Miracle-dz/UniFAR-FTUs huggingface dataset:
Video directly observed therapy to improve adherence of human immunodeficiency virus infected adolescents to combination antiretroviral therapy: a proof-of-concept study

ABSTRACT Adherence to antiretroviral therapy (ART) is a major challenge for many youth living with HIV (YLWH). In this prospective proof-of-concept study, we assessed the feasibility and acceptability of conducting a study of video directly observed therapy (VDOT) as a method of improving medication adherence in YLWH who had a history of poor adherence to ART. The study had four phases; phase I – VDOT daily (4 months) using Facetime®; phase II – daily texting (2 months); phase III – weekly texting (3 months); phase IV – no intervention (3 months). Participants were seen in clinic on a monthly basis for assessment and laboratory evaluation. Five of eight eligible participants were enrolled. All achieved virologic suppression one month after enrollment. Three of five completed the study protocol and maintained virologic suppression through the 12-month period of study. Participant responses to the end-of-study questionnaire indicated satisfaction with the intervention and thought VDOT was helpful to them. Healthcare providers thought that the intervention was effective for some youth but was at times burdensome. This proof-of-concept study demonstrated that VDOT may be effective at improving medication adherence in previously poorly adherent YLWH and that larger studies of VDOT for such patients are both feasible and warranted.
Iron status of blood donors

Purpose of review This review examines recent research on the prevalence and importance of iron deficiency in blood donors, and on efforts to mitigate it. Recent findings Premenopausal females, teenagers, and high-frequency donors are at the highest risk for donation-induced iron deficiency, in both high-resource and low-resource settings. The physiology relating iron stores to hemoglobin levels and low hemoglobin deferral is well elucidated in blood donor populations, yet the clinical effects attributable to iron loss in the absence of anemia are challenging to identify. Expanded adoption of ferritin testing is improving donor management but may cause decreases in the blood supply from temporary donor loss. The potential for personalized donor management is emerging with development of computational models that predict individual interdonation intervals that aim to optimize blood collected from each donor while minimizing low hemoglobin deferrals. Summary Measures to reduce iron deficiency are available that can be deployed on a standardized or, increasingly, personalized basis. Blood centers, regulators, and donors should continue to evaluate different tactics for addressing this problem, to obtain a balanced approach that is optimal for maintaining adequate collections while safeguarding donor health.
Dietary Soybean (Glycine max (L.) Merr.) Improved the ZP2 Expression in Female Swiss Mice

Objective This study aimed to determine the effects of soybean (Glycine max) administration on ZP2 expression in female mice. Methods This research used Mus musculus, six-week-old female SWISS strain mice divided into three groups (group without soybean administration and groups with mixed feed with soybeans and pelleted 50:50 and 25:75). Soybean feed for mice was 360 grams per kilogram of mouse body weight for 2 weeks. The percentage of follicles was measured and analyzed using Hematoxylin-Eosin staining, and the expression of ZP2 was analyzed using immunohistochemistry. We assessed the data using one-way ANOVA and paired t-test using the SPSS 17. Results Some of the follicles in the ovaries do not develop until their final stage of follicle maturation. The administration of soybean before and after treatment in all groups was not significantly different, but the numbers of atretic follicles in groups 1 and 2 were significantly different. Soybean administration at a ratio of 50:50 has the effect of increasing the percentage of the ZP2 expression in tertiary follicles (p=0.001), whereas soybean administration at a ratio of 25:75 was not able to maintain or increase the formation of ZP2 in tertiary follicles (p=0.77). Conclusion Soybean administration with a ratio of 50:50 significantly increased the percentage of the ZP2 expression in tertiary follicles.
Effects of natural RNA modifications on the activity of SARS‐CoV‐2 RNA‐dependent RNA polymerase

