Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of exogenous melatonin on sleep quality and menopausal symptoms in menopausal women: a systematic review and meta-analysis of randomized controlled trials

Supplemental Digital Content is available in the text Abstract Importance: Because of the bothersome symptoms during women's menopausal period and the severe side effects of hormone therapy, it is meaningful to find new breakthroughs in improving menopausal women's quality of life. Objective: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating melatonin intake on the improvement of sleep quality, general menopausal symptom, mood states, as well as interaction of estradiol levels and body mass index (BMI) in menopausal women. Evidence Review: We used the search terms “melatonin” together with “menopause” or “post-menopause” or “peri-menopause” in multiple databases online including PubMed, Web of Science, Embase, Clinical trial, Cochrane Library, and China National Knowledge Infrastructure from the first publication year to October 2020. Interesting data included characteristics of the study design, study participants, intervention, and outcome measures. Risk of biases in RCTs was evaluated with the Cochrane tool. Fixed-effect models and random-effect models were used for meta-analysis according to heterogeneity. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in our study. Findings: Eight cohorts (n = 812) evaluating the effects of melatonin in menopausal women were included. Melatonin was used in every study with differences existing in dose (1 mg - 5 mg) and duration (3 to 12 mo). Improved physical symptoms (standard mean difference [SMD] −0.376; 95% CI, −0.599 to −0.153, P = 0.001) merged in four RCTs. Melatonin treatment resulted in no benefits to sleep quality (SMD −0.659; 95% CI, −1.535 to 0.217, P = 0.141) and general menopause symptoms (SMD −0.625; 95% CI, −1.354 to 0.105, P = 0.093) in four and three RCTs, respectively. More specifically, melatonin did not solve the psychological (SMD −0.026; 95% CI, −0.372 to 0.321, P = 0.884, I2 = 70.3%), sexual (SMD −0.661; 95% CI, −1.416 to 0.093, P = 0.086) and vasomotor (SMD −0.256; 95% CI, −0.701 to 0.188, P = 0.258) issues. No significant changes were observed in anxiety (SMD 0.018; 95% CI, −0.519 to 0.556, P = 0.946), depression (SMD 0.133; 95% CI, −0.435 to 0.702, P = 0.646), BMI (weighted mean difference 0.029 kg/m2; 95% CI, −0.183 to 0.240, P = 0.790) or estradiol levels (weighted mean difference 0.016 pg/mL; 95% CI, −1.220 to 1.252, P = 0.980). Conclusions: Melatonin seems to improve physical symptoms in menopausal women, but the general menopausal symptoms, sleep quality, mood state, estradiol levels, and BMI did not improve under melatonin intervention. However, multiple large-scale clinical randomized trials are needed to validate our conclusions.
ASPECTS-based selection for late endovascular treatment: a retrospective two-site cohort study

Introduction The DAWN trial demonstrated the effectiveness of late endovascular treatment in acute ischemic stroke patients selected on the basis of a clinical-core mismatch. We explored in a real-world sample of endovascular treatment patients if a clinical-ASPECTS (Alberta Stroke Program Early CT Score) mismatch was associated with an outcome benefit after late endovascular treatment. Methods We retrospectively analyzed all consecutive acute ischemic stroke patients admitted 6–24 h after last proof of good health in two stroke centers, with initial National Institutes of Health Stroke Scale (NIHSS) ≥10 and an internal carotid artery or M1 occlusion. We defined clinical-ASPECTS mismatch as NIHSS ≥ 10 and ASPECTS ≥ 7, or NIHSS ≥ 20 and ASPECTS ≥ 5. We assessed the interaction between the presence of the clinical-ASPECTS mismatch and late endovascular treatment using ordinal shift analysis of the three-month modified Rankin Scale and adjusting for multiple confounders. Results The included 337 patients had a median age of 73 years (IQR = 61–82), admission NIHSS of 18 (15–22), and baseline ASPECTS of 7 (5–9). Out of 196 (58.2%) patients showing clinical-ASPECTS mismatch, 146 (74.5%) underwent late endovascular treatment. Among 141 (41.8%) mismatch negative patients, late endovascular treatment was performed in 72 (51.1%) patients. In the adjusted analysis, late endovascular treatment was significantly associated with a better outcome in the presence of clinical-ASPECTS mismatch (adjusted odd ratio, aOR = 2.83; 95% confidence interval, CI: 1.48–5.58) but not in its absence (aOR = 1.32; 95%CI: 0.61–2.84). The p-value for the interaction term between clinical-ASPECTS mismatch and late endovascular treatment was 0.073. Conclusions In our retrospective two-site analysis, late endovascular treatment seemed effective in the presence of a clinical-ASPECTS mismatch, but not in its absence. If confirmed in randomized trials, this finding could support the use of an ASPECTS-based selection for late endovascular treatment decisions, obviating the need for advanced imaging.
Hsa_circ_0032463 acts as the tumor promoter in osteosarcoma by regulating the miR-330-3p/PNN axis

