Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of platelet turnover on long‐term adverse cardiovascular outcomes in patients undergoing percutaneous coronary intervention

Increased platelet turnover and high platelet reactivity are associated with short‐term major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) or stable coronary artery disease (SCAD). We investigated the impact of platelet turnover on long‐term MACE.
Assisted HIV partner notification services in resource‐limited settings: experiences and achievements from Cameroon

In 2007, the Cameroon Baptist Convention Health Services (CBCHS) initiated an assisted partner notification services (aPNS) public health programme to increase HIV case identification and reduce HIV incidence in the most affected regions of Cameroon. We describe large‐scale implementation of aPNS and overall programmatic achievements in a resource‐limited setting through 2015.
Inhibition of ubiquitin‑specific protease 14 promotes connexin 32 internalization and counteracts cisplatin cytotoxicity in human ovarian cancer cells.

Although cisplatin is one of the most accepted therapies for ovarian cancer, recurrence and drug resistance remain problematic. Both the ubiquitin‑proteasome system (UPS) and connexin (Cx) are closely related to tumor progression. However, the role of ubiquitin‑specific protease 14 (USP14) and Cx in mediating drug resistance remains unclear. In the present study, we aimed to determine whether USP14 is involved in cisplatin resistance and modulates the internalization of connexin 32 (Cx32) in ovarian cancer. The results of the deubiquitinase (DUB) trap assay and western blot analysis revealed that the expression and activity levels of USP14 were downregulated in A2780 cisplatin‑resistant cells (A2780‑CDDP) relative to these levels in A2780 cisplatin‑sensitive cells (A2780). CCK‑8 assay results showed that inhibition of USP14 by a specific inhibitor or siRNA decreased cisplatin cytotoxicity in A2780 cells. Additionally, USP14 inhibition increased the expression of Cx32 without changing its mRNA and ubiquitination levels, as showed by Real‑time qPCR and immunoprecipitation assay respectively. Cisplatin resistance induced by USP14 inhibition was counteracted by Cx32 knockdown. Moreover, USP14 inhibition contributed to Cx32 internalization, as determined by western blot analysis and a reduction in gap junction intercellular communication (GJIC), as showed by parachute dye‑coupling assay. Collectively, these data suggest that Cx32 internalization by USP14 inhibition modulates the cisplatin resistance in ovarian cancer cells, thus serving as a potential drug target to challenge chemotherapy failure. In addition, USP14 can also be used as a marker to monitor the development of cisplatin resistance in ovarian cancer treatment.
Activins, follistatin and immunoregulation in the epididymis

The interface between the epididymis and the immune system is implicated in many male reproductive pathologies. The resident immune cell populations and immune‐environment within the epididymis are significantly different from the testis, which is an immune‐privileged site. Moreover, the immune cell subsets and immunological responses between different regions of the epididymis vary considerably. The cauda epididymis is more susceptible to autoimmune responses than the caput in rodent models of active immunization or suppressed immune tolerance, and in men with congenital or physical damage to the reproductive tract. Activins are members of the transforming growth factor‐β family of cytokines that are crucial for testis and epididymal development; however, they also have complex immunoregulatory properties and may play an essential role in the regulation of immunity in the reproductive tract.
Distribution of Volatile Compounds in Different Fruit Structures in Four Tomato Cultivars