RNA‐dependent RNA polymerase (RdRp) plays a key role in the replication of RNA viruses, including SARS‐CoV‐2. Processive RNA synthesis by RdRp is crucial for successful genome replication and expression, especially in the case of very long coronaviral genomes. Here, we analysed the activity of SARS‐CoV‐2 RdRp (the nsp12–nsp7–nsp8 complex) on synthetic primer–templates of various structures, including substrates with mismatched primers or template RNA modifications. It has been shown that RdRp cannot efficiently extend RNA primers containing mismatches and has no intrinsic RNA cleavage activity to remove the primer 3′‐end, thus necessitating the action of exoribonuclease for proofreading. Similar to DNA‐dependent RNA polymerases, RdRp can perform processive pyrophosphorolysis of the nascent RNA product but this reaction is also blocked in the presence of mismatches. Furthermore, we have demonstrated that several natural post‐transcriptional modifications in the RNA template, which do not prevent complementary interactions (N6‐methyladenosine, 5‐methylcytosine, inosine and pseudouridine), do not change RdRp processivity. At the same time, certain modifications of RNA bases and ribose residues strongly block RNA synthesis, either prior to nucleotide incorporation (3‐methyluridine and 1‐methylguanosine) or immediately after it (2'‐O‐methylation). The results demonstrate that the activity of SARS‐CoV‐2 RdRp can be strongly inhibited by common modifications of the RNA template suggesting a way to design novel antiviral compounds.
On the Primordial Helium Abundance and the DeltaY/DeltaO Ratio

We present a review on the determination of the primordial helium abundance, Yp, based on the study of hydrogen and helium recombination lines in extragalactic H II regions. We also discuss the observational determinations of the increase of helium to the increase of oxygen by mass Delta Y/Delta O, and compare them with predictions based on models of galactic chemical evolution.
KS0365, a novel activator of the transient receptor potential vanilloid 3 (TRPV3) channel, accelerates keratinocyte migration

Ca2+ signalling mediated by the thermosensitive, non‐selective, Ca2+‐permeable transient receptor potential channel TRPV3 is assumed to play a critical role in regulating several aspects of skin functions, such as keratinocyte proliferation, differentiation, skin barrier formation and wound healing. Studying the function of TRPV3 in skin homeostasis, however, is still constrained by a lack of potent and selective pharmacological modulators of TRPV3.
Diabetes Prevalence, Risk Factors, and Care in Asian American and Pacific Islanders of Texas: Data From the 2015–2019 Behavioral Risk Factors Surveillance System

Purpose: The purpose of this study was to investigate the health status and needs of the Asian American/Pacific Islander (AAPI) population with diabetes in Texas. Methods: This was a cross-sectional secondary analysis of data collected from the Behavioral Risk Factors Surveillance System in Texas from 2015 to 2019 for non-Hispanic White (NHW) and AAPI adults. Results: Although the overall crude diabetes prevalence was lower in AAPI adults, age-adjusted diabetes prevalence was higher than in NHWs. Significant risk factors associated with diabetes in the AAPI group included being male, marital status, lower education levels, lower income, being overweight/obese, and having a sedentary lifestyle. Engagement in self-management activities (checking blood glucose, checking feet, attending a diabetes management course) was lower in AAPIs than in NHWs. Conclusions: Given stiff barriers to adequate screening and self-management support in diabetes care among ethnic populations such as AAPIs, targeted efforts to improve diabetes screening and effective care are warranted. Because today’s AAPI populations are predominantly first-generation immigrant groups who suffer from language barriers, efforts should be made to develop health surveys in multiple languages for wider inclusion of understudied groups like AAPIs in diabetes-related research.
BRAF increases endothelial cell stiffness through reorganization of the actin cytoskeleton

