bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher Total White Blood Cell and Neutrophil Counts Are Associated With Increased Stroke Mortality Risk: The Guangzhou Biobank Cohort Study
Authors: Hu Zhi-bing. , Lu Ze-xiong , Zhu Feng , Jiang Cao-qiang , Zhang Wei-sen , Pan Jin , Jin Ya-li , Xu Lin , Thomas G. Neil , Cheng Karkeung , Lam Taihing 
Published: March 2021

Abstract
Background: To investigate the relations of white blood cell (WBC) count and its dynamic change with future stroke mortality risk in a relatively healthy elderly population.Methods: A total of 27811 participants without stroke history at baseline were included and followed up for an average of 11.5 (SD=2.3) years. After review of available records, 399 stroke (277 ischaemic and 172 haemorrhagic) deaths were recorded among all-cause mortality. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).Results: Compared with the lowest quartile, the highest quartile of WBC count showed 53% and 67% increased mortality risk for total (adjusted HR [aHR]=1.53, 95% CI 1.16-2.02, P=0.003) and haemorrhagic (aHR=1.67, 95% CI 1.10-2.67, P=0.03) stroke, respectively; the highest neutrophil count showed 45% and 65% increased mortality risk for total (aHR=1.45, 95% CI 1.10-1.89, P=0.008) and ischaemic (aHR=1.65, 95% CI 1.10-2.47 P=0.02) stroke. The same results found for total and ischaemic stroke but not for haemorrhagic stroke were observed for both WBCs and neutrophils within the normal range level after further C-reactive protein (CRP) adjustment. Compared with the stable group, the 25% increased groups of both WBCs (aHR=1.60, 95% CI 1.07-2.40, P=0.02) and neutrophils (aHR=1.45, 95% CI 1.02-2.05, P =0.04) showed 60% and 45% increased stroke mortality risk, respectively.Conclusions: These findings support the role of WBCs, especially neutrophils, as simple, inexpensive and readily available predictors of future stroke mortality in an elderly population. Trial registration: The Guangzhou Medical Ethics Committee of the Chinese Medical Association approved the study.
Electroacupuncture Reduces Cold Stress-Induced Pain through Microglial Inactivation and Transient Receptor Potential V1 in Mice
Authors: Liao Hsien-Yin , Lin Yi-Wen 
Published: March 2021

Abstract
Background

Fibromyalgia pain lacks objective parameters to measure treatment efficacy. Fibromyalgia patients suffer from chronic and persistent widespread pain and generalized tenderness. Transient receptor potential V1 (TRPV1), which is reported as a Ca2+ permeable ion channel that can be activated by inflammation, is reported to be involved in the development of fibromyalgia pain.
Methods

The current study explored the transient receptor potential vanilloid 1 (TRPV1) channel functions as a noxious sensory input in mice cold stress model. It remains unknown whether electroacupuncture (EA) attenuates fibromyalgia pain or affects the TRPV1 pathway.
Results

We show that cold stress increases mechanical and thermal pain (Day 7: mechanical: 1.69 ± 0.41 g; thermal: 4.68 ± 0.56 s), and that EA and Trpv1 deletion counter this increase. EA and Trpv1 deletion reduced the cold stress-induced increase in inflammatory mediators and TRPV1-related molecules in the hypothalamus, periaqueductal gray (PAG), and cerebellum of mice.
Conclusions

Our results imply that EA has an analgesic effect associated with TRPV1 downregulation. We provide novel evidence that these inflammatory mediators can modulate the TRPV1 signaling pathway and suggest new potential therapeutic targets for fibromyalgia pain.
Comprehensive characterization of the chemical constituents in Yiganmingmu oral liquid and the absorbed prototypes in cynomolgus monkey plasma after oral administration by UPLC-Q-TOF-MS based on the self built components database
Authors: wei wei , Li Siwei , Cheng Linyou , Hao Erwei , Hou Xiaotao , Zhou Hua , Deng Jiagang , Yao Xinsheng 
Published: March 2021

