bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-27a-3p and miR-30b-5p inhibited-vitamin D receptor involved in the progression of tuberculosis
Authors: Xiao Min , Yang Song , Zhou An , Li Tongxin , Liu Jingjing , Chen Yang , Luo Ya , Qian Chunfang , Yang Fuping , Tang Bo , Li Chunhua , Su Na , Li Jing , Jiang Mingying , Yang Shiming , Lin Hui 
Published: October 2022

BackgroundMicroRNAs (miRNAs) play a vital role in tuberculosis (TB). Vitamin D receptor (VDR), an miRNA target gene, and its ligand, vitamin D3 (VitD3), have been reported to exert protective effects against TB. However, whether miRNAs can affect the progression of TB by targeting VDR has not been reported.Materials and methodsResearch subjects were selected according to defined inclusion criteria. A clinical database of 360 samples was established, including the subjects’ demographic information, miRNA expression profiles and cellular experimental results. Two candidate miRNAs, miR-27a-3p, and miR-30b-5p, were identified by a high-throughput sequencing screen and validated by qRT–PCR assays. Univariate and multivariate statistical analyses were performed. VDR and NF-kB p65 protein levels were detected by Western blot assays. Proinflammatory cytokine expression levels were detected by enzyme-linked immunosorbent assay (ELISA). Luciferase assays and fluorescence-activated cell sorting (FACS) were further applied to elucidate the detailed mechanisms.ResultsDifferential miRNA expression profiles were obtained, and miR-27a-3p and miR-30b-5p were highly expressed in patients with TB. These results showed that the two miRNAs were able to induce M1 macrophage differentiation and inhibit M2 macrophage differentiation. Further experiments showed that the two miRNAs decreased the VDR protein level and increased proinflammatory cytokine secretion by macrophages. Mechanistically, the miRNAs targeted the 3′ untranslated region (3′UTR) of the VDR mRNA and thereby downregulated VDR protein levels by post-transcriptional regulation. Then, due to the reduction in VDR protein levels, the NF-kB inflammatory cytokine signaling pathway was activated, thus promoting the progression of TB.ConclusionOur study not only identified differentially expressed miRNAs between the TB and control groups but also revealed that miR-27a-3p and miR-30b-5p regulate proinflammatory cytokine secretion and macrophage differentiation through VDR in macrophages. Thus, these two miRNAs influence the progression of TB.
Alpha-Synuclein species in oral mucosa as potential biomarkers for multiple system atrophy
Authors: Zheng Yuanchu , Cai Huihui , Zhao Jiajia , Yu Zhenwei , Feng Tao 
Published: October 2022

BackgroundThe definitive diagnosis of Multiple system atrophy (MSA) requires the evidence of abnormal deposition of α-Synuclein (α-Syn) through brain pathology which is unable to achieve in vivo. Deposition of α-Syn is not limited to the central nervous system (CNS), but also extended to peripheral tissues. Detection of pathological α-Syn deposition in extracerebral tissues also contributes to the diagnosis of MSA. We recently reported the increased expressions of α-Syn, phosphorylated α-Synuclein at Ser129 (pS129), and α-Syn aggregates in oral mucosal cells of Parkinson’s disease (PD), which serve as potential biomarkers for PD. To date, little is known about the α-Syn expression pattern in oral mucosa of MSA which is also a synucleinopathy. Here, we intend to investigate whether abnormal α-Syn deposition occurs in oral mucosal cells of MSA, and to determine whether α-Syn, pS129, and α-Syn aggregates in oral mucosa are potential biomarkers for MSA.MethodsThe oral mucosal cells were collected by using cytobrush from 42 MSA patients (23 MSA-P and 19 MSA-C) and 47 age-matched healthy controls (HCs). Immunofluorescence analysis was used to investigate the presence of α-Syn, pS129, and α-Syn aggregates in the oral mucosal cells. Then, the concentrations of α-Syn species in oral mucosa samples were measured using electrochemiluminescence assays.ResultsImmunofluorescence images indicated elevated α-Syn, pS129, and α-Syn aggregates levels in oral mucosal cells of MSA than HCs. The concentrations of three α-Syn species were significantly higher in oral mucosal cells of MSA than HCs (α-Syn, p &lt; 0.001; pS129, p = 0.042; α-Syn aggregates, p &lt; 0.0001). In MSA patients, the oral mucosa α-Syn levels negatively correlated with disease duration (r = −0.398, p = 0.009). The area under curve (AUC) of receiver operating characteristic (ROC) analysis using an integrative model including age, gender, α-Syn, pS129, and α-Syn aggregates for MSA diagnosis was 0.825, with 73.8% sensitivity and 78.7% specificity.ConclusionThe α-Syn levels in oral mucosal cells elevated in patients with MSA, which may be promising biomarkers for MSA.
The effect and mechanism of traditional Chinese exercise for chronic low back pain in middle-aged and elderly patients: A systematic review
Authors: Wang Xue-Qiang , Xiong Huan-Yu , Du Shu-Hao , Yang Qi-Hao , Hu Li 
Published: October 2022

