Miracle-dz/UniFAR-FTUs huggingface dataset:
Placental Ischemia Says “NO” to Proper NOS-Mediated Control of Vascular Tone and Blood Pressure in Preeclampsia

In this review, we first provide a brief overview of the nitric oxide synthase (NOS) isoforms and biochemistry. This is followed by describing what is known about NOS-mediated blood pressure control during normal pregnancy. Circulating nitric oxide (NO) bioavailability has been assessed by measuring its metabolites, nitrite (NO2) and/or nitrate (NO3), and shown to rise throughout normal pregnancy in humans and rats and decline postpartum. In contrast, placental malperfusion/ischemia leads to systemic reductions in NO bioavailability leading to maternal endothelial and vascular dysfunction with subsequent development of hypertension in PE. We end this article by describing emergent risk factors for placental malperfusion and ischemic disease and discussing strategies to target the NOS system therapeutically to increase NO bioavailability in preeclamptic patients. Throughout this discussion, we highlight the critical importance that experimental animal studies have played in our current understanding of NOS biology in normal pregnancy and their use in finding novel ways to preserve this signaling pathway to prevent the development, treat symptoms, or reduce the severity of PE.
Epidemiology of Football-Related Sudden Cardiac Death in Turkey

Background and Objectives: Sudden cardiac death (SCD), particular among elite footballers, has attracted much attention in recent times. However, limited information exists on football-related SCD in Turkey. Autopsy-based studies of sports-related sudden deaths in Turkey are rare and often have small sample sizes. To address this, this study aimed to determine the population-based incidence and profile of football-related SCD nationally in Turkey. Materials and Methods: Due to a lack of national data on this issue, football-related SCD (non-elite competitive or recreational football) between 1 January 2011, and 31 December 2019 were identified by dual, independent identification and screening of online media reports. Deaths were explored by sex, age group, season, and phase of exercise. Descriptive statistics were utilised. Age-specific mortality rates and proportional mortality rates were calculated. Results: In total, 118 football-related SCD were identified, a crude mortality rate of 0.41 per 100,000 population. All fatalities were males and the mean age was 35.5 years ± 10.4. Those aged 40–49 years recorded the highest mortality rate (0.67/100,000), three times the risk of those aged 50–59 years (RR = 3.1; 95%CI:1.5–6.4). Those aged 30–39 recorded the highest age-specific proportional mortality rate (0.86/1000 deaths). The highest risk occurred while playing football (n = 97; 82.2%), with another 15% of deaths (n = 18) occurring within 1 h of play. Almost all fatalities (n = 113; 95.8%) occurred during participation in recreational football. Conclusions: This study has identified football-related SCD most commonly occurs during recreational football among males aged 30–49 years. It is recommended males of this age participating in recreational football be encouraged to seek pre-participation heart health checks. Given the value of automated external defibrillators (AEDs) in responding to out-of-hospital cardiac arrest, future research should explore the feasibility and effectiveness of AEDs in preventing football-related SCD in Turkey including training of first responders in cardiopulmonary resuscitation and AED use.
Gene Duplication and Differential Expression of Flower Symmetry Genes in Rhododendron (Ericaceae)

Bilaterally symmetric flowers have evolved over a hundred times in angiosperms, yet orthologs of the transcription factors CYCLOIDEA (CYC), RADIALIS (RAD), and DIVARICATA (DIV) are repeatedly implicated in floral symmetry changes. We examined these candidate genes to elucidate the genetic underpinnings of floral symmetry changes in florally diverse Rhododendron, reconstructing gene trees and comparing gene expression across floral organs in representative species with radial and bilateral flower symmetries. Radially symmetric R. taxifolium Merr. and bilaterally symmetric R. beyerinckianum Koord. had four and five CYC orthologs, respectively, from shared tandem duplications. CYC orthologs were expressed in the longer dorsal petals and stamens and highly expressed in R. beyerinckianum pistils, whereas they were either ubiquitously expressed, lost from the genome, or weakly expressed in R. taxifolium. Both species had two RAD and DIV orthologs uniformly expressed across all floral organs. Differences in gene structure and expression of Rhododendron RAD compared to other asterids suggest that these genes may not be regulated by CYC orthologs. Our evidence supports CYC orthologs as the primary regulators of differential organ growth in Rhododendron flowers, while also suggesting certain deviations from the typical asterid gene regulatory network for flower symmetry.
Phytochemical Screening of Himatanthus sucuuba (Spruce) Woodson (Apocynaceae) Latex, In Vitro Cytotoxicity and Incision Wound Repair in Mice

