Miracle-dz/UniFAR-FTUs huggingface dataset:
Diet-Derived Circulating Antioxidants and Risk of Stroke: A Mendelian Randomization Study

Background Oxidative stress is crucial in stroke pathogenesis. Many cohort-based studies suggested that the intake of exogenous antioxidants originated from food may prevent stroke. However, the corresponding randomized controlled trials did not show diet-derived antioxidants have a protective effect on stroke. Objectives To examine the association of genetically proxied diet-derived antioxidants with stroke risk using Mendelian randomization. Methods We performed a two-sample Mendelian randomization (MR) analysis to evaluate the causal effect of diet-derived antioxidants on stroke risk. For exposure data, we extracted genetic variants as instrumental variables (IVs) that are strongly associated with frequently used diet-derived antioxidants, including vitamin C, vitamin E (α-tocopherol, γ-tocopherol), carotene, retinol, zinc, and selenium, from a large-scale genome-wide association study (GWAS). We obtained IVs' corresponding effect estimates on the risk of total stroke and ischemic stroke from a GWAS meta-analysis with 40,585 cases and 406,111 controls. Finally, we applied five types of Mendelian randomization analysis to obtain preliminary MR results and performed four three kinds of sensitivity analysis to verify them. Results According to the primary MR estimations and further sensitivity analyses, we established two robust associations after Bonferroni correction: genetically proxied circulating γ-tocopherol was causally associated with total stroke [odds ratio (OR) = 0.68, 95% confidence interval (CI) (0.52-0.88), p = 3.78E − 03] and ischemic stroke [OR = 0.66, 95% CI (0.51-0.86), p = 2.34E − 03]. There was no evidence to support the causal effect of other diet-derived antioxidants on the risk of total stroke and ischemic stroke. Conclusion Our study revealed a protective impact of genetic susceptibility to high circulating γ-tocopherol levels on stroke risk, providing new information on the potential therapeutic targets for primary stroke prevention.
Policy windows for drug consumption rooms in Finland

Background: Use of drug consumption rooms is a novel harm reduction approach to reach marginalised and isolated people who used drugs, under the high risk of overdose deaths and infectious diseases. The aim of this article was to evaluate the policy opportunities and barriers of the Helsinki City initiative for establishing the first drug consumption room (DCR) in Finland from the multiple streams framework. Method: A qualitative interview research method is used to evaluate the perspectives of stakeholders. By including 23 participants, we analysed the political, social and policy level advantages and disadvantages of the current initiative. Findings: Our results show that the cost of DCRs, the COVID-19 burdens on public resources, the requirement of legislative change, public unawareness, potential policy failure of DCRs, and its impacts on electoral votes constitute the main policy barriers. On the other hand, an increase in drug-related deaths, economic benefits of DCR for society, its effects on street safety and public order, being a local initiative, prospectus change in national drug strategy plans and motivation to catch up with EU standards were underlined as policy opportunities. Four issues, leadership, moral perspective, social change and generational differences, act as mediating factors, which are fluctuated according to public opinions and political environment. Conclusion: By applying the multiple streams framework, our results show that experts’ DCR problematisation is still beyond the public and political interest, which needs additional effort around problem identification and prioritisation. Besides public unawareness, the COVID-19 situation seems to be postponing policy progress since the primary attention and available funds have already been dedicated to public health. Already having a local initiative and an upcoming drug strategy plan might be good formal leverage, but unexpected events might also trigger discussions.
Transcriptomic and Metabolomic Analyses Reveal Inhibition of Hepatic Adipogenesis and Fat Catabolism in Yak for Adaptation to Forage Shortage During Cold Season