BackgroundIncreasing lines of evidence indicate that traditional Chinese exercise (TCE) has potential benefits in improving chronic low back pain (CLBP) symptoms. To assess the clinical efficacy of TCE in the treatment of CLBP, we performed a systematic review of existing randomized controlled trials (RCTs) of CLBP and summarized the neural mechanisms underlying TCE in the treatment of CLBP.MethodsA systematic search was conducted in four electronic databases: PubMed, Embase, the Cochrane Library, and EBSCO from January 1991 to March 2022. The quality of all included RCTs was evaluated by the Physiotherapy Evidence Database Scale (PEDro). The primary outcomes included pain severity and pain-related disability.ResultsA total of 11 RCTs with 1,256 middle-aged and elderly patients with CLBP were included. The quality of all 11 included RCTs ranged from moderate to high according to PEDro. Results suggested that TCE could considerably reduce pain intensity in patients with CLBP. Overall, most studies did not find any difference in secondary outcomes (quality of life, depression, and sleep quality).ConclusionThe neurophysiological mechanism of TCE for treating CLBP could be linked to meditation and breathing, posture control, strength and flexibility training, and regulation of pain-related brain networks. Our systematic review showed that TCE appears to be effective in alleviating pain in patients with CLBP.
Heart dose and cardiac comorbidities influence death with a cardiac cause following hypofractionated radiotherapy for lung cancer
Authors: Banfill Kathryn , Abravan Azadeh , van Herk Marcel , Sun Fei , Franks Kevin , McWilliam Alan , Faivre-Finn Corinne 
Published: October 2022

BackgroundThere is increasing evidence of cardiac toxicity of thoracic radiotherapy however, it is difficult to draw conclusions on cardiac dose constraints due to the heterogeneity of published studies. Moreover, few studies record data on cause of death. The aim of this paper is to investigate the relationship between conventional cardiac dosimetric parameters and death with cardiac causes using data from the UK national cause of death registry.MethodsData on cancer diagnosis, treatment and cause of death following radical lung cancer radiotherapy were obtained from Public Health England for all patients treated at the Christie NHS Foundation Trust between 1/1/10 and 31/12/16. Individuals with metastatic disease and those who received multiple courses of thoracic radiotherapy where excluded. All patients who received &gt; 45Gy in 20 fractions were included. Cardiac cause of death was defined as the following ICD-10 codes on death certificate: I20-I25; I30-I32; I34-I37; I40-I52. Cardiac V5Gy, V30Gy, V50Gy and mean heart dose (MHD) were extracted. Cumulative incidence of death with cardiac causes were plotted for each cardiac dosimetric parameter. Multi-variable Fine and Gray competing risk analysis was used to model predictors for cardiac death with non-cardiac death as a competing risk.ResultsCardiac dosimetric parameters were available for 967 individuals, 110 died with a cardiac cause (11.4%). Patients with a cardiac comorbidity had an increased risk of death with a cardiac cause compared with those without a cardiac comorbidity (2-year cumulative incidence 21.3% v 6.2%, p&lt;0.001). In patients with a pre-existing cardiac comorbidity, heart V30Gy ≥ 15% was associated with higher cumulative incidence of death with a cardiac cause compared to patients with heart V30Gy &lt;15% (2-year rate 25.8% v 17.3%, p=0.05). In patients without a cardiac comorbidity, after adjusting for tumour and cardiac risk factors, MHD (aHR 1.07, 1.01-1.13, p=0.021), heart V5Gy (aHR 1.01, 1-1.13, p=0.05) and heart V30Gy (aHR 1.04, 1-1.07, p=0.039) were associated with cardiac death.ConclusionThe effect of cardiac radiation dose on cardiac-related death following thoracic radiotherapy is different in patients with and without cardiac comorbidities. Therefore patients’ cardiovascular risk factors should be identified and managed alongside radiotherapy for lung cancer.
Impact of automated methods for quantitative evaluation of immunostaining: Towards digital pathology
Authors: Elie Nicolas , Giffard Florence , Blanc-Fournier Cécile , Morice Pierre-Marie , Brachet Pierre-Emmanuel , Dutoit Soizic , Plancoulaine Benoît , Poulain Laurent 
Published: October 2022

