bluuebunny/crossref_metadata_2025 huggingface dataset:
Downregulation of TREM2 Expression Exacerbates Neuroinflammatory Responses Through TLR4-Mediated MAPK Signaling Pathway in a Transgenic Mouse Model of Alzheimer’s Disease
Authors: Ruganzu John Bosco , Peng Xiaoqian , He Yingying , Wu Xiangyuan , Zheng Quzhao , Ding Bo , Lin Chengheng , Yang Weina
Published: March 2021

Activation of glial cells and neuroinflammation play an important role in the onset and development of Alzheimer’s disease (AD). Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-specific receptor in the brain that is involved in regulating neuroinflammation. However, the precise effects of TREM2 on neuroinflammatory responses and its underlying molecular mechanisms in AD have not been studied in detail. Here, we employed a lentiviral-mediated strategy to downregulation of TREM2 expression on microglia in the brain of APPswe/PS1dE9 (APP/PS1) transgenic mice and BV2 cells. Our results showed that TREM2 downregulation significantly aggravated AD-related neuropathology including Aβ accumulation, peri-plaque microgliosis and astrocytosis, as well as neuronal and synapse-associated proteins loss, which was accompanied by a decline in cognitive ability. The further mechanistic study revealed that downregulation of TREM2 expression initiated neuroinflammatory responses through toll-like receptor 4 (TLR4)-mediated mitogen-activated protein kinase (MAPK) signaling pathway and subsequent stimulating the production of pro-inflammatory cytokines in vivo and in vitro. Moreover, blockade of p38, JNK, and ERK1/2 inhibited the release of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) induced by Aβ1−42 in TREM2-knocked down BV2 cells. Taken together, these findings indicated that TREM2 might be a potential therapeutic target for AD and other neuroinflammation related diseases.
Oral Health Team in Primary Health Care Favors the Early Diagnosis of Oral and Oropharyngeal Cancers: A Nationwide Study
Authors: Vargas Deborah Gomes Miranda , Probst Livia Fernandes , Cunha Amanda Ramos da , Tagliaferro Elaine Pereira da Silva , Zafalon Edílson José , Pereira Paulo Zárate , De-Carli Alessandro Diogo
Published: March 2021

Background

Oral and oropharyngeal cancers are considered an important public health problem around all world. The most effective way to improve survival and reduce disease-related morbidity and mortality is the prevention of its major risk factors combined with early detection. This study aims to analyze the association between late diagnosis of oral and oropharyngeal cancers in Brazil and the contextual socioeconomic and coverage indicators of Primary Health Care (PHC), as well as to assess the temporal trend of the late diagnosis.
Methods

This observational study evaluated secondary data with a time series analysis. All Brazilian cities that reported at least one case of oral and oropharyngeal cancers each year, between 2000 and 2013 were included. These data were obtained from the National Cancer Institute José Alencar Gomes da Silva (INCA); the staging was analyzed by calculating the ratio risk for late diagnosis by municipality. The association between staging and socioeconomic variables and PHC provision was calculated using multiple linear regression. The time trend of the risk ratio for late-stage diagnosis was calculated using the Prais-Winsten method.
Results

One hundred and sixty Brazilian municipalities had at least one annual case of oral and oropharyngeal cancers notified to the INCA hospital system between 2000 and 2013. The adjusted model identified that the higher the Gini value (greater social inequality) and the lower the HDI value (less human development), the greater the number of tumors diagnosed at a late stage, considering the size of the tumor. A greater risk for late diagnosis was identified, already in the stage of lymph node involvement, when there is greater social inequality and less coverage of Oral Health Team (OHT) in PHC. The greater the social inequality, the greater the risk of late diagnosis, already in the metastasis stage.
Conclusions

Better socioeconomic indicators and greater coverage by the OHT were associated with the diagnosis of oral and oropharyngeal cancers still in the early stages. During the evaluated period, there was an increase in the number of cases diagnosed at the most advanced stage.
Prescribers Factors and Patients Socio-Demographic Factors Influencing Quality Care Management of Febrile Illnesses in Ghana.
Authors: Samuel Asante Koranteng , Kwasi Brenyah Joseph , Kofi Mensah Akohene , Peter Agyei -Baffour , Daniel Opoku , Perditer Okyere
Published: March 2021

