 men, 2340 women) were analyzed. The proportions of participants with gingivitis or periodontitis were 87.6% and 25.9%, respectively. In covariate adjusted models, lowest education (PRs, 1.03; 95% CI, 1.01–1.06) and UCS (PRs, 1.05; 95% CI, 1.02–1.08) yielded significantly higher PRs for gingivitis, whereas lowest education (PRs, 1.20; 95% CI, 1.05–1.37) and UCS (PRs, 1.17; 95% CI, 1.02–1.34) yielded substantially higher PRs for periodontitis. Insurance schemes may be social predictors of periodontal disease. For better oral health, reduced insurance inequalities are required to increase access to regular dental visits and utilization in Thailand.
University of Birmingham Investigating cooking activity patterns and perceptions of air quality interventions among women in urban Rwanda

: Household air pollution (HAP) from biomass cooking with traditional stoves is a major cause of morbidity and mortality in low-and-middle-income countries (LMICs) worldwide. Air quality interventions such as improved cookstoves (ICS) may mitigate HAP-related impacts; how-ever, poor understanding of contextual socio-cultural factors such as local cooking practices have limited their widespread adoption. Policymakers and stakeholders require an understanding of local cooking practices to inform effective HAP interventions which meet end-user needs. A semi-structured questionnaire was administered to 36 women residing in biomass-cooking fuel households in Kigali, Rwanda to identify cooking activity patterns, awareness of HAP-related health risks and ICS intervention preferences. Overall, 94% of respondents exclusively used charcoal cooking fuel and 53% cooked one meal each day (range = 1–3 meals). Women were signiﬁcantly more likely to cook outdoors compared to indoors (64% vs. 36%; p < 0.05). Over half of respondents (53%) were unaware of HAP-related health risks and 64% had no prior awareness of ICS. Participants expressed preferences for stove mobility (89%) and facility for multiple pans (53%) within an ICS intervention. Our ﬁndings highlight the need for HAP interventions to be ﬂexible to suit a range of cooking patterns and preferred features for end-users in this context.
Child Farm-Related Injury in Australia: A Review of the Literature

Children on farms have been identified as a population vulnerable to injury. This review seeks to identify child farm-related injury rates in Australia and to determine the key hazards and contributing risk factors. This critical review utilised the PRISMA guidelines for database searching. Research from the year 2000 onward was included as well as earlier seminal texts. Reference lists were searched, and the relevant research material was explored. Our primary focus was on Australian peer-reviewed literature with international and grey literature examples included. Evidence suggests that there is limited Australian research focusing on child farm-related injuries. Child representation in farm-related injuries in Australia has remained consistent over time, and the key hazards causing these injuries have remained the same for over 20 years. The factors contributing to child rates of farm injury described in the literature include child development and exposure to dangerous environments, the risk-taking culture, multi-generational farming families, lack of supervision, child labour and lack of regulation, limited targeted farm safety programs, underuse of safe play areas, financial priorities and poor understanding and operationalisation of the hierarchy of control. It is well known that children experience injury on farms, and the key hazards that cause this have been clearly identified. However, the level of exposure to hazards and the typical attitudes, behaviours and actions of children and their parents around the farm that contribute to chid injury remain unexplored.
Evaluation of Somatic Mutations in Solid Metastatic Pan-Cancer Patients

Simple Summary Cancer metastasis significantly contributes to cancer-related mortality. Our retrospective cohort study aimed to evaluate the mutational landscape of seven solid metastatic tumors and mutational effects on survival using a single molecular testing panel. Additionally, we assessed the treatments used in advanced cancer. We identified somatic mutations that were mutually exclusive in seven gene pairs. Among them, somatic mutations in APC and CDKN2A showed an opposite effect on overall survival (OS). Longer OS was associated with metastatic cases diagnosed post-2015. Progression-free survival was associated with the use of targeted treatments. Our results highlight complex interactions of mutational landscape with a single molecular test, time of metastatic diagnosis, and the impact of targeted therapy usage on survival using a pan-cancer cohort. Abstract Metastasis continues to be the primary cause of all cancer-related deaths despite the recent advancements in cancer treatments. To evaluate the role of mutations in overall survival (OS) and treatment outcomes, we analyzed 957 metastatic patients with seven major cancer types who had available molecular testing results with a FoundationOne CDx® panel. The most prevalent genes with somatic mutations were TP53, KRAS, APC, and LRP1B. In this analysis, these genes had mutation frequencies higher than in publicly available datasets. We identified that the somatic mutations were seven mutually exclusive gene pairs and an additional fifty-two co-occurring gene pairs. Mutations in the mutually exclusive gene pair APC and CDKN2A showed an opposite effect on the overall survival. However, patients with CDKN2A mutations showed significantly shorter OS (HR: 1.72, 95% CI: 1.34–2.21, p < 0.001) after adjusting for cancer type, age at diagnosis, and sex. Five-year post metastatic diagnosis survival analysis showed a significant improvement in OS (median survival 28 and 43 months in pre-2015 and post-2015 metastatic diagnosis, respectively, p = 0.00021) based on the year of metastatic diagnosis. Although the use of targeted therapies after metastatic diagnosis prolonged OS, the benefit was not statistically significant. However, longer five-year progression-free survival (PFS) was significantly associated with targeted therapy use (median 10.9 months (CI: 9.7–11.9 months) compared to 9.1 months (CI: 8.1–10.1 months) for non-targeted therapy, respectively, p = 0.0029). Our results provide a clinically relevant overview of the complex molecular landscape and survival mechanisms in metastatic solid cancers.
Connectivity Map Analysis Indicates PI3K/Akt/mTOR Inhibitors as Potential Anti-Hypoxia Drugs in Neuroblastoma