IntroductionWe sought to develop a novel method for a fully automated, robust quantification of protein biomarker expression within the epithelial component of high-grade serous ovarian tumors (HGSOC). Rather than defining thresholds for a given biomarker, the objective of this study in a small cohort of patients was to develop a method applicable to the many clinical situations in which immunomarkers need to be quantified. We aimed to quantify biomarker expression by correlating it with the heterogeneity of staining, using a non-subjective choice of scoring thresholds based on classical mathematical approaches. This could lead to a universal method for quantifying other immunohistochemical markers to guide pathologists in therapeutic decision-making.MethodsWe studied a cohort of 25 cases of HGSOC for which three biomarkers predictive of the response observed ex vivo to the BH3 mimetic molecule ABT-737 had been previously validated by a pathologist. We calibrated our algorithms using Stereology analyses performed by two experts to detect immunohistochemical staining and epithelial/stromal compartments. Immunostaining quantification within Stereology grids of hexagons was then performed for each histological slice. To define thresholds from the staining distribution histograms and to classify staining within each hexagon as low, medium, or high, we used the Gaussian Mixture Model (GMM).ResultsStereology analysis of this calibration process produced a good correlation between the experts for both epithelium and immunostaining detection. There was also a good correlation between the experts and image processing. Image processing clearly revealed the respective proportions of low, medium, and high areas in a single tumor and showed that this parameter of heterogeneity could be included in a composite score, thus decreasing the level of discrepancy. Therefore, agreement with the pathologist was increased by taking heterogeneity into account.Conclusion and discussionThis simple, robust, calibrated method using basic tools and known parameters can be used to quantify and characterize the expression of protein biomarkers within the different tumor compartments. It is based on known mathematical thresholds and takes the intratumoral heterogeneity of staining into account. Although some discrepancies need to be diminished, correlation with the pathologist’s classification was satisfactory. The method is replicable and can be used to analyze other biological and medical issues. This non-subjective technique for assessing protein biomarker expression uses a fully automated choice of thresholds (GMM) and defined composite scores that take the intra-tumor heterogeneity of immunostaining into account. It could help to avoid the misclassification of patients and its subsequent negative impact on therapeutic care.
Global trends and regional differences in the burden of cancer attributable to secondhand smoke in 204 countries and territories, 1990–2019
Authors: Maimaitiming Mailikezhati , Wang Minmin , Luo Yanan , Wang Jia , Jin Yinzi , Zheng Zhi-Jie 
Published: October 2022

