Miracle-dz/UniFAR-FTUs huggingface dataset:
miR-206 Promotes Cancer Progression by Targeting Full-Length Neurokinin-1 Receptor in Breast Cancer

Substance P plays a pivotal role in human cancer development and progression by binding to its receptor, neurokinin-1. Neurokinin-1 has 2 isoforms: full-length neurokinin-1 and truncated neurokinin-1, the latter lacking the cytoplasmic terminal 96-amino acid residues of the full-length protein. We have identified 3 candidate miR-206 target sites within the 3′-untranslated region of the full-length neurokinin-1 gene from bioinformatics database searches. In the present study, real-time quantitative polymerase chain reaction was performed to quantify the expression of miR-206, and the expression of neurokinin-1 and full-length neurokinin-1 was detected by immunohistochemistry in 82 clinical cases of breast cancer and paired adjacent normal tissues. The miR-206 target gene was demonstrated by using a dual-luciferase reporter assay, quantitative real-time polymerase chain reaction, and Western blotting. Transwell migration and invasion, colony formation, and proliferation assays were performed to evaluate the effects of miR-206 expression on various aspects of breast cancer cell behavior in vitro. We showed that miR-206 expression is upregulated in breast cancer cell lines and breast cancer tissues when compared to that in adjacent normal tissues, and full-length neurokinin-1 expression inversely correlates with Tumor Lymph Node Metastasis (TNM) stage and lymph node metastasis. Western blotting, quantitative real-time polymerase chain reaction, and dual-luciferase reporter assays demonstrated that miR-206 binds the 3′-untranslated region of full-length neurokinin-1 messenger RNA, regulating protein expression. We showed that the overexpression of miR-206 promotes breast cancer cell invasion, migration, proliferation, and colony formation in vitro. The present study furthers the current understanding of the mechanisms underlying breast cancer pathogenesis and may be useful for the development of novel targeted therapies.
Role of Knowledge, Sociodemographic, and Behavioral Factors on Lifetime HIV Testing among Adult Population in Nepal: Evidence from a Cross-Sectional National Survey

Human immunodeficiency virus (HIV) testing is important to HIV prevention, treatment, and care. We aimed to assess the role of sociodemographic, behavioral factors and HIV knowledge on HIV testing among people aged 15–49 years in Nepal. The 2011 Nepal Demographic and Health Survey data was used for secondary data analysis. Herein, 9843 women and 3017 men who had experienced coitus were included. The respondents were asked if they underwent HIV testing and received the test results in their lifetime. Chi-square test and multivariate logistic regression analysis were applied at 5% level of significance. Adjusted odds ratios and 95% confidence intervals were computed separately for women and men. Of the total, 18.0% of men and 7.4% of women had been tested for HIV in their lifetime. As compared to the age of 15 to 24 years, males aged 25 to 29 years were more likely to report, whereas females aged 35 to 49 years were less likely to report HIV testing. Lower caste groups had more likelihood of reporting HIV testing than the other caste in both sexes. The odds of being tested for HIV were significantly higher among those who had higher education in both sexes. There was significant positive association between HIV testing and economic status in males whereas this association was reverse among females. The male respondents who spent more than one month away from home in the last 12 months were 1.68 times more likely to have been tested for HIV in their lifetime. Having multiple sexual partners was associated with higher odds of testing for HIV in both sexes. Having comprehensive HIV knowledge was independently associated with the reporting of higher odds of HIV testing in females. Promotion of HIV testing should consider sociodemographic factors, sexual behavior, and imparting comprehensive HIV knowledge.
Sigma‐1 receptor protects against ferroptosis in hepatocellular carcinoma cells

