Miracle-dz/UniFAR-FTUs huggingface dataset:
Reducing stress concentration on the cup rim of hip implants under edge loading

High stress concentration under edge loading on the cup rim contact due to micro‐separation causes accelerated striping wear, fracture, and fatigue in hip implant components. While continuous effort is devoted into improving bearing design and surgical procedure to tackle the problem, the concern still has remained forcing biomedical engineers to seek for new and alternative solutions. The current paper aims to investigate the effect of a new geometry “spline” introduced at the cup's rim corner to minimise stress concentration under edge loading. Three‐dimensional finite element modelling of a metal‐on‐metal hip implant is developed, where contact pressure, von Mises stress, and strain are predicted for three spline geometries, ie, equivalent characteristic arc radius (R = 0.5, 1.0, and 1.5 mm) at four micro‐separations (of 1.0, 1.5, 2.0, and 2.5 mm) simulating edge loading on the rim contact via the application of a constant vertical load of 3 kN. The efficacy of the spline is compared with that of circular arc and sharp corner (ie, no arc) geometries. Overall, the spline outperforms both sharp corner and circular arc in reducing contact pressure, stress, and strain. The benefit of the spline over the circular arc is quite promising at larger micro‐separation but fairly marginal at smaller arc radius and micro‐separation. The findings indicate that, as an alternative to the circular fillet, the spline can be considered a potential geometry to be incorporated at the rim corner of the cup.
Are the effects of internal focus instructions different from external focus instructions given during balance training in stroke patients? A double-blind randomized controlled trial

Objective: This study aimed to assess if external focus instructions result in greater improvements in motor skill and automaticity compared to internal focus instructions in stroke patients. Design: Double-blind randomized controlled trial. Setting: Inpatient stroke rehabilitation unit. Subjects: A total of 63 stroke patients (Meanage = 59.6 ± 10.7 years; Meandays since stroke = 28.5 ± 16.6; MedianFunctional Ambulation Categories = 4). Interventions: Patients were randomly assigned to an internal (N = 31) or external (N = 32) focus instruction group. Both groups practiced a balance board stabilization task, three times per week, for three weeks. Balance performance was assessed at baseline, and after one and three weeks of practice. Main measures: Primary outcome was the threshold stiffness (Nm/rad) at which patients could stay balanced. Secondary outcomes were patients’ sway (root-mean-square error in degrees) at the baseline threshold stiffness under single- and dual-task conditions, and their performance on the Timed Up and Go Test and Utrecht Scale for Evaluation of Rehabilitation. Results: Both groups achieved similar improvements in threshold stiffness (∆= 27.1 ± 21.1 Nm/rad), and single- (∆= 1.8 ± 2.3° root-mean-square error) and dual-task sway (∆= 1.7 ± 2.1° root-mean-square error) after three weeks of practice. No differences were found in improvements in clinical tests of balance and mobility. Patients with comparatively good balance and sensory function, and low attention capacity showed greatest improvements with external focus instructions. Conclusion: External focus instructions did not result in greater improvement in balance skill in stroke patients compared to internal focus instructions. Results suggest that tailoring instructions to the individual stroke patient may result in optimal improvements in motor skill.
SpoVID functions as a non‐competitive hub that connects the modules for assembly of the inner and outer spore coat layers in Bacillus subtilis

During sporulation in Bacillus subtilis, a group of mother cell‐specific proteins guides the assembly of the coat, a multiprotein structure that protects the spore and influences many of its environmental interactions. SafA and CotE behave as party hubs, governing assembly of the inner and outer coat layers. Targeting of coat proteins to the developing spore is followed by encasement. Encasement by SafA and CotE requires E, a region of 11 amino acids in the encasement protein SpoVID, with which CotE interacts directly. Here, we identified two single alanine substitutions in E that prevent binding of SafA, but not of CotE, to SpoVID, and block encasement. The substitutions result in the accumulation of SafA, CotE and their dependent proteins at the mother cell proximal spore pole, phenocopying a spoVID null mutant and suggesting that mislocalized SafA acts as an attractor for the rest of the coat. The requirement for E in SafA binding is bypassed by a peptide with the sequence of E provided in trans. We suggest that E allows binding of SafA to a second region in SpoVID, enabling CotE to interact with E and SpoVID to function as a non‐competitive hub during spore encasement.
Endolysosomal degradation of Tau and its role in glucocorticoid-driven hippocampal malfunction