Abstract
Background: Yiganmingmu oral liquid (YGMM), a well known over-the-counter (OTC) drug in China, is composed of 12 types of valuable herbal medicines and has been widely used in clinical for the treatment of soreness and weakness of waist and knees, dizziness, memory loss, and fatigue. However, the chemical compositions of YGMM and its absorbed compounds in plasma remain unclear. Methods: Since chemical investigation is the first important step to reveal effects and action mechanisms of traditional Chinese medicine (TCM), in this study, based on the self built components database, systematic characterization of the chemical profile of YGMM in vivo was carried out by using a reliable UPLC-Q-TOF-MS method. Moreover, to obtain better understanding of the absorbed prototypes in plasma, serum pharmacochemistry analysis of YGMM after oral administration was conducted by using cynomolgus monkeys as animal model. Results: A total of 667 constituents from the 12 single herbal medicines were collected in the self built components database by searching the reported literatures, and 415 of them were initially screened as candidate compounds in YGMM by comparison of their experimental accurate mass measurements with those theoretical values. After that, 117 compounds including 17 phenolic acids, 25 flavonoids, 4 alkaloids, 10 phthalides, 5 monoterpenes, 8 triterpenoid saponins, 9 anthraquinones, and 39 other compounds, were unambiguously identified or tentatively characterized by analysing their MS/MS fragmentation patterns, and also by comparison with reference standards and those data reported in the literatures. 61 prototypes absorbed in plasma of cynomolgus monkey, including 13 phenolic acids, 21 flavonoids, 8 phthalides, 3 monoterpenes, 4 triterpenoid saponins, and 12 other compounds were tentatively assigned by serum pharmacochemistry analysis after oral administration. Conclusion: It was the first comprehensive analysis of chemical constituents of YGMM and prototypes in plasma, and the data analysis strategy developed in this study showed high efficiency in the structural elucidations. The results might provide scientific evidence for further research on material basis of YGMM.
The Determination of 10 Compounds of GuiZhi Decoction in Rat Plasma after Oral Administration by HPLC-MS/MS and its Application to a Pharmacokinetic Study
Authors: Gao Huan , Guo Qin , Zhang Lishi , Song Jiannan , Bai Dong , Wu Xiaoxia 
Published: March 2021

Abstract
Background: Guizhi Decoction (GZD), a traditional Chinese medical formula, has been commonly used to treat fever, sweating, and cold in China. Methods: The high performance liquid chromatography -tandem mass spectrometry ( HPLC-MS/MS ) method was established for the determination of 10 compounds, including cinnamic acid , paeoniflorin, albiflorin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, and 6-gingerol. And the specificity, linearity, lower limit of quantification (LLOQ), lower limit of detection (LLOD), precision and accuracy, recovery, matrix effect, and stability were used to verify the HPLC-MS/MS method. This validated method was successfully applied for pharmacokinetic study of the 10 compounds in rat plasma after oral administration of GZD in three doses (40 g crude drug·kg −1 , 20 g crude drug·kg −1 , 10 g crude drug·kg −1 ) and intravenous injection of GZD extraction at a dose of 2.0 g crude drug·kg −1 .The measurements of pharmacokinetic parameters including AUC 0–∞ , T 1/2 , T max , C max , Vz_F, Cl_F, and MRT, were performed using a non-compartmental model with Winnonlin 8.1 software. Results: The results showed that 10 compounds were detected in plasma after oral administration of GZD. the compounds (except for glycyrrhetinic acid) reached the maximum blood concentration quickly, whose Tmax was about 0.1-0.2 min. And a total of 9 compounds were detected after intravenous injection of GZD. The plasma concentration-time curve of these compounds declines rapidly at the beginning, and then decreased slowly, indicating that the plasma concentration-time curves were double exponential function curves. Conclusions: In this study, the developed method was suitable for pharmacokinetic analysis of the main compounds of GZD in rat plasma, and may reveal the pharmacodynamic material basis of GZD and provide a reference for the rational use of GZD in the clinic.
Screening of Hematopoietic Small Molecules Facilitates the Establishment of a Chemically Defined Hsc Expansion Medium With Enhanced Performance
Authors: Albayrak Esra , Akgol Sezer , Turan Raife Dilek , Kocabas Fatih 
Published: March 2021