Osteosarcoma (OS), also known as bone cancer, is a threat to the lives of millions of adolescents worldwide. Although dedicated efforts have been invested in reducing the mortality rate of this bone cancer, the research community is yet to find the exact causes of OS. Thus, the present research aimed to study the association between circular RNA circ_0032463 and OS progression. The impact of circ_0032463 on cells with OS was first evaluated using reverse transcription-quantitative PCR. This evaluation was followed by the assessment of cell proliferation, viability, apoptosis, invasion and adhesion using BrdU, Cell Counting Kit-8, flow cytometry, Transwell and cell adhesion assays, respectively. RNA pull-down, RNA immunoprecipitation chip and dual-luciferase reporter systems were utilized to investigate the relationship between circ_0032463, microRNA (miR)-330-3p and Pinin desmosome associated protein (PNN) in OS. The findings indicated that circ_0032463 and PNN were highly expressed in OS tissues and OS cell lines, and that they facilitated cell proliferation, viability, invasion and adhesion, but attenuated cell apoptosis in OS cells. The low expression of miR-330-3p suppressed OS development. It was also noted that circ_0032463 inhibited miR-330-3p to upregulate PNN expression. In conclusion, this study confirmed that by regulating the miR-330-3p/PNN axis, circular RNA circ_0032463 could function as a tumor enhancer in cells with OS.
Associations between physical activity, basic motor competencies and automatic evaluations of exercise

ABSTRACT Dual process theories suggest that the decision to be physically active is influenced by reflective and automatic processes. However, associations of automatic (affective) evaluations of exercise with physical activity and underlying basic motor competencies have not yet been investigated in children and young adolescents. Ninety-one participants (52 male; age: 10–14 years) were recruited from academic high schools in Germany and Switzerland. Automatic evaluations of exercise were measured with the Single-Target Implicit Association Test (ST-IAT) and a D-score was calculated. Moderate-to-vigorous physical activity (MVPA) and vigorous physical activity (VPA) per day were determined via wrist-worn actigraphy over the course of seven days. Basic motor competencies were measured using the MOBAK-5 test battery. Pearson correlations showed non-significant associations of automatic evaluations of exercise with MVPA, but significant associations with VPA. Basic motor competencies were associated with automatic evaluations of exercise, and the MOBAK subscale of object movement was associated with both MVPA and VPA. Our results underscore the relevance of affective processes for physical activity behaviour. This could potentially be relevant for interventions targeting physical activity promotion. Longitudinal investigations and intervention studies are necessary to verify causal relationships and potential underlying mechanisms.
Individual Hearing Aid Benefit in Real Life Evaluated Using Ecological Momentary Assessment

Ecological momentary assessment (EMA) was used in 24 adults with mild-to-moderate hearing loss who were seeking first hearing-aid (HA) fitting or HA renewal. At two stages in the aural rehabilitation process, just before HA fitting and after an average 3-month HA adjustment period, the participants used a smartphone-based EMA system for 3 to 4 days. A questionnaire app allowed for the description of the environmental context as well as assessments of various hearing-related dimensions and of well-being. In total, 2,042 surveys were collected. The main objectives of the analysis were threefold: First, describing the “auditory reality” of future and experienced HA users; second, examining the effects of HA fitting for individual participants, as well as for the subgroup of first-time HA-users; and third, reviewing whether the EMA data collected in the unaided condition predicted who ultimately decided for or against permanent HA use. The participants reported hearing-related disabilities across the full range of daily listening tasks, but communication events took the largest share. The effect of the HA intervention was small in experienced HA users. Generally, much larger changes and larger interindividual differences were observed in first-time compared with experienced HA users in all hearing-related dimensions. Changes were not correlated with hearing loss or with the duration of the HA adjustment period. EMA data collected in the unaided condition did not predict the cancelation of HA fitting. The study showed that EMA is feasible in a general population of HA candidates for establishing individual and multidimensional profiles of real-life hearing experiences.
Direction Control and Adaptive Path Following of 3-D Snake-Like Robot Motion

This work investigates direction control and path following of a 3-D snake-like robot. In order to control such robots accurately, this work researches the relationships between its phase offsets of pitch joints and directions. A new direction control method is proposed for the robot based on these relationships. An adaptive path-following algorithm based on the line-of-sight guidance law is proposed and combined with the direction control method to steer the robot to move forward and along desired paths. Simulation and experimental results are presented to demonstrate the performances of the proposed 3-D model and control methods. They well outperform the classical and commonly used path-following method.
Upregulation of the pathogenic transcription factor SPI1/PU.1 in tuberous sclerosis complex and focal cortical dysplasia by oxidative stress