The dynamics of the actin cytoskeleton and its connection to endothelial cell–cell junctions determine the barrier function of endothelial cells. The proper regulation of barrier opening/closing is necessary for the normal function of vessels, and its dysregulation can result in chronic and acute inflammation leading to edema formation. By using atomic force microscopy, we show here that thrombin‐induced permeability of human umbilical vein endothelial cells, associated with actin stress fiber formation, stiffens the cell center. The depletion of the MEK/ERK kinase BRAF reduces thrombin‐induced permeability prevents stress fiber formation and cell stiffening. The peripheral actin ring becomes stabilized by phosphorylated myosin light chain, while cofilin is excluded from the cell periphery. All these changes can be reverted by the inhibition of ROCK, but not of the MEK/ERK module. We propose that the balance between the binding of cofilin and myosin to F‐actin in the cell periphery, which is regulated by the activity of ROCK, determines the local dynamics of actin reorganization, ultimately driving or preventing stress fiber formation.
Sustained inhibition of NPY/AgRP neuronal activity by FGF1

In rodent models of type 2 diabetes (T2D), central administration of FGF1 normalizes elevated blood glucose levels in a manner that is sustained for weeks or months. Increased activity of NPY/AgRP neurons in the hypothalamic arcuate nucleus (ARC) is implicated in the pathogenesis of hyperglycemia in these animals, and the ARC is a key brain area for the antidiabetic action of FGF1. We therefore sought to determine whether FGF1 inhibits NPY/AgRP neurons and, if so, whether this inhibitory effect is sufficiently durable to offer a feasible explanation for sustained diabetes remission induced by central administration of FGF1. Here, we show that FGF1 inhibited ARC NPY/AgRP neuron activity, both after intracerebroventricular injection in vivo and when applied ex vivo in a slice preparation; we also showed that the underlying mechanism involved increased input from presynaptic GABAergic neurons. Following central administration, the inhibitory effect of FGF1 on NPY/AgRP neurons was also highly durable, lasting for at least 2 weeks. To our knowledge, no precedent for such a prolonged inhibitory effect exists. Future studies are warranted to determine whether NPY/AgRP neuron inhibition contributes to the sustained antidiabetic action elicited by intracerebroventricular FGF1 injection in rodent models of T2D.
Multistate-Constrained Multiobjective Differential Evolution Algorithm With Variable Neighborhood Strategy

Multiobjective differential evolution (DE) algorithm (MODE) has been widely used in multiobjective optimization problems. However, due to the complex feasible regions, the optimization efficiency of MODE may decrease when solving constrained multiobjective problems. It is challenging to promote the evolution of population with few feasible solutions. In this article, a multistate-constrained MODE with variable neighborhood strategy (MSCMODE-VNS) is proposed to enhance the optimization effectiveness with complex feasible regions. First, a variable neighborhood DE strategy, based on a specially designed convergence indicator, is designed to accelerate the generation of feasible solutions. Second, a multistate population updating strategy with a comprehensive solution evaluation mechanism is devised to update the population of the next generation to improve the performance of solutions. Third, the convergence analysis, based on the probability theory, is derived to verify the effectiveness of the proposed MSCMODE-VNS algorithm. Finally, experimental results indicate that MSCMODE-VNS can achieve a satisfactory performance on three benchmark test suites and two real-world-constrained multiobjective problems.
Actin network architecture can ensure robust centering or sensitive decentering of the centrosome

The orientation of cell polarity depends on the position of the centrosome, the main microtubule‐organizing center (MTOC). Microtubules (MTs) transmit pushing forces to the MTOC as they grow against the cell periphery. How the actin network regulates these forces remains unclear. Here, in a cell‐free assay, we used purified proteins to reconstitute the interaction of a microtubule aster with actin networks of various architectures in cell‐sized microwells. In the absence of actin filaments, MTOC positioning was highly sensitive to variations in microtubule length. The presence of a bulk actin network limited microtubule displacement, and MTOCs were held in place. In contrast, the assembly of a branched actin network along the well edges centered the MTOCs by maintaining an isotropic balance of pushing forces. An anisotropic peripheral actin network caused the MTOC to decenter by focusing the pushing forces. Overall, our results show that actin networks can limit the sensitivity of MTOC positioning to microtubule length and enforce robust MTOC centering or decentering depending on the isotropy of its architecture.
P2Y12-inhibitor monotherapy after coronary stenting: are all P2Y12-inhibitors equal?

