Miracle-dz/UniFAR-FTUs huggingface dataset:
Moving the Needle on Hypertension: What Knowledge Is Needed?

This review highlights the gaps in knowledge and methodological challenges discussed during the Experimental Biology 2019 expert panel session titled "Moving the Needle on Hypertension: What Knowledge Is Needed? " Hypertension is a critical public health burden. Despite a demonstrated benefit of blood pressure reduction on measures of hypertension-related morbidity and mortality, rates for successful blood pressure control remain low. Dietary sodium reduction has been shown to reduce both systolic blood pressure by approximately 3.2 mm Hg and diastolic blood pressure by 2.3 mm Hg, depending on baseline blood pressure and degree of sodium reduction. The updated Dietary Reference Intakes for adults released by the National Academies of Sciences, Engineering, and Medicine include a Chronic Disease Risk Reduction sodium intake level of 2300 mg/d, highlighting the importance of dietary sodium intake in reducing elevated blood pressure and indicating that reducing intakes to this level is expected to reduce blood pressure and risk of cardiovascular disease. The average US daily sodium intake of 3400 mg/d is well above the Chronic Disease Risk Reduction of 2300 mg/d, suggesting that dietary sodium reduction has the potential to significantly improve public health. Although the National Academies of Sciences, Engineering, and Medicine report presents intake recommendations based on a systematic, comprehensive, and thorough evaluation of the evidence, several challenges to moving the needle on hypertension remain. Success will require a more advanced understanding of sodium and potassium physiology, as well as development of the tools needed to effectively address existing research gaps and reduce barriers to sodium intake reduction.
FoxO3a Gene Down-regulation in Pathogenesis of Pediatric Acute Lymphoblastic Leukemia

Abstract Introduction: Acute lymphoblastic leukemia (ALL) is the most common malignancy found in the pediatrics with the peak prevalence between the ages of 2 and 5 years. The constitutive activation of PI3K/AKT pathway inhibits the tumor-suppressor role of FoxO3a (a member of the forkhead class O [FoxO] transcription factor family) in a variety of cancers and leads to tumorigenesis. This study aims to investigate the expression of FoxO3a in three different stages of pediatric ALL in mRNA level. Subjects and Methods: In this case-control study, 70 patients with childhood ALL and 70 healthy age- and gender-matched as the control group were enrolled. Real-time quantitative RT-polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression level of FoxO3a in children with different stages of ALL and healthy children as a control group. Results: Data showed that the expression of FoxO3a mRNA was lower in newly diagnosed ALL patients compared to controls (P < 0.0001), maintenance (P = 0.0342), and relapse (P = 0.0006) groups, while no difference was observed between other groups. In addition, T-ALL patients showed decreased expression of FoxO3a compared to Pre-B ALL ones (P < 0.0001). Conclusion: The study results suggest that FoxO3a plays a tumor-suppressor role in ALL. Thus, its up-regulation seems to be a plausible therapeutic strategy for this type of tumor.
Diabetic Retinopathy–An Underdiagnosed and Undertreated Inflammatory, Neuro-Vascular Complication of Diabetes

Diabetes mellitus is a world-wide epidemic and diabetic retinopathy, a devastating, vision-threatening condition, is one of the most common diabetes-specific complications. Diabetic retinopathy is now recognized to be an inflammatory, neuro-vascular complication with neuronal injury/dysfunction preceding clinical microvascular damage. Importantly, the same pathophysiologic mechanisms that damage the pancreatic β-cell (e.g., inflammation, epigenetic changes, insulin resistance, fuel excess, and abnormal metabolic environment), also lead to cell and tissue damage causing organ dysfunction, elevating the risk of all complications, including diabetic retinopathy. Viewing diabetic retinopathy within the context whereby diabetes and all its complications arise from common pathophysiologic factors allows for the consideration of a wider array of potential ocular as well as systemic treatments for this common and devastating complication. Moreover, it also raises the importance of the need for methods that will provide more timely detection and prediction of the course in order to address early damage to the neurovascular unit prior to the clinical observation of microangiopathy. Currently, treatment success is limited as it is often initiated far too late and after significant neurodegeneration has occurred. This forward-thinking approach of earlier detection and treatment with a wider array of possible therapies broadens the physician's armamentarium and increases the opportunity for prevention and early treatment of diabetic retinopathy with preservation of good vision, as well the prevention of similar destructive processes occurring among other organs.
Paraphrase-Sense-Tagged Sentences

