bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of concomitant systemic treatments on toxicity and intracerebral response after stereotactic radiotherapy for brain metastases
Authors: Guénolé Morgan , Lucia François , Bourbonne Vincent , Dissaux Gurvan , Reygagne Emmanuelle , Goasduff Gaëlle , Pradier Olivier , Schick Ulrike 
Published: October 2020

Abstract
Background: The aim of this study was to determine the safety and efficacy of fractionated stereotactic radiotherapy (SRT) in combination with systemic therapies (ST) for brain metastases (BM). Methods: 99 patients (171 BM) received SRT and concurrent ST (group 1) and 95 patients (131 BM) received SRT alone without concurrent ST (group 2). SRT was planned on a linear accelerator, using volumetric modulated arc therapy. All ST were allowed including chemotherapy (CT), immunotherapy (IT), targeted therapy (TT) and hormonotherapy (HT). Treatment was considered to be concurrent if the timing between the drug administration and SRT did not exceed 1 month. Local control (LC), freedom for distant brain metastases (FFDBM), overall survival (OS) and radionecrosis (RN) were evaluated. Results: After a median follow-up of 11.9 months (range 0.7-29.7), there was no significant difference between the two groups. However, patients who received concurrent IT (n=30) had better 1-year LC, OS, FFDBM but a higher RN rate compared to patients who did not: 96% versus 78% (p=0.02), 89% versus 77% (p=0.02), 76% versus 53% (p=0.004) and 80% versus 90% (p=0.03), respectively. In multivariate analysis, concurrent IT (p=0.022) and tumor volume <2.07cc (p=0.039) were significantly correlated with improvement of LC. The addition of IT to SRT compared to SRT alone was associated with an increased risk of RN (p=0.03).Conclusion: SRT delivered concurrently with IT seems to be associated with improved LC, FFDBM and OS as well as with a higher rate of RN.
A post-GWAS confirming the genetic effects and functional polymorphisms of AGPAT3 gene on milk fatty acids in dairy cattle
Authors: Shi Lijun , Wu Xin , Ma Zhu , Lv Xiaoqing , Liu Lin , Li Yanhua , Zhao Feng , Han Bo , Yang Yuze , Sun Dongxiao 
Published: October 2020

Abstract
Background: People are paying more attention to the healthy and balanced diet with the improvement of their living standards. Milk fatty acids (FAs) have been reported that they were related to some atherosclerosis and coronary heart diseases in human. In our previous genome-wide association study (GWAS) on milk FAs in dairy cattle, 83 genome-wide significant single nucleotide polymorphisms (SNPs) were detected. Among them, two SNPs, ARS-BFGL-NGS-109493 and BTA-56389-no-rs associated with C18index (P = 0.0459), were located in the upstream of 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3) gene. AGPAT3 is involved in glycerol-lipid, glycerol-phospholipid metabolism and phospholipase D signaling pathways. Hence, it was inferred as a candidate gene for milk FAs. The aim of this study was to further confirm the genetic effects of the AGPAT3 gene on milk FA traits in dairy cattle.Results: Through re-sequencing the complete coding region, and 3,000bp of 5' and 3' regulatory regions of the AGPAT3 gene, a total of 17 SNPs were identified, including four in 5' regulatory region, one in 5' untranslated region (UTR), three in introns, one in 3' UTR, and eight in 3' regulatory region. By the linkage disequilibrium (LD) analysis with Haploview4.1 software, two haplotype blocks were observed that were formed by four and 12 identified SNPs, respectively. Using SAS9.2, we performed single locus-based and haplotype-based association analysis on 24 milk FAs in 1,065 Chinese Holstein cows, and discovered that all the SNPs and the haplotype blocks were significantly associated with C6:0, C8:0 and C10:0 (P < 0.0001~ 0.0384). Further, with Genomatix, we predicted that four SNPs in 5' regulatory region (g.146702957G>A, g.146704373A>G g.146704618A>G and g.146704699G>A) changed the transcription factor binding sites (TFBSs) for transcription factors SMARCA3, REX1, VMYB, BRACH, NKX26, ZBED4, SP1, USF1, ARNT and FOXA1. Out of them, two SNPs were validated to impact transcriptional activity by performing luciferase assay that the alleles A of both SNPs, g.146704373A>G and g.146704618A>G, increased the transcriptional activities of AGPAT3 promoter compared with alleles G (P = 0.0004).Conclusions: In conclusion, our findings first demonstrated the significant genetic associations of the AGPAT3 gene with milk FAs in dairy cattle, and two potential causal mutations were detected.
Factors influencing the result of superior oblique weakening procedures in patients with superior oblique overaction in horizontal strabismus
Authors: Chun Junwoo , Kim Seong-Joon 
Published: October 2020