Introduction Febrile illnesses in children and its management (especially infectious diseases) continue to result in an enormous increase in morbidity and mortality in developing countries causing a global public health concern. However, most low-middle-income countries have failed to institute systematic outcome assessment measures to ensure quality in the management of these conditions at one breadth. This study therefore aimed at assessing the quality care management of febrile illness in under five (5) in health facilities in the Atwima Kwanwoma district of Ashanti Region, Ghana.Methods The study was quantitative using a cross-sectional study design. Data were collected from 58 healthcare providers and 390 folders of children treated for febrile illnesses. Data were analyzed using STATA version 14. Univariate and multivariate analyses were performed to identify socio-demographic, patient and prescribers’ factors influencing management of febrile illness among children under 5 years. Statistical significance for all testing was set as 0.05.Results The mean age and standard deviation of the prescribers were 30.2 ± 3.4. Majority of the prescribers (65.5%) were aged between 23-30years and the rest (34.5%) between 31-37years. About 67.3% were females and the rest (32.7%) were males, more than half of the prescribers (70.7%) were married and the rest (29.3%) were single. More than half (55.6%) of patients seen were females and 44.4% were males. Most of the patients (43.8%) who presented with febrile illnesses were between 0-11 months, while 29.1% and 27.2% of them were between 1-2 years and 3-5 years respectively. The average age of children was 5.7 ± 2.3 months for those who were less than a year and 2.8±1.4 years for those between 1-5years. Patients who believed in superstition were less likely to receive quality care management of febrile illness as compared with those who did not believe in superstitions (AOR=0.50; 95% CI= 0.03-0.70).The results depict that socio-demographic factors such as age of a child and gender, influenced quality care management of febrile illness as detailed in Table 4. For instance, children below 1 year were less likely to receive quality care management of febrile illness as compared with those above 3 years (AOR=0.05; 95% CI= 0.08-0.28). Also, female children were more likely to receive quality care management of febrile illness as compared with their male counterparts (AOR=1.50; 95% CI=0.03-0.70).Conclusion The study concludes that, prescribers’ factors such as those who believed in superstition and socio-demographic factors of children such as age and gender influenced quality care management of febrile illness.Recommendations Health policy makers should promote health education to reduce the negative effects of supersitition in health care management.
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

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

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

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

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

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

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

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

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 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

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

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

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

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.
Community Outpatient Psychotherapy Engagement Service for Self-harm (COPESS): A Feasibility Trial Protocol
Authors: Saini Pooja , Hunt Anna , Taylor Peter , Mills Catherine , Clements Caroline , Mulholland Helen , Kullu Cecil , Hann Mark , Duarte Rui , Mattocks Felicity , Guthrie Else
Published: March 2021

Background: People who self-harm are at high risk for future suicide and often suffer considerable emotional distress. Depression is common among people who self-harm and may be an underlying driver of self-harm behaviour. Self-harm is often repeated, and risk of repetition is highest immediately after an act of self-harm. Readily accessible brief talking therapies show promise in helping people who self-harm, but further evaluation of these approaches is needed. A brief talking therapy intervention for depression and self-harm, has been designed for use in a community setting. This mixed methods feasibility study with repeated measures will examine the feasibility and acceptability of the Community Outpatient Psychological Engagement Service for Self-Harm (COPESS) for people with self-harm and depression in the community compared to routine care. Methods: We will recruit 60 participants with a history of self-harm within the last six months, who are also currently depressed, to take part in a feasibility single blind randomised controlled trial (RCT). We will randomise participants 1:1 to receive COPESS plus treatment as usual (TAU) or TAU alone. Recruitment will take place via GP practices and self-referral. Assessment of feasibility and acceptability will be assessed via quantitative and qualitative methods including measures of recruitment and retention to the trial, participants’ experience of therapy, completion / completeness of outcome measures at relevant time-points and completion of a service use questionnaire. Discussion: The results will indicate whether it is feasible to conduct a definitive trial to determine whether COPESS is a clinically, cost-effective intervention for those who self-harm in the community. The qualitative and quantitative data will help identify the potential strengths or challenges of brief community-based interventions for self-harm. Trial registration: NCT04191122 registered 9th December 2019, https://clinicaltrials.gov/ct2/show/NCT04191122?term=NCT04191122&draw=2&rank=1
Water Balance and Influence Mechanism Analysis: A case study of Hongjiannao Lake, China
Authors: Yue Hui , Liu Ying
Published: March 2021