Sigma‐1 receptor (S1R) regulates reactive oxygen species (ROS) accumulation via nuclear factor erythroid 2‐related factor 2 (NRF2), which plays a vital role in ferroptosis. Sorafenib is a strong inducer of ferroptosis but not of apoptosis. However, the mechanism of sorafenib‐induced ferroptosis in hepatocellular carcinoma (HCC) remains unclear. In this study, we found for the first time that sorafenib induced most of S1Rs away from nucleus compared to control groups in Huh‐7 cells, and ferrostatin‐1 completely blocked the translocation. S1R protein expression, but not mRNA expression, in HCC cells was significantly up‐regulated by sorafenib. Knockdown of NRF2, but not of p53 or hypoxia‐inducible factor 1‐alpha (HIF1α), markedly induced S1R mRNA expression in HCC cells. Inhibition of S1R (by RNAi or antagonists) increased sorafenib‐induced HCC cell death in vitro and in vivo. Knockdown of S1R blocked the expression of glutathione peroxidase 4 (GPX4), one of the core targets of ferroptosis, in vitro and in vivo. Iron metabolism and lipid peroxidation increased in the S1R knockdown groups treated with sorafenib compared to the control counterpart. Ferritin heavy chain 1 (FTH1) and transferrin receotor protein 1 (TFR1), both of which are critical for iron metabolism, were markedly up‐regulated in HCC cells treated with erastin and sorafenib, whereas knockdown of S1R inhibited these increases. In conclusion, we demonstrate that S1R protects HCC cells against sorafenib and subsequent ferroptosis. A better understanding of the role of S1R in ferroptosis may provide novel insight into this biological process.
The Health and Wellbeing of Staff Members at a Tertiary Institution in New Zealand.

The purpose of this study was to determine the physical, psychological and biochemical health status of staff members at a higher educational institution (Institute of Technology). Relative large numbers of subjects were identified with hypertension (18.5%), stress symptoms (32.1%), job stress (36%) and emotional exhaustion (11.4%). Thirty percent presented with more than three risk factors, 49% with one or two risk factors while only 21% were risk free. Cardiovascular fitness showed positive associations with body fat, body weight, stress, emotional exhaustion and fasting blood glucose levels. Psychological health correlated significantly (p≤0.05) with measures of coronary risk, health status, body composition and cardiovascular fitness. Staff assistance programs focusing on exercise, weight management and job stress could potentially have a positive impact on overall health of staff at tertiary institutions.
Micro and Nano Hemispherical 3D Imprints Modulate the Osteogenic Differentiation and Mineralization Tendency of Bone Cells.

Surface topography has been reported to play a key role in modulating cell behaviors, yet the mechanism through which it modulates these behaviors is not fully understood, especially in the case of three-dimensional (3D) topographies. In this study, a series of novel hemispherical 3D imprints ranging from the nanoscale to the microscale were prepared on titanium (Ti) surfaces using a customized interfacial lithography method. Mouse embryo osteoblast precursor cells (MC3T3-E1) were selected to investigate the solitary effect of specific hemispherical 3D imprints on cellular behaviors. The results indicated that varied hemispherical 3D imprints can affect the formation of filopodia and the arrangement of the cytoskeleton in different ways. Specifically, they can alter the spreading morphologies of cells and lead to deformation of the nucleus, which eventually affects cell proliferation and osteogenic differentiation. Cells cultured on different hemispherical 3D imprints exhibited promoted proliferation and osteogenic differentiation to different degrees; for example, cells cultured on 90- and 500-nm hemispherical imprints formed abundant filopodia and exhibited the highest ALP activity and osteogenic gene expression, respectively. Four-week tibia implantation also confirmed that 90-nm hemispherical imprints improved osteogenic ability in vivo compared with an unpatterned Ti substrate. In addition to promoted proliferation, colonization of more cells on the surface of implants and induction of rapid osteogenic differentiation can occur. Our work provides a rational way to balance cell proliferation and differentiation, which can accelerate bone integration of an implant and host tissue.
Secular Trends of Hip Fractures in Lebanon, 2006 to 2017: Implications for Clinical Practice and Public Health Policy in the Middle East Region