Abstract
Hematopoietic stem cells (HSC), known for their ability to multipotent and self-renew, are often used in HSC transplantation for the treatment of hematological diseases and malignancies. Umbilical cord blood (UCB) and mobilized peripheral blood (mPB), which are alternatives to bone marrow (BM) for HSC transplantation, have reduced HSC. To address this restriction, the ex vivo expansion of HSCs is a highly promising therapeutic approach rather than the use of a double-cord blood unit that induces delays in hematopoietic recovery. We have previously shown that knockout of HSC quiescence genes could increase the HSC pool in vivo. Thus, we thought that targeting HSC quiescence regulators using small molecules could be used for ex vivo expansion of both mPB and UCB-HSC. The goal was to identify novel hematopoietic small molecules (HSMs) and their combinations, and to enhance performance of human HSC expansion medium. We identified and analyzed 35 possible HSMs targeting HSC quiescence factors. We assessed their impact on human HSPC activity, including expansion, quiescence, multilineage capacity, cycling capability and metabolism. We have also investigated their cytotoxic and genotoxic effects on human HSPCs. On the other hand, a transplantation study was performed on immunocompromised mice for the evaluation of the repopulation and engraftment capacities of the expanded cells. We observed that BML-260 and TAME molecules robustly increased both the mPB and UCB-HSPC content and activated the re-entry of HSCs into the cell cycle. Colony Forming Unit (CFU) assay confirmed their improved multilineage capacity. BML-260 proved safer for the viability of expanded cells based on cytotoxicity and genotoxicity assays. In addition, gene expression analysis showed that BML-260 and TAME molecules contributed to HSC expansion by modulating cell cycle kinetics, including p27, Skp2 and Cdh1. In conjunction with these in vitro results, we have observed that BML-260-expanded HSCs had a strong hematopoietic reconstitution capacity. After the determination of the most effective molecule as BML-260, a comparative study of chemically defined media, including various supplements, was analyzed in addition to the BML-260 molecule. These results from in vitro and xenotransplantation experiments have shown that BML-260 molecules can be used therapeutically for human HSC expansion and regulation of HSC activity. In addition, the medium composition found may be a novel platform for human HSC expansion to used in clinical trials.
Incremental Changes in Qrs Duration as Predictor for Incident Cardiovascular Disease: a Prospective Follow-up of a Randomly Selected General Population Sample During a Decade Beyond
Authors: Chen Xiaojing , Hansson Per-Olof , Thunström Erik , Mandalenakis Zacharias , Caidahl Kenneth , Fu Michael 
Published: March 2021

Abstract
Background: The QRS complex has been shown to be a prognostic marker in coronary artery disease. However, the changes in QRS duration over time, and its predictive value for cardiovascular disease in the general population is poorly studied.Hypothesis: Increased QRS duration from the age of 50 to 60 is associated with increased risk of major cardiovascular events during a further follow-up to age 71. Method: A random population sample of 798 men born in 1943 were examined in 1993 at 50 years of age, and re-examined in 2003 at age 60 and 2014 at age 71. Participants who developed cardiovascular disease before the re-examination in 2003 (n=86) or missing value of QRS duration in 2003 (n=127) were excluded. ΔQRS was defined as increase in QRS duration from age 50 to 60. Participants were divided into three groups: group 1: ΔQRS <4ms, group 2: 4ms ≤ ΔQRS < 8ms, group 3: ΔQRS ≥ 8ms. Endpoints were major cardiovascular events. Result: Compared with men in group 1 (ΔQRS < 4ms), men with ΔQRS ≥ 8ms had a 56% increased risk of MACE during follow-up to 71 years of age after adjusted for BMI, systolic blood pressure, smoking, hyperlipidemia, diabetes and heart rate in a multivariable Cox regression analysis (HR 1.56, 95% CI:1.07-2.27, P=0.022).Conclusion: In this longitudinal follow-up over a decade QRS duration increased in almost two out of three men between age 50 and 60. The increased QRS duration in middle age is an independent predictor of major cardiovascular events.
Smoking Effect on Peripapillary and Macular Microvascular Structure in Inactive Graves’ Ophthalmopathy
Authors: CEYLANOGLU Kubra SERBEST , Sen Emine Malkoc , Doguizi Sibel , Hondur Gozde 
Published: March 2021

Abstract
ObjectiveThe aim of this study was to evaluate the smoking effect on peripapillary and macular microvascular structure in patients with inactive Graves’ ophthalmopathy (GO) and to compare these structures with those of healthy control subjects.MethodsA total of 34 healty participants (control group), 22 inactive GO patients with smoking (smoker group) and 19 inactive GO patients with nonsmoking (non-smoker group) were recruited in this prospective study. After detailed ophthalmological examination, vessel densities (VD) of the superficial capillary plexus (SCP), deep capillary plexus (DCP), retinal peripapillary capillary (RPC) and foveal avascular zone (FAZ) area, acircularity index (AI) of the FAZ were analyzed with optical coherence tomography angiography (OCTA) for each eye.ResultsVessel density in the total peripapillary; superior and inferior sectors of RPC were significantly lower in inactive GO patients with smoking (p<0.05 for all sectors) compared to control group. Besides, the FAZ AI was significantly higher in smoker and non-smoker inactive GO groups compared to healthy subjects (p=0.0001, p=0.0001, respectively). No significant difference was found in the FAZ area, and all SCP, DCP macular measurements between groups (p>0.05 for all).Conclusion﻿OCTA findings of lower peripapillary VD in the smoker group show smoking effect on the optic disc head microvasculature in inactive GO patients. These results could reflect early subclinical optic disc vasculature damage in smoker inactive GO subjects.
Elicitation of Phenylpropanoids in Maqui (Aristotelia chilensis [Mol.] Stuntz) Plants Micropropagated in Photomixotrophic Temporary Immersion Bioreactors (TIBs).
Authors: Trentini Giulia E , Rojas Makarena , Gajardo Daniela , Alburquenque Débora , Villagra Evelyn , Gómez Aleydis , Arru Laura , Arencibia Ariel D 
Published: March 2021