BackgroundTo describe the status quo and trends in the global burden of all cancers caused by secondhand smoke during 1990–2019.MethodsData on cancer associated with secondhand smoke were extracted from the Global Heath Data Exchange. Cancer burden was measured by cancer-related deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs).ResultsIn 2019, age-standardized rates of death, DALYs and YLLs among the cancer population globally caused by secondhand smoke were 1.60, 38.54 and 37.77, respectively. The proportions of these in the total cancer burden for all risk factors combined decreased slightly from 1990 to 2003 and then increased from 2004 to 2019. In 2019, &gt;50% of the cancer burden was concentrated in men aged 55–75 years and women aged 50–70 years. Between 1990 and 2019, there was an increase in age-standardized rates of death, DALYs, YLDs and YLLs among those aged ≥70 years. The age-standardized YLDs rate attributable to secondhand smoke was higher among women; it decreased in men but increased in women, causing a wider gap between the sexes. A greater cancer burden was mainly seen in North America in 1990 and Europe in 2019. Reductions in the annual rate change of cancer burden were found mainly in North America and Oceania, while increases were found in Africa and Asia. In 2019, high–middle- and middle-SDI countries had higher age-standardized rates of deaths, DALYs, YLDs and YLLs than the global level. During 1990 and 2019, the largest decline in cancer burden was seen in high-SDI countries, while middle- or low-SDI countries experienced increases in all age-standardized rates.ConclusionsCancer burden attributable to secondhand smoke is concerning given the increasing health loss and differences in distribution of cancer burden worldwide. Further studies are needed to investigate the causes of disparities in cancer burden attributable to secondhand smoke and to improve understanding of the contribution of secondhand smoke to the burden of different types of cancer.
Chronic oral mucocutaneous candidiasis, recurrent respiratory infection, hepatosplenomegaly, and autoimmune diabetes mellitus: A case report of a gain-of-function mutation of STAT1 in a Chinese boy
Authors: Cao Bingyan , Liu Meijuan , Zhao Yun , Gong Chunxiu 
Published: October 2022

BackgroundSignal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations are characterized by chronic mucocutaneous candidiasis and autoimmune diseases. Type 1 diabetes mellitus is one of the well-characterized autoimmune conditions.Case presentationWe reported a 5-year-old boy who presented with polydipsia and polyuria, with a medical history of chronic oral mucocutaneous candidiasis, recurrent respiratory infection, hepatosplenomegaly, and abnormal liver function. Genetic analysis identified a heterozygous GOF mutation (c.866A &gt; G, p.Y289C) in STAT1.ResultsVarious medicines were given to the boy during the follow-up, including insulin to keep blood glucose stable, intravenous immunoglobulin and antifungal agents for recurrent infections, and antituberculosis drugs (isoniazid, rifampicin) to combat tuberculosis infection. He did not show recurrent infection, but chronic oral mucocutaneous candidiasis still occurred twice per month. The blood glucose level was well controlled.ConclusionThis article illustrates that early diagnosis and identification of STAT1 mutation are essential for assessing the severity of the disease and determining reasonable treatment options.
Hepatotoxic metabolites in Polygoni Multiflori Radix— Comparative toxicology in mice
Authors: Wang Shixiao , Kong Xiang , Chen Ning , Hu Pengwei , Boucetta Hamza , Hu Zhaoliang , Xu Xin , Zhang Pei , Zhan Xiang , Chang Ming , Cheng Rui , Wu Wei , Song Min , Lu Yuting , Hang Taijun 
Published: October 2022

