Miracle-dz/UniFAR-FTUs huggingface dataset:
Endothelial dysfunction in human intramyocardial small arteries in atherosclerosis and hypercholesterolemia.

Vascular responses of human intramyocardial small arteries were examined in vitro to assess the influence of atherosclerosis and risk factors for coronary artery disease on endothelium-dependent relaxation. Recipient hearts were obtained from patients with ischemic ( n = 14) and nonischemic ( n = 13) cardiomyopathy undergoing heart transplantation. Small intramyocardial coronary arteries (mean internal diameter 313 ± 11 μm) were mounted on a wire myograph for measurement of morphology and isometric tension. Vasodilation was examined after preconstriction with U-46619, a thromboxane A2 analog. Endothelium-dependent relaxation to acetylcholine and bradykinin was impaired in patients with ischemic compared with nonischemic cardiomyopathy ( P < 0.01 and P < 0.001, respectively). Endothelium-independent relaxation to sodium nitroprusside was preserved. Incubation withl-arginine (3 mmol/l) did not improve endothelium-dependent relaxation to acetylcholine or bradykinin. With the use of stepwise multivariate analysis, hypercholesterolemia, but no other risk factor for atherosclerosis, was independently associated with impaired endothelium-dependent relaxation to acetylcholine ( r = -0.50, P = 0.05) but not to bradykinin. Endothelial dysfunction in intramyocardial small arteries may predispose patients with nonobstructive epicardial atherosclerosis and hypercholesterolemia to myocardial ischemia.
A Bee Evolutionary Guiding Nondominated Sorting Genetic Algorithm II for Multiobjective Flexible Job-Shop Scheduling

Flexible job-shop scheduling problem (FJSP) is an NP-hard puzzle which inherits the job-shop scheduling problem (JSP) characteristics. This paper presents a bee evolutionary guiding nondominated sorting genetic algorithm II (BEG-NSGA-II) for multiobjective FJSP (MO-FJSP) with the objectives to minimize the maximal completion time, the workload of the most loaded machine, and the total workload of all machines. It adopts a two-stage optimization mechanism during the optimizing process. In the first stage, the NSGA-II algorithm with T iteration times is first used to obtain the initial population N, in which a bee evolutionary guiding scheme is presented to exploit the solution space extensively. In the second stage, the NSGA-II algorithm with GEN iteration times is used again to obtain the Pareto-optimal solutions. In order to enhance the searching ability and avoid the premature convergence, an updating mechanism is employed in this stage. More specifically, its population consists of three parts, and each of them changes with the iteration times. What is more, numerical simulations are carried out which are based on some published benchmark instances. Finally, the effectiveness of the proposed BEG-NSGA-II algorithm is shown by comparing the experimental results and the results of some well-known algorithms already existed.
A Bayesian Framework for Multiple Trait Colocalization from Summary Association Statistics

Most genetic variants implicated in complex diseases by genome-wide association studies (GWAS) are non-coding, making it challenging to understand the causative genes involved in disease. Integrating external information such as quantitative trait locus (QTL) mapping of molecular traits (e.g., expression, methylation) is a powerful approach to identify the subset of GWAS signals explained by regulatory effects. In particular, expression QTLs (eQTLs) help pinpoint the responsible gene among the GWAS regions that harbor many genes, while methylation QTLs (mQTLs) help identify the epigenetic mechanisms that impact gene expression which in turn affect disease risk. In this work we propose multiple-trait-coloc (moloc), a Bayesian statistical framework that integrates GWAS summary data with multiple molecular QTL data to identify regulatory effects at GWAS risk loci. We applied moloc to schizophrenia (SCZ) and eQTL/mQTL data derived from human brain tissue and identified 52 candidate genes that influence SCZ through methylation. Our method can be applied to any GWAS and relevant functional data to help prioritize disease associated genes. AUTHOR SUMMARY In this paper, we propose multiple-trait-coloc (moloc), a statistical method that can use single variant summary statistics from multiple studies to test for colocalization. Using moloc, we integrate risk variants identified through genome-wide association studies (GWAS) in schizophrenia with quantitative trait loci that affect gene expression (eQTL) and DNA methylation (mQTL). Our method links non-coding risk variants with transcripts to identify possible biological mechanisms that affect the cis regulation of gene expression. Overall, we find that integrating mQTL, eQTL and GWAS increases discovery power as compared to standard pairwise colocalization. Our approach is publically available as an R package from https://github.com/clagiamba/moloc.
Aldosterone stimulates intestinal Na+ absorption in rats by increasing NHE3 expression of the proximal colon.