Animals have adapted behavioral and physiological strategies to conserve energy during periods of adverse conditions. Hepatic glucose is one such adaptation used by grazing animals. While large vertebrates have been shown to have feed utilization and deposition of nutrients—fluctuations in metabolic rate—little is known about the regulating mechanism that controls hepatic metabolism in yaks under grazing conditions in the cold season. Hence, the objective of this research was to integrate transcriptomic and metabolomic data to better understand how the hepatic responds to chronic nutrient stress. Our analyses indicated that the blood parameters related to energy metabolism (glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein lipase, insulin, and insulin-like growth factor 1) were significantly (p < 0.05) lower in the cold season. The RNA-Seq results showed that malnutrition inhibited lipid synthesis (particularly fatty acid, cholesterol, and steroid synthesis), fatty acid oxidation, and lipid catabolism and promoted gluconeogenesis by inhibiting the peroxisome proliferator-activated receptor (PPAR) and PI3K-Akt signaling pathways. For metabolite profiles, 359 metabolites were significantly altered in two groups. Interestingly, the cold season group remarkably decreased glutathione and phosphatidylcholine (18:2 (2E, 4E)/0:0). Moreover, integrative analysis of the transcriptome and metabolome demonstrated that glycolysis or gluconeogenesis, PPAR signaling pathway, fatty acid biosynthesis, steroid biosynthesis, and glutathione metabolism play an important role in the potential relationship between differential expression genes and metabolites. The reduced lipid synthesis, fatty acid oxidation, and fat catabolism facilitated gluconeogenesis by inhibiting the PPAR and PI3K-Akt signaling pathways to maintain the energy homeostasis of the whole body in the yak, thereby coping with the shortage of forages and adapting to the extreme environment of the Qinghai-Tibetan Plateau (QTP).
Endogenous pH 6.0 β-Galactosidase Activity Is Linked to Neuronal Differentiation in the Olfactory Epithelium

The histochemical detection of β-galactosidase enzymatic activity at pH 6.0 (β-gal-pH6) is a widely used biomarker of cellular senescence in aging tissues. This histochemical assay also detects the presence of programmed cell senescence during specific time windows in degenerating structures of vertebrate embryos. However, it has recently been shown that this enzymatic activity is also enhanced in subpopulations of differentiating neurons in the developing central nervous system in vertebrates. The present study addressed the histochemical detection of β-gal-pH6 enzymatic activity in the developing postnatal olfactory epithelium in the mouse. This activity was detected in the intermediate layer of the olfactory epithelium. As development progressed, the band of β-gal-pH6 labeling in this layer increased in width. Immunohistochemistry and lectin histochemistry showed the β-gal-pH6 staining to be strongly correlated with the immunolabeling of the olfactory marker protein (OMP) that identifies mature olfactory sensory neurons. The cell somata of a subpopulation of differentiated olfactory neurons that were recognized with the Dolichos biflorus agglutinin (DBA) were always located inside this band of β-gal-pH6 staining. However, the β-gal-pH6 histochemical signal was always absent from the apical region where the cytokeratin-8 positive supporting cells were located. Furthermore, no β-gal-pH6 staining was found in the basal region of the olfactory epithelium where PCNA/pHisH3 immunoreactive proliferating progenitor cells, GAP43 positive immature neurons, and cytokeratin-5 positive horizontal basal cells were located. Therefore, β-gal-pH6 seems to be linked to neuronal differentiation and cannot be regarded as a biomarker of cellular senescence during olfactory epithelium development in mice.
Efficacy and Safety of Immunotherapy for Cervical Cancer—A Systematic Review of Clinical Trials

