Miracle-dz/UniFAR-FTUs huggingface dataset:
Homocysteine Upregulates Soluble Epoxide Hydrolase in Vascular Endothelium In Vitro and In Vivo

Rationale: Hyperhomocysteinemia is a risk factor of atherogenesis. Soluble epoxide hydrolase (sEH) is a major enzyme that hydrolyzes epoxyeicosatrienoic acids and attenuates their cardiovascular protective effects. Whether homocysteine (Hcy) regulates sEH and the underlying mechanism remains elusive. Objective: To elucidate the mechanism by which Hcy regulates sEH expression and endothelial activation in vitro and in vivo. Methods and Results: Hcy treatment in cultured human endothelial cells dose-dependently and time-dependently upregulated sEH mRNA and protein. Hcy increased the expression of adhesion molecules, which was markedly reversed by inhibiting sEH activity. Hcy-induced sEH upregulation is associated with activation of activating transcription factor-6 (ATF6). Bioinformatics analysis revealed a putative ATF6-binding motif in the promoter region of the sEH gene, which was found at a methylation site. Site-directed mutagenesis and chromatin immunoprecipitation assays demonstrated that Hcy treatment or ATF6 overexpression promoted ATF6 binding to the promoter of sEH and increased its activity. Results of methylation-specific polymerase chain reaction revealed that the ATF6 binding site on the sEH promoter was partially methylated and was demethylated with Hcy. SiRNA knockdown of ATF6&agr; or SP1 blocked and ATF6 overexpression and DNA methyltransferase inhibitor mimicked the effect of homocysteine on sEH upregulation. In vivo, immunofluorescence assay revealed elevated expression of sEH and adhesion molecules in the aortic intima of mice with mild hyperhomocysteinemia, which was attenuated by sEH deletion or inhibition. Conclusion: ATF6 activation and DNA demethylation may coordinately contribute to Hcy-induced sEH expression and endothelial activation. Inhibition of sEH may be a therapeutic approach for treating Hcy-induced cardiovascular diseases.
The integration of morphological design and topology optimization to enhance the visual quality of electricity pylons

Purpose: This paper aims to enhance the visual quality of artificial above-ground structures, like pylons, masts, and towers of infrastructures and facilities, through a systematic design method for their morphological and structural optimization. Design/methodology/approach: The method achieves the functional and aesthetic goals based on the application of computer-aided tools. In particular, this is achieved according to three key steps: • Morphological development of landscape-related symbolism, environment, or culture and social needs. • Topology optimization of the design concept to reduce the structural weight and its visual impact. • Engineering of the resulting optimized structure. Practical implications: As a case study, the method is used for designing electricity pylons for the coastal territory of a Mediterranean European country, such as Italy. Citizens were involved during the identification phase of a symbolic shape for the concept development and during the final assessment phase. Research limitations/implications: The engineering phase has been performed by assembling standard lattice components with welded connections. Even if the use of this truss-like structure should lead to a minimum cost, the developed structure employs an additional 15%–20% of trusses and sheet metal covers the final cost is higher than a standard lattice pylon. Findings: The result is a structure with enhanced visual quality according to the international guidelines and fully complying with mandatory and functional requirements, such as regulatory and industrial feasibility, as well as those arising from social components. Originality/value: The method shows its potential in defining a custom design for lightweight structures with enhanced visual quality regarding the critical situation discussed here. The method considers both the subjective perception of citizens and their priorities and the landscape where the structures will be installed.
Predictors of early vocabulary growth in children born preterm and full term: A study of processing speed and medical complications