Abstract
Background: Few studies have evaluated the surgical outcome of superior oblique weakening procedures in patients with superior oblique overaction associated with exotropia or esotropia. This study aimed to evaluate the outcome of superior oblique muscle weakening and the influencing factors in patients with superior oblique overaction. Methods: The medical charts of 37 patients (55 eyes) with superior oblique overaction associated with esotropia or exotropia who were treated with a superior oblique weakening procedure at the Seoul National University Hospital from January 2010 to June 2017 were retrospectively reviewed. Superior oblique overaction was graded using, a 6-point scale ranging from +0.5 to +3, and pre- and postoperative grades were recorded for all patients. Results: The mean age of the patients was 91.81 ± 59.37 months. Superior oblique muscle suture spacer and superior oblique posterior tenectomy were performed for 17 (23 eyes) and 20 (32 eyes) patients, respectively. Surgical success was achieved in 15 (65.2%) eyes in the suture spacer group and 23 (71.9%) eyes in the posterior tenectomy group. Surgical success was achieved for 69.1% (38/55 eyes) of patients. Dissociated vertical deviation exhibited a significant negative association with the surgical success rate (p<0.001). Conclusions: There was no significant difference in surgical success rate between the superior oblique posterior tenectomy and superior oblique suture spacer groups in superior oblique overaction associated with horizontal strabismus. Associated dissociated vertical deviation can affect the surgical success of the superior oblique weakening procedure.
Induction of leukocyte adhesion molecules and renal physiologically active molecules in Porphyromonas gingivalis lipopolysaccharide-induced diabetic nephropathy
Authors: Kajiwara Koichiro , Sawa Yoshihiko , Fujita Takahiro , Tamaoki Sachio 
Published: October 2020

Abstract
Background

We recently reported that the glomerular endothelium expresses toll-like receptor (TLR)2 and TLR4 in diabetic environments and established that the TLR2 ligand Porphyromonas (P.) gingivalis lipopolysaccharides (LPS) induces nephropathy in diabetic mice. It is thought that P. gingivalis LPS promotes the chronic inflammation with the overexpression of leukocyte adhesion molecules and renal-specific metabolic enzymes by the recognition of P. gingivalis LPS via TLR in the diabetic kidneys. The present study aims to examine the expression of leukocyte adhesion molecules and renal metabolic factors in mouse kidneys with periodontal pathogen P. gingivalis LPS-induced diabetic nephropathy that was recently established.
Methods

The immunohistochemical investigation was performed on mouse kidney with P. gingivalis LPS-induced diabetic nephropathy model with glomerulosclerosis in glomeruli.
Results

There were no vessels which expressed vascular cell adhesion molecule-1 (VCAM-1), E-selectin, or fibroblast growth factor (FGF) 23 in diabetic mice, or in healthy mice administered P. gingivalis LPS. However, in diabetic mouse kidneys with P. gingivalis LPS-induced nephropathy the expression of VCAM-1 and the accumulation of FGF23 were established in renal tubules and glomeruli, and the expression of E-selectin was established in renal parenchyma and glomeruli. The angiotensin-converting enzyme 2 (ACE2) was detected in the proximal tubules but not in other regions including not in distal tubules of diabetic mice without LPS, and not in healthy mice administered P. gingivalis LPS. In diabetic mouse kidneys with P. gingivalis LPS-induced nephropathy ACE2 was detected both in renal tubules as well as in glomeruli. The macrophage-1 (Mac-1) and podoplanin-positive cells increased in the renal parenchyma with diabetic condition and there was accumulation in P. gingivalis LPS-induced diabetic nephropathy. As the expression of VCAM-1 and E-selectin is upregulated in glomeruli, tubules, and intertubular capillaries, it is thought that the inflammatory infiltration of the monocyte-macrophage lineage promoted in kidneys with P. gingivalis LPS-induced the diabetic nephropathy.
Conclusions

P. gingivalis LPS may progressively accelerate the development of the renal inflammatory environment in LPS-accumulated glomeruli with the macrophage infiltration via the renal expression of VCAM-1 and E-selectin, and with ACE2 overexpression and FGF23 accumulation. Periodontitis may be a critical factor in the progress of nephropathy in diabetic patients.
Health-related quality of life in children with congenital heart disease aged 5 to 7 years: a multicentre controlled cross-sectional study
Authors: Abassi Hamouda , Huguet Helena , Picot Marie-Christine , Vincenti Marie , Gauillaumont Sophie , Auer Annie , Werner Oscar , Villeon Grégoire De La , Lavastre Kathleen , Gavotto Arthur , Auquier Pascal , Amedro Pascal 
Published: October 2020