Simple Summary Cervical cancer is the 4th leading cause of cancer deaths in women worldwide. Surgery, chemotherapy, radiotherapy and chemoradiation therapy are routinely used in the treatment of cervical cancer, while immunotherapy remains a novelty. The aim of our systematic review was to provide an extensive overview of the efficacy and safety of immunotherapy in cervical cancer patients. A total of 50 clinical trials assessed immune checkpoint inhibitors, therapeutic vaccines and adaptive cell transfer therapy. Overall, immunotherapy showed an acceptable safety profile. While the level of evidence on efficacy is still low, promising results, including few complete remissions in heavily pretreated women with metastatic disease, have been observed. Furthermore, a recent phase III trial assessing pembrolizumab in combination with chemotherapy (±bevacizumab) demonstrated a prolonged overall survival and has now led to a new standard of care for first-line systemic treatment in persistent, metastatic or recurrent cervical cancer patients. Abstract Purpose: To systematically review the current body of evidence on the efficacy and safety of immunotherapy for cervical cancer (CC). Material and Methods: Medline, the Cochrane Central Register of Controlled Trials and Web of Science were searched for prospective trials assessing immunotherapy in CC patients in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Full-text articles in English and German reporting outcomes of survival, response rates or safety were eligible. Results: Of 4655 screened studies, 51 were included (immune checkpoint inhibitors (ICI) n=20; therapeutic vaccines n = 25; adoptive cell transfer therapy n=9). Of these, one qualified as a phase III randomized controlled trial and demonstrated increased overall survival following treatment with pembrolizumab, chemotherapy and bevacizumab. A minority of studies included a control group (n = 7) or more than 50 patients (n = 15). Overall, response rates were low to moderate. No response to ICIs was seen in PD-L1 negative patients. However, few remarkable results were achieved in heavily pretreated patients. There were no safety concerns in any of the included studies. Conclusion: Strong evidence on the efficacy of strategies to treat recurrent or metastatic cervical cancer is currently limited to pembrolizumab in combination with chemotherapy and bevacizumab, which substantiates an urgent need for large confirmatory trials on alternative immunotherapies. Overall, there is sound evidence on the safety of immunotherapy in CC.
Waspadai Dampak Penggunaan Gadget Terhadap Perkembangan Sosial Anak Usia Dini

Artikel ini bertujuan untuk mengetahui dampak penggunaan pada anak usia dini serta mengimplementasikan solusi dari dampak penggunaan gadget terhadap anak usia dini. Gadget adalah media yang di pakai sebagai alat komunikasi modern. Gadget semakin mempermudah kegiatan komunikasi manusia. Kini kegiatan komunikasi telah berkembang semakin lebih maju dengan munculnya gadget. Diantaranya smartphone seperti iphone, android, blackberry serta notebook. Dalam psikologi perkembangan anak usia dini dikatakan sebagai anak yang berumur 0-6 tahun. Gadget berdampak terhadap perkembangan sosial anak usia dini . Dampak penggunaan gadget terhadap perkembangan sosial anak usia dini terdapat dampak positif dan dampak negatif. Penggunaan gadget yang berlebihan akan membawa dampak buruk bagi perkembangan sosial dan emosional anak. Dampak buruk penggunaan gadget pada anak antara lain anak menjadi pribadi tertutup, gangguan tidur, suka menyendiri, perilaku kekerasan, pudarnya kreativitas, dan ancaman cyberbullying. Solusi terhadap permasalahan pemakaian gadget pada anak usia dini dengan cara membatasi pemakaian gadget, mengawasi anak dalam bermain gadget dengan figur orang tua yang berperan sangat penting serta memberi jadwal waktu yang tepat saat anak bermain gadget, agar gadget tidak dapat menghambat perkembangan sosial anak usia dini.
A survey of hysterectomies in young patients in Eastern Uttar Pradesh: are the wombs being removed unnecessarily?

Background: There are reports of unnecessary hysterectomies in young patients in some parts of Eastern Uttar Pradesh and adjoining regions. This study was conducted to know the indications of hysterectomies done at less than 35 years of age. Methods: This study was conducted in the outpatient Department of Gynaecology and Obstetrics, Sir Sundar Hospital, Institute of Medical Sciences, Banaras Hindu University Varanasi over a period of one year. Hysterectomised patients with age less than 35 years were included in the study. After getting an informed consent, a detailed history was taken, patient’s past medical record was reviewed and their socio-demographic profiles, indication for hysterectomy and any surgical complications were recorded. Statistical analysis of data was done using SPSS and results were recorded as mean and percentage. Results: One hundred patients were included in the study over a period of one year. Mean age of the study population was 28 years. The 32% patient were below 25 years of age, 44% were between 25 to 30 years of age whereas 24% were in the age group of 30 to 35 years. Unevaluated Vaginal discharge (28%) and pain in pelvic region (25%) were the main indication for hysterectomy. Menstrual abnormalities (13%), asymptomatic uterine fibroid (12%), small functional ovarian cyst (10%) and abnormal colposcopic images (12%) were other indications.Conclusions: There is a high prevalence of unnecessary hysterectomies in eastern part of Uttar Pradesh, India. Such practice must be discouraged and stopped. Public awareness, adherence to medical ethics and strict action against those involved in medical malpractice would be helpful in decreasing the number of unnecessary hysterectomies in the young women.
ROUGHNESS AND ROADWAY SAFETY