ABSTRACT Delays in expressive vocabulary may be harbingers of long-term language difficulties. In toddlers born full term (FT), individual differences in language processing speed are associated with variation in expressive vocabulary growth. Children born preterm (PT) are at increased risk for persistent language deficits. Here, we evaluate predictors of early vocabulary growth in PT toddlers in relation to two sources of variability: language processing speed and medical complications of prematurity. Vocabulary growth from 16 to 30 months (adjusted for degree of prematurity) was modeled longitudinally using parent reports in English-speaking FT (n = 63; ≥37 weeks, ≥2495 g) and PT (n = 69; ≤32 weeks, <1800 g) children, matched on sex and socioeconomic status. Children were tested in the “looking-while-listening task” at 18 months to derive a measure of language processing speed. Each PT child was assessed for number of medical complications (13 maximum), based on medical chart reviews. PT and FT children displayed similar vocabulary trajectories; however, birth group disparities began to emerge by 30 months. PT children were slower in language processing speed than FT children. Critically, language processing speed predicted expressive vocabulary size at 30 months; interactions with birth group were not significant (all p > .20). In PT children, faster language processing speed predicted stronger outcomes regardless of number of medical complications; slower processing speed and more medical complications predicted poorer outcomes. Faster processing speed reflected favorable neuropsychological processes associated with faster expressive vocabulary growth that overrode the impact of medical complications on language outcomes in PT children.
TOP1α regulates FLOWERING LOCUS C expression by coupling histone modification and transcription machinery

ABSTRACT The key steps of transcription are coupled with the opening of the DNA helical structure and establishment of active chromatin to facilitate the movement of the transcription machinery. Type I topoisomerases cleave one DNA strand and relax the supercoiled structure of transcribed templates. How topoisomerase-mediated DNA topological changes promote transcription and establish a permissive histone modification for transcription elongation is largely unknown. Here, we show that TOPOISOMERASE 1α in plants regulates FLOWERING LOCUS C transcription by coupling histone modification and transcription machinery. We demonstrate that TOP1α directly interacts with the methyltransferase SDG8 to establish high levels of H3K36 methylation downstream of FLC transcription start sites and recruits RNA polymerase II to facilitate transcription elongation. Our results provide a mechanistic framework for TOP1α control of the main steps of early transcription and demonstrate how topoisomerases couple RNA polymerase II and permissive histone modifications to initiate transcription elongation. Summary: TOP1α interacts with SDG8 and recruits RNA polymerase II to promote early transcriptional elongation by maintaining the open chromatin state and adding histone markers associated with active transcription.
Testing Darwin’s Hypothesis about the Wonderful Venus Flytrap: Marginal Spikes Form a “Horrid Prison” for Moderate-Sized Insect Prey

Botanical carnivory is a novel feeding strategy associated with numerous physiological and morphological adaptations. However, the benefits of these novel carnivorous traits are rarely tested. We used field observations, lab experiments, and a seminatural experiment to test prey capture function of the marginal spikes on snap traps of the Venus flytrap (Dionaea muscipula). Our field and laboratory results suggested inefficient capture success: fewer than one in four prey encounters led to prey capture. Removing the marginal spikes decreased the rate of prey capture success for moderate-sized cricket prey by 90%, but this effect disappeared for larger prey. The nonlinear benefit of spikes suggests that they provide a better cage for capturing more abundant insects of moderate and small sizes, but they may also provide a foothold for rare large prey to escape. Our observations support Darwin’s hypothesis that the marginal spikes form a “horrid prison” that increases prey capture success for moderate-sized prey, but the decreasing benefit for larger prey is unexpected and previously undocumented. Thus, we find surprising complexity in the adaptive landscape for one of the most wonderful evolutionary innovations among all plants. These findings enrich understanding of the evolution and diversification of novel trap morphology in carnivorous plants.
Different Brain Activities Predict Retrieval Success during Emotional and Semantic Encoding