Hongjiannao groundwater exchange was the largest desert freshwater lake in China (57.25 km2 in 1986). However, it shrank sharply over the past 34a (1986–2019), with the smallest lake area 31.41 km2 in 2015. The objective of this study was to use the Landsat images, ASTER GDEM V2 data, and meteorology and statistics data, in combination with the water balance model to calculate the dynamics of water balance elements, quantify and characterize the interannual variations in lake-groundwater exchanges, and analyzed its influencing factors by using the geographical detector. The results showed that in the stable stage (1986–1997), the average rate of the lake area, water level, and lake volume change was − 0.26 km2/a, -0.0483 m/a, and − 0.0009 km3/a, respectively. Precipitation, river inflow, and groundwater were 0.0203 km3, 0.0485 km3, and 0.0098 km3, which accounts for the whole input were 25.83%, 61.70%, and 12.47%, respectively, evaporation was 0.0786 km3. In the reduction stage (1998–2015), the average rate of the lake area, water level, and lake volume change was − 1.21 km2/a, -0.2422 m/a, and − 0.0101 km3/a, respectively. Before 2006, precipitation, river inflow, and groundwater were 0.0154 km3, 0.0475 km3, and − 0.0025 km3, respectively; from 2006 to 2009, precipitation, river inflow, and groundwater were 0.0143 km3, 0.0334 km3, and 0.0058 km3, respectively; after 2009, precipitation, river inflow, and groundwater were 0.0139 km3, 0.0199 km3, and 0.0085 km3, respectively. Evaporation decreased from 0.0714 km3 to 0.0480 km3 from 1998 to 2015. In the growth stage (2016–2019), the average rate of the lake area, water level, and lake volume change were 1.38 km2/a, 0.27 m/a, and 0.0088 km3/a, respectively. Precipitation, river inflow, and groundwater were 0.0209 km3, 0.0005 km3, and 0.0373 km3, which accounts for the whole input were 46.63 %, 52.12 %, and 1.25 %, respectively, evaporation was 0.0187 km3. Compared with the stable stage, groundwater in the growth stage reduced from 12.47 % (0.0098 km3) to only 1.25 % (0.0005 km3). From 1998 to 2004, Hongjiannao Lake experienced continuous losing conditions (discharge from the lake to groundwater), with a variable exchange volume of up to -0.01582 km3 in 1999. Through geographical detector analysis, it was found that temperature was the dominant factor from 1988 to 1997, while human factors were the dominant factors from1998 to 2015.
Analyzing and validating the prognostic value and immune microenvironment of clear cell renal cell carcinoma
Authors: Ke Jingwei , Chen Jie , Liu Xin
Published: March 2021

Background: There is still controversy regarding immunotherapy biomarkers. Therefore, we aimed to identify prognostic biomarkers related to immunotherapy for clear cell renal cell carcinoma (ccRCC).Methods: Fragments Per Kilobase Million (FPKM) data and clinical characteristics for ccRCC patients from The Cancer Genome Atlas (TCGA) database were downloaded. Unsupervised consensus clustering analysis was performed to divide patients into different immune subgroups according to their single-sample gene set enrichment analysis (ssGSEA) scores. Then, we validated the differences in immune cell infiltration, prognosis, clinical characteristics and expression levels of HLA and immune checkpoint genes between different immune subgroups. Weighted gene coexpression network analysis (WGCNA) was used to identify the significant modules and hub genes that were related to the immune subgroups. A nomogram was established to predict the overall survival (OS) outcomes after independent prognostic factors were identified by least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses.Results: Five clusters (immune subgroups) were identified. There was no significant difference in age, sex or N stage. And there were significant differences in race, T stage, M stage, grade, prognosis and tumor microenvironment. HLA gene families and CTLA4 showed significant differences between the five clusters, while PD1 and PDL1 did not. The red module was significant, and 14 hub genes were obtained. In addition, the nomogram containing LAG3 and GZMK accurately predicted OS outcomes of ccRCC patients.Conclusion: LAG3 and GZMK are strongly related to immunity and may provide suggestions for ccRCC immunotherapy.
Swimming turn performance: the distinguishing factor in 1500m World championship freestyle races?
Authors: Polach Marek , Thiel Dan , Kreník Jan , Born Dennis-Peter
Published: March 2021