Tuberous sclerosis complex (TSC) is a congenital disorder characterized by cortical malformations and concomitant epilepsy caused by loss‐of‐function mutations in the mTOR suppressors TSC1 or TSC2. While the underlying molecular changes caused by mTOR activation in TSC have previously been investigated, the drivers of these transcriptional change have not been fully elucidated. A better understanding of the perturbed transcriptional regulation could lead to the identification of novel pathways for therapeutic intervention not only in TSC, but other genetic epilepsies in which mTOR activation plays a key role, such as focal cortical dysplasia 2b (FCD). Here, we analyzed RNA sequencing data from cortical tubers and a tsc2−/− zebrafish. We identified differential expression of the transcription factors (TFs) SPI1/PU.1, IRF8, GBX2, and IKZF1 of which SPI1/PU.1 and IRF8 targets were enriched among the differentially expressed genes. Furthermore, for SPI1/PU.1 these findings were conserved in TSC zebrafish model. Next, we confirmed overexpression of SPI1/PU.1 on the RNA and protein level in a separate cohort of surgically resected TSC tubers and FCD tissue, in fetal TSC tissue, and a Tsc1GFAP−/− mouse model of TSC. Subsequently, we validated the expression of SPI1/PU.1 in dysmorphic cells with mTOR activation in TSC tubers. In fetal TSC, we detected SPI1/PU.1 expression prenatally and elevated RNA Spi1 expression in Tsc1GFAP−/− mice before the development of seizures. Finally, in vitro, we identified that in astrocytes and neurons SPI1 transcription was driven by H2O2‐induced oxidative stress, independent of mTOR. We identified SPI1/PU.1 as a novel TF involved in the pro‐inflammatory gene expression of malformed cells in TSC and FCD 2b. This transcriptional program is activated in response to oxidative stress and already present prenatally. Importantly, SPI1/PU.1 protein appears to be strictly limited to malformed cells, as we did not find SPI1/PU.1 protein expression in mice nor in our in vitro models.
MiR-17-92 cluster-enriched exosomes derived from human bone marrow mesenchymal stromal cells improve tissue and functional recovery in rats after traumatic brain injury.

Exosomes play an important role in intercellular communication by delivering microRNAs to recipient cells. Previous studies have demonstrated that multipotent mesenchymal stromal cell (MSC)-derived exosomes improve functional recovery after experimental traumatic brain injury (TBI). This study was performed to determine efficacy of miR-17-92 cluster-enriched exosomes (Exo-17-92) harvested from human bone marrow MSCs transfected with a miR-17-92 cluster plasmid in enhancing tissue and neurological recovery compared to exosomes derived from MSCs transfected with an empty plasmid vector (Exo-empty) for treatment of traumatic brain injury (TBI). Adult male rats were subjected to a unilateral moderate cortical contusion. Animals received a single intravenous injection of miR-17-92 cluster-enriched exosomes (100 µg/rat, approximately 3.75x1011 particles, Exo-17-92) or control exosomes (100 µg/rat, Exo-empty) or Vehicle (phosphate-buffered solution) 1 day after injury. A battery of neurological functional tests were performed weekly after TBI for 5 weeks. Spatial learning and memory were measured on days 31-35 after TBI using the Morris water maze test. All animals were sacrificed 5 weeks after injury. Their brains were processed for histopathological and immunohistochemical analyses of lesion volume, cell loss, angiogenesis, neurogenesis and neuroinflammation. Compared to the vehicle, both Exo-17-92 and Exo-empty treatments significantly improved sensorimotor and cognitive function, reduced neuroinflammation and hippocampal neuronal cell loss, promoted angiogenesis and neurogenesis without altering the lesion volume. Moreover, Exo-17-92 treatment exhibited a significantly more robust therapeutic effect on improvement in functional recovery by reducing neuroinflammation and cell loss, enhancing angiogenesis and neurogenesis than did Exo-empty treatment. Exosomes enriched with miR-17-92 cluster have a significantly better effect on improving functional recovery after TBI compared to Exo-empty, likely by reducing neuroinflammation and enhancing endogenous angiogenesis and neurogenesis. Engineering specific miRNA in exosomes may provide a novel therapeutic strategy for treatment of unilateral moderate cortical contusion TBI.
The Framing of COVID-19 in Italian Media and Its Relationship with Community Mobility: A Mixed-Method Approach

