Miracle-dz/UniFAR-FTUs huggingface dataset:
Association analysis of telomere length related gene ACYP2 with the gastric cancer risk in the northwest Chinese Han population

Gastric cancer (GC) is a complex multifactorial disease, and genetic factors are believed the predominant cause to the occurrence of GC. We sought to investigate the associations between single nucleotide polymorphisms (SNPs) in ACYP2 gene and the risk of GC in the Northwest Chinese Han population. We recruited 302 GC cases and 300 controls from northwest China and selected 13 SNPs from ACYP2 gene. SNPs were genotyped using Sequenom Mass-ARRAY technology. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the association. Bonferroni's multiple adjustment was applied to the level of significance, which was set at P < 0.00078 (0.05/65). We found that the minor alleles of rs6713088, rs11125529, rs12615793, rs843711, rs11896604, rs843706 and rs17045754 significantly stimulated the risk of GC, and homozygous alleles of above SNPs except rs6713088 were also found increasing the GC risk (P < 0.05). Under additive model and recessive model, rs11125529, rs12615793, rs843711, rs11896604, and rs17045754 also activated the risk of GC (P < 0.05). However, after Bonferroni's multiple adjusted was applied to our data, no SNP in our study was significantly related to GC risk. Further results of haplotype analysis founds that the haplotypes “TTCTAATG” (rs1682111, rs843752, rs10439478, rs843645, rs11125529, rs12615793, rs843711, and rs11896604) and “AC” (rs843706 and rs17045754) were more frequency among patients with GC, on the contrary, the haplotypes “CG” had a protective role in the GC risk (P < 0.05). Our results indicate that ACYP2 polymorphisms may influence the GC risk and may serve as a new precursory biomarker in the northwest Chinese Han population.
The imidazoline receptor in control of blood pressure by clonidine and allied drugs.

Clonidine, moxonidine, and rilmenidine are centrally acting antihypertensive agents that lower arterial pressure by inhibiting the tonic activity of sympathoexcitatory neurons in the rostral ventrolateral medulla. Competing hypotheses have been put forward by different investigators to explain the sympathoinhibition evoked by "imidazoline drugs": either via central actions at α2-adrenergic receptors or novel I1-imidazoline receptors. These different perspectives are presented in the accompanying reviews.
Physiology of transgenic mice with brown fat ablation: obesity is due to lowered body temperature.

We investigated the physiological basis for development of obesity in uncoupling protein-diphtheria toxin A chain (UCP-DTA) transgenic mice. In these mice the promoter of the brown adipose tissue (BAT)-specific UCP was used to drive expression of DTA, resulting in decreased BAT function and development of obesity and insulin resistance (Lowell, B. B., S. V. Susulic, A. Hamann, J. A. Lawitts, J. Himms-Hagen, B. B. Boyer, L. Kozak, and J. S. Flier. Nature 366: 740-742, 1994). In adult UCP-DTA mice, we measured food intake and food assimilation, locomotor activity, metabolic rate, and body temperature in comparison to control animals. No differences could be observed in food intake or assimilation and locomotor activity. Weight-specific metabolic rates at temperatures between 20 and 37°C, however, were consistently lower in transgenic mice. Continuous telemetric recording of core body temperature showed that transgenic mice displayed a downshift in body temperature levels of ∼0.9°C. In summary, we provide evidence that attenuated body temperature levels alone can be responsible for development of obesity and that BAT thermogenesis is a major determinant of body temperature levels in rodents.
Cardiovascular, endocrine, and body fluid-electrolyte responses to salt loading in mRen-2 transgenic rats.