Na+ retention by the colon in response to salt deprivation is mediated in part by the resulting secondary hyperaldosteronism. We show that experimental hyperaldosteronism, to levels seen with salt deprivation, causes an increase in the selective expression and activity of NHE3, an apically located isoform of the Na+/H+exchange family that functions in transepithelial Na+ absorption. The effect of aldosterone on NHE3 expression is tissue specific, occurring in intestine and not in kidney. Within the intestine, these effects are regional, being observed only in proximal colon, and different in distribution from that observed with glucocorticoids, where the predominant effect occurs in ileum. Although glucocorticoids are well known to exert many effects via regulation of transcript levels, the present study demonstrates that aldosterone stimulates intestinal Na+ absorption by increasing cellular NHE3 expression, a response that is tissue and region specific.
Single-stage Anterior and Posterior Fusion Surgery for Correction of Cervical Kyphotic Deformity Using Intervertebral Cages and Cervical Lateral Mass Screws: Postoperative Changes in Total Spine Sagittal Alignment in Three Cases with a Minimum Follow-up of Five Years

The surgical treatment of cervical kyphotic deformity remains challenging. As a surgical method that is safer and avoids major complications, the authors present a procedure of single-stage anterior and posterior fusion to correct cervical kyphosis using anterior interbody fusion cages without plating, as illustrated by three consecutive cases. Case 1 was a 78-year-old woman who presented with a dropped head caused by degeneration of her cervical spine. Case 2 was a 54-year-old woman with athetoid cerebral palsy. She presented with cervical myelopathy and cervical kyphosis. Case 3 was a 71-year-old woman with cervical kyphotic deformity following a laminectomy. All three patients underwent anterior release and interbody fusion with cages and posterior fusion with cervical lateral mass screw (LMS) fixation. Postoperative radiographs showed that correction of kyphosis was 39° in case 1, 43° in case 2, and 39° in case 3. In all three cases, improvement of symptoms was established without major perioperative complications, solid fusion was achieved, and no loss of correction was observed at a minimum follow-up of 61 months. We also report that preoperative total spine sagittal malalignment was improved after corrective surgery for cervical kyphosis and was maintained at the latest follow-up in all three cases. The combination of anterior fusion cages and LMS is considered a safe and effective procedure in cases of severe cervical kyphotic deformity. Preoperative total spine sagittal malalignment improved, accompanied by correction of cervical kyphosis, and was maintained at last follow-up in all three cases.
Swelling-activated cation-selective channels in A6 epithelia are permeable to large cations.

Effects of basolateral monovalent cation replacements (Na+ by Li+, K+, Cs+, methylammonium, and guanidinium) on permeability to86Rb of volume-sensitive cation channels (VSCC) in the basolateral membrane and on regulatory volume decrease (RVD), elicited by a hyposmotic shock, were studied in A6 epithelia in the absence of apical Na+ uptake. A complete and quick RVD occurred only when the cells were perfused with Na+ or Li+ saline. With both cations, hypotonicity increased basolateral86Rb release ([Formula: see text]), which reached a maximum after 15 min and declined back to control level. When the major cation was K+, Cs+, methylammonium, or guanidinium, the RVD was abolished. Methylammonium induced a biphasic time course of cell thickness (Tc), with an initial decline of Tc followed by a gradual increase. With K+, Cs+, or guanidinium, Tc increased monotonously after the rapid initial rise evoked by the hypotonic challenge. In the presence of K+, Cs+, or methylammonium,[Formula: see text] remained high during most of the hypotonic period, whereas with guanidinium blockage of[Formula: see text] was initiated after 6 min of hypotonicity, suggesting an intracellular location of the site of action. With all cations, 0.5 mM basolateral Gd3+ completely blocked RVD and fully abolished the [Formula: see text] increase induced by the hypotonic shock. The lanthanide also blocked the additional volume increase induced by Cs+, K+, guanidinium, or methylammonium. When pH was lowered from 7.4 to 6.0, RVD and[Formula: see text] were markedly inhibited. This study demonstrates that the VSCCs in the basolateral membrane of A6 cells are permeable to K+, Rb+, Cs+, methylammonium, and guanidinium, whereas a marked inhibitory effect is exerted by Gd3+, protons, and possibly intracellular guanidinium.
The influence of NAFLD on the risk of atherosclerosis and cardiovascular diseases