Distribution of volatile compounds in different fruit structures were analyzed in four tomato cultivars by headspace-solid-phase microextraction (SPME)-gas chromatography-mass spectrometry (GC-MS). A total of 36 volatile compounds were identified in fruit samples, which were primarily aldehydes, hydrocarbons, alcohols, ketones, furans, esters, nitrogen compounds, and sulfur and nitrogen-containing heterocyclic compounds. The volatile compositions in pericarp (PE), septa and columella (SC), locular gel and seeds (LS), and stem end (SE) tissues showed different profiles. The PE tissue showed the highest total volatile concentration due to a high abundance of aldehydes, especially cis-3-hexenal and benzaldehyde. Meanwhile, it showed higher aromatic proportion and herbaceous series intensity than other tissues. Floral and fruity series showed higher intensity in SC and LS tissues. The concentration of alcohols in the LS was higher than that in other tissues in association with the higher abundances of 2-methyl propanol, 3-methyl butanol, and 2-methyl butanol. However, the numbers and concentrations of volatile compounds, especially cis-3-hexenal, benzaldehyde, and geranyl acetone were lower in SE than in the other tissues, indicating less tomato aromas in SE. SE tissues were also lacking in floral and fruity characteristic compounds, such as geranyl acetone, 1-nitro-pentane, and 1-nitro-2-phenylethane. “FL 47” contained more volatile compounds than the other three, and the contents of aldehydes, ketones and oxygen-containing heterocyclic compounds in the “Tygress” fruit were higher than the other cultivars.
NF-κB Signaling Pathways in Osteoarthritic Cartilage Destruction

Osteoarthritis (OA) is a type of joint disease associated with wear and tear, inflammation, and aging. Mechanical stress along with synovial inflammation promotes the degradation of the extracellular matrix in the cartilage, leading to the breakdown of joint cartilage. The nuclear factor-kappaB (NF-κB) transcription factor has long been recognized as a disease-contributing factor and, thus, has become a therapeutic target for OA. Because NF-κB is a versatile and multi-functional transcription factor involved in various biological processes, a comprehensive understanding of the functions or regulation of NF-κB in the OA pathology will aid in the development of targeted therapeutic strategies to protect the cartilage from OA damage and reduce the risk of potential side-effects. In this review, we discuss the roles of NF-κB in OA chondrocytes and related signaling pathways, including recent findings, to better understand pathological cartilage remodeling and provide potential therapeutic targets that can interfere with NF-κB signaling for OA treatment.
Sustained effect of continuous treatment with bevacizumab following bevacizumab in combination with chemotherapy in a human ovarian clear cell carcinoma xenograft model

Although bevacizumab maintenance following bevacizumab in combination with chemotherapy has demonstrated significant prolongation of progression-free survival in clinical studies in patients with ovarian cancer, the majority of the cancer cases in the study were of the serous histotype; therefore, data regarding clear cell carcinoma is limited. Furthermore, the efficacy of bevacizumab beyond progression has not yet been demonstrated in ovarian cancer. A xenograft model using the human ovarian clear cell carcinoma cell line RMG-I was used to investigate the antitumor effects and the mechanisms of bevacizumab in maintenance treatment and bevacizumab when administered beyond disease progression. In the RMG-I model, bevacizumab maintenance following bevacizumab in combination with paclitaxel exhibited increased tumor suppression, compared with its absence, and inhibited the increase of microvessel density (MVD) in tumors. Following disease progression during bevacizumab maintenance, continued bevacizumab treatment in combination with PEGylated liposomal doxorubicin as a secondary chemotherapeutic agent had increased efficacy, compared with PEGylated liposomal doxorubicin alone, and resulted in lower MVD accompanied with lower levels of insulin-like growth factor binding protein-3, which is reported to have angiogenic activity. Continuous suppression of angiogenesis by bevacizumab may contribute to the superior efficacy of bevacizumab maintenance and bevacizumab beyond progression in ovarian cancer.
DNA hypermethylation of aurora kinase A in hepatitis C virus-positive hepatocellular carcinoma