We previously demonstrated that mRen-2 transgenic [Tg(+)] rats are sensitive to chronic high NaCl intake, showing increased arterial pressure and vasopressin (VP) secretion. In this study, we determined the effect of a chronic osmotic challenge, 4 days of drinking 2% NaCl, on direct arterial blood pressure, heart rate, fluid-electrolyte balance, circadian rhythm of mean arterial pressure (MAP), and changes in plasma VP and catecholamines. Under baseline conditions, male Tg(+) rats showed a significant shift in the peak in circadian MAP into the light portion of the day-night cycle. Substitution of 2% NaCl for drinking water caused a rapid increase in MAP, 20 ± 5 mmHg in Tg(+) rats within 6 h. Whereas the amplitude of circadian MAP fluctuations increased in salt-loaded Tg(+) rats, there was no significant change in the circadian timing of peak MAP with salt loading. Tg(+) rats showed exaggerated osmotic-induced increases in plasma VP, norepinephrine (NE), and epinephrine (Epi) compared with Tg(-) rats. Plasma NE and Epi were increased two- and fourfold, respectively, in the hypertensive rats with no significant change in the Tg(-) rats. Intravenous administration of a VP antagonist did not alter arterial pressure in either Tg(+) or Tg(-) rats. Tg(+) and Tg(-) rats showed a positive sodium balance with no significant difference observed between the groups. Tg(+) rats showed a significant increase in salt consumption, plasma sodium, osmolality, and hematocrit, accompanied by a negative water balance. We conclude that Tg(+) rats are sensitive to acute and chronic osmotic stimuli in terms of blood pressure, fluid-electrolyte balance, and plasma VP and catecholamines. Whereas elevated plasma VP does not contribute to the hypertensive response, increased sympathetic drive may mediate the salt-induced blood pressure changes in this model.
Determining optimal maintenance schedules for adjuvant intravesical bacillus Calmette–Guerin immunotherapy in non-muscle-invasive bladder cancer: a systematic review and network meta-analysis

Abstract Objectives: To figure out optimal bacillus Calmette–Guerin (BCG) maintenance schedules for non-muscle-invasive bladder cancer (NMIBC) patients by comparing different schedules in a systematic review using conventional and network meta-analysis. Materials and methods: Literature was searched in the databases of Medline, Embase, Cochrane library, Clinicaltrials.gov, Wanfang, CNKI and SinoMed in April 2016 and 9 randomized clinical trials comparing intravesical BCG maintenance therapy with BCG induction-only therapy or comparing different BCG maintenance schedules (induction-only, 1 year, 1.5 year, 2 year, 3 year maintenance) in NMIBC patients were included. Conventional and network meta-analyses within a Bayesian framework were performed to calculate odds ratios of tumor recurrence, progression and side effects (cystitis, hematuria, general malaise and fever). The surface under the cumulative ranking curve (SUCRA) mean ranking was used to obtain schedule hierarchy. Results: Data from 1951 patients showed that longer-term maintenance BCG therapy does not significantly decrease tumor recurrence and progression rate of NMIBC compared to shorter-term maintenance BCG therapy. However, longer-maintenance therapy does not increase side effect incidence compared to induction-only therapy. According to SUCRA results, induction-only therapy has the highest probability of recurrence and progression but least probability of side effects. Conclusions: Longer BCG maintenance therapy (such as 3 years) is not superior to shorter maintenance therapy (such as 1 year). But maintenance therapy overall is better than induction-only BCG therapy while not increasing side effects. Though further evidence and clinical practice with balanced confounding factors (risk stratification and BCG strain) are wished for, the current study suggests the common use of 1 year intravesical BCG instillation for NMIBC patients.
Fracture Risk Is Decreased in Women With Polycystic Ovary Syndrome: A Register‐Based and Population‐Based Cohort Study

Hyperandrogenism, obesity, and hyperinsulinemia may protect against osteoporosis, whereas amenorrhea, increased cortisol, and low growth hormone may be associated with higher fracture risk in polycystic ovary syndrome (PCOS). The objective of this study was to investigate fracture risk in PCOS. In the PCOS Denmark study, women with PCOS and/or hirsutism were identified in the Danish National Patient Register (1995–2012). Each patient was assigned three age‐matched controls on the index date of PCOS diagnosis. Individuals with a previous endocrine diagnosis were excluded. Within PCOS Denmark, we embedded a well‐characterized subcohort of patients, PCOS OUH, diagnosed with PCOS at Odense University Hospital (n = 1217). We identified incident fractures by International Classification of Diseases, 10th Revision (ICD‐10) codes and used conditional Cox regression analyses to compare fracture risk. In the PCOS Denmark study, there were 19,199 women with PCOS and 57,483 controls were included, mean age 30.6 years (range, 12–60 years). Fracture rates were decreased in PCOS Denmark (10.3/1000 patient years) versus controls (13.6/1000 patient years). The adjusted ORs were 0.76 (95% CI, 0.71 to 0.80) for all fractures, 0.82 (95% CI, 0.74 to 0.92) for major osteoporotic fractures, and 0.57 (95% CI, 0.47 to 0.70) for fractures of head and face. The risk reduction was more pronounced below the age of 30 years at diagnosis. Women with PCOS had significant more hospital contacts due to strains and sprains. In the PCOS OUH subcohort, the risk reduction of fractures did not differ between PCOS women with elevated versus normal testosterone levels and the risk reduction was nominally smaller in overweight versus normal weight PCOS women. Women with PCOS had reduced risk of fractures, in particular of the appendicular skeleton. The risk reduction was greater in women with younger age at diagnosis suggesting that the skeletal effects of PCOS may be greater in women who have not yet reached peak bone mass. Reduced participation in sports activities was probably not the reason for the reduced risk of fractures. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).
Mapping and Predicting Non-Linear Brassica rapa Growth Phenotypes Based on Bayesian and Frequentist Complex Trait Estimation