Simple Summary A large percentage of patients with neuroblastoma relapse and die, despite treatment, thus demanding new personalized strategies and therapeutic targets. Hypoxia, a condition of reduced oxygenation in several solid tumors, has profound effects on the neuroblastoma (NB) tumor biology and patient prognosis. Establishing new connections between hypoxia and pharmacological compounds may provide novel treatment strategies for NB patients. In the present study, we successfully identified 19 compounds mainly belonging to the class of PI3K/Akt/mTOR inhibitors, whose anti-hypoxia effect was shown on the gene expression profile of nine distinct cell lines using connectivity map software. We independently confirmed these findings on NB cells cultured under hypoxia conditions and treated with the mTORC inhibitor PP242. PI3K/Akt/mTOR inhibitors represent a potential effective class of compounds targeting hypoxia in neuroblastoma. PI3K/Akt/mTOR inhibitors may thus find future applicability as a new adjuvant therapy in randomized clinical trials involving neuroblastoma patients with hypoxic tumors. Abstract Neuroblastoma (NB) is one of the deadliest pediatric cancers, accounting for 15% of deaths in childhood. Hypoxia is a condition of low oxygen tension occurring in solid tumors and has an unfavorable prognostic factor for NB. In the present study, we aimed to identify novel promising drugs for NB treatment. Connectivity Map (CMap), an online resource for drug repurposing, was used to identify connections between hypoxia-modulated genes in NB tumors and compounds. Two sets of 34 and 21 genes up- and down-regulated between hypoxic and normoxic primary NB tumors, respectively, were analyzed with CMap. The analysis reported a significant negative connectivity score across nine cell lines for 19 compounds mainly belonging to the class of PI3K/Akt/mTOR inhibitors. The gene expression profiles of NB cells cultured under hypoxic conditions and treated with the mTORC complex inhibitor PP242, referred to as the Mohlin dataset, was used to validate the CMap findings. A heat map representation of hypoxia-modulated genes in the Mohlin dataset and the gene set enrichment analysis (GSEA) showed an opposite regulation of these genes in the set of NB cells treated with the mTORC inhibitor PP242. In conclusion, our analysis identified inhibitors of the PI3K/Akt/mTOR signaling pathway as novel candidate compounds to treat NB patients with hypoxic tumors and a poor prognosis.
Structural Features and Toxicity of α-Synuclein Oligomers Grown in the Presence of DOPAC

The interplay between α-synuclein and dopamine derivatives is associated with oxidative stress-dependent neurodegeneration in Parkinson’s disease (PD). The formation in the dopaminergic neurons of intraneuronal inclusions containing aggregates of α-synuclein is a typical hallmark of PD. Even though the biochemical events underlying the aberrant aggregation of α-synuclein are not completely understood, strong evidence correlates this process with the levels of dopamine metabolites. In vitro, 3,4-dihydroxyphenylacetaldehyde (DOPAL) and the other two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylethanol (DOPET), share the property to inhibit the growth of mature amyloid fibrils of α-synuclein. Although this effect occurs with the formation of differently toxic products, the molecular basis of this inhibition is still unclear. Here, we provide information on the effect of DOPAC on the aggregation properties of α-synuclein and its ability to interact with membranes. DOPAC inhibits α-synuclein aggregation, stabilizing monomer and inducing the formation of dimers and trimers. DOPAC-induced oligomers did not undergo conformational transition in the presence of membranes, and penetrated the cell, where they triggered autophagic processes. Cellular assays showed that DOPAC reduced cytotoxicity and ROS production induced by α-synuclein aggregates. Our findings show that the early radicals resulting from DOPAC autoxidation produced covalent modifications of the protein, which were not by themselves a primary cause of either fibrillation or membrane binding inhibition. These findings are discussed in the light of the potential mechanism of DOPAC protection against the toxicity of α-synuclein aggregates to better understand protein and catecholamine biology and to eventually suggest a scaffold that can help in the design of candidate molecules able to interfere in α-synuclein aggregation.
Whole Lung Irradiation after High-Dose Busulfan/Melphalan in Ewing Sarcoma with Lung Metastases: An Italian Sarcoma Group and Associazione Italiana Ematologia Oncologia Pediatrica Joint Study