Changes in the methylation levels of tumor suppressor genes or proto-oncogenes are involved in the pathogenesis of hepatitis C virus (HCV) infection-induced hepatocellular carcinoma (HCC). The aim of the present study was to identify novel aberrantly methylated differentially expressed genes by integrating mRNA expression profile (GSE19665 and GSE62232) and methylation profile (GSE60753) microarrays downloaded from the Gene Expression Omnibus database. Functional enrichment analysis of screened genes was performed using the DAVID software and BinGO database. Protein-protein interaction (PPI) networks were constructed using the STRING database, followed by module analysis with MCODE software. The transcriptional and translational expression levels of crucial genes were confirmed using The Cancer Genome Atlas (TCGA) datasets and Human Protein Atlas database (HPA). A total of 122 downregulated/hypermethylated genes and 63 upregulated/hypomethylated genes were identified. These genes were enriched in the Gene Ontology biological processes terms of ‘inflammatory response’ [Fos proto-oncogene, AP-1 transcription factor subunit (FOS)] and ‘cell cycle process’ [aurora kinase A (AURKA), cyclin dependent kinase inhibitor 3 (CDKN3) and ubiquitin conjugating enzyme E2 C (UBE2C)]. PPI network and module analysis indicated that human oncogenes FOS, AURKA, CDKN3 and UBE2C may be hub genes. mRNA, protein expression and methylation levels of AURKA and FOS were validated by TCGA and HPA data. In conclusion, aberrantly methylated AURKA and FOS may be potential therapeutic targets for HCV-positive HCC.
Selective androgen receptor modulators (SARMs) have specific impacts on the mouse uterus

Selective androgen receptor modulators (SARMs) have been proposed as therapeutics for women suffering from breast cancer, muscle wasting or urinary incontinence. The androgen receptor (AR) is expressed in the uterus but the impact of SARMs on the function of this organ is unknown. We used a mouse model to compare the impact of SARMs (GTx-007/Andarine®, GTx-024/Enobosarm®), Danazol (a synthetic androstane steroid) and dihydrotestosterone (DHT) on tissue architecture, cell proliferation and gene expression. Ovariectomised mice were treated daily for 7 days with compound or vehicle control (VC). Uterine morphometric characteristics were quantified using high-throughput image analysis (StrataQuest; TissueGnostics), protein and gene expression were evaluated by immunohistochemistry and RT-qPCR, respectively. Treatment with GTx-024, Danazol or DHT induced significant increases in body weight, uterine weight and the surface area of the endometrial stromal and epithelial compartments compared to VC. Treatment with GTx-007 had no impact on these parameters. GTx-024, Danazol and DHT all significantly increased the percentage of Ki67-positive cells in the stroma, but only GTx-024 had an impact on epithelial cell proliferation. GTx-007 significantly increased uterine expression of Wnt4 and Wnt7a, whereas GTx-024 and Danazol decreased their expression. In summary, the impact of GTx-024 and Danazol on uterine cells mirrored that of DHT, whereas GTx-007 had minimal impact on the tested parameters. This study has identified endpoints that have revealed differences in the effects of SARMs on uterine tissue and provides a template for preclinical studies comparing the impact of compounds targeting the AR on endometrial function.
Lactic Acidosis and The Role of Sodium Bicarbonate: A Narrative Opinion.

Lactic acidosis occurs commonly and can be a marker of significant physiologic derangements. However what an elevated lactate level and acidemia connotes and what should be done about it is subject to inconsistent interpretations. This review examines the varied etiologies of lactic acidosis, the physiologic consequences, and the known effects of its treatment with sodium bicarbonate. Lactic acidosis is often assumed to be a marker of hypoperfusion, but it can also result from medications, organ dysfunction, and sepsis even in the absence of malperfusion. Acidemia causes deleterious effects in almost every organ system but it can also have positive effects, increasing localized blood flow and oxygen delivery, as well as providing protection against hypoxic cellular injury. The use of sodium bicarbonate to correct severe acidemia may be tempting to clinicians, but previous studies have failed to show improved patient outcomes following bicarbonate administration. Bicarbonate use is known to decrease vasomotor tone, decrease myocardial contractility, and induce intracellular acidosis. This suggests that mild to moderate acidemia does not require correction. Most recently, a randomized control trial found a survival benefit in a subgroup of critically ill patients with serum pH levels <7.2 with concomitant acute kidney injury. There is no known benefit of correcting serum pH levels ≥ 7.2, and sparse evidence supports bicarbonate use <7.2. If administered, bicarbonate is best given as a slow IV infusion in the setting of adequate ventilation and calcium replacement to mitigate its untoward effects.
Prediction Model for Hospital-Acquired Pressure Ulcer Development: Retrospective Cohort Study