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed countries and is associated with obesity, dyslipidaemia, diabetes, and metabolic syndrome. Atherosclerosis and cardiovascular diseases are also highly prevalent in this group of patients, due to the presence of shared risk factors. The incidences of coronary artery calcification, hypertension, aortic valve sclerosis, diastolic dysfunction, atherosclerotic plaques, and increased carotid intima-media thickness were more common in patients with NAFLD than in those without. The present paper reviews the medical literature concerning the association between NAFLD and cardiovascular events.
Co-targeting cancer stem-like cells and bulk cancer cells with a bispecific antibody

ABSTRACT Epidermal growth factor receptor (EGFR) is a widely recognized target for tumors, but resistance is commonly reported. Recently, we reported that dual targeting of EGFR and NOTCH2/3 receptors with antibody CT16 showed a strong anti-stem effect both in vitro and in vivo to overcome resistance of EGFR inhibitors and radiation.
Peroxide resistance of ER Ca2+ pump in endothelium: implications to coronary artery function.

We examined the effects of peroxide on the sarco(endo)plasmic reticulum Ca2+ (SERCA) pump in pig coronary artery endothelium and smooth muscle at three organizational levels: Ca2+ transport in permeabilized cells, cytosolic Ca2+ concentration in intact cells, and contractile function of artery rings. We monitored the ATP-dependent, azide-insensitive, oxalate-stimulated45Ca2+uptake by saponin-permeabilized cultured cells. Low concentrations of peroxide inhibited the uptake less effectively in endothelium than in smooth muscle whether we added the peroxide directly to the Ca2+ uptake solution or treated intact cells with peroxide and washed them before the permeabilization. An acylphosphate formation assay confirmed the greater resistance of the SERCA pump in endothelial cells than in smooth muscle cells. Pretreating smooth muscle cells with 300 μM peroxide inhibited (by 77 ± 2%) the cyclopiazonic acid (CPA)-induced increase in cytosolic Ca2+ concentration in a Ca2+-free solution, but it did not affect the endothelial cells. Peroxide pretreatment inhibited the CPA-induced contraction in deendothelialized arteries with a 50% inhibitory concentration of 97 ± 13 μM, but up to 500 μM peroxide did not affect the endothelium-dependent, CPA-induced relaxation. Similarly, 500 μM peroxide inhibited the angiotensin-induced contractions in deendothelialized arteries by 93 ± 2%, but it inhibited the bradykinin-induced, endothelium-dependent relaxation by only 40 ± 13%. The greater resistance of the endothelium to reactive oxygen may be important during ischemia-reperfusion or in the postinfection immune response.
Regulation of a cloned epithelial Na+ channel by its β- and γ-subunits.

Using the Xenopus oocyte expression system, we examined the mechanisms by which the β- and γ-subunits of an epithelial Na+channel (ENaC) regulate α-subunit channel activity and the mechanisms by which β-subunit truncations cause ENaC activation. Expression of α-ENaC alone produced small amiloride-sensitive currents (-43 ± 10 nA, n = 7). These currents increased >30-fold with the coexpression of β- and γ-ENaC to -1,476 ± 254 nA ( n = 20). This increase was accompanied by a 3.1- and 2.7-fold increase of membrane fluorescence intensity in the animal and vegetal poles of the oocyte, respectively, with use of an antibody directed against the α-subunit of ENaC. Truncation of the last 75 amino acids of the β-subunit COOH terminus, as found in the original pedigree of individuals with Liddle's syndrome, caused a 4.4-fold ( n = 17) increase of the amiloride-sensitive currents compared with wild-type αβγ-ENaC. This was accompanied by a 35% increase of animal pole membrane fluorescence intensity. Injection of a 30-amino acid peptide with sequence identity to the COOH terminus of the human β-ENaC significantly reduced the amiloride-sensitive currents by 40-50%. These observations suggest a tonic inhibitory role on the channel's open probability ( P o) by the COOH terminus of β-ENaC. We conclude that the changes of current observed with coexpression of the β- and γ-subunits or those observed with β-subunit truncation are likely the result of changes of channel density in combination with large changes of P o.
Effects of hypoxia on energy state and pH in resting pulmonary and femoral arterial smooth muscles.