Abstract Many natural language processing tasks require discriminating the particular meaning of a word in context, but building corpora for developing sense-aware models can be a challenge. We present a large resource of example usages for words having a particular meaning, called Paraphrase-Sense-Tagged Sentences (PSTS). Built on the premise that a word’s paraphrases instantiate its fine-grained meanings (i.e., bug has different meanings corresponding to its paraphrases fly and microbe) the resource contains up to 10,000 sentences for each of 3 million target-paraphrase pairs where the target word takes on the meaning of the paraphrase. We describe an automatic method based on bilingual pivoting used to enumerate sentences for PSTS, and present two models for ranking PSTS sentences based on their quality. Finally, we demonstrate the utility of PSTS by using it to build a dataset for the task of hypernym prediction in context. Training a model on this automatically generated dataset produces accuracy that is competitive with a model trained on smaller datasets crafted with some manual effort.
How Pre-service Teachers' Conceptions of Assessment Change Over Practicum: Implications for Teacher Assessment Literacy

Practicum poses great challenges for pre-service teachers who learn to assess because their conceptions of assessment (CoA) may undergo dramatic changes. This multiple case study reports on how three pre-service teachers’ CoA changed over practicum at a primary school in China. Findings show that pre-service teachers’ CoA have experienced a rapid change from a superficial perception of assessment for academic achievement and moral character development, to a more comprehensive understanding of varied assessment purposes, constructs in assessment criteria, feedback, fairness in classroom assessment, and students’ involvement in and engagement with assessment. A range of factors are found to have exerted varying degrees of influence on these conception changes, such as personal factor (i.e., agency in assessment), experiential factors (i.e., school-based assessment practices, interactions with students, and (anti-)apprenticeship of observation about assessment) and contextual factors (i.e., mentoring, classroom reality, school assessment culture, and national assessment policy). These findings are discussed in terms of how these changes are diverse but limited, as well as how the mediating factors have exerted differentiated influences in positive or negative ways. This paper concludes with implications for research on teachers’ CoA and professional development for assessment literacy.
False Recognition in Short-Term Memory – Age-Differences in Confidence

Compared to young adults, older adults are more susceptible to endorse false memories as genuine and exhibit higher confidence in their decisions to do so. While most studies to date have addressed this phenomenon in the context of episodic memory, the literature on age-differences in false recognition during short-term memory (STM) is scarce. Hence, the present study investigated age-related differences in the rate of false alarms (FA) and subsequent confidence judgments in STM. Thirty-three young and thirty-three older adults performed a visual short-term recognition memory task. In each trial, participants encoded a single abstract object, then made a “same” or “different” decision on a subsequent test, followed by a confidence judgment. We found significant age-related differences in performance as measured by the sensitivity index (d′), but not in the rate of FAs. Older adults were more confident in their erroneous recognition decisions than younger adults. The results are discussed in the context of age-differences in monitoring and associative processes.
Di (2-ethylhexyl) Phthalate Exposure Impairs the microRNAs Expression Profile During Primordial Follicle Assembly