Background A pressure ulcer is injury to the skin or underlying tissue, caused by pressure, friction, and moisture. Hospital-acquired pressure ulcers (HAPUs) may not only result in additional length of hospital stay and associated care costs but also lead to undesirable patient outcomes. Intensive care unit (ICU) patients show higher risk for HAPU development than general patients. We hypothesize that the care team’s decisions relative to HAPU risk assessment and prevention may be better supported by a data-driven, ICU-specific prediction model. Objective The aim of this study was to determine whether multiple logistic regression with ICU-specific predictor variables was suitable for ICU HAPU prediction and to compare the performance of the model with the Braden scale on this specific population. Methods We conducted a retrospective cohort study by using the data retrieved from the enterprise data warehouse of an academic medical center. Bivariate analyses were performed to compare the HAPU and non-HAPU groups. Multiple logistic regression was used to develop a prediction model with significant predictor variables from the bivariate analyses. Sensitivity, specificity, positive predictive values, negative predictive values, area under the receiver operating characteristic curve (AUC), and Youden index were used to compare with the Braden scale. Results The total number of patient encounters studied was 12,654. The number of patients who developed an HAPU during their ICU stay was 735 (5.81% of the incidence rate). Age, gender, weight, diabetes, vasopressor, isolation, endotracheal tube, ventilator episode, Braden score, and ventilator days were significantly associated with HAPU. The overall accuracy of the model was 91.7%, and the AUC was . 737. The sensitivity, specificity, positive predictive value, negative predictive value, and Youden index were . 650, . 693, . 211, 956, and . 342, respectively. Male patients were 1.5 times more, patients with diabetes were 1.5 times more, and patients under isolation were 3.1 times more likely to have an HAPU than female patients, patients without diabetes, and patients not under isolation, respectively. Conclusions Using an extremely large, electronic health record–derived dataset enabled us to compare characteristics of patients who develop an HAPU during their ICU stay with those who did not, and it also enabled us to develop a prediction model from the empirical data. The model showed acceptable performance compared with the Braden scale. The model may assist with clinicians’ decision on risk assessment, in addition to the Braden scale, as it is not difficult to interpret and apply to clinical practice. This approach may support avoidable reductions in HAPU incidence in intensive care.
Evidence that Tenecteplase Is Noninferior to Alteplase for Acute Ischemic Stroke.

Background and Purpose- TNK (tenecteplase), a newer fibrinolytic agent, has practical delivery advantages over ALT (alteplase) that would make it a useful agent if noninferior in acute ischemic stroke treatment outcome. Accordingly, the most recent US American Heart Association/American Stroke Association acute ischemic stroke guideline recognized TNK as an alternative to ALT, but only based on informal consideration, rather than formal meta-analysis, of completed randomized control trials. Methods- Systematic literature search and formal meta-analysis were conducted per PRISMA guidelines (Preferred Reporting Items for Systemic Reviews and Meta-Analyses), adapted to noninferiority analysis. The primary outcome of freedom from disability (modified Rankin Scale score, 0-1) outcome at 3 m, and additional efficacy and safety outcomes, were analyzed. Results- Systematic search identified 5 trials enrolling 1585 patients (828 TNK, 757 ALT). Across all trials, mean age was 70.8, 58.5% male, baseline National Institutes of Health Stroke Scale mean 7.0, and time from last known well to treatment start mean 148 minutes. All ALT patients received standard 0.9 mg/kg dosing, while TNK dosing was 0.1 mg/kg in 6.8%, 0.25 mg/kg in 24.6%, and 0.4 mg/kg in 68.6%. For the primary end point, crude cumulative rates of disability-free (modified Rankin Scale score, 0-1) 3 m outcome were TNK 57.9% versus ALT 55.4%. Informal, random-effects meta-analysis, the risk difference was 4% (95% CI, -1% to 8%). The lower 95% CI bound fell well within the prespecified noninferiority margin. Similar results were seen for the additional efficacy end points: functional independence (modified Rankin Scale score, 0-2): crude TNK 71.9% versus ALT 70.5%, risk difference 2% (95% CI, -3% to 6%); and modified Rankin Scale shift analysis, common odds ratio 1.21 (95% CI, 0.93-1.57). For safety end points, lower event rates reduced power, but point estimates were also consistent with noninferiority Conclusions- Accumulated clinical trial data provides strong evidence that TNK is noninferior to ALT in the treatment of acute ischemic stroke. These findings provide formal support for the recent guideline recommendation to consider TNK an alternative to ALT.
Draft Genome Sequences of Six Bacteria Isolated from the Benham Bank, Philippine Rise, Philippines