Media framing of epidemics was found to influence public perceptions and behaviors in experiments, yet no research has been conducted on real-world behaviors during public health crises. We examined the relationship between Italian news media coverage of COVID-19 and compliance with stay-at-home orders, which could impact the spread of epidemics. We used a computational method for framing analysis (ANTMN) and combined it with Google’s Community Mobility data. A time-series analysis using vector autoregressive models showed that the Italian media used media frames that were largely congruent with ones used by journalists in other countries: A scientific frame focusing on symptoms and health effects, a containment frame focusing on attempts to ameliorate risks, and a social frame, focusing on political and social impact. The prominence of different media frames over time was associated with changes in Italians’ mobility patterns. Specifically, we found that the social frame was associated with increased mobility, whereas the containment frame was associated with decreased mobility. The results demonstrate that the ways the news media discuss epidemics can influence changes in community mobility, above and beyond the effect of the number of deaths per day.
Osteoporosis in Adult Patients with Intellectual and Developmental Disabilities: Special Considerations for Diagnosis, Prevention, and Management

The purpose of this literature review is to further explore osteoporosis (OP) in adults with intellectual and developmental disabilities (IDD). OP is a disease of particular importance because it may present earlier and with greater severity in patients with IDD. OP leads to skeletal fragility and an increased risk of fracture and is especially hazardous in patients with IDD because fractures increase morbidity and mortality and exacerbate existing disability. Clinical trials to determine safe and effective treatments for OP in this unique population are lacking, and there is a need for educational literature on this topic. Abstract As medical care progresses, patients with intellectual and developmental disabilities are living longer and beginning to experience diseases that commonly afflict the aging population, such as osteoporosis. Osteoporosis and resultant fractures increase disability and threaten the independence of this vulnerable population. In addition, the diagnosis, prevention, and management of osteoporosis present unique challenges in these patients. Critical preventive targets include exercise modification, fall prevention, and monitoring for nutrient deficiencies. Commonly used in diagnosis and treatment monitoring, dual-energy x-ray absorptiometry (DXA) scan of the hip and spine may not be feasible, whereas peripheral DXA or computed tomography may be more accessible for patients with physical disabilities. Pharmacological treatment should be tailored to the individual patient, considering factors such as adherence and comorbidities. Finally, bone turnover markers are a noninvasive, cost-effective option for monitoring treatment response in patients who cannot undergo DXA.
Crystal structures of influenza nucleoprotein complexed with nucleic acid provide insights into the mechanism of RNA interaction

Abstract The nucleoprotein (NP) of influenza virus is the core component of the ribonucleoprotein (RNP) and performs multiple structural and functional roles. Structures of the influenza A, B and D NP molecules have been solved previously, but structural information on how NP interacts with RNA remains elusive. Here we present the crystal structure of an obligate monomer of H5N1 NP in complex with RNA nucleotides to 2.3 Å, and a C-terminal truncation of this mutant, also in complex with RNA nucleotides, to 3 Å. In both structures, three nucleotides were identified near two positive grooves of NP suggested to be important for RNA binding. Structural evidence supports that conformational changes of flexible loops and the C-terminal tail both play important roles in the binding of RNA. Based on the structure, we propose a mechanism by which NP captures RNA by flexible loops and transfers it onto the positive binding grooves. Binding of RNA by NP is a crucial step for template re-encapsidation during transcription and replication and cRNP formation. Our structures thus provide insights into the molecular virology of the influenza virus.
A coordinated non-orthogonal multiple access strategy for integrated terrestrial-satellite networks

In this paper, we investigate the outage probability and ergodic sum capacity of the downlink of the integrated satellite-terrestrial networks (ISTN) with a cooperative non-orthogonal multiple access (CNOMA) scheme, in which a user with better channel condition acts as a relay node and forwards information to the other users. In this paper, a pilot-based channel estimation method is considered which can verify the performance of this scheme with the imperfect channel state information. In this model, all these users are equipped with multi-antennas, and all of them are both in the coverage of a same beam of the satellite. Specifically, the exact analytical expression for the outage probability and ergodic sum capacity of the system is derived. The result shows that this coordinated non-orthogonal multiple access (CNOMA) scheme performs better than that of OMA (TDMA) in this model. Finally, the future research directions are given to further enhance the system capacity.
The new (Version 9) American Joint Committee on Cancer tumor, node, metastasis staging for cervical cancer

The American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging for all cancer sites has been periodically updated as a published manual for many years. The last update, the eighth edition AJCC Cancer Staging Manual went into use on January 1, 2018. The AJCC has since restructured and updated its processes, and all AJCC staging‐related data are now housed on its new application programming interface. Consequently, the next AJCC TNM staging update, AJCC version 9 TNM staging, will be published electronically and will be released chapter by chapter. The first chapter of version 9 AJCC TNM staging is the updated cervical cancer staging, which is now published. This article highlights the changes to the AJCC TNM cervical cancer staging; these changes align with the International Federation of Gynecology and Obstetrics staging. The most important of the changes are: 1) the incorporation of imaging and surgical findings, 2) the elimination of lateral spread from T1a, 3) the addition of a subcategory to T1b (T1b3), and 4) histopathology is updated to reflect human papillomavirus‐associated and human papillomavirus‐independent carcinomas.