ABSTRACT Introduction P2Y12-inhibitor monotherapy following 1–3 months of dual antiplatelet therapy (DAPT) reduces (major) bleeding without an apparent increase in ischemic events and has therefore emerged as an alternative to 6–12 months of DAPT following percutaneous coronary intervention (PCI). However, there are important differences between the available P2Y12-inhibitors (clopidogrel, prasugrel, and ticagrelor) as agents of choice for P2Y12-inhibitor monotherapy. Areas covered This review critically appraises the evidence for P2Y12-inhibitor monotherapy after PCI using either clopidogrel, prasugrel, or ticagrelor. Furthermore, we discuss ongoing trials and future directions for research. Expert opinion P2Y12-inhibitor monotherapy following 1–3 months of DAPT is an alternative to 6–12 months of DAPT following PCI. Ticagrelor may be considered the current preferred option due to its reliable effect on platelet reactivity and its predominant use in clinical trials. Prasugrel could serve as a useful substitute for those not tolerating ticagrelor, but more research into prasugrel monotherapy is warranted. Alternatively, clopidogrel can be used, although there are concerns of high platelet reactivity, especially when genotyping and/or platelet function testing are not used. Future research will need to address the minimal duration of DAPT before switching to P2Y12-inhibitor monotherapy and what the optimal antithrombotic therapy beyond 12 months is.
Prevalence and risk factors of chronic low back pain in university athletes: a cross-sectional study

ABSTRACT Aim This study aimed to establish the prevalence of chronic low back pain (CLBP) in university-level athletes and to examine the influence of age, sex, body mass index (BMI), sports discipline, sleep, anxiety, and depression on CLBP. The secondary purpose was to check the association of certain variables in athletes having CLBP with the sports discipline and chronicity of LBP. Methods A total of 340 players (100% response rate) from different sports, aged 18–30 years with at least 1 year of participation in sports at the university level were screened for the present study. The subjects completed a detailed, semi-structured questionnaire that gathered data regarding their demographic variables, personal and pain-related factors. The study was registered on the clinical trials registry, India (CTRI/2021/09/036675). Results The results revealed the sport-wise point prevalence as follows: cricket (18.5%), basketball (15.6%), volleyball (20.0%), football (11.4%), badminton (7.7%) and tennis (7.7%). A higher number of years at university-level participation (>4 years), smoking, anxiety and BMI (>25 kg/m2) are risk factors for CLBP. The type of LBP, the intensity of the pain (current and last week), variation of the pain intensity, disability, intake of oral medications, physiotherapy for CLBP, number of missed days of training and number of missed matches are not significantly related to the chronicity of LBP or the sports discipline. Only the number of missed days of training had a significant association with the chronicity of LBP. Conclusions CLBP is a common complaint in Indian university athletes, and our findings indicate the necessity for a specific prevention program.
Treatment of Demodex Blepharitis: A Prospective, Randomized, Controlled, Double-Masked Clinical Trial Comparing Topical Lotilaner Ophthalmic Solution, 0.25% Eyedrops to Vehicle

ABSTRACT Purpose To evaluate the efficacy and safety of lotilaner ophthalmic solution, 0.25% eyedrops compared to vehicle for the treatment of Demodex blepharitis. Methods In this randomized, controlled, double-masked clinical trial, 54 participants were randomly assigned in a 1:1 ratio to receive either lotilaner ophthalmic solution, 0.25% (study group) or the vehicle (control group) bilaterally, twice daily for 42 days. Outcome measures were collarette cure (collarette grade 0, upper eyelid), mite eradication (mite density of 0 mites/lash), and composite cure (grade 0 for collarettes and erythema). Results The proportion of participants achieving collarette cure (80.0% vs 15.8%; p < .001), mite eradication (73.3% vs 21.1%, p = .003) and composite cure (73.3% vs 10.5%, p < .001) at Day 42 was statistically significantly higher in the study group than the control group. Conclusion Twice-daily 42-day treatment with novel lotilaner ophthalmic solution, 0.25% is safe and effective for the treatment of Demodex blepharitis compared to the vehicle control. (Registry number: ACTRN12620000320954, dated 09/03/2020).
LncRNA UBE2R2-AS1, as prognostic marker, promotes cell proliferation and EMT in prostate cancer.