To determine the effects of hypoxia on energy state and intracellular pH (pHi) in resting pulmonary and systemic arterial smooth muscles, we used31P nuclear magnetic resonance spectroscopy and colorimetric and enzymatic assays to measure pHi; intracellular concentrations of ATP, phosphocreatine, creatine, and Pi; and phosphorylation potential in superfused tissue segments from porcine proximal intrapulmonary and superficial femoral arteries. Under baseline conditions ([Formula: see text] 467 ± 12.1 mmHg), energy state and total creatine (phosphocreatine + creatine) concentration were lower and pHi was higher in pulmonary arteries. During hypoxia ([Formula: see text] 23 ± 2.4 mmHg), energy state deteriorated more in femoral arteries than in pulmonary arteries. pHi fell in both tissues but was always more alkaline in pulmonary arteries. Reoxygenation reversed the changes induced by hypoxia. These results suggest that production and/or elimination of ATP and H+ was different in resting pulmonary and systemic arterial smooth muscles under baseline and hypoxic conditions. Because energy state and pHi affect a wide variety of cellular processes, including signal transduction, contractile protein interaction, and activities of ion pumps and channels, further investigation is indicated to determine whether these differences have functional significance.
The First 10 Years (2006–15) of Epizootic Hemorrhagic Disease Virus Serotype 6 in the USA

Abstract Epizootic hemorrhagic disease virus (EHDV) is a Culicoides biting midge–transmitted orbivirus (family Reoviridae) of wild and domestic ruminants and is an important pathogen of white-tailed deer (Odocoileus virginianus). Historically, only two serotypes, EHDV-1 and EHDV-2, have been known to be endemic in the US. However, in 2006, an exotic serotype (EHDV-6) was first detected in the US by a long-term passive surveillance system for EHDV and bluetongue viruses. Here we report EHDV-6 detections made through these passive surveillance efforts by the Southeastern Cooperative Wildlife Disease Study (University of Georgia, Athens, Georgia, USA) and the National Veterinary Services Laboratories (US Department of Agriculture, Ames, Iowa, USA) over a 10-yr period (2006–15). The results demonstrated that EHDV-6 was detected from ruminants every year since 2006 and was widespread in the central and eastern US, providing evidence that EHDV-6 is likely now established in the US.
Association of GII.P16-GII.2 Recombinant Norovirus Strain with Increased Norovirus Outbreaks, Guangdong, China, 2016

An unusual prevalence of recombinant GII.2 noroviruses (GII.P16-GII.2) in Guangdong, China, at the end of 2016 caused a sharp increase in outbreaks of acute gastroenteritis. This event was another non-GII.4 epidemic that emerged after the GII.17 viruses in 2014 and 2015 and warrants global surveillance.
Microwave sintering and properties of AlN/TiB_2 composites

The effect of TiB_2 on the densification behavior and properties of microwave-sintered AlN/TiB_2 ceramic was investigated. The densification of the composite was significantly retarded in nitrogen atmosphere due to strong nitridation of TiB_2 compared to sintering in argon atmosphere. The densities of the AlN/TiB_2 composites containing different amounts of TiB_2 all reached 99% of the theoretical density during 2 h of sintering at 1850 and 1900 °C. Microstructure analysis revealed that the TiB_2 particles were dispersed in the AlN matrix while AlN grains retained its contiguity. This microstructure led to a composite with superior properties; thermal conductivity as high as 149 W/(m K) was achieved. The microwave sintered composites are harder and tougher than pure AlN. Microwave-sintered AlN/TiB_2 composite is a promising material for structural applications in which high thermal conductivity and controlled dielectric loss are important.
Development of a model care pathway for adults undergoing colorectal cancer surgery: Evidence‐based key interventions and indicators