Himatanthus sucuuba, also known as “Bellaco caspi”, is a medicinal plant whose latex, stem bark, and leaves possess phenolic acids, lupeol, β-dihydro-plumbericinic acid, plumericin, and plumeride, among other components. Some of these have been linked to such biological activities as antiulcer, anti-inflammatory, and wound healing. The aim of this study was to determine the phytochemical compounds of H. sucuuba latex, as well as its in vitro cytotoxicity and wound healing effect in mice. Latex was collected in the province of Iquitos, Peru. Phytochemical analysis was carried out with UPLC-ESI-MS/MS. The cytotoxicity was evaluated on two colon tumor cell lines (SW480 and SW620) and non-malignant cells (human keratinocytes, HaCaT, and Chinese hamster ovary, CHO-K1). The mice were distributed into two groups, as follows: Group I—control (n = 10; without treatment); II—(n = 10) H. sucuuba latex; wounds were induced with a scalpel in the dorsal–cervical area and treatments were applied topically twice a day on the incision for 10 days. Molecular docking was carried out on the glycogen synthase kinase 3β protein. Twenty-four chemical compounds were determined, mainly flavonoid-type compounds. Latex did not have a cytotoxic effect on tumor cells with IC50 values of more than 500 µg/mL. The latex had a regenerative effect on wounds in mice. Acacetin-7-O-neohesperidoside had the best docking score of −9.9 kcal/mol. In conclusion, H. sucuuba latex had a wound healing effect in mice, as confirmed by histological study. However, a non-cytotoxic effect was observed on colon tumor cells SW480 and SW620.
The Predominant Role of Arrestin3 in General GPCR Desensitization in Platelets

Arrestins in concert with GPCR kinases (GRKs) function in G protein-coupled receptor (GPCR) desensitization in various cells. Therefore, we characterized the functional differences of arrestin3 versus arrestin2 in the regulation of GPCR signaling and its desensitization in platelets using mice lacking arrestin3 and arrestin2. In contrast to arrestin2, platelet aggregation and dense granule secretion induced by 2-MeSADP, U46619, thrombin, and AYPGKF were significantly potentiated in arrestin3-deficient platelets compared to wild-type (WT) platelets, while non-GPCR agonist CRP-induced platelet aggregation and secretion were not affected. Surprisingly, in contrast to GRK6, platelet aggregation induced by the co-stimulation of serotonin and epinephrine was significantly potentiated in arrestin3-deficient platelets, suggesting the central role of arrestin3 in general GPCR desensitization in platelets. In addition, the second challenge of ADP and AYPGKF restored platelet aggregation in arrestin3-deficient platelets but failed to do so in WT and arrestin2-deficient platelets, confirming that arrestin3 contributes to GPCR desensitization. Furthermore, ADP- and AYPGKF-induced Akt and ERK phosphorylation were significantly increased in arrestin3-deficient platelets. Finally, we found that arrestin3 is critical for thrombus formation in vivo. In conclusion, arrestin3, not arrestin2, plays a central role in the regulation of platelet functional responses and thrombus formation through general GPCR desensitization in platelets.
Vitamin D Status and Physical Activity during Wintertime in Forensic Inpatients—A Randomized Clinical Trial

This study aimed to gain deeper knowledge about the relationship between vitamin D and physical activity in a sample of forensic inpatients. Sixty-seven male forensic inpatients participated. Participants were randomly assigned into an Intervention group (vitamin D) or a Control group (placebo). The Physical Activity–Rating (PA-R) questionnaire was used to measure physical activity from January to May. Vitamin D status was measured as 25-hydroxy vitamin D (25-OHD) pre- and post-intervention. The results revealed that vitamin D status at post-test was positively correlated with physical activity, but there was no effect of vitamin D supplementation looking at the two randomized groups. However, controlling for body mass index (BMI), the results showed an effect of BMI and a main effect of groups with a higher level of physical activity in the Intervention group. No interaction effects were found. Participants were also assigned into High and Low vitamin D groups based on the vitamin D status at post-test; i.e., the upper (75.1 nmol/L) and lower quartile (46.7 nmol/L). T-tests revealed that participants with a vitamin D status above 75 nmol/L showed significantly higher levels of physical activity than participants with a vitamin D status below 46.7 nmol/L. Thus, a vitamin D status above 75 nmol/L seems to be an optimal level.
Epstein-Barr Virus miR-BART1-3p Regulates the miR-17-92 Cluster by Targeting E2F3