This research was performed to estimate the potential effects of Di (2-ethylhexyl) phthalate (DEHP) on changes of ovarian miRNA expression profile during mouse primordial follicle assembly using miRNAs-seq analysis. The ovaries of newborn mice were collected and in vitro cultured with different concentration of DEHP for 72 h. Then they were prepared for miRNAs-seq analysis. The results indicated that DEHP exposure altered ovarian miRNA expression profile of newborn mice. Eighteen differentially expressed miRNAs were screened after 100 μM DEHP exposure. The target mRNAs of differentially expressed miRNAs were predicted and further analyzed through gene ontology (GO) enrichment analysis and pathway enrichment analysis. Our results showed that the differentially expressed miRNAs from DEHP exposure can regulate ovarian development by targeting mRNAs involved in MAPK, mTOR, FoxO signaling pathways. Three miRNAs of miR-32-5p, miR-19a-3p, and miR-141-3p were randomly selected from the differentially expressed miRNAs to quantify their expression level by miRNA qRT-PCR. The results of qRT-PCR and miRNA-seq were consistent. Considering one of its target gene PTEN of miR-19a-3p and the decreased level of pAKT and increased Bax/Bcl-2 under DEHP exposure, we speculated that the altered expression of miR-19a-3p by DEHP exposure affected mouse primordial follicle assembly via PI3K/AKT1/mTOR signaling pathway. Epigenetic changes are one of the most important targets of toxicant exposure. The effects of DEHP exposure on microRNA (one of the epigenetic regulators) expression profile were uncovered to enrich the research on relationship of epigenetics and toxicant exposure.
Pharmacological and biochemical properties of Zingiber zerumbet (L.) Roscoe ex Sm. and its therapeutic efficacy on osteoarthritis of knee

Osteoarthritis (OA) as the most frequent form of knee arthritis is one of the most annoying complications amongst old peoples. There are different pharmacological and non-pharmacological remedies which could be applied for treatment of knee OA. It's while, significant side effects mostly in patients who are older are the dangerous limiting factors. Integrative, supplementary, traditional remedies have been applied from long time ago in treatment of such chronic diseases like OA. Various topical and oral remedies have been presented in treatment of OA worldwide. In spite of the fact there are multiple remedies for reduction symptoms of patients who suffer from disorders and related inabilities which could enhance their life quality. Remedies which have been applied for a long time for treatment of OA have newly discovered to induce injury to some patients. On the other side, additional knowledge about alternative and supplementary remedies is a main way for enhancing health of patients who suffer from OA disorders. Zingiber zerumbet (Z. zerumbeton) is a kind of herb of the ginger family and is a natural compound with various biomedical characteristics like anti-proliferative, anti-inflammatory, and antioxidant effect. However, Z. zerumbet could be applied for reduction of OA symptoms because of its circulatory stimulant and anti-inflammatory effects. Anyway, up to now there is not any methodical literature review for evaluating the Z. zerumbet clinical effectiveness productiveness in treatment of OA. The main aim of the current study is to review scientific resources around therapeutic effectiveness of Zingiber zerumbet in treatment of adverse symptoms of OA disorder.
Structural Design, Synthesis, and Preliminary Biological Evaluation of Novel Dihomooxacalix[4]arene-Based Anti-tumor Agents

Calixarene and its derivatives have extensively served as promising anti-tumor agents. Previously, we have synthesized a series of calix[n]arene polyhydroxyamine derivatives (n = 4, 6, 8) and found that 5,11,17,23-tetra-tert-butyl-25,27-bis [N-(2-hydroxyethyl)aminocarbonylmethoxyl] calix[4]arene (CLX-4) displayed significant effect toward SKOV3, A549, SW1990, HeLa, Raji, and MDA-MB-231 cancer cells. In the present work, we find a replacement of calix[4]arene bone and synthesized 19 novel structurally related dihomooxacalix[4]arene amide derivatives 4A−4S to optimize its efficacy. Their abilities to induce cytotoxicity in human lung carcinoma (A549) cells, breast cancer (MCF-7) cells, cervical cancer (HeLa) cells, hepatocellular carcinoma (HepG2) cells, as well as human umbilical vein endothelial (HUVEC) cells are evaluated in vitro. Encouraging results show that the majority of dihomooxacalix[4]arene amide derivatives are effective at inhibiting A549 cell proliferation with the corresponding IC50 ranging from 0.6 to 20.1 μM. In particular, compounds 4A, 4D, and 4L explore markedly increased potency (IC50 value is 2.0 ± 0.5 μM, 0.7 ± 0.1 μM, and 1.7 ± 0.4 μM) over the cytotoxicity profiles of control CLX-4, whose IC50 value is 2.8 ± 0.3 μM. More interestingly, 4A also demonstrates the perfect cytotoxic effect against MCF-7, HeLa, and HepG2 cells with IC50 values of 1.0 ± 0.1 μM, 0.8 ± 0.2 μM, and 2.7 ± 0.4 μM. In addition, the results proved that our synthesized 4A has much lower toxicity (41%) to normal cells at a concentration of 10 μM than that of 4D (90%). To reveal the mechanisms, the key indicators including the cell cycle and apoptosis are observed by the flow cytometry analysis in MCF-7 cells. The results demonstrate that both 4A and 4D can induce the MCF-7 cell cycle arrest in G0/G1 phase and cell apoptosis. Therefore, our finding proves that the dihomooxacalix[4]arene amide derivatives are convenient platforms for potential supramolecular anticancer agents.
GLRT Detection of Nonfluctuating Targets in Background Noise Using Phased Arrays