RATIONALE, AIMS, AND OBJECTIVES During the last decades, perioperative care for patients with colorectal cancer has shifted towards more standardized care, so-called "enhanced recovery after surgery. " Those programs aim to optimize interventions in perioperative care to decrease the rate of postoperative complications, improve patients' recovery, and shorten hospital stay. The purpose of this literature review is to identify, summarize, and operationalize the clinical content of both key interventions and clinical indicators to develop an evidence-based model pathway for surgical patients with colorectal cancer. METHODS A systematic search in 3 databases was conducted to identify key interventions (KIs) and indicators to measure the effect of implementation of care pathways. The KIs from the enhanced recovery after surgery protocol were listed and used as framework to identify and match KIs used in the included studies. The Clinical Pathway Compass was used to categorize the indicators. RESULTS Fifteen studies were included. The number of KI used in the study protocols ranged from 9 to 20. In total, 33 KIs were identified. Little information was available concerning the implementation of and compliance to the protocol. Length of stay and complication rate are the most common used indicators (used in 15/15 and 14/15 of the studies), followed by 21 other measures. All but one of the included studies reported a reduction in length of stay. CONCLUSION There is a considerable variation in both number of KIs and indicators as well as operationalization of key interventions, for surgical patients with colorectal cancer documented in literature. Therefore, we summarized the input from different studies and developed an evidence-based model pathway, which can serve as a basis for a local/regional care pathway team to build their own pathway.
Risk Factors for Graft Loss in Pediatric Renal Transplant Recipients After Transfer of Care

Background: Improvements in transplantation have increased the survival of children after kidney transplantation. These patients have complex needs, and the current medical system is not prepared to effectively transfer the care of these individuals from pediatric to adult health-care systems. Too often, transfer occurs during moments of crisis and is associated with poor outcomes. Objective: The aim of this study was to use a national database, the Scientific Registry of Transplant Recipients, to test the hypothesis that the increased risk of graft loss after transfer of care (from pediatric to adult services) for young adult kidney transplant recipients over a 2- to 3-year posttransfer follow-up period was related to these posttransfer risk factors (medication noncompliance, acute rejection, insurance status). Design: A retrospective, longitudinal, correlational design using secondary data was used to evaluate the transfer of care of 250 kidney transplant recipients (ages 16-25). Results: Seventy-seven (30.8%) individuals lost their graft within 3 years after transfer of care. Medication noncompliance, acute rejection, and serum creatinine >2.0 mg/dL at transfer were significant predictors of graft loss after accounting for multiple other factors. Conclusion: These individuals are at risk for graft loss after transfer of care and may benefit from increased personalized care during this risky period.
Temperature-related power loss modeling for buck converter

: The power loss modeling is a key procedure during designing the converter, especially in high temperature operation. This letter presents a practical method for predicting the temperature-related power losses for buck converter. In order to build the loss model, the datasheet driven method is adopted which requires only the information in device datasheets. The accuracy of the proposed model is demonstrated by the experiment. Experimental results are consistent with the theoretical analysis over the entire temperature range.
Microencapsulação do pesticida cipermetrina em blendas de P(3HB/PCL): caracterização e ensaio de liberação in vitro

A aplicacao de polimeros biodegradaveis para encapsular pesticidas e uma estrategia que permite, a partir de diferentes proporcoes entre os polimeros, modificar o perfil de liberacao do agente. Este trabalho avaliou a liberacao controlada do pesticida cipermetrina encapsulado em microesferas de blendas de P(3HB)/PCL (100/0, 0/100, 97/03, 95/05, 90/10, 80/20 e 70/30) obtidas pelo metodo de emulsificacao-evaporacao do solvente. As imagens de microscopia eletronica de varredura revelam a forte influencia da PCL na porosidade das microesferas. As analises de infravermelho mostraram a presenca do pesticida em todas as composicoes de polimeros avaliadas. O ensaio de liberacao de cipermetrina sugere que, no intervalo de 4 horas, o teor de cipermetrina liberada e dependente da composicao das blendas utilizadas. As microesferas de PHB e blendas com menores teores de PCL, 97/03 e 95/05 liberaram 75% a 85% enquanto a composicao 70/30 liberou 100% de cipermetrina.