There is an increasing line of evidence supporting the idea that the formation of lasting memories involves neural activity preceding stimulus presentation. Following this line, we presented words in an incidental learning setting and manipulated the prestimulus state by asking the participants to perform either an emotional (neutral or emotional) or a semantic (animate or inanimate) decision task. Later, we tested the retrieval of each previously presented word with a recognition memory test. For both conditions, the subsequent memory effect (SME) was defined as ERP difference between subsequently remembered and forgotten words. Comparing the prestimulus SME between and within the two conditions yielded topographic differences in the time interval from −1300 to −700 msec before stimulus onset. This indicates that the activity of brain areas involved in incidental encoding of semantic information varied in the spatial distribution of ERPs, depending on the emotional and semantic requirements of the task. These findings provide evidence that there is a difference in semantic and emotional preparatory processes, which modulates successful encoding into episodic memory. This difference suggests that there are multiple task-specific functional neural systems that support memory formation. These systems differ in location and/or relative contribution of some of the brain structures that generate the measured scalp electric fields. Consequently, the cognitive processes that enable memory formation depend on the differential semantic nature of the study task and reflect differences in the preparatory processing of the multiple semantic components of a word's meaning.
Ultrasonographically diagnosed dermoid cysts do not influence ovarian stimulation response in an in vitro fertilization cycle

Abstract To determine if patients with a DC respond similarly to ovarian stimulation when compared to patients without a DC. Infertility patients with a DC that underwent IVF between January 2009 and December 2016 were included. A cystic mass with mixed echogenicity, internal echoes similar to thick bands, fatty-fluid level, or an echogenic tubercle with acoustic shadow (Rokitansky nodule) within two years of the cycle characterized the diagnosis. The z-score compared the standard deviations (SDs) in patients with/without a DC and were compared to a nomogram (expected oocytes minus oocytes obtained divided by the SD), adjusted for age and number of oocytes retrieved, built utilizing cycles from noninfertile female patients. Thirty-nine patients with DC and 7839 patients without DC were identified. The mean number of oocytes (8.6 ± 5.8 vs. 8.5 ± 7.7, p = .43) and MIIs (6.7 ± 4.7 vs. 7.0 ± 6.7, p = .74) retrieved were similar. When cycles with and without a DC were compared to the nomogram (z-score of 0), cycles with a DC presented a z-score for ovarian response of 0.1921 SDs from the mean, and patients without DC presented a z-score of −0.2065 SDs from the mean (similar and less than −1.0). After building a population ‘normal’ response as a template, patients with and without a DC responded similar to COS.
Prenatal Nitrate Exposure and Childhood Asthma. Influence of Maternal Prenatal Stress and Fetal Sex

Rationale: Impact of ambient pollution upon children's asthma may differ by sex, and exposure dose and timing. Psychosocial stress can also modify pollutant effects. These associations have not been examined for in utero ambient nitrate exposure. Objectives: We implemented Bayesian‐distributed lag interaction models to identify sensitive prenatal windows for the influence of nitrate (NO3−) on child asthma, accounting for effect modification by sex and stress. Methods: Analyses included 752 mother‐child dyads. Daily ambient NO3− exposure during pregnancy was derived using a hybrid chemical transport (Geos‐Chem)/land‐use regression model and natural log transformed. Prenatal maternal stress was indexed by a negative life events score (high [>2] vs. low [≤2]). The outcome was clinician‐diagnosed asthma by age 6 years. Measurements and Main Results: Most mothers were Hispanic (54%) or black (29%), had a high school education or less (66%), never smoked (80%), and reported low prenatal stress (58%); 15% of children developed asthma. BDILMs adjusted for maternal age, race, education, prepregnancy obesity, atopy, and smoking status identified two sensitive windows (7‐19 and 33‐40 wk gestation), during which increased NO3− was associated with greater odds of asthma, specifically among boys born to mothers reporting high prenatal stress. Cumulative effects of NO3− across pregnancy were also significant in this subgroup (odds ratio = 2.64, 95% confidence interval = 1.27‐5.39; per interquartile range increase in ln NO3−). Conclusions: Prenatal NO3− exposure during distinct sensitive windows was associated with incident asthma in boys concurrently exposed to high prenatal stress.
Metabolic Syndrome is Associated with Ceramide Accumulation in Visceral Adipose Tissue of Women with Morbid Obesity