We report here the draft genome sequences of six bacteria isolated from the near-bottom waters and surface sediments of the Benham Bank, Philippine Rise, Philippines. These genome sequences represent candidate novel species and/or strains from the families Flavobacteriaceae and Dermacoccaceae and the genera Idiomarina, Bacillus, and Vibrio. ABSTRACT We report here the draft genome sequences of six bacteria isolated from the near-bottom waters and surface sediments of the Benham Bank, Philippine Rise, Philippines. These genome sequences represent candidate novel species and/or strains from the families Flavobacteriaceae and Dermacoccaceae and the genera Idiomarina, Bacillus, and Vibrio.
Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study

Background: The androgen receptor (AR) has emerged as a potential therapeutic target for AR-positive triple-negative breast cancer (TNBC). However, conflicting reports regarding AR’s prognostic role in TNBC are putting its usefulness in question. Some studies conclude that AR positivity indicates a good prognosis in TNBC, whereas others suggest the opposite, and some show that AR status has no significant bearing on the patients’ prognosis. Methods: We evaluated the prognostic value of AR in resected primary tumors from TNBC patients from six international cohorts {US (n = 420), UK (n = 239), Norway (n = 104), Ireland (n = 222), Nigeria (n = 180), and India (n = 242); total n = 1407}. All TNBC samples were stained with the same anti-AR antibody using the same immunohistochemistry protocol, and samples with ≥1% of AR-positive nuclei were deemed AR-positive TNBCs. Results: AR status shows population-specific patterns of association with patients’ overall survival after controlling for age, grade, population, and chemotherapy. We found AR-positive status to be a marker of good prognosis in US and Nigerian cohorts, a marker of poor prognosis in Norway, Ireland and Indian cohorts, and neutral in UK cohort. Conclusion: AR status, on its own, is not a reliable prognostic marker. More research to investigate molecular subtype composition among the different cohorts is warranted.
Determinants of voluntary early retirement for older workers with and without chronic diseases: A Danish prospective study

Aims: This study explored differences in determinants (i.e. health-related, work-related and social factors) of voluntary early retirement between older workers with and without chronic diseases in Denmark. Methods: Workers aged 56–64 years who were members of a voluntary early retirement scheme were selected from the Danish National Working Environment Survey (2008–2009) and were followed in a public register for four years. Cox regression analyses were performed separately for older workers with and without chronic disease to identify the associations between determinants and voluntary early retirement. To explore the differences between groups, an interaction term between the determinant and having a chronic disease was included in the analyses for the total population. Results: Among 1861 eligible older workers, determinants associated with a higher risk of voluntary early retirement included poorer self-rated health, more depressive symptoms, a higher physical workload, lower job satisfaction and lower influence at work. For older workers with a chronic disease (n=1185), the presence of work–family conflict was also associated with a higher risk of voluntary early retirement, whereas for those with no chronic disease (n=676), a poorer relationship with colleagues was an additional determinant. Higher emotional demands, a higher work pace and higher quantitative demands were not significantly associated with voluntary early retirement for either group. None of the interaction terms was found to be statistically significant (p>0.05). Conclusions: Determinants associated with voluntary early retirement did not significantly differ between older workers with or without a chronic disease in Denmark. We conclude that several health-related, work-related and social factors are important for prolonged labour force participation of older workers (with and without a chronic disease).