BACKGROUND Long noncoding RNA ubiquitin-conjugating enzyme E2 R2 antisense RNA 1 (UBE2R2-AS1) has been recently reported to participate in the progression of tumors, including glioma and liver cancer. However, the roles of UBE2R2-AS1 in prostate cancer (PC) remained poorly understood. METHODS The expression of UBE2R2-AS1 was determined in tumor tissues and paired adjacent tissues from PC patients using quantitative reverse transcription PCR analysis. Correlation between UBE2R2-AS1 expression and clinicopathological parameters and overall survival were investigated by Chi-square test and Kaplan-Meier method analysis. The in vitro experiments, including CCK-8 assay, colony formation, flow cytometry and transwell assay were performed to investigate the functional role of UBE2R2-AS1 knockdown or overexpression on PC cell lines (PC-3 and DU145). Related protein expression levels were measured by western blot analysis. RESULTS Our data showed that UBE2R2-AS1 expression was significantly upregulated in PC tissues compared with that in adjacent tissues. The high levels of UBE2R2-AS1 were associated with high Gleason score, advanced clinical T stage, lymph node metastasis and poor prognosis. Knockdown of UBE2R2-AS1 suppressed cell proliferation, migration and invasion, induced cell cycle G0/G1 arrest and apoptosis in PC cells, along with decreased expression of PCNA, CDK4, Cyclin D1, Bcl-2, N-cadherin and Vimentin, and increased E-cadherin expression. Overexpression of UBE12R2-AS1 obtained the opposite results in PC cells. CONCLUSIONS Our findings suggest that UBE2R2-AS1 might be a potential diagnostic and/or therapeutic target in PC.
Multilevel Decompression Surgery for Degenerative Lumbar Spinal Canal Stenosis Is Similarly Effective With Single-level Decompression Surgery

Study Design. Retrospective case series. Objective. The purpose of this study was to investigate the outcome of multilevel posterior decompression surgery for degenerative lumbar spinal stenosis compared with single-level surgery. Summary of Background Data. The clinical outcomes of multilevel decompression surgery are still controversial because previous studies have not been designed to randomize or adjust the patient background. Materials and Methods. A retrospective review of prospectively collected data from 659 surgically treated lumbar spinal stenosis patients with a minimum 2-year follow-up was performed. Among them, we compared baseline and 2-year postoperative patient-reported outcomes (PROs) including the Visual Analog Scale and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire scores of 122 patients who underwent three or more levels of surgery (M group) and 304 patients who underwent single-level surgery (S group). Further analyses were performed of 116 paired patients from both groups who were propensity score matched by age and baseline PROs. Results. The number of perioperative complications including extradural hematoma, surgical site infection, and spinal fluid leakage [M vs. S: 10 (8%) vs. 19 (6%), P=0.47], and frequency of revision surgery [5 (4%) vs. 23 (8%), P=0.10] were similar between the two groups. In the analysis of propensity score–matched patients, there were comparable improvements in the Visual Analog Scale score for lower back pain (2.6 vs. 2.4, P=0.55), buttock-leg pain (3.1 vs. 3.4, P=0.48), and buttock-leg numbness (2.9 vs. 2.9, P=0.77) in both groups. There were also similar improvements in the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire scores including lower back pain, lumbar function, walking ability, and mental health domains, except for the social life function domain (20.7±26.5 vs. 28.0±27.5, P=0.04). Conclusions. Despite the longer surgical time and a larger volume of estimated blood loss, multilevel decompression surgery showed similar improvement to that of single-level surgery in terms of recovery of PROs and frequency of revision surgery. Multilevel decompression surgery provides good clinical outcomes with acceptable complication and revision rates when selecting appropriate patient and spinal levels.