Abstract
A biotechnological system for the production of plants biomass and phenylpropanoids of maqui was developed in photomixotrophic TIBs. The in vitro maqui multiplication was evaluated using combinations of TDZ and BAP in TIBs 1L capacity. Treatment of MS basal supplemented with TDZ 1 mg/l shows the best results for the variables fresh weight and multiplication rate. Photomixotrophic conditions were standardized in media with 3%, 2%, 1%, 0% sucrose at a light intensity of 100 µM m− 2s− 1. The treatments reduced in sucrose (1% and 2%) and air supplemented with 0.4 MPa CO2 do not differ significantly in biomass production (fresh weight per cluster of plants) compared to the control treatment with sucrose 3% and standard air. Treatment with ABA (1m/l) induced the production and accumulation of phenylpropanoids metabolites in maqui cultures bioreactors. Phenylpropanoids in in vitro biomass of maqui and culture medium from TIBs were determined in parallel with control samples from wild plants and mature fruits. After the third day of analysis, not significant differences in polyphenols and anthocyanin contents were verified between the treatments of maqui in TIBs + ABA and controls. The non-significant differences in the contents of polyphenols and anthocyanin were maintained until the 15 days of analysis. The antioxidant capacity comparing samples of maqui in bioreactors and wild plants showed no significant differences by the ORAC test from day 5 to day 15 of the study.
An Immunotherapy Strategy Targeting Programmed Cell Death Ligand 1 and CD73 with Macrophage-Derived&nbsp;Mimetic Nanovesicles to Treat Bladder Cancer
Authors: Zhou Qidong , Ding Weihong , Qian Zhiyu , Zhu Quangang , Sun Chuanyu , Yu Qin , Tai Zongguang , Xu Ke 
Published: March 2021

Abstract
BackgroundThe tumor microenvironment in bladder cancer exerts an inhibitory effect on immune effector cells. Thus, removing this inhibitory effect could help improve the efficacy of immune checkpoint inhibitors, and combination immunotherapy is a promising strategy for increasing the proportion of patients with bladder cancer who benefit from immune checkpoint inhibitors. However, it is difficult to effectively and simultaneously deliver multiple drugs to the tumor tissue. In this study, we describe the design and in vivo validation of macrophage-derived exosome-mimetic nanovesicles (EMVs) as a nanoplatform for coloading and targeted delivery of a CD73 inhibitor (AB680) and monoclonal antibodies targeting programmed cell death ligand 1 (aPDL1). ResultsOur results indicated that these nanocomplexes (AB680@EMVs-aPDL1) were highly stable, provided adequate biosafety in vivo, and exhibited enhanced targeting in a mouse model of bladder cancer. Moreover, the CD73 inhibitor reduced extracellular adenosine production, and the combination therapy significantly promoted activation of cytotoxic T lymphocytes, resulting in suppression of tumor growth in vivo. ConclusionsTherefore, using EMVs to deliver a combination of aPDL1 and a CD73 inhibitor may be an effective combined immunotherapy strategy for treating bladder cancer.
Evaluation of Diagnostic Performance of BD Max EBP Assay in Patients with Diarrheal Illness.
Authors: OZYURT Ozlem KOYUNCU , SAGLIK Imran , OZHAK Betil , MUTLU Derya , LEVENT Belkıs , DONMEZ Levent , GUNSEREN Filiz , ONGUT Gozde , COLAK Dilek , OGUNC Dilara 
Published: March 2021