Accelerated transmembrane transport of long‐chain fatty acids dependent on fatty acid transporters is responsible for lipid accumulation and, eventually, the development of metabolic syndrome. This study determined the content of lipids (ceramide [CER], diacylglycerol [DAG], triacylglycerol, and free fatty acid [FFA]) and the expression of fatty acid translocase (FAT/CD36) and plasma membrane fatty acid‐binding protein in visceral adipose tissue (VAT) and subcutaneous adipose tissue of women with morbid obesity without metabolic syndrome (MetSx−) or with metabolic syndrome (MetSx+) and compared the results with those of lean controls without metabolic syndrome.
Unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression: a meta-analysis of randomized controlled trials over 2 decades

Background Approximately 35% of people with depression do not respond to 2 courses of antidepressant medications of adequate dosage, and treatment-resistant depression (TRD) is still a major clinical concern with a great impact on patients, their families, society and the health system. The present meta-analysis evaluates antidepressant efficacy of unilateral and bilateral repetitive transcranial magnetic stimulation (rTMS) in patients with unipolar TRD. Methods We searched for randomized controlled trials that compared rTMS with sham treatment and were published by Apr. 3, 2017. The primary outcome was improvement in depression scores measured using the Hamilton Rating Scale for Depression. The secondary outcomes were remission and response rates. Two independent review authors screened the studies and extracted the data. Results Twenty-three studies met the inclusion criteria. Meta-analysis of the depression scores showed a weighted mean difference (WMD) of 3.36 (95% confidence interval [CI] 1.85–4.88) between unilateral rTMS and sham treatment. Stratified data showed that the effect was relatively higher when rTMS was used as an add-on to antidepressant medications (WMD 3.64, 95% CI 1.52–5.76) than when it was used as a stand-alone treatment (WMD 2.47, 95% CI 0.90–4.05). The WMD between bilateral rTMS and sham was 2.67 (95% CI 0.83–4.51), and all studies that contributed to this outcome used rTMS while participants were taking antidepressant medications. The pooled remission and response rates for unilateral rTMS versus sham treatment were 16.0% and 25.1% for rTMS and 5.7% and 11.0% for sham treatment, respectively. The pooled remission and response rates for bilateral rTMS versus sham treatment were 16.6% and 25.4% for rTMS and 2.0% and 6.8% for sham treatment, respectively. Conclusion This study suggests that rTMS has moderate antidepressant effects and appears to be promising in the short-term treatment of patients with unipolar TRD.
Effect of prophylactic treatment with levetiracetam on the incidence of postattenuation seizures in dogs undergoing surgical management of single congenital extrahepatic portosystemic shunts

OBJECTIVE To report the incidence of postattenuation seizures (PAS) in dogs that underwent single congenital extrahepatic portosystemic shunt (cEHPSS) attenuation and to compare incidence of PAS in dogs that either did or did not receive prophylactic treatment with levetiracetam (LEV). STUDY DESIGN Multi-institutional retrospective study. POPULATION Nine hundred forty dogs. METHODS Medical records were reviewed to identify dogs that underwent surgical attenuation of a single cEHPSS from January 2005 through July 2017 and developed PAS within 7 days postoperatively. Dogs were divided into 3 groups: no LEV (LEV-); LEV at ≥15 mg/kg every 8 hours for ≥24 hours preoperatively or a 60 mg/kg intravenous loading dose perioperatively, followed by ≥15 mg/kg every 8 hours postoperatively (LEV1); and LEV at <15 mg/kg every 8 hours, for <24 hours preoperatively, or continued at <15 mg/kg every 8 hours postoperatively (LEV2). RESULTS Seventy-five (8.0%) dogs developed PAS. Incidence of PAS was 35 of 523 (6.7%), 21 of 188 (11.2%), and 19 of 228 (8.3%) in groups LEV-, LEV1, and LEV2, respectively. This difference was not statistically significant (P = .14). No differences between groups of dogs that seized with respect to investigated variables were identified. CONCLUSION The overall incidence of PAS was low (8%). Prophylactic treatment with LEV according to the protocols that were investigated in our study was not associated with a reduced incidence of PAS. CLINICAL SIGNIFICANCE Prophylactic treatment with LEV does not afford protection against development of PAS. Surgically treated dogs should continue to be monitored closely during the first 7 days postoperatively for seizures.
Trajectories of Response to Dorsolateral Prefrontal rTMS in Major Depression: A THREE-D Study.