Emerging studies implicate Tau as an essential mediator of neuronal atrophy and cognitive impairment in Alzheimer’s disease (AD), yet the factors that precipitate Tau dysfunction in AD are poorly understood. Chronic environmental stress and elevated glucocorticoids (GC), the major stress hormones, are associated with increased risk of AD, and have been shown to trigger intracellular Tau accumulation and downstream Tau-dependent neuronal dysfunction. However, the mechanisms through which stress and GC disrupt Tau clearance and degradation in neurons remain unclear. Here, we demonstrate that Tau undergoes degradation via endolysosomal sorting in a pathway requiring the small GTPase Rab35 and the endosomal sorting complex required for transport (ESCRT) machinery. Furthermore, we find that GC impair Tau degradation by decreasing Rab35 levels, and that AAV-mediated expression of Rab35 in the hippocampus rescues GC-induced Tau accumulation and related neurostructural deficits. These studies indicate that the Rab35/ESCRT pathway is essential for Tau clearance and part of the mechanism through which GC precipitate brain pathology.
Changes in left atrial size and function early after cardiac resynchronization therapy as assessed by conventional two-dimensional echocardiography.

AIMS Cardiac resynchronization therapy (CRT) was shown to improve left atrial (LA) size and function within months after the procedure. We aimed to assess the impact of CRT on left atrial (LA) size and function within days after the procedure. Materials and methods: Twenty-eight consecutive patients with CRT were evaluated before the procedure and within 3 days afterwards, and 25 of them were also examined at three months. Echocardiography was performed to assess LA size and function: LA volumes indexed to body surface (LAVIs) were measured at different moments during the cardiac cycle: ventricular end-systole - maximum LAVI (LAVImax), before atrial systole (LAVIpreA), and at ventricular end-diastole - minimum LAVI (LAVImin). These measurements were further used to calculate LA function parameters: LA total emptying fraction, activeemptying fraction and passive emptying fraction. RESULTS LAVImax decreased within days after the procedure - 45.5 mL/ m2 (38.2-56.7) vs. 42.9 mL/m2 (32.1- 56.2), p <0.05, as did LAVImin - 27.1 mL/m2 (22.9-41.9) vs. 25.9 mL/m2 (17.8-38.1), p <0.05, and LAVIpreA - 40.0 mL/m2 (31.3-53.0) vs. 35.5 mL/m2 (25.8-49.1), without significant changes in functional parameters. All LAVIs were correlated to the diastolic filling time/RR interval ratio after CRT, but not before. CONCLUSIONS LAVIs may be reduced within days after the implant procedure in responders to CRT, while atrial functional parameters remain unchanged. Correlations beween LAVIs and the diastolic filling time/RR interval ratio after CRT suggest that early optimization of atrio-ventricular and ventriculo-ventricular delays may have a positive and immediate impact on LA size.
Myth and fact in the origins of cellular life on Earth

Research into the origins of the first protocell is of a multidisciplinary nature. It draws evidence from what we know about the Earth’s early atmosphere and environment, and about the most ancient features of the cell’s structure and composition. Such data provides the input for the hypothesis generation and experimental reconstruction necessary to mimic steps in the formation of the first protocell. While research into the origins of the first protocell is condemned to focus upon laboratory experiments, it should be guided by a detailed study of real evidence pertaining to the environment on Earth 4 billion years ago. In this review, we take stock of the research that has been performed to date across the main disciplines of earth sciences, biochemistry, and molecular biology. We seek to identify the progress made in laying down a sequence for the events that led up to the first protocell. We also assess the strengths and weaknesses of the experimental designs and suggest some future approaches. While the field has made many important advances, from the original Stanley Miller experiment establishing ‘life from chemistry’ products such as amino acids, through to Deamer’s findings on fatty acid membranes and Szostack’s work on lipids, there is still a long and challenging journey ahead to understand how cellular life began. The experiments required to make more rapid progress in the field will likely be more elaborate, costly, and time consuming.
“Hurdles on the path to 90-90-90 and beyond”: Qualitative analysis of barriers to engagement in HIV care among individuals in rural East Africa in the context of test-and-treat