Simple Summary The lung is the most frequent site of metastasis in Ewing sarcoma, the second most common bone cancer affecting children, adolescents and young adults. The five-year overall survival of patients with isolated lung metastasis is approximately 50% after multimodal treatments including chemotherapy, surgery and radiotherapy. This retrospective study aimed to investigate the feasibility and the predictors of survival in 68 Ewing sarcoma patients with lung metastases who received high-dose chemotherapy with busulfan and melphalan, followed by reduced dose whole-lung irradiation, as part of two prospective and consecutive treatment protocols. This combined treatment strategy is feasible and might contribute to the disease control in lung metastatic Ewing sarcoma with responsive disease. Furthermore, the results of this study provide support to explore the treatment stratification for lung metastatic Ewing sarcoma based on the histological response of the primary tumor. Abstract Purpose: To analyze toxicity and outcome predictors in Ewing sarcoma patients with lung metastases treated with busulfan and melphalan (BU-MEL) followed by whole-lung irradiation (WLI). Methods: This retrospective study included 68 lung metastatic Ewing Sarcoma patients who underwent WLI after BU-MEL with autologous stem cell transplantation, as part of two prospective and consecutive treatment protocols. WLI 12 Gy for <14 years old and 15 Gy for ≥14 years old patients were applied at least eight weeks after BU-MEL. Toxicity, overall survival (OS), event-free survival (EFS) and pulmonary relapse-free survival (PRFS) were estimated and analyzed. Results: After WLI, grade 1–2 and grade 3 clinical toxicity was reported in 16.2% and 5.9% patients, respectively. The five-year OS, EFS and PRFS with 95% confidence interval (CI) were 69.8% (57.1–79.3), 61.2% (48.4–71.7) and 70.5% (56.3–80.8), respectively. Patients with good histological necrosis of the primary tumor after neoadjuvant chemotherapy showed a significant decreased risk of pulmonary relapse or death compared to patients with poor histological necrosis. Conclusions: WLI at recommended doses and time interval after BU-MEL is feasible and might contribute to the disease control in Ewing sarcoma with lung metastases and responsive disease. Further studies are needed to explore the treatment stratification based on the histological response of the primary tumor.
Methods and Designs of Modern Breast Cancer Confirmatory Trials

Simple Summary The benefit–risk assessments of new drugs for breast cancer (BC) face several challenges, as all stakeholders do not agree on the evidence bar required for market authorization, and by the fragmentation of breast cancer diagnosis. In this study, we describe the methods and designs of breast cancer confirmatory trials published between 2001 and 2020. We found that the quality of the evidence supporting new breast cancer drugs was improving over time, but that patient-relevant endpoints such as survival and quality of life remained unfrequently used as primary endpoints. Abstract Background: The benefit–risk assessments of new drugs for breast cancer (BC) face several challenges, as all stakeholders do not agree on the evidence bar required for market authorization, and by the fragmentation of breast cancer diagnosis. The aim of this study was to describe the changes in methods and designs of breast cancer confirmatory trials. Methods: All phase III randomized trials published between 2001 and 2020 and assessing systemic BC therapies were included. Trials’ main characteristics, endpoints, and statistical methods were collected using a standardized data extraction form. Results: A total of 347 randomized controlled trials (RCTs) met the inclusion criteria. While most older trials (79%) included all subtypes of breast cancer, most recent trials populations were limited to one large intrinsic BC subgroup (69%). The use of gatekeeping testing strategies increased dramatically from 9% to 71%. The use of overall survival (OS) as an endpoint in the trials increased over time, but its use as a primary endpoint remained infrequent. The inclusion of OS testing in a hierarchical sequence in case of positive testing of a tumor-centered or composite endpoint appeared to have become the new standard. Conclusion: Our findings indicate some improvements in the quality of the evidence-base supporting new breast cancer drugs. The rigorous assessment of patient-relevant endpoints has increased over time, but this improvement is mainly related to the analysis of OS as a secondary endpoint analyzed in a hierarchical sequence.
Psychological Impact of the COVID-19 Outbreak on Mental Health Outcomes among Youth: A Rapid Narrative Review