Objective

Turn sections represent the second largest part of total race time in 1500 m freestyle races and may substantially affect race results. Therefore, the aim of the study was to investigate individual race strategies and compare the effect of start, swim, and turn performances between short-course and long-course races. Video footages were collected from all male finalists at the 2018 short- (n = 8, age 22.8 ± 2.4 years, FINA points 953 ± 27) and 2019 long-course World swimming championships (n = 8, age 23.3 ± 2.2 years, FINA points 951 ± 23) for subsequently analysis of start, turn, and swim performance.
Results

The larger number of turns in short-course races resulted in significantly faster race times (p < 0.001), but slower mean turn times compared to long-course races (p < 0.001). Total race time closely correlated with swim and turn but not start section time in short- (r ≥ 0.76, p ≤ 0.030) and long-course races (r ≥ 0.96, p < 0.001). Analysis of individual race strategies showed that turn performance affected race results in 9 of the 16 world-best 1500 m swimmers and improved medal standing of 1st, 3rd, and 4th ranked short- as well as 1st and 2nd ranked long-course finalist. Coaches, athletes, and performance analysts may carefully consider the importance of turn performance additionally to free-swimming skills.
Decorin is an early CSF biomarker of Alzheimer’s Aβ amyloidosis
Authors: Jiang Richeng , Smailovic Una , Haytural Hazal , Haret Robert , Shevchenko Ganna , Tijms Betty , Gobom Johan , Abelein Axel , Bogdanovic Nenad , Zetterberg Henrik , winblad bengt , Frykman Susanne , Jelic Vesna , Bergquist Jonas , Visser Pieter Jelle , Nilsson Per
Published: March 2021

Alzheimer’s disease (AD) is characterized by impaired protein homeostasis leading to amyloid-beta (Aβ) amyloidosis. Here, we show that autophagy is similarly inhibited in AD brains and App knock-in AD mouse models. To determine how pathologies translate to cerebrospinal fluid (CSF), label-free mass spectrometry of mouse CSF was used. This identified autophagy-related extracellular matrix (ECM) protein decorin as significantly and similarly increased in App knock-in mice and cognitively normal human subjects with abnormal CSF-amyloid. Notably, a switch from negative to positive correlation of CSF-decorin and CSF-amyloid occurs in cognitively normal subjects when CSF-amyloid becomes abnormal, indicating an early change in CSF-decorin induced by Aβ amyloidosis. In App knock-in mice increased CSF-decorin correlated with accentuated decorin expression in choroid plexus and decreased interneuronal decorin. Furthermore, decorin activates neuronal autophagy-lysosomal system by enhancing lysosomal degradation. Therefore, decorin is a potential CSF biomarker that reflects ECM and autophagy alterations in early AD Aβ amyloidosis.
Dedifferentiated liposarcoma with abrupt transition of low-grade and high-grade dedifferentiated components: A case report
Authors: WEN YANG , HE XIANGLEI , ZHAO MING
Published: March 2021