Predicting phenotypes based on genotypes and understanding the effects of complex multi-locus traits on plant performance requires a description of the underlying developmental processes, growth trajectories, and their genomic architecture. Using data from Brassica rapa genotypes grown in multiple density settings and seasons, we applied a hierarchical Bayesian Function-Valued Trait (FVT) approach to fit logistic growth curves to leaf phenotypic data (length and width) and characterize leaf development. We found evidence of genetic variation in phenotypic plasticity of rate and duration of leaf growth to growing season. In contrast, the magnitude of the plastic response for maximum leaf size was relatively small, suggesting that growth dynamics vs. final leaf sizes have distinct patterns of environmental sensitivity. Consistent with patterns of phenotypic plasticity, several QTL-by-year interactions were significant for parameters describing leaf growth rates and durations but not leaf size. In comparison to frequentist approaches for estimating leaf FVT, Bayesian trait estimation resulted in more mapped QTL that tended to have greater average LOD scores and to explain a greater proportion of trait variance. We then constructed QTL-based predictive models for leaf growth rate and final size using data from one treatment (uncrowded plants in one growing season). Models successfully predicted non-linear developmental phenotypes for genotypes not used in model construction and, due to a lack of QTL-by-treatment interactions, predicted phenotypes across sites differing in plant density.
Augmentation of eosinophil degranulation and LTC4 secretion by integrin-mediated endothelial cell adhesion.

We examined the effect of eosinophil ligation to cultured human umbilical vein endothelial cells (HUVECs) in augmenting the stimulated secretion of leukotriene (LT) C4 and eosinophil peroxidase (EPO). The effects of adhesion were compared before and after specific blockade with monoclonal antibodies directed against eosinophil surface integrins or endothelial counterligands. Adhesion to HUVECs augmented EPO release caused by formyl-methionyl-leucyl-phenylalanine plus cytochalasin B from 403 ± 15.3 (BSA control) to 778 ± 225 ng/106 cells for eosinophils exposed to interleukin-1α-treated HUVECs ( P < 0.05) and also caused a twofold increase in stimulated LTC4secretion ( P < 0.05). To determine whether augmented secretion resulted directly from adhesive ligation, studies were also performed with paraformaldehyde-treated HUVECs; stimulated secretion of LTC4 from eosinophils was comparable to that for living HUVECs. Our study is the first demonstration that adhesion to HUVECs through ligation to α4- or β2-integrin on the eosinophil surface causes augmentation of stimulated secretion of both EPO and LTC4 and that blockade of adhesion molecules on either eosinophils or HUVECs prevents the priming effect on eosinophil secretion.
DNA sequences within glioma-derived extracellular vesicles can cross the intact blood-brain barrier and be detected in peripheral blood of patients

Tumor-cell-secreted extracellular vesicles (EVs) can cross the disrupted blood-brain barrier (BBB) into the bloodstream. However, in certain gliomas, the BBB remains intact, which might limit EVs release. To evaluate the ability of tumor-derived EVs to cross the BBB, we used an orthotopic xenotransplant mouse model of human glioma-cancer stem cells featuring an intact BBB. We demonstrated that all types of tumor cells-derived EVs−apoptotic bodies, shedding microvesicles and exosomes−cross the intact BBB and can be detected in the peripheral blood, which provides a minimally invasive method for their detection compared to liquid biopsies obtained from cerebrospinal fluid (CSF). Furthermore, these EVs can be readily distinguished from total murine EVs, since they carry human-specific DNA sequences relevant for GBM biology. In a small cohort of glioma patients, we finally demonstrated that peripheral blood EVs cargo can be successfully used to detect the presence of IDH1G395A, an essential biomarker in the current management of human glioma
Laryngeal closure impedes non-invasive ventilation at birth