Background Despite substantial progress, gaps in the HIV care cascade remain large: globally, while about 36.7 million people were living with HIV in 2015, 11.9 million of these individuals did not know their HIV status, 12.7 million were in need of antiretroviral therapy (ART) and 13.0 million were not virally suppressed. We sought to deepen understanding of the barriers to care engagement at three critical steps of the care cascade proposed to make greatest impact for attaining the UNAIDS 90-90-90 targets aimed at shutting down the HIV epidemic. Methods Analyses were conducted among HIV-infected adults in rural East Africa. Qualitative data were collected using in-depth interviews among 63 individuals participating in an ongoing test-and treat trial (NCT01864683) in its baseline year (July 2013-June 2014). Audio recordings were transcribed, translated into English, and coded using Atlas.ti software. Data were analyzed using a thematic framework for explaining barriers to care engagement that drew upon both theory and prior empirical research in similar settings. Results Multiple barriers to engagement in care were observed. HIV-related stigma across dimensions of anticipated, internalized and enacted stigma manifested in denial and fears of disclosure, and influenced lapses in care engagement across multiple steps in the cascade. Poverty (lack of food and transport), lack of social support, work interference, prior negative experiences with health services, drug side effects, and treatment fatigue also negatively affected ART adherence and viral suppression. Gender differences were observed, with work interference and denial disproportionately affecting men compared to women. Conclusion Multiple barriers to HIV care engagement still pervade rural sub-Saharan settings threatening the realization of the UNAIDS 90-90-90 targets. To control the epidemic, efforts need to be accelerated to combat stigma. Patient economic empowerment, innovative drug formulations, as well as more patient-responsive health systems, may help overcome barriers to engagement in care.
MicroRNA-495 Ameliorates Cardiac Microvascular Endothelial Cell Injury and Inflammatory Reaction by Suppressing the NLRP3 Inflammasome Signaling Pathway

Background/Aims: In recent years, microRNA-495 (miR-495) has been reported to be a tumor-suppressor miR that is down-modulated in cancers. However, its potential mechanism remains unknown. Therefore, this study aimed to demonstrate the role of miR-495 in cardiac microvascular endothelial cell (CMEC) injury and inflammatory reaction by mediating the pyrin domain-containing 3 (NLRP3) inflammasome signaling pathway. Methods: Overall, 40 mice were assigned into myocardial ischemia/reperfusion injury (MIR) and sham groups. After model establishment, the levels of troponin T (TnT), troponin I (TnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase isoenzyme MB (CK-MB), myoglobin (MYO), tumor necrosis factor-alpha (TNF-α), and interleukin 1beta (IL-1β) were detected by Enzyme-Linked Immunosorbent Assay (ELISA). Apoptosis was evaluated using Terminal deoxy (d)-UTP nick end labeling (TUNEL) staining, the level of NLRP3 protein was determined by immunohistochemical assay, and miR-495 was detected by in situ hybridization (ISH). The infarct size was determined using 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The expression of miR-495 and the mRNA and protein levels of NLRP3, TNF-α, IL-1β, IL-18 and caspase-1 were evaluated by RT-qPCR and western blot analysis. After transfection, the cells were treated with a miR-495 mimic, a miR-495 inhibitor, or siNLRP3. Cell proliferation was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and cell cycle and apoptosis by flow cytometry. Results: Mice with myocardial I/R injury had elevated levels of TnT, TnI, NT-proBNP, CK-MB, MYO, TNF-α and IL-1β; enhanced cell apoptosis; increased expression of NLRP3, TNF-α, IL-1β, IL-18 and caspase-1; and decreased miR-495 expression. MiR-495 was confirmed to target NLRP3. Moreover, miR-495 reduced the mRNA and protein levels of NLRP3, TNF-α, IL-1β, IL-18 and caspase-1, inhibited cell apoptosis and decreased cells at the G0/G1 phase while improving cell proliferation and increasing cells at the S phase. However, the effects of NLRP4 were proved to be reciprocal. Conclusion: In conclusion, the current study indicated that miR-495 improved CMEC injury and inflammation by suppressing the NLRP3 inflammasome signaling pathway.
The impact of geographic access on institutional delivery care use in low and middle-income countries: Systematic review and meta-analysis