This work assesses the performance of a phased array radar working in background noise. To do so, we consider the presence of a nonfluctuating target embedded in complex white Gaussian noise (CWGN), in which the amplitude of the target echo and the noise power are assumed to be unknown. Making use of the generalized likelihood ratio test (GLRT), we design and analyze a detector based on the phased-array front end. We obtain exact closed-form expressions for the probability density functions (PDFs) corresponding to the detection statistics. In addition, we derive a fast convergent series for the probability of detection (PD). The derived series presents a low computational cost while maintaining a tractable and efficient solution. Numerical results and Monte Carlo simulations corroborate the validity of our expressions. The performance of the proposed detector is also compared with the idealized Neyman-Pearson (NP) detector to quantify the practical losses in terms of the signal-to-noise ratio (SNR).
Genetic Variants in Group-Specific Component (GC) Gene Are Associated with Breast Cancer Risk among Chinese Women

The group-specific component (GC) gene, one of the vitamin D pathway genes, seems to play an important role in cancer development. A population-based breast cancer study including 818 cases and 935 controls in a Chinese population was carried out to evaluate the potential associations of four polymorphisms (rs16847024, rs17467825, rs2298850, and rs3755967) in the GC gene with risk of breast cancer. We detected three SNPs with statistically significant effects on breast cancer development after adjusting for age, menopausal status, body mass index (BMI), family history of breast cancer, income, waist circumference, and education (rs17467825: adjusted OR = 0.80, 95% CI = 0.65–0.99; rs2298850: adjusted OR = 0.80, 95% CI = 0.65–0.98; rs3755967: adjusted OR = 0.80, 95% CI = 0.65–0.98). Stratified analysis found that when an individual had a waist circumference <80 cm, rs17467825, rs2298850, and rs3755967 could markedly reduce the risk of breast cancer. Significant interactions between polymorphisms of rs2298850 and rs3755967 and waist circumference were also observed for breast cancer risk. Combined analysis revealed a significant association among the allele numbers of protective effects with decreased breast cancer risk (Ptrend=0.043). These results indicated that, in the GC gene, genetic mutations might be related to breast cancer susceptibility in Chinese women.
Carvedilol Inhibits Angiotensin II-Induced Proliferation and Contraction in Hepatic Stellate Cells through the RhoA/Rho-Kinase Pathway

Aim Carvedilol is a nonselective beta-blocker used to reduce portal hypertension. This study investigated the effects and potential mechanisms of carvedilol in angiotensin II- (Ang II-) induced hepatic stellate cell (HSC) proliferation and contraction. Methods The effect of carvedilol on HSC proliferation was measured by Cell Counting Kit-8 (CCK-8). Cell cycle progression and apoptosis in HSCs were determined by flow cytometry. A collagen gel assay was used to confirm HSC contraction. The extent of liver fibrosis in mice was evaluated by hematoxylin-eosin (H&E) and Sirius Red staining. Western blot analyses were performed to detect the expression of collagen I, collagen III, α-smooth muscle actin (α-SMA), Ang II type I receptor (AT1R), RhoA, Rho-kinase 2 (ROCK2), and others. Results The results showed that carvedilol inhibited HSC proliferation and arrested the cell cycle at the G0/G1 phase in a dose-dependent manner. Carvedilol also modulated Bcl-2 family proteins and increased apoptosis in Ang II-treated HSCs. Furthermore, carvedilol inhibited HSC contraction induced by Ang II, an effect that was associated with AT1R-mediated RhoA/ROCK2 pathway interference. In addition, carvedilol reduced α-SMA expression and collagen deposition and attenuated liver fibrosis in carbon tetrachloride (CCl4)-treated mice. The in vivo data further confirmed that carvedilol inhibited the expression of angiotensin-converting enzyme (ACE), AT1R, RhoA, and ROCK2. Conclusions The results indicated that carvedilol dose-dependently inhibited Ang II-induced HSC proliferation by impeding cell cycle progression, thus alleviating hepatic fibrosis. Furthermore, carvedilol could inhibit Ang II-induced HSC contraction by interfering with the AT1R-mediated RhoA/ROCK2 pathway.
Monotherapy with Metformin versus Sulfonylureas and Risk of Cancer in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis

Background Accumulating evidence suggests that patients with type 2 diabetes mellitus and hyperinsulinemia are at an increased risk of developing malignancies. It remains to be fully elucidated whether the use of metformin, an insulin sensitizer, and/or sulfonylureas, insulin secretagogues, affects cancer incidence in subjects with type 2 diabetes mellitus. Objective A systematic review and meta-analysis was performed to compare the risk of cancer incidence associated with monotherapy with metformin compared with monotherapy with sulfonylureas in type 2 diabetes mellitus patients. Methods Search was performed throughout MEDLINE/PubMed, EMBASE, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov up until December 2018. In this meta-analysis, each raw data (unadjusted) and study-specific (adjusted) relative risks (RRs) was combined and the pooled unadjusted and adjusted RRs with the 95% CI were calculated using the random-effects model with inverse-variance weighting. Heterogeneity among the studies was evaluated using I2 statistics. Publication bias was evaluated using the funnel plot asymmetry test. The Newcastle-Ottawa scale (NOS) was used to assess the study quality. Results A total of 8 cohort studies were included in the meta-analysis. Obvious heterogeneity was noted, and monotherapy with metformin was associated with a lower risk of cancer incidence (unadjusted RR = 0.74, 95% CI: 0.55-0.99, I2 = 97.89%, p < 0.00001; adjusted RR = 0.76, 95% CI: 0.54–1.07, I2 = 98.12%, p < 0.00001) compared with monotherapy with sulfonylurea, using the random-effects model with inverse-variance weighting. Conclusions According to this review, the monotherapy with metformin appears to be associated with a lower risk of cancer incidence than monotherapy with sulfonylurea in patients with type 2 diabetes. This analysis is mainly based on cohort studies, and our findings underscore the need for large-scale randomized controlled trials to establish the effect of metformin monotherapy, relative to sulfonylureas monotherapy on cancer.
5α,6α-Epoxyphytosterols and 5α,6α-Epoxycholesterol Increase Oxidative Stress in Rats on Low-Cholesterol Diet

Objective Cholesterol oxidation products have an established proatherogenic and cytotoxic effect. An increased exposure to these substances may be associated with the development of atherosclerosis and cancers. Relatively little, though, is known about the effect of phytosterol oxidation products, although phytosterols are present in commonly available and industrial food products. Thus, the aim of the research was to assess the effect of 5α,6α-epoxyphytosterols, which are important phytosterol oxidation products, on redox state in rats. Material and Methods The animals were divided into 3 groups and exposed to nutritional sterols by receiving feed containing 5α,6α-epoxyphytosterols (ES group) and 5α,6α-epoxycholesterol (Ech group) or sterol-free feed (C group). The levels of malondialdehyde (MDA), conjugated dienes (CD), and ferric reducing antioxidant potential (FRAP) were assayed in the plasma; anti-7-ketocholesterol antibodies and activity of paraoxonase-1 (PON1) were determined in serum, whereas the activity of catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), S-glutathione transferase (GST), and superoxide dismutase (SOD) were assayed in RBCs. Results During the experiment, the levels of lipid peroxidation products increased, such as CD and anti-7-ketocholesterol antibodies. At the same time, the plasma levels of FRAP and serum activity of PON1 decreased alongside the reduced activity of GPx, GR, and SOD in RBCs. There was no effect of the studied compounds on the plasma MDA levels or on the activity of CAT and GST in RBCs. Conclusions Both 5α,6α-epoxyphytosterols and 5α,6α-epoxycholesterols similarly dysregulate the redox state in experimental animal model and may significantly impact atherogenesis.