Roughness can play a significant role in roadway accidents and should be considered when evaluating pavement safety as well as when planning and designing safety improvements. Roadway roughness can cause problems with steering, braking, maneuvering, and response that can lead to loss of vehicle control and can result in an accident. In addition, rough pavements can sometimes shake or bounce a vehicle so severely that it will lose part or all of the load it is carrying, which then leads to lost-load accidents. This paper discusses the magnitude of the various problems associated with vehicle performance on rough roads and the types of accidents and safety problems that result. The various individual parameters that cause roughness are examined and their overall effect on safety are prioritized. Examples of corrective actions and their benefits are discussed. In the future additional consideration should be given to this problem and to using safety funds to make rehabilitations that decrease roughness and improve the ride quality and safety of a highway. (Author)
Augmented Magnetic Response and Spin-Transfer in Copper Corrole/Graphene Hybrids - A DFT Study

The search for hybrid materials with outstanding electronic performance is highly demanding Since copper corroles have emerged as versatile building blocks providing outstanding electronic, and reactivity properties, a new series of non-covalent hybrid materials were computationally investigated based on pristine graphene and A3-type copper corrole complexes. The corrole complexes contain strong electron-withdrawing fluorinated substituents at the meso positions. Our results show that the non-innocent character of corrole moiety modulates the structural, electronic, and magnetic properties of the hybrid systems. The graphene-corrole hybrids display outstanding stability via the interplay of dispersion and electrostatic driving forces while graphene act as an electron reservoir for more conductive cases. Furthermore, the hybrid structures display an intriguing magneto-chemical performance since a detailed analysis of magnetic properties evidence how structural and electronic changes contribute to the amplification of the magnetic response also for ferromagnetic and antiferromagnetic cases. This amplification is accompanied by the spin transfer which characterized by a directional spin polarization from the corrole through the graphene surface. Main results suggest that graphene-corrole hybrids are excellent candidates for technologic applications due to the ferromagnetic tendency, the augmented magnetic response, the tunability due to substituents, and the potential conductive properties. Finally, a statistical analysis of magnetic properties suggests correlations between spin transfer, augmented magnetic response, and the geometrical distortion of the copper ligand field, offering exciting hints about how to modulate the magnetic response in the studied hybrid systems.
Energy Poverty and Depression in Rural China: Evidence from the Quantile Regression Approach

Despite the growing awareness and interest in the impact of energy poverty on depression, studies in developing economies are relative limited, and there is a gap of knowledge of such impact among rural individuals in China. In this study, we investigate the impact of energy poverty on depression among rural Chinese individuals aged 16 and above, and our sample includes 13,784 individuals from 6103 households. With data from the 2018 China Family Panel Studies, we apply the instrumental variable (IV) quantile regression approach to address the potential endogeneity of energy poverty and allow for heterogeneous effects of energy poverty on depression across individuals with different levels of depression. Our estimates from the IV quantile regression suggest a strong positive impact of energy poverty on depression at the upper quantile of depression scores, but no impact at the middle and lower quantiles. The primary results are robust and consistent with alternative energy poverty measures, and we find that energy poverty does not affect depression of low-risk individuals (with low depression scores), but it does affect that of high-risk individuals. We also find individual socio-demographic factors of age, gender, household size, religious belief, education, marriage and employment status play roles in affecting depression. The findings of this study generate policy implications for energy poverty alleviation and mental health promotion.
Fundamental movement proficiency of Welsh primary school children and the influence of the relative age effect on skill performance – implications for teaching