Background Geographic access to obstetric care facilities has a significant influence on women’s uptake of institutional delivery care. However, this effect was not consistent across studies. Some studies reported that geographic access to obstetric care facilities had no influence on the use of facility delivery. Therefore, this systematic review and meta-analysis synthesized and pooled the influence of geographic access on institutional delivery service uptake in low and middle-income countries. Methods Multiple combinations of search terms were used to search articles from six databases and a hand search of reference lists performed. We included observational studies conducted in low and middle-income countries which reported the influence of geographic access on delivery care use. The pooled effects of geographic access on institutional delivery care use were calculated using a random-effects model with a 95% confidence interval. Findings In this study a total of 31 studies were included. Among these studies, 15 met criteria for inclusion in the meta-analyses, while the remaining 16 were summarized using qualitative synthesis. Studies included in the analysis where women had to walk 60 minutes or less to access a health facility delivery were significantly heterogeneous. Having access to obstetric care facilities within five kilometres was significantly associated with institutional deliveries (pooled OR = 2.27; 95% CI = 1.82, 2.82). Similarly, a travelling time of 60 minutes or less was significantly associated with higher odds of health facility delivery (pooled OR = 3.30; 95% CI = 1.97, 5.53). Every one-hour and one-kilometre increase in travel time and distance, respectively, was negatively associated with institutional delivery care use. Interpretation Geographic access measured in either physical distance and/or travel time was significantly associated with women’s use of facility delivery. The greater the distance and/or travel time to obstetric care facilities, the greater the barrier and the lesser the service uptake.
Investigating the relationships among neighborhood factors and asthma control in African American children: A study protocol

Over 2 million children in the US have uncontrolled asthma. African American children are disproportionately affected with a risk of dying from asthma that is 7.6 times higher than non-Hispanic White children. Racial disparities in childhood asthma are partially attributed to differential exposures to poverty; unsafe and stressful neighborhoods; and unhealthy physical environments. This paper describes the protocol for an ongoing National Institutes of Health/National Institute of Nursing Research-funded descriptive, cross-sectional study to investigate two neighborhood factors that may influence children's asthma. Building on an existing dataset, this study examines associations among neighborhood greenspace, neighborhood safety, and level of asthma control while controlling for indoor asthma triggers in an urban sample of predominantly low-income, African American children with persistent asthma. Two new variables are added to the dataset: availability of neighborhood greenspace and neighborhood violent crime rate. Greenspace is being accessed using geographic information systems and measured using the normalized difference vegetation index. Neighborhood violent crime rate is calculated using geocoded, point locations for crimes downloaded from the city police department. It is hypothesized that parents living in unsafe neighborhoods are likely to keep their children indoors, thereby increasing their children's exposure to indoor asthma triggers and limiting the potential benefits of neighborhood greenspace. The biggest challenges thus far are related to limited variability in greenspace and violent crime rates. Progress to date and strategies to address these challenges are discussed. Results have the potential to inform interventions to improve asthmatic children's health and influence public health policy.
Delivery of a TNF‐α–derived peptide by nanoparticles enhances its antitumor activity by inducing cell‐cycle arrest and caspase‐dependent apoptosis