Background Non-invasive ventilation is sometimes unable to provide the respiratory needs of very premature infants in the delivery room. While airway obstruction is thought to be the main problem, the site of obstruction is unknown. We investigated whether closure of the larynx and epiglottis is a major site of airway obstruction. Methods We used phase contrast X-ray imaging to visualise laryngeal function in spontaneously breathing premature rabbits immediately after birth and at approximately 1 hour after birth. Non-invasive respiratory support was applied via a facemask and images were analysed to determine the percentage of the time the glottis and the epiglottis were open. Hypothesis Immediately after birth, the larynx is predominantly closed, only opening briefly during a breath, making non-invasive intermittent positive pressure ventilation (iPPV) ineffective, whereas after lung aeration, the larynx is predominantly open allowing non-invasive iPPV to ventilate the lung. Results The larynx and epiglottis were predominantly closed (open 25.5%±1.1% and 17.1%±1.6% of the time, respectively) in pups with unaerated lungs and unstable breathing patterns immediately after birth. In contrast, the larynx and the epiglottis were mostly open (90.5%±1.9% and 72.3%±2.3% of the time, respectively) in pups with aerated lungs and stable breathing patterns irrespective of time after birth. Conclusion Laryngeal closure impedes non-invasive iPPV at birth and may reduce the effectiveness of non-invasive respiratory support in premature infants immediately after birth.
The MEH-PPV/YAG:Ce hybrid nanocomposite material for solution processing fabrication of optoelectronic device

The fabrication and the property investigation of the hybrid nanocomposite material made of poly[2-methoxy-5-(2′-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV) polymer and Y3Al5O12:Ce (YAG:Ce) with the relative weight ratio of 1:1 in order to apply for optoelectronic devices are reported. Thermal analysis showed the hybrid material's deterioration or decomposition when the temperature exceeded 200°C under inert gas atmosphere. Rheological measurement concluded that the material solution can be used for spinning or soft moulding lithography making large- or flexible substrate surface. Optical properties of the hybrid material are investigated. The effect of thermal treatment on the optical properties showed that, at 180°C under inert gas environment, the optical properties were enhanced. An MEH-PPV/YAG:Ce hybrid nanocomposite converted LED lamp was fabricated showing that the hybrid material is suitable as conversion material for white LED fabrication.
31P NMR studies of creatine kinase flux in M-creatine kinase-deficient mouse heart.

Hearts of wild-type and cytosolic muscle creatine kinase (M-CK)-knockout mice were perfused with Krebs-Henseleit buffer containing 10 mM glucose and 5 mM pyruvate and studied during pacing at 400 and 600 beats/min and during K+ arrest. Phosphocreatine (PCr) and ATP concentrations in M-CK-deficient hearts were not significantly different from those in wild-type hearts. With the use of31P NMR saturation transfer, the flux mediated predominantly by mitochondrial creatine kinase (Mi-CK) was clearly detected in M-CK-deficient hearts. Mi-CK flux was 4.8 ± 0.6 and 4.5 ± 0.6 mM/s during pacing at 400 and 600 beats/min, respectively, and was 3.5 ± 0.4 mM/s during cardiac arrest. In control hearts total CK flux was 7.8 ± 1.1 and 6.6 ± 1.3 mM/s during pacing at 400 and 600 beats/min, respectively, and decreased to 3.8 ± 0.5 mM/s during arrest. It is suggested that the relative contribution of Mi-CK to the total NMR-measured CK flux in the wild-type heart is higher than that of the homodimeric M-CK isoform (MM-CK).
Diffusion tensor imaging MRI of sickle cell kidney disease: initial results and comparison with iron deposition