Country‐specific hip fracture incidence rates (IRs) and longevity allow the Fracture Risk Assessment Tool (FRAX) to be adapted to individual countries. Secular trends can affect tool calibration. Data on hip fracture IRs in the Middle East is scarce, and long‐term secular trend studies are nonexistent. Using the Ministry of Public Health hip fracture registry, we calculated age‐ and sex‐specific hip fracture IRs in Lebanon, from 2006 to 2017, among individuals aged ≥50 years. We used Kendall's tau‐b (τb) test to determine the correlation between time and hip fracture IRs, and calculated both the annual % change in IRs and the % change in IR compared to the baseline period (2006 to 2008). The registry recorded 6985 hip fractures, 74% at the femoral neck, 23% intertrochanteric, and 3% subtrochanteric. Men constituted 32% of the population, and were significantly younger than women (76.5 ± 11.0 years versus 77.7 ± 10.3 years; p < 0.001). Annual overall IRs, per 100,000, ranged from 126.6 in 2014 to 213.2 in 2017 in women, and 61.4 in 2015 to 111.7 in 2017 in men. The average women to men IR ratio was 1.8 (range, 1.5 to 2.1). IRs steadily increased with age, and IR ratios increased in parallel in both sexes, with a steeper and earlier rise (by 5 years) in women. Data showed a consistent decline in hip fracture IRs starting in 2006 in women, and in 2009 in men. There was a significant negative correlation between time (2006 to 2014) and hip fracture IRs in women (τb = −0.611, p = 0.022) but not in men (τb = −0.444, p = 0.095). The steady decrease in IRs reversed after 2015 in both sexes. This long‐term data on secular trends in the Middle East is novel and consistent with worldwide changes in hip fracture rates. The impact of such changes on national FRAX‐derived estimates is unclear, should be assessed, and may necessitate an update in the FRAX Lebanon calculator. © 2019 American Society for Bone and Mineral Research.
Understanding the role of community resilience in addressing the Ebola virus disease epidemic in Liberia: a qualitative study (community resilience in Liberia)

ABSTRACT Background: There is an increasing recognition that community resilience plays a significant role in addressing health shocks like the Ebola virus disease (EVD) epidemic. However, the factors that constitute community resilience, and how these operate dynamically with other health system factors are less understood. Objective: This paper seeks to understand key factors that constitute community resilience and their role in responding to the EVD outbreak in Liberia. Methods: Key informant interviews were conducted between November 2017 and April 2018 with community representatives in Bomi, Margibi and Montserrado counties, and other national stakeholders involved in the EVD response in Liberia from 2014 to 2016. A national stakeholder meeting was conducted to verify and interpret information emerging from the interviews. Results: Factors that were critical for addressing the EVD epidemic in Liberia were identified as: strong leadership, tight bonds and sense of kinship at the community level; trusted communication channels; and trust among various health system stakeholders. These factors facilitated collective actions within communities and helped to direct response initiatives from other levels of the health system to the community. Foreign assistance was seen as crucial for recovery and revitalization of affected communities. However, such aid is often not targeted at addressing critical challenges in a sustainable way, especially when the assistance is highly restricted to specific activities, and those activities are determined without consultation with local actors and community groups. Conclusion: Efforts to systematically build responsible leadership and social capital at community level, including those that strengthen bonds in communities and trust across key actors in the health system, are needed to address health shocks like EVD outbreaks. Without building such capabilities in community resilience, it will be difficult to reap the expected gains from investments focusing on building physical capital and technical capabilities in health services and emergency preparedness.
The opposing effects of genetic drift and Haldane's sieve on floral‐morph frequencies in tristylous metapopulations