ABSTRACT The primary aim of this study was to identify levels of fundamental movement skills (FMS) proficiency in primary school children. A secondary aim was to establish if these FMS proficiency levels differentiated between children born in different quartiles of the school year. The results demonstrated overall levels of FMS proficiency were low in both genders with significant differences in FMS proficiency established between genders on several of the skills. In addition, significant differences were shown with some FMS and quartiles of the school year in boys only. In summary, these findings suggest that there is a greater need for a clearer strategy or focus to promote and develop FMS proficiency within the primary school environment. It is also important, for PE teachers, and practitioners, to be aware of the effect of the RAE with FMS proficiency on development, assessment, and selection at this age.
Durability Assessment of ETICS: Comparative Evaluation of Different Insulating Materials

The External Thermal Insulation Composite System (ETICS) is a common cladding technology that is widely used thanks to its well-known advantages. Despite previous studies dealing with ETICS durability in real-building case studies or involving accelerated ageing tests in climatic chambers, little progress has been made in the knowledge of the long-term durability of the system. In order to realize optimized maintenance plans for this component, the durability of the whole system, and of the most-used insulating materials for the ETICS (i.e., cork, polyurethane, rock wool, glass wool, grey EPS, and fiberfill wood), has been investigated. Based on previous experiments on ageing cycles, different climatic chambers were used to accelerate performance decay by simulating natural outdoor exposure in order to assess different physical and thermal characteristics (thermal transmittance, decrement factor, time shift, water absorption, thermal resistance, and conductivity). Recorded trends show that materials with lower thermal conductivity exhibit lower performance decay, and vice versa. The durability of the ETICS with different insulating materials (as the only variable in the different samples) was evaluated in order to quantify service life and then correctly plan maintenance interventions. Life-cycle assessment must take into account service life and durability for each material of the system. A higher durability of insulating materials allows for the execution of less maintenance interventions, with the loss of less performance over time. This study shows the physical and thermal behavior of the ETICS during its service life, comparing the differences induced by the most-used insulating materials. As a result of accelerated ageing cycles, the analyzed ETICS reveals a low grade of decay and measured performances show little degradation; for thermal conductivity, differences between the measured and the declared conductivities by technical datasheet were observed.
Effectiveness of a Per-Meal Protein Prescription and Nutrition Education with versus without Diet Coaching on Dietary Protein Intake and Muscle Health in Middle-Aged Women

Sufficient dietary protein intake is vital to maintaining muscle health with aging. Yet protein intake among adults is often inadequate. This study’s main objective was to examine the impact of nutrition education (NE) and a per-meal protein prescription (PRx) with versus without diet coaching on protein intake. A secondary objective examined its effects on muscle health. Participants included 53 women, age 45–64 years. All participants received NE and PRx; those randomized to coached-group received 10-weeks of diet coaching. Assessments included: protein intake at baseline, weeks 4 and 12 and muscle health (muscle mass, grip strength, five-chair rise test, 4 mgait speed test). The Chi-square test examined percentages of participants meeting PRx between groups. Repeated measures analysis of variance assessed within group and intervention effects on protein intake and muscle health parameters. Protein intake (g/kg body weight) increased (p < 0.001): not-coached (n = 28) 0.8 ± 0.2 to 1.2 ± 0.3 and coached (n = 25) 1.0 ± 0.2 to 1.4 ± 0.3 with no significant difference between groups. A greater percentage of coached-group participants met (p = 0.04) breakfast (72%) and met (p < 0.001) three-meal (76%) PRx versus not-coached participants (25% and 53%, respectively). Participants in both groups exhibited significantly (p < 0.001) improved times for the five-chair rise test and 4 mgait speed test. Diet coaching in conjunction with a PRx and NE should be considered to assist individuals in improving protein intake through self-selection of protein-rich foods.