OBJECTIVE Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for refractory major depressive disorder, yet no studies have characterized trajectories of rTMS response. The aim of this study was to characterize response trajectories for patients with major depression undergoing left dorsolateral prefrontal cortex rTMS and to determine associated baseline clinical characteristics. METHODS This was a secondary analysis of a randomized noninferiority trial (N=388) comparing conventional 10-Hz rTMS and intermittent theta burst stimulation (iTBS) rTMS. Participants were adult outpatients who had a primary diagnosis of major depressive disorder, had a score ≥18 on the 17-item Hamilton Depression Rating Scale (HAM-D), and did not respond to one to three adequate antidepressant trials. Treatment was either conventional 10-Hz rTMS or iTBS rTMS applied to the dorsolateral prefrontal cortex, 5 days/week over 4-6 weeks (20-30 sessions). Group-based trajectory modeling was applied to identify HAM-D response trajectories, and regression techniques were used to identify associated characteristics. RESULTS Four trajectories were identified: nonresponse (N=43, 11%); rapid response (N=73, 19%); higher baseline symptoms, linear response (N=118, 30%); and lower baseline symptoms, linear response (N=154, 40%). Significant differences in response and remission rates between trajectories were detectable by week 1. There was no association between treatment protocol and response trajectory. Higher baseline scores on the HAM-D and the Quick Inventory of Depression Symptomatology-Self-Report (QIDS-SR) were associated with the nonresponse trajectory, and older age, lower QIDS-SR score, and lack of benzodiazepine use were associated with the rapid response trajectory. CONCLUSIONS Major depression shows distinct response trajectories to rTMS, which are associated with baseline clinical characteristics but not treatment protocol. These response trajectories with differential response to rTMS raise the possibility of developing individualized treatment protocols.
The cerebral blood flow in male subjects as measured by the nitrous oxide technique; normal values for blood flow, oxygen utilization, glucose utilization and peripheral resistance, with observations on the effect of tilting and anxiety.

The nitrous oxide technique for the semiquantitative measurement of cerebral blood flow devised by Kety and Schmidt (1, 2) has made it desirable to restudy the cerebral circulation in man in various physiologic states. By measuring arterio-internal jugular differences of oxygen and glucose, the relation between changes in cerebral blood flow and cerebral metabolism can be observed. The purpose of this report is to record our findings in the use of the nitrous oxide technique in 33 observations on 20 normal young men; in the comparison of certain cerebral metabolic functions on 14 normal young men in the supine and erect postures; and in observations on the effects of apprehension on the cerebral circulation.
Gene‐based sequential burden association test

Detecting the association between a set of variants and a phenotype of interest is the first and important step in genetic and genomic studies. Although it attracted a large amount of attention in the scientific community and several related statistical approaches have been proposed in the literature, powerful and robust statistical tests are still highly desired and yet to be developed in this area. In this paper, we propose a powerful and robust association test, which combines information from each individual single‐nucleotide polymorphisms based on sequential independent burden tests. We compare the proposed approach with some popular tests through a comprehensive simulation study and real data application. Our results show that, in general, the new test is more powerful; the gain in detecting power can be substantial in many situations, compared to other methods.