Epstein-Barr virus (EBV) is associated with several tumors and generates BamHI A rightward transcript (BART) microRNAs (miRNAs) from BART transcript introns. These BART miRNAs are expressed at higher levels in EBV-associated epithelial malignancies than in EBV-infected B lymphomas. To test the effects of EBV miRNA on the cell cycle and cell growth, we transfected miR-BART1-3p, a highly expressed EBV-associated miRNA, into gastric carcinoma cells. We found that miR-BART1-3p induced G0/G1 arrest and suppressed cell growth in gastric carcinoma cells. As our microarray analyses showed that E2F3, a cell cycle regulator, was inhibited by EBV infection, we hypothesized that miR-BART1-3p regulates E2F3. Luciferase assays revealed that miR-BART1-3p directly targeted the 3′-UTR of E2F3 mRNA. Both E2F3 mRNA and encoded protein levels were reduced following miR-BART1-3p transfection. In contrast, E2F3 expression in AGS-EBV cells transfected with a miR-BART1-3p inhibitor was enhanced. As E2F3 has been shown to regulate the expression of highly conserved miR-17-92 clusters in vertebrates, we examined whether this expression is affected by miR-BART1-3p, which can downregulate E2F3. The expression of E2F3, miR-17-92a-1 cluster host gene (MIR17HG), and miR-17-92 cluster miRNAs was significantly reduced in EBV-associated gastric carcinoma (EBVaGC) patients compared with EBV-negative gastric carcinoma (EBVnGC) patients. Further, miR-BART1-3p as well as the siRNA specific to E2F3 inhibited the expression of the miR-17-92 cluster, while inhibition of miR-BART1-3p enhanced the expression of the miR-17-92 cluster in cultured GC cells. Our results suggest a possible role of miR-BART1-3p in cell cycle regulation and in regulation of the miR-17-92 cluster through E2F3 suppression.
Reinforced Concrete Beam under Support Removal—Parametric Analysis

This paper investigates the behaviour of a reinforced concrete beam under a support removal. A detailed parametric analysis is carried out, covering the effect of support removal rate on dynamic response. The linear elastic and nonlinear inelastic responses are computed and studied in detail. Critical parameters during the structural response are identified. In order to determine the ultimate load, the vertical pushover analysis is performed. The key parameters driving the beam response are assumed as random variables, and respective reliability study makes it possible to check the overall uncertainty of the dynamic response. In particular, the response spectrum measuring the effect of support removal rate has been computed. It has been demonstrated that the critical vertical response occurs when the time of support removal is up to to 17% of the first natural period. The vertical pushover analysis results in obtaining capacity curves and showed the order in which two plastic hinges occur for various load patterns. Finally, the reliability-based sensitivity analysis indicates the geometric cross-section cover and height are the most sensitive parameters of the beam response.
Update on Dihydropteroate Synthase (DHPS) Mutations in Pneumocystis jirovecii

A Pneumocystis jirovecii is one of the most important microorganisms that cause pneumonia in immunosupressed individuals. The guideline for treatment and prophylaxis of Pneumocystis pneumonia (PcP) is the use of a combination of sulfa drug-containing trimethroprim and sulfamethoxazole. In the absence of a reliable method to culture Pneumocystis, molecular techniques have been developed to detect mutations in the dihydropteroate synthase gene, the target of sulfa drugs, where mutations are related to sulfa resistance in other microorganisms. The presence of dihydropteroate synthase (DHPS) mutations has been described at codon 55 and 57 and found almost around the world. In the current work, we analyzed the most common methods to identify these mutations, their geographical distribution around the world, and their clinical implications. In addition, we describe new emerging DHPS mutations. Other aspects, such as the possibility of transmitting Pneumocystis mutated organisms between susceptible patients is also described, as well as a brief summary of approaches to study these mutations in a heterologous expression system.
Mechanisms Involved in the Relationship between Vitamin D and Insulin Resistance: Impact on Clinical Practice