Abstract
Background: In the context of tremendous progress in congenital cardiology, more attention has been given to patient-related outcomes, especially in assessing health-related quality of life (HRQoL) of patients with congenital heart diseases (CHD). However, most studies have mainly focused on teenagers or adults and currently, few HRQoL controlled data is available in young children. This study aimed to evaluate HRQoL of children with CHD aged 5 to 7 y.o., in comparison with contemporary peers recruited in school, as well as the factors associated with HRQoL in this population. Methods: This multicentre controlled prospective cross-sectional study included 124 children with a CHD (mean age=6.0±0.8 y, 45% female) during their outpatient visit and 125 controls (mean age=6.2±0.8 y, 54% female) recruited at school. A generic paediatric HRQoL instrument was used (PedsQL 4.0). Results: Self-reported HRQoL in children with CHD was similar to controls, overall (73.5±1.2 vs. 72.8±1.2, P=0.68, respectively), and for each dimension. Parents-reported HRQoL was significantly lower in the CHD group than in controls. HRQoL was predicted by the disease severity and by repeated invasive cardiac procedures (surgery or catheterization). Conclusion: HRQoL in young children with CHD aged 5 to 7 years old was good and similar to controls. HRQoL in this population correlated with CHD severity, especially when assessed by the infant heart failure Ross classification. This study contributed to the growing body of knowledge on HRQoL in congenital cardiology and emphasized the need for child and family support in the most complex CHD. Trial registration: This study was approved by the institutional review board of Montpellier University Hospital (2019_IRB-MTP_02-19) on 22 February 2019 and was registered on ClinicalTrials.gov (NCT03931096) on 30 April 2019, https://clinicaltrials.gov/ct2/show/NCT03931096.
Reliability and Validity of Pelvic Floor Muscle Strength Assessment Using the MizCure Perineometer
Authors: Abe-Takahashi Yui , Kitta Takeya , Ouchi Mifuka , Okayauchi Minori , Chiba Hiroki , Higuchi Madoka , Togo Mio , Shinohara Nobuo 
Published: October 2020

Abstract
Background: The purpose of this study was to clarify the reliability and validity of pelvic floor muscle (PFM) strength assessment using the MizCure perineometer in healthy women.Methods: Twenty healthy women (age 20-45 years) participated in this study. The vaginal pressure measured using the MizCure and validated Peritron perineometers were repeated during PFM contraction in the supine and standing positions. All women were evaluated twice by examiners 1 and 2. Following the measurements in the first session (Test 1), they were repeated after an interval of between 2 and 6 weeks (Test 2). Within- and between-session intra- and inter-rater reliabilities in vaginal pressure were analyzed using intraclass correlation coefficients (ICC) (1, 1) and (2, 1), respectively. Validity was assessed by Pearson’s product-moment correlation coefficient and Spearman’s rank correlation analysis.Results: Within-session intra-rater reliabilities for both examiners 1 and 2 for all vaginal pressures in Tests 1 and 2 were 0.90 to 0.96 for both perineometers. Between-session intra-rater reliability for the MizCure was 0.72 to 0.79 for both positions for examiner 1, and 0.63 in the supine position and 0.80 in the standing position for examiner 2. Inter-rater reliability for Test 1 was 0.91 in the supine position and 0.87 in the standing position for the MizCure. The vaginal pressures using the MizCure and Peritron were significantly associated with the supine position (r = 0.68, P < .001) and the standing position (rs = 0.82, P < .001).Conclusion: MizCure perineometer is a validated tool to measure PFM strength in both supine and standing positions in healthy nulliparous women.
Clinical Efficacy Evaluation of Full-endoscopic Foraminoplasty and Discectomy Under General Anesthesia in the Treatment of L5-S1 Disc Herniation
Authors: Meng Dongfang , Wang Lihe , Wang Tao , Tu Ji , Du Chenyang , Li Huiying 
Published: October 2020