The coronavirus disease (COVID-19) outbreak has affected not only physical health but also mental health and psychological wellbeing. This narrative review aimed to map the literature on the psychological impact on the young generation of the COVID-19 pandemic, social restrictions, and extraordinary measures to curb the spread of coronavirus. We performed a systematic search of MEDLINE through PubMed and Web of Science [Science Citation Index Expanded, SCI-EXPANDED), Social Sciences Citation Index (SSCI), and Emerging Sources Citation Index (ESCI)] of all scientific literature published from May 2020 until 15 March 2021. Based on inclusion and exclusion criteria, a total of 15 articles were included. We conducted a narrative review. The reviewed articles suggested the impact of the pandemic and lockdown measures on young persons for several mental symptoms as well as anxiety, stress, depression, event-specific distress, decrease in psychological wellbeing, and changes in sleep habits. Psychological symptoms were related to the experience of several stressors, such as risk for reduction of academic perspectives, massive e-learning adoption, economic issues, social restrictions, and implications for daily life related to the COVID-19 outbreak. This narrative review points out the negative psychological impact of the pandemic outbreak and the high vulnerability of the young in the development of psychological distress, highlighting the relevant focus on the mental health of young people during the pandemic and the need for structured and tailored psychological support and interventions focused to the improvement of Quality of Life of university students after the pandemic experience.
The Health Behaviour of German Outpatient Caregivers in Relation to Their Working Conditions: A Qualitative Study

Ongoing demographic change is leading to an increasingly older society and a rising proportion of people in need of care in the German population. Therefore, the professional group of outpatient caregivers is highly relevant. Their work is characterised not only by interacting with patients in a mobile setting but also by working in shifts. Health behaviour under these specific working conditions is crucial for ensuring long-term work ability and performance. Little is known about the health behaviour of German outpatient caregivers and its potential impact on their work. The aims of the study were (1) to examine health behavioural patterns (nutrition, exercise, smoking, regeneration) of outpatient caregivers, (2) to illuminate their personal health-promoting behaviours, and (3) to identify potential work-related factors influencing their health behaviour. Fifteen problem-centred interviews were conducted with outpatient caregivers working in Northern Germany in the period January–April 2020. Interviews were analysed by using qualitative content analysis. Outpatient caregivers reported improvable nutrition and hydration, with simultaneous high coffee consumption, low physical activity, poor regeneration (breaks and sleep quality), and good personal health-promoting behaviour (e.g., back-friendly habits), although the majority were smokers. Barriers to the implementation of health-promoting behaviours were a high perception of stress due to increased workload and time pressure, while aids to better health-promoting behaviour were described as being social support and personal resources. The respondents perceived their working conditions as potentially influencing their health behaviour. On the basis of their descriptions, various practice-relevant strategies were derived. The data explore a potential need for outpatient care services to develop interventions on behavioural and structural levels that can help create healthier working conditions for their employees so these caregivers can adopt better health behaviours.
Effect of Cellulose and Cellulose Nanocrystal Contents on the Biodegradation, under Composting Conditions, of Hierarchical PLA Biocomposites

In this work, the effect of microfibrillated cellulose (MFC) and cellulose nanocrystals (CNCs) on the biodegradation, under composting conditions, of hierarchical PLA biocomposites (HBCs) was studied using a full 22 factorial experimental design. The HBCs were prepared by extrusion processing and were composted for 180 days. At certain time intervals, the specimens were removed from the compost for their chemical, thermal and morphological characterizations. An ANOVA analysis was carried out at different composting times to study MFC and CNCs’ effects on biodegradation. The specimen’s mass loss and molecular weight loss were selected as independent variables. The results show that the presence of MFC enhances the PLA biodegradation, while with CNCs it decreases. However, when both cellulosic fibers are present, a synergistic effect was evident—i.e., in the presence of the MFC, the inclusion of the CNCs accelerates the HBCs biodegradation. Analysis of the ANOVA results confirms the relevance of the synergistic role between both cellulosic fibers over the HBC biodegradation under composting conditions. The results also suggest that during the first 90 days of incubation, the hydrolytic PLA degradation prevails, whereas, beyond that, the enzymatic microbial biodegradation dominates. The SEM results show MFC’s presence enhances the surface biodeterioration to a greater extent than the CNCs and that their simultaneous presence enhances PLA biodegradation. The SEM results also indicate that the biodegradation process begins from hydrophilic cellulosic fibers and promotes PLA biodegradation.