Summary Tristyly is a genetic floral polymorphism in which three floral morphs are maintained at equal frequencies by negative frequency‐dependent selection on alleles at two interacting loci. Because dominant alleles at these loci are maintained at a lower frequency than their recessive counterparts, they are more likely to be lost by founder events and genetic drift. Here we examine the hypothesis that dominant alleles under negative frequency‐dependent selection should also be more likely to re‐invade populations than recessive alleles, due to Haldane's Sieve, because recessive alleles not expressed in a heterozygote state cannot benefit from positive selection when rare. We used computer simulations of tristylous metapopulations to verify that Haldane's Sieve acting on migrants into occupied demes can indeed reverse the bias in allele frequencies expected for small single tristylous populations, particularly in situations of rapid population growth following colonisation. This effect is manifest both locally and at the metapopulation level. Our study illustrates the potential effect of Haldane's Sieve in the novel context of an iconic plant sexual‐system polymorphism under the influence of metapopulation dynamics.
Dynamics of genomic, epigenomic, and transcriptomic aberrations during stepwise hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) undergoes a stepwise progression from liver cirrhosis (LC) to low-grade dysplastic nodule (LGDN), high-grade dysplastic nodule (HGDN), early HCC (eHCC), and progressed HCC (pHCC). Here, we profiled multi-layered genomic, epigenomic, and transcriptomic aberrations in the stepwise hepatocarcinogenesis. Initial DNA methylation was observed in eHCC (e.g., DKK3, SALL3, and SOX1) while more extensive methylation was observed in pHCC. In addition, eHCCs showed an initial loss of DNA copy numbers of tumor suppressor genes in the 4q and 13q regions, thereby conferring survival benefits to cancer cells. Transcriptome analysis revealed that HGDNs expressed endoplasmic reticulum (ER) stress-related genes, while eHCC started to express oncogenes. Furthermore, integrative analysis indicated that expression of the serine peptidase inhibitor, Kazal type 1 (SPINK1), played a pivotal role in eHCC development. Significant demethylation of SPINK1 was observed in eHCC compared to HGDN. The study also demonstrated that ER stress may induce SPINK1 demethylation and expression in liver cancer cells. In conclusion, these results reveal the dynamics of multiomic aberrations during malignant conversion of liver cancer, thus providing novel pathobiological insights into hepatocarcinogenesis.
The neural mechanisms of social reward in early psychosis

Abstract In chronic psychosis, reduced trust is associated with a neural insensitivity to social reward and reduced theory of mind (ToM). Here we investigate whether these mechanisms could underlie emerging social impairments in early psychosis. Twenty-two participants with early psychosis and 25 controls (male, 13–19 years) participated in two interactive trust games against a cooperative and unfair partner. Region of interest neuroimaging analyses included right caudate, medial prefrontal cortex (mPFC) and right temporoparietal junction (rTPJ), involved in reward and ToM processing. Both groups showed similar levels of trust (i.e. investments). However, individuals with psychosis failed to activate the caudate differentially in response to cooperation and unfairness while making decisions to trust. During cooperative returns, patients showed reduced and controls increased caudate activation. Patients demonstrated greater rTPJ activation than controls, possibly pointing towards compensatory mechanisms. Effects were associated with Wechsler Abbreviated Scale of Intelligence vocabulary scores. No group differences emerged in mPFC activation. Early psychosis is associated with an aberrant neural sensitivity to social reward. This could foster reduced social motivation and social isolation. Absent behavioural differences in early, relative to chronic psychosis could indicate that trust is achieved through increased compensatory demand on ToM.
Effects of probiotic supplementation and postmortem storage condition on the oxidative stability of M. Pectoralis major of laying hens

Dietary probiotic supplementation is a promising alternative to antibiotics in the poultry industry, and some studies have found its positive impacts on meat quality attributes. The objective of this study was to evaluate the effects of dietary treatments on oxidative stability of postmortem chicken fillet (M. Pectoralis major) muscles during 7 d of storage under either high oxygen (HIOX) or vacuum (VAC) conditions. A total of 264 Hy-Line Brown laying hens (11 birds per cage) were assigned to 2 different dietary treatments (regular diet or 300 ppm probiotic, Sporulin enhanced diet) before being sacrificed. At 17 wk, one bird per cage from 6 cages per treatment was randomly selected and slaughtered (n = 12). Chicken fillets from both sides were collected and randomly assigned to HIOX or VAC conditions. Within each fillet side, the muscle was divided into 3 portions, assigned to 1 or 7 d storage period, while the caudal portion was allocated as the 0 d samples for proximate composition and fatty acid profiling. Results revealed that the muscle crude compositions were not altered in laying hens that were fed probiotic supplementary diet compared to controls (P > 0.05). However, the muscle samples from probiotic fed laying hens had higher proportions of unsaturated fatty acid (74.76 vs. 71.65%, P < 0.05) and 2-thiobarbituric acid reactive substances (0.79 vs. 0.67 mg malondialdehyde/kg meat, P < 0.05) than the samples from the control. In addition, the probiotic fed laying hens, but not controls, had higher levels of conjugated dienes (3.32 vs. 2.63 μg/g meat) and peroxides (0.40 vs. 0.30 milliequivalent O2/kg fat) in the muscle samples after 7 d of storage (P < 0.05). The results from the present study indicated that postmortem fillet muscles obtained from the laying hens fed with probiotic supplementation would be more prone to be oxidized, especially under more oxidizing conditions (HIOX and extended storage time).
National Trends in the Adoption of Pharmacy Curriculum Outcomes Assessment for Student Assessment and Remediation