Abstract
Background: Percutaneous transforaminal endoscopic discectomy (PTED) is a minimally invasive surgical method for the treatment of spinal diseases. However, the operation procedure relied on the radiative interventional technology, and was conducted under local anesthesia. Method: From June 2016 to December 2019, we performed a newly developed full-endoscopic visualized foraminoplasty and discectomy under general anesthesia in 30 patients with L5/S1 LDH. In this retrospective study, the outcomes and neurological complications of this approach were evaluated. Results: The mean visual analog scale (VAS) and Oswestry Disability Index (ODI) were significantly improved after surgery. The postoperative MRI reexamination revealed that the degree of intervertebral disc degeneration of each subject was improved significantly to different degrees as compared with that before surgery. The learning curve showed operative time rapidly decreased over the earlier cases, and then tapered to a steady state in the latter cases. Conclusions: Full-endoscopic foraminoplasty and discectomy under general anesthesia is efficient and safe for the treatment of the L5-S1 disc herniation.Trial registration: N/A
Incidence of inherited metabolic disorders in southern Israel: A comparison between consanguinity and non-consanguinity communities
Authors: Hazan Guy , Hershkovitz Eliyahu , Staretz-Chacham O 
Published: October 2020

Abstract
Background - Inherited metabolic disorders (IMDs) are group of rare monogenic diseases, usually derived from reduced or absent activity in a single metabolic pathway. Most of the IMDs are inherited in an autosomal recessive manner. The incidence of IMDs varies from country to country and within different ethnic groups, but data is still scarce. Consanguinity rate among populations is highly contributor factor for IMDs incidence. There are no reports comparing the incidence of IMD in consanguineous and non-consanguineous populations from the same geographic region with the same diagnostic capabilities. Our study objective is to compare the incidence of IMDs between between the relatively low consanguineous Jewish population and the consanguineous Bedouin population, both living in the southern of Israel.Results - During 1990-2017 there were 393,772 live births in the Negev district, of Southern of Israel. Among them 187,049 were of Jewish origin while 206,723 were of Bedouin-Muslim origin. A total of 223 children were diagnosed in this study period with IMDs. Among those 223 children with IMD, 33 were of Jewish origin while the other 190 children were of Bedouin-Muslim origin. The overall incidence for IMDs of the overall Negev population was 56.6/100,000 live birth. The incidence for IMD's among the Bedouin population was significantly higher than among Jewish population.Conclusions - IMDs are extremely more common in the consanguineous Bedouin compared with the relatively non-consanguineous Jewish population of Southern Israel. Health policy makers should consider these data and prepare educational and genetic counselling problems accordingly.
WITHDRAWN: The thermochemical non-equilibrium expansion effects of the high enthalpy nozzle
Authors: Shen Junmou , Chen Xing , Lu Hongbo , Shao Zongjie , Yao Dapeng , Bi Zhixian , Ma Handong 
Published: October 2020

Abstract
The high enthalpy shock tunnel can simulate the free-flow speed above 3km/s. The characteristic of the flow is that the kinetic energy of the high enthalpy stagnation gas is high enough to effectuate high-temperature effects such as dissociation even ionization of fluid molecules. The stagnation gas is converted into the hypervelocity free flow through the high enthalpy nozzle. The flow of high enthalpy flow in the high enthalpy nozzle can be divided into three regions: an equilibrium region, a non-equilibrium region and a frozen region. The equilibrium flow region is upstream of the throat, the non-equilibrium flow region is near the throat, and the frozen flow region is not far downstream of the throat. The study focuses on the conical nozzle, testing thermochemical non-equilibrium expansion effects under the different expansion angle of the expansion section, the curvature radius of the throat, the throat radius, and the convergence angle of the convergent section. A multi-block solver for axisymmetric compressible Navier-Stokes equations is applied to simulate the thermochemical non-equilibrium flow in several high enthalpy conical nozzles. The significant conclusions of this study contain tripartite. Firstly, the thermochemical non-equilibrium effects are sensitive to the maximum expansion angle and throat radius, but not to the radius of throat curvature and the contraction angle. Secondly, as the maximum expansion angle decreases and the throat radius increases, the flow approaches equilibrium. Finally, the maximum expansion angle and the throat radius not only affect the position of the freezing point but also impacts the flow field parameters, such as temperature, Mach number, and species mass concentration.
Clinical Predictors of Mortality of Patients With Acute Kidney Injury Requiring Renal Replacement Therapy
Authors: Rattananukrom Chitchai , Tonsawan Pantipa , Panitchote Anupol 
Published: October 2020