Recent evidence has revealed anti-inflammatory properties of vitamin D as well as extra-skeletal activity. In this context, vitamin D seems to be involved in infections, autoimmune diseases, cardiometabolic diseases, and cancer development. In recent years, the relationship between vitamin D and insulin resistance has been a topic of growing interest. Low 25-hydroxyvitamin D (25(OH)D) levels appear to be associated with most of the insulin resistance disorders described to date. In fact, vitamin D deficiency may be one of the factors accelerating the development of insulin resistance. Vitamin D deficiency is a common problem in the population and may be associated with the pathogenesis of diseases related to insulin resistance, such as obesity, diabetes, metabolic syndrome (MS) and polycystic ovary syndrome (PCOS). An important question is the identification of 25(OH)D levels capable of generating an effect on insulin resistance, glucose metabolism and to decrease the risk of developing insulin resistance related disorders. The benefits of 25(OH)D supplementation/repletion on bone health are well known, and although there is a biological plausibility linking the status of vitamin D and insulin resistance supported by basic and clinical research findings, well-designed randomized clinical trials as well as basic research are necessary to know the molecular pathways involved in this association.
Post-traumatic stress disorder and childhood emotional abuse are markers of subthreshold bipolarity and worse treatment outcome in major depressive disorder

Post-traumatic stress disorder (PTSD) and childhood maltreatment (CMT: parental neglect; emotional, physical and sexual abuse) have been linked to bipolar disorder but they are also common in major depressive disorder (MDD). Our objective was to investigate their association with the bipolar spectrum and antidepressant treatment outcome in 482 outpatients with DSM-IV MDD treated in the Combining Medications to Enhance Depression Outcomes trial for 28 weeks Bipolar spectrum score included age of onset <21 years, subthreshold hypomania (a period of elated or irritable mood with at least two concurrent hypomanic symptoms, which did not fulfill DSM criteria for hypomanic/manic episode) and depressive mixed state (DMX). PTSD subjects (n = 107; 22%) had more severe depression (P < 0.0001), work and social impairment (P = 0.0031), comorbid anxiety disorders (P < 0.0001) and increased suicidality (P = 0.0003). Bipolar spectrum score was higher with PTSD comorbidity (P = 0.0063) and childhood emotional abuse (P = 0.0001). PTSD comorbidity was associated with residual suicidality (P = 0.0218) after 6 weeks of antidepressant use whereas childhood emotional abuse [odds ratio (OR), 1.01–2.22], subthreshold hypomania (OR, 1.04–4.09) and DMX (OR, 1.00–4.19) were predictors of mood switch. These results corroborate the role of PTSD and childhood emotional abuse as markers of bipolar spectrum and prognostic factors during antidepressant treatment.
Total and Free Sugar Levels and Main Types of Sugars Used in 18,784 Local and Imported Pre-Packaged Foods and Beverages Sold in Hong Kong

There is limited information regarding the free sugar content of pre-packaged foods in Hong Kong. This study aims to assess the free sugar content and identify the most frequently used free sugar ingredients (FSI) in pre-packaged foods in Hong Kong. Data from 18,784 products from the 2019 FoodSwitch Hong Kong database were used in this analysis. Ingredient lists were screened to identify FSI. Total sugar content was derived from nutrition labels on packaging. Free sugar content was estimated based on adaptation of a previously established systematic methodology. Descriptive statistics of the total sugar and free sugar content, as well as the mean ± SD contribution of free sugar to total sugar of the audited products were calculated, stratified by food groups. Almost two-thirds (64.5%) of the pre-packaged foods contained at least one FSI. ‘Sugar (sucrose)’ was the most popular FSI that was found in more than half (54.7%) of the products. ‘Fruit and vegetable juices’ (median 10.0; IQR 8.3–11.5 g/100 mL) were found to have a higher median free sugar content than ‘Soft drinks’ (8.0; 6.0–10.6 g/100 mL). Mean ± SD contribution of free sugar to the total sugar content was 65.8 ± 43.4%, with 8 out of 14 food groups having >70% total sugar as free sugar. To conclude, free sugar, especially sucrose, was extensively used in a wide variety of pre-packaged products sold in Hong Kong. Further studies are needed to assess the population intake of free sugar in Hong Kong to inform public health policy on free sugar reduction.
Bazedoxifene, a Selective Estrogen Receptor Modulator, Promotes Functional Recovery in a Spinal Cord Injury Rat Model