BackgroundDedifferentiated liposarcoma (DDLPS) is a unique subtype of liposarcoma, which has obvious histological heterogeneity. In affected patients, the condition typically manifests as the dedifferentiation of high-grade histological morphology, but it may also manifest as the dedifferentiation of low-grade histological morphology. In some cases, unique histological or immunophenotypic characteristics are observed. We describe, herein, a rare case of dedifferentiated liposarcoma, in which the high-grade and low-grade dedifferentiated components coexisted with a relatively sharp transition in pathology.Case presentationA 69-year-old woman with severe abdominal pain lasting for 1 hour presented to our hospital. Physical examination revealed a mobile large left abdominal mass, Magnetic resonance imaging (MRI) scan showed a huge mass with typical fat components and the non-fatty nodule in the left retroperitoneal cavity. After laparotomy, histologic analysis of the specimens could find the atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) and DDLPS components. Fluorescence in situ hybridization (FISH) analysis suggested the presence of MDM2 gene amplification. These findings supported a diagnosis of DDLPS.ConclusionIn our case, the high-grade and low-grade dedifferentiated components coexisted with a relatively sharp transition in pathology. We hypothesize that low-grade dedifferentiation may be a precursor to high-grade dedifferentiation. MRI images cannot distinguish the two components.
Expression of a novel DREB 5-A subgroup transcription factor gene from Ricinus communis (RcDREB1) enhanced growth, drought tolerance and pollen viability in tobacco
Authors: Aragão Francisco Lima , Rego Tomas Felipe Costa do , Santos Mirella Pupo , Cabral Glaucia Barbosa , Cipriano Thaís de Moura , de Sousa Natália Lima , Neto Otacílio Antônio de Souza
Published: March 2021

Climate change has increased the frequency of long periods of drought, affecting crop cultivation worldwide. Losses due to water stress exceed ten percent of world production of major crops, reaching three-quarters of production areas, with severe economic losses. Therefore, the generation of environmental stress-tolerant genotypes that are more efficient in water use is extremely important. We have previously isolated and characterized a DREB transcription factor coding gene, named RcDREB1, from castor bean (Ricinus communis L.), which probably belongs to the CBF/DREB subfamily subgroup A-5. Aiming to develop drought-tolerant lines, we have stably introduced and expressed the RcDREB1 transgene into tobacco. Transgenic lines have revealed an enhanced drought tolerance. Genetically modified lines cultivated under water deficit presented a higher photosynthetic rate, stomatal conductance, leaf water potential and leaf water content when compared to the control. Transgenic lines revealed lower transpiration rates. In addition, biometric analyses showed that transgenic lines cultivated under water stress presented higher biomass, higher fresh and dry weight and higher plant height than the non-transgenic lines. After re-watering, transgenic lines recovered faster than non-transgenic plants. Moreover, pollen grains from transgenic plants revealed a remarkable increase in viability after exposure to heat (38 ºC) and desiccation stresses. The results presented here will be the foundation for production of commercial crops that are more tolerant to environmental stresses and long-life pollen grains, increasing pollination and in consequence, productivity.
Correlational study on the levels of 25-hydroxyvitamin D and non-alcoholic fatty liver disease in type 2 diabetic patients
Authors: Yuanyuan Zhang , Li Juyi , Ni Yingqun , Wang Yan , Liu Huaizhen
Published: March 2021

Background

It is widely acknowledged that nonalcoholic fatty liver disease(NAFLD) and type 2 diabetes mellitus(T2DM) are all chronic metabolic diseases.The objective of this study is to retrospectively probe the association between the 25-hydroxyvitamin D(25-(OH)D) and NAFLD in type 2 diabetic patients.
Methods

339 T2DM patients participated in this research and from November 2018 to September 2019 and were divided into simple T2DM group(108 cases) and T2DM with NAFLD group(231 cases) in conformity with abdominal ultrasound diagnosis. The NAFLD fibrosis score (NFS) ≥ 0.676 was defined as progressive liver fibrosis.231 T2DM with NAFLD patients were categorized into two subgroups: progressive liver fibrosis subgroup(48 cases) and without progressive liver fibrosis subgroup(183 cases).
Results

The prevalence of NAFLD by Abdominal ultrasonography was 68%.The results indicated that the levels of 25-(OH)D were significantly lower in T2DM with NAFLD group than that in simple T2DM group(P < 0.01).The levels of 25-(OH)D were significantly lower in progressive liver fibrosis subgroup than that in patients without progressive liver fibrosis and simple T2DM,and 25-(OH)D levels were lower in without progressive liver fibrosis subgroup than that in simple T2DM group(p < 0.01 or p < 0.05).Multivariate logistic regression analysis showed that levels of 25-(OH)D were negative correlation with risk of NAFLD and progressive liver fibrosis(p = 0.011、p = 0.044,respectively).
Conclusions

we could come to a conclusion that low levels of 25-(OH)D was a risk factor for NAFLD and progressive liver fibrosis in T2DM patients.