Objective. To determine and describe the current uses of the Pharmacy Curriculum Outcomes Assessment (PCOA) by US schools and colleges of pharmacy. Methods. Assessment professionals from 135 US schools and colleges of pharmacy were invited to complete a 38-item electronic survey. Survey items were designed to investigate common uses of the PCOA, cut points, and “stakes” assigned to the PCOA, identification of at-risk students, and remediation approaches. Results. The school response rate was 68%. The most common uses of the PCOA included curricular assessment (76%), individual student performance assessment (74%), and cohort performance assessment (71%). The PCOA was most frequently administered to third-year pharmacy (P3) students. The approach for assigning “stakes” to PCOA performance varied among programs depending on the student’s professional year in the curriculum. Programs used a variety of approaches to establish the benchmark (or cut point) for PCOA performance. Remediation for at risk students was required by less than 25% of programs. Remediation was most commonly required for P3 students (22%). Conclusion. Survey results indicate wide variability between programs regarding PCOA cut points (benchmarks), stakes, and remediation approaches. In the future, it will be important for pharmacy educators to identify and study best practices for use of PCOA within student assessment and remediation plans.
Circular code motifs in the ribosome: a missing link in the evolution of translation?

The origin of the genetic code remains enigmatic five decades after it was elucidated, although there is growing evidence that the code coevolved progressively with the ribosome. A number of primordial codes were proposed as ancestors of the modern genetic code, including comma-free codes such as the RRY, RNY, or GNC codes (R = G or A, Y = C or T, N = any nucleotide), and the X circular code, an error-correcting code that also allows identification and maintenance of the reading frame. It was demonstrated previously that motifs of the X circular code are significantly enriched in the protein-coding genes of most organisms, from bacteria to eukaryotes. Here, we show that imprints of this code also exist in the ribosomal RNA (rRNA). In a large-scale study involving 133 organisms representative of the three domains of life, we identified 32 universal X motifs that are conserved in the rRNA of >90% of the organisms. Intriguingly, most of the universal X motifs are located in rRNA regions involved in important ribosome functions, notably in the peptidyl transferase center and the decoding center that form the original “proto-ribosome. ” Building on the existing accretion models for ribosome evolution, we propose that error-correcting circular codes represented an important step in the emergence of the modern genetic code. Thus, circular codes would have allowed the simultaneous coding of amino acids and synchronization of the reading frame in primitive translation systems, prior to the emergence of more sophisticated start codon recognition and translation initiation mechanisms.
Tolerance of High Oral Doses of Nonradioactive and Radioactive Caesium Chloride in the Pale Grass Blue Butterfly Zizeeria maha

The biological effects of the Fukushima nuclear accident have been examined in the pale grass blue butterfly, Zizeeria maha (Lepidoptera: Lycaenidae). In previous internal exposure experiments, larvae were given field-collected contaminated host plant leaves that contained up to 43.5 kBq/kg (leaf) of radioactive caesium. Larvae ingested up to 480 kBq/kg (larva), resulting in high mortality and abnormality rates. However, these results need to be compared with the toxicological data of caesium. Here, we examined the toxicity of both nonradioactive and radioactive caesium chloride on the pale grass blue butterfly. Larvae were fed a caesium-containing artificial diet, ingesting up to 149 MBq/kg (larva) of radioactive caesium (137Cs) or a much higher amount of nonradioactive caesium. We examined the pupation rate, eclosion rate, survival rate up to the adult stage, and the forewing size. In contrast to previous internal exposure experiments using field-collected contaminated leaves, we could not detect any effect. We conclude that the butterfly is tolerant to ionising radiation from 137Cs in the range tested but is vulnerable to radioactive contamination in the field. These results suggest that the biological effects in the field may be mediated through ecological systems and cannot be estimated solely based on radiation doses.