In research on various central nervous system injuries, bazedoxifene acetate (BZA) has shown two main effects: neuroprotection by suppressing the inflammatory response and remyelination by enhancing oligodendrocyte precursor cell differentiation and oligodendrocyte proliferation. We examined the effects of BZA in a rat spinal cord injury (SCI) model. Anti-inflammatory and anti-apoptotic effects were investigated in RAW 264.7 cells, and blood-spinal cord barrier (BSCB) permeability and angiogenesis were evaluated in a human brain endothelial cell line (hCMEC/D3). In vivo experiments were carried out on female Sprague Dawley rats subjected to moderate static compression SCI. The rats were intraperitoneally injected with either vehicle or BZA (1mg/kg pre-SCI and 3 mg/kg for 7 days post-SCI) daily. BZA decreased the lipopolysaccharide-induced production of proinflammatory cytokines and nitric oxide in RAW 264.7 cells and preserved BSCB disruption in hCMEC/D3 cells. In the rats, BZA reduced caspase-3 activity at 1 day post-injury (dpi) and suppressed phosphorylation of MAPK (p38 and ERK) at dpi 2, hence reducing the expression of IL-6, a proinflammatory cytokine. BZA also led to remyelination at dpi 20. BZA contributed to improvements in locomotor recovery after compressive SCI. This evidence suggests that BZA may have therapeutic potential to promote neuroprotection, remyelination, and functional outcomes following SCI.
Synergistic Interaction of Dietary Pattern and Concordance Lifestyle with Abnormal Liver Function among Young Adults in Taiwan: A Population-Based Longitudinal Study

While diet and lifestyle are independently implicated in the etiology of liver disease, the interaction of diet and lifestyle may be more helpful for determining the risk of liver abnormality. Thus, our study aimed to evaluate the interaction between the dietary pattern associated with liver biomarkers and lifestyle factors among Taiwanese adults with abnormal liver enzymes. A liver-associated dietary pattern, generated using reduced rank regression, was characterized by high intake of soy sauce or other dips, sugar sweetened beverages, and preserved and processed foods, but low intake of seafood, fruits, eggs, and dark-colored vegetables. In the fully adjusted model, liver-associated dietary patterns or unhealthy concordance lifestyle factors were associated with an increased risk of having liver function abnormality (OR = 1.08, 95% CI: 1.04, 1.12 and OR = 1.42, 95% CI: 1.31, 1.53, respectively). Moreover, the interaction between liver-associated dietary pattern and unhealthy concordance lifestyle factors showed more significant correlation, with an elevated risk of abnormal liver function (OR = 2.14, 95% CI: 2.02, 2.26). Therefore, our study suggests that participants who have a strong liver-associated dietary pattern along with unhealthy concordance lifestyles are likely to have increased odds of abnormal liver function.
Analysis of the Efficiency and Prognostic Value of the Sentinel Node Technique in Oral Squamous Cell Carcinoma after Seven Years

Background and objectives: The purpose of this study was to analyse the diagnostic and prognostic efficiency of the sentinel lymph node biopsy technique (SLNB). Materials and Methods: This is a prospective observational study performed by the Hospital Complex in Santiago de Compostela (CHUS) in Spain, between February 2013 and June 2020. The study included 60 patients, who had been diagnosed with OSCC in stage T1/T2N0M0. Results: 10 patients (16.7%) presented with SN+ (sentinel node positive). The majority (80%) only presented subcapsular affection, however one case also presented with extracapsular affection. Using the Kaplan–Meier curves, we determined that the average survival estimation for SN− patients was 74.0 months (CI95% 67.6–80.5) and it was 45.4 months (CI95% 10.9–24.0) for SN+ patients (p = 0.002). SN+ patients presented an OR = 11.000 (CI95% 2.393–50.589, p = 0.002) for cancer-related mortality. In terms of the diagnostic performance of the SN (sentinel node) test, a 55% sensitivity, a 100% specificity, 100% PPV and a 84% NPV were obtained. The analysis using ROC (receiver operating characteristic) curves revealed an AUC = 0.671 (CI95% 0.492–0.850, p = 0.046). Conclusions: SLNB seems to be an adequate technique for the detection of hidden metastases.