Prostate cancer is the second‐most common malignancy of the male genitourinary system. TNF‐α has attracted intense attention as a potential therapeutic agent against various cancers. However, its therapeutic application is restricted by short half life and severe toxic side‐effects. In this study, we constructed a stable nanodrug called TNF‐α–derived polypeptide (P16)‐conjugated, chitosan (CTS)‐modified selenium nanoparticle (SC; SCP), which is composed of SC as a slow‐release carrier conjugated to P16. SCP had significant inhibitory effects on multiple types of tumor cells, especially DU145 prostate cancer cells, but not on RWPE‐1 normal human prostate epithelial cells. SCP could induce G0/G1 cell‐cycle arrest and apoptosis in DU145 cells more effectively than could P16 and TNF‐α. In DU145 xenograft tumor models, SCP exerted much stronger antitumor effects than P16 or estramustine (the clinical drug for prostate cancer) but caused fewer toxic side‐effects. In addition, SCP significantly inhibited proliferation and accelerated apoptosis in DU145 xenograft tumors. Further mechanistic studies revealed that SCP exerted antitumor effects via activation of the p38 MAPK/JNK pathway, thus inducing G0/G1 cell‐cycle arrest and caspase‐dependent apoptosis. These findings suggest that SCP may represent a potential long‐lasting therapeutic agent for human prostate cancer with fewer side effects. —Yan, Q. , Chen, X. , Gong H. , Qiu, P., Xiao, X. , Dang S. , Hong A. , Ma, Y. Delivery of a TNF‐α–derived peptide by nanoparticles enhances its antitumor activity by inducing cell‐cycle arrest and caspase‐dependent apoptosis. FASEB J. 32, 6948–6964 (2018). www.fasebj. org
Resistance training does not induce uniform adaptations to quadriceps

Resistance training may differentially affect morphological adaptations along the length of uni-articular and bi-articular muscles. The purpose of this study was to compare changes in muscle morphology along the length of the rectus femoris (RF) and vastus lateralis (VL) in response to resistance training. Following a 2-wk preparatory phase, 15 resistance-trained men (24.0 ± 3.0 y, 90.0 ± 13.8 kg, 174.9 ± 20.7 cm) completed pre-training (PRE) assessments of muscle thickness (MT), pennation angle (PA), cross-sectional area (CSA), and echo-intensity in the RF and VL at 30, 50, and 70% of each muscle’s length; fascicle length (FL) was estimated from respective measurements of MT and PA within each muscle and region. Participants then began a high intensity, low volume (4 × 3 − 5 repetitions, 3min rest) lower-body resistance training program, and repeated all PRE-assessments after 8 weeks (2 d · wk−1) of training (POST). Although three-way (muscle [RF, VL] × region [30, 50, 70%] × time [PRE, POST]) repeated measures analysis of variance did not reveal significant interactions for any assessment of morphology, significant simple (muscle × time) effects were observed for CSA (p = 0.002) and FL (p = 0.016). Specifically, average CSA changes favored the VL (2.96 ± 0.69 cm2, pp < 0.001) over the RF (0.59 ± 0.20 cm2, p = 0.011), while significant decreases in average FL were noted for the RF (–1.03 ± 0.30 cm, p = 0.004) but not the VL (–0.05 ± 0.36 cm, p = 0.901). No other significant differences were observed. The findings of this study demonstrate the occurrence of non-homogenous adaptations in RF and VL muscle size and architecture following 8 weeks of high-intensity resistance training in resistance-trained men. However, training does not appear to influence region-specific adaptations in either muscle.
Briquettes production as teaching aids physics for improving science process skills

The aim of this research is production briquettes as teaching aids in order to improve students’ science process skill. Research design used in this study was using experimental methods. One of the learning methods that can be used to equip student’s science process skill is the experimental method. In this study, students utilize agricultural waste and plantations around the school. Then they make the briquettes from the waste. This research used waste rice husk waste, durian leather and coconut fiber. After that, the results of briquettes will be assessed as the feasibility of teaching aids. The results of students’ affective and psychomotor ratings show excellent results. Among them are: classical affective average score for group 1 is 82.80; group 2 is 87.20; and group 3 is 85.20. While the classical average psychomotor score for group 1 is 82.80; group 2 is 86.20; and group 3 is 84.20.