Abstract
Background: Detection of the etiological agents in patients with acute diarrhea is challenging due to a wide variety of pathogens. Detection and identification of the pathogens of acute diarrhea are important for both individual patient care and public health. The aim of this study is to evaluate the diagnostic performance of BD Max Enteric Bacterial Pathogens (EBP) PCR assay in patients with diarrheal illness. Methods: Between 1 January 2014 and 31 May 2015, one thousand two hundred twenty four stool samples from pediatric or adult patients with diarrhea submitted for routine analysis of bacterial stool pathogens were included in the study. We compared the BD Max EBP PCR assay to culture for the detection of Salmonella spp., Shigella spp., Campylobacter jejuni, and Campylobacter coli and an EIA (Enzym Immun Assay) for Shiga toxins 1 and 2. Discordant results were adjudicated by either antigen detection methods or Film array GI (Gastro Intestinal) Panel. Coinfections were excluded. The chi-square test was used for comparisons of PPA and NPA.Results: The PPA (positive percent agreement) values for the BD Max EBP assay was 100% and NPA (negative percent agreement) was between 98.0%-99.7%, when compared with culture and EIA. After discrepant analysis, the PPA values for the BD Max EBP assay was 100% and NPA was between 99.5%-100%. Conclusion: The BD Max EBP assay showed a high correlation rate with conventional and molecular methods for the detection of stool pathogens.
Development of morphology tuned SnS hierarchical structures for enhanced photosensitive photodiode fabrication
Authors: Abhiram N. , Marnadu R. , Gunasekaran S. , Santhana V. , Chandrasekaran J. , Devi N.S.M.P. Latha , Thangaraju D 
Published: March 2021

Abstract
Hierarchical structure transformation and surface modification of solvothermal method synthesized SnS with oleic acid in ethylene glycol solvent were discussed in detail. The structural, optical, and morphology of as prepared SnS samples were examined by X-ray diffraction (XRD), Raman Spectroscopy, and Field Emission Scanning Electron Microscopy (FE-SEM). XRD verifies the orthorhombic crystal structure of the SnS phase for all synthesized samples. Single-phase nature of synthesized particles was confirmed with Raman characterization. Morphology evolution of SnS from regular to hierarchical structures upon adding oleic acid is performed through FE-SEM analysis. Junction diodes p-SnS/n-Si fabricated with different oleic acid concentrations (0.5, 1.5, and 2.5 mL) synthesized SnS particles show better photo-response, which can be used in photodiode applications.
Traditional Growing Rod for Early Onset Scoliosis in High Altitude Regions: a Retrospective Study
Authors: Jiang Haijun , Hai Junrui Jonathan , Yin Peng , Su Qingjun , Zhu Shiqi , Pan Aixing , Wang YunSheng , Hai Yong 
Published: March 2021

Abstract
Background: Children with early-onset scoliosis (EOS) living in high-altitude areas have serious deformities and poor nutritional status. There are no reports on the treatment of EOS with traditional growing rods (TGRs)in children in high-altitude areas. This study aimed to analyze the outcomes of patients in high-altitude areas treated with TGRs and compare their results according to whether altitude had an effect on therapy.Methods: Between September 2007 and December 2017, 59 consecutive patients with EOS underwent systematic surgical correction using TGRs. Patients were divided into the high-altitude group(H-A group) and low-altitude group(L-A group), and differences in surgical efficacy and complications between the groups were analyzed pre- and postoperatively. Radiographic measurements included the Cobb angle, thoracic kyphosis (TK), lumbar lordosis, T1–S1range,T1–T12 range, sagittal balance, coronal balance, distance between the C7PL and sagittal vertical axis, pelvic incidence, sacral slope, and pelvic tilt, assessed preoperatively, postoperatively, and at the last follow-up. Paired or independent Student’s t-tests were used to analyze continuous data. The χ2 test was used to analyze enumeration data. Repeated measurement analysis of variance was used to compare continuous data preoperatively, postoperatively, and at the last follow-up.Results: Mean age of all patients at the initial surgery was 8.9±2.4(5–14) years; mean duration of follow-up was 51.91±25.23months.The number of surgical procedures for all patients was 234.The average interval between operations was 11.4±3.0months.The average Cobb angle was similar in both groups preoperatively and at the last follow-up(P>0.05),although it was significantly different postoperatively (P<0.05). TK was significantly different preoperatively, postoperatively, and at the last follow-up(P<0.05).T1-S1and T1-T12lengths were significantly different preoperatively (P<0.05) but not postoperatively and at the last follow-up(P>0.05). The overall rates of complications and implant-related complications did not differ significantly between the groups(P>0.05).Conclusion: Deformity in patients with EOS in high-altitude areas was more serious, and treatment using TGRs yielded a satisfactory therapeutic effect.