Chronic kidney disease (CKD) occurs in over one‐third of patients with sickle cell disease (SCD) and can progress to end‐stage renal disease. Unfortunately, current clinical assessments of kidney function are insensitive to early‐stage CKD. Previous studies have shown that diffusion magnetic resonance imaging (MRI) can sensitively detect regional renal microstructural changes associated with early‐stage CKD. However, previous MRI studies in patients with SCD have been largely limited to the detection of renal iron deposition assessed by T2* relaxometry. In this pilot imaging study, we compare MRI assessments of renal microstructure (diffusion) and iron deposition (T2*) in patients with SCD and in non‐SCD control subjects. Diffusion tensor imaging (DTI) and T2* relaxometry MRI data were obtained for pediatric (n = 5) and adult (n = 4) patients with SCD, as well as for non‐SCD control subjects (n = 10), on a Siemens Espree 1.5‐T MRI scanner. A region‐of‐interest analysis was used to calculate mean medullary and cortical values for each MRI metric. MRI findings were also compared with clinical assessments of renal function and hemolysis. Patients with SCD showed a significant decrease in medullary fractional anisotropy (FA, p = 0.0001) in comparison with non‐SCD subjects, indicative of microstructural alterations in the renal medulla of patients with SCD. Cortical and medullary reductions in T2* (increased iron deposition, p = ≤0.0001) were also observed. Significant correlations were also observed between kidney T2* assessments and multiple measures of hemolysis. This is the first DTI MRI study of patients with SCD to demonstrate reductions in medullary FA despite no overt CKD [estimated glomerular filtration rate (eGFR) > 100 mL/min/1.73 m2]. These medullary FA changes are consistent with previous studies in patients with CKD, and suggest that DTI MRI can provide a useful measure of kidney injury to complement MRI assessments of iron deposition.
Toroidal Localized Spoof Plasmons on Compact Metadisks

Localized spoof surface plasmons (LSSPs) have recently emerged as a new research frontier due to their unique properties and increasing applications. Despite the importance, most of the current researches only focus on electric/magnetic LSSPs. Very recent research has revealed that toroidal LSSPs, LSSPs modes with multipole toroidal moments, can be achieved at a point defect in a 2D groove metal array. However, this metamaterial shows the limitations of large volume and poor compatibility to photonic integrated circuits. To overcome the above challenges, here it is proposed and experimentally demonstrated compact planar metadisks based on split ring resonators to support the toroidal LSSPs at microwave frequencies. Additionally, it is experimentally demonstrated that the toroidal LSSPs resonance is very sensitive to the structure changes and the background medium. These might facilitate its utilization in the design and application of plasmonic deformation sensors and the refractive index sensors.
The role of germline alterations in the DNA damage response genes BRIP1 and BRCA2 in melanoma susceptibility

We applied a targeted sequencing approach to identify germline mutations conferring a moderately to highly increased risk of cutaneous and uveal melanoma. Ninety‐two high‐risk melanoma patients were screened for inherited variation in 120 melanoma candidate genes. Observed gene variants were filtered based on frequency in reference populations, cosegregation with melanoma in families and predicted functional effect. Several novel or rare genetic variants in genes involved in DNA damage response, cell‐cycle regulation and transcriptional control were identified in melanoma patients. Among identified genetic alterations was an extremely rare variant (minor allele frequency of 0.00008) in the BRIP1 gene that was found to cosegregate with the melanoma phenotype. We also found a rare nonsense variant in the BRCA2 gene (rs11571833), previously associated with cancer susceptibility but not with melanoma, which showed weak association with melanoma susceptibility in the Swedish population. Our results add to the growing knowledge about genetic factors associated with melanoma susceptibility and also emphasize the role of DNA damage response as an important factor in melanoma etiology. © 2016 Wiley Periodicals, Inc.
Antihyperglycemic Activity of Herb Extracts on Streptozotocin-Induced Diabetic Rats

We investigated the effects of herb extracts, Rhus verniciflua, Agrimonia pilosa, Sophora japonica, and Paeonia suffruticosa, on the lowering of blood glucose levels and thiobarbituric acid reactive substances (TBARS) in streptozotocin (STZ)-induced diabetic rats. After 4 weeks, oral administration of Rhus verniciflua extract (50 mg/kg) exhibited a significant decrease in blood glucose levels in diabetic rats (P<0.05). Blood TBARS concentrations, the products of glucose oxidation in blood, were also lowered by Rhus verniciflua extract supplementation. In addition, Sophora japonica and Paeonia suffruticosa extracts significantly reduced TBARS levels versus diabetic controls. Serum concentrations of liver-function marker enzymes, GOT and GPT, were also restored by Rhus verniciflua (50 mg/kg) supplementation in diabetic rats.