Abstract
Background: Acute kidney injury (AKI) is frequently encountered around 40% in critically ill patients and associate with a high mortality particularly in AKI patients requiring renal replacement therapy (RRT). The objective of this study was to assess the clinical predictors for 28-day mortality in AKI patients requiring RRT.Methods: This is a retrospective cohort study from prospectively collected data over a year (2014-2015). AKI patients requiring RRT were included. We collected demographic and laboratory data of AKI patients requiring RRT within 24 hours before initiation of RRT. We excluded patients with pre-existing chronic kidney disease stage 5 and AKI patients requiring peritoneal dialysis. We compared clinical characteristics and analyzed the predictors of mortality of survivors and non-survivors according to 28-day mortality.Results: We included 122 AKI patients requiring RRT. Mortality rate at day 28 and 90 after AKI diagnosis were 59% (95% confidence interval [CI] 49.7-67.8) and 72.1% (95%CI 63.3-79.9). On multivariable analysis, clinical predictors for 28-day mortality were baseline serum creatinine (hazard ratio [HR] 0.57, 95% CI 0.36-0.90), SOFA score before initiation of RRT (HR 1.08, 95%CI 1.01-1.15), presence of vasopressors before initiation of RRT (HR 3.04, 95%CI 1.12-8.25), serum lactate > 4 mmol/L before initiation of RRT effect <10 days of survival time (HR 2.49, 95%CI 1.17-5.26), and serum lactate > 4 mmol/L before initiation of RRT effect ≥10 days of survival time (HR 1.31, 95%CI 0.47-3.60).Conclusion: A lower baseline serum creatinine was associated with the mortality in AKI patients requiring RRT. SOFA score, presence of vasopressors, and a higher serum lactate before initiation of RRT are useful clinical predictors for the 28-day mortality.
Potential of Sustained Release Microparticles of Metformin in Veterinary Medicine: An in Vivo Pharmacokinetic Study of Metformin Microparticles as Oral Sustained Release Formulation in Rabbits.
Authors: Bouriche Sihem , Alonso-García Angela , Cárceles-Rodríguez Carlos M , Rezgui Farouk , Fernández-Varón Emilio 
Published: October 2020

Abstract
Background: Metformin hydrochloride a biguanide derivative has been widely used in the treatment of type 2 diabetes in humans. In veterinary medicine, metformin has been increasing his potential in different species as equids for insulin dysregulation, dogs and cats with diabetes. It is a highly soluble hydrophilic drug, shows incomplete absorption from the gastrointestinal tract and the absolute bioavailability is 40-60 % with a short biological half-life of 1.5-1.6 h in humans. In this study, to improve its efficacy a sustained-release microparticles of metformin was developed by loading within poly lactic acid (PLA) polymer followed by an in vivo pharmacokinetics study in rabbits. Results: Pharmacokinetic study in rabbits showed the sustained-release characteristic from the prepared microparticles with delayed time to reach maximum concentrations Tmax, decreased Cmax, increased Mean Residence Time (MRT) and half-life compared to the pure drug solution. Physicochemical characterization suggested that PLA and metformin hydrochloride interacted within the microparticles via hydrogen bonds and that the drug was transformed to an amorphous state. Conclusions: The The pharmacokinetics parameters resulted in delayed Tmax, increased MRT and t1/2, decreased Cmax of metformin from microparticles that show promise for prolonged/sustained release of metformin after oral administration in different animal species affected by insulin disorders. PLA microparticles provided sustained release of the drug, and these systems can be useful as drug carriers for hydrophilic drugs in long term disease treatment such as diabetes.
Crystal-Structures-Guided Design of Fragment-Based Drugs for Inhibiting the Main Protease of SARS-CoV-2
Authors: Luan Binquan , Huynh Tien 
Published: October 2020

Abstract
Since the beginning of the COVID-19 pandemic, researchers and scientists across the globe are racing to find a cure for the highly contagious infectious disease caused by the SARS-CoV-2 virus. Despite many promising ongoing progress, there are currently no FDA approved drugs to treat infected patients. Among the various protein targets of SARS-CoV-2 virus, the main protease (Mpro) has attracted most interests. Recently, the crowdsourcing of drug discovery for inhibiting Mpro have yielded
a plenty of drug fragments resolved inside the active site of Mpro via the crystallography method. Following the principle of fragment-based drug design (FBDD), we are motivated to design a potent drug molecule through merging several of these newly discovered drug fragments. Among various designed ligands, we found that B19 by merging three fragments JFM, U0P and HWH is the most stable one, evidenced through extensive (~10 μs totally) all-atom molecular dynamics simulation. We further estimated that the binding free energy of B19 is comparable or even a little better than that of a native protein ligand processed by Mpro. Our promising results suggest that B19 can potentially be an efficacious drug molecule for inhibiting Mpro of SARS-CoV-2.