Polygoni Multiflori Radix (PM) and Rhei radix et rhizoma (rhubarb) contain similar hepatocyte-toxic anthraquinones such as emodin (major free anthraquinone in PM), physcion and their glycosides. In clinical practice, PM hepatotoxicity has been widely reported, although rhubarb is not recognized as hepatotoxic. To clarify the substances basis (key components) of PM hepatotoxicity, based on the characteristic components’ similarity within PM, rhubarb and their concocted forms, a comparative sub-acute toxicity study was designed in mice. Nine groups of mice with 28 days of oral administration of these herbal extracts or 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG, major and unique characteristic component in PM)-herb combinations were set as follows: Group-1, control; Group-2, PM ethanol-extract (PME); Group-3, PM praeparata ethanol-extract (PMPE); Group-4, Rhubarb ethanol-extract (RME); Group-5, Steamed rhubarb ethanol-extract (RMPE); Group-6, TSG; Group-7, PMPE-TSG combination; Group-8, RME-TSG combination; Group-9, RMPE-TSG combination. Each experimental group received an equivalent emodin dose of 29 mg/kg except for the TSG group, and an equivalent TSG dose of 1,345 mg/kg except for the PMPE, RME and RMPE groups. The results showed that PME, PMPE-TSG and RME-TSG induced liver lesions and biochemical abnormalities of liver function compared with the control. In contrast, PMPE, RME, RMPE, TSG and RMPE-TSG caused no liver lesions and fewer biochemical abnormalities. Considering the related components, only the co-administration of high doses of TSG and emodin-8-O-β-D-glucoside (EMG, major anthraquinone glycoside in PM) in these groups could cause liver lesions. According to tissue distribution and correlation analysis, EMG dose was positively correlated with the high hepatic emodin and TSG exposure, and the hepatic emodin and TSG exposure were positively correlated with the biochemical abnormalities of liver function. Cell viability test in vitro showed emodin was more hepatotoxic than TSG and EMG, and mainly emodin and TSG of the three had synergistic hepatotoxic effects. Therefore, creatively using rhubarb as a reference, this study revealed that PM hepatotoxicity in mice mainly came from the integrative contribution of TSG, EMG and emodin.
Incidence, characteristics and risk factors of hypofibrinogenemia associated with tigecycline: A multicenter retrospective study in China
Authors: Leng Bing , Shen Chengwu , Gao Tiantian , Zhao Kai , Zhao Xuemei , Guo Yujin , Wu Jiyong , Yang Jing , Fang Wei , Zhang Jicheng , Zhang Yahui , Sun Chao , Duan Lei , Huang Jing , Qi Yougang , Yan Genquan 
Published: October 2022

Background: Tigecycline was recently found to cause coagulation disorders, especially hypofibrinogenemia, which may interfere with the administration of antimicrobial therapy. This study aimed to investigate the incidence and clinical characteristics of and risk factors for tigecycline-associated hypofibrinogenemia.Methods: In this multicenter retrospective study, patients receiving tigecycline or imipenem–cilastatin to treat Gram-negative bacterial infections in nine Chinese tertiary hospitals between January 2020 and December 2020 were enrolled. Baseline data and coagulation variables were compared using cohort and case–control studies.Results: Totals of 485 patients treated with tigecycline and 490 patients treated with imipenem–cilastatin were included in this study. Compared with imipenem–cilastatin, tigecycline was associated with reduced fibrinogen and prolonged activated partial thromboplastin time and prothrombin time (all p &lt; 0.001), with the most remarkable change in fibrinogen (down by 48.0%). The incidence of hypofibrinogenemia in patients treated with tigecycline was &gt;50%, with propensity score-matched analysis or not. The relative risk of hypofibrinogenemia with tigecycline versus imipenem–cilastatin was 2.947 (95% CI: 2.151–4.039) at baseline balance. Tigecycline-associated hypofibrinogenemia led to a higher incidence (12.1%) of bleeding events. However, none of supplemental therapies after withdrawal had an effect on the normalization of fibrinogen levels. The risk factors for tigecycline-associated hypofibrinogenemia were treatment duration ≥6 days (odds ratio [OR] 5.214, 95% confidence interval [CI] 2.957–9.191, p &lt; 0.001), baseline fibrinogen &lt;4 g/L (OR 4.625, 95% CI 2.911–7.346, p &lt; 0.001), cumulative dose ≥1,000 mg (OR 2.637, 95% CI 1.439–4.832, p = 0.002), receiving CRRT (OR 2.436, 95% CI 1.179–5.031, p = 0.016), baseline PT &gt; 14 s (OR 2.110, 95% CI 1.317–3.380, p = 0.002) and baseline total bilirubin &gt;21 μmol/L (OR 1.867, 95% CI 1.107–3.147, p = 0.019), while the protective factor was skin and soft tissue infection (OR 0.110, 95% CI 0.026–0.473, p = 0.003).Conclusion: The clinical characteristics of and risk factors for tigecycline-associated hypofibrinogenemia identified in this study can offer practical reference for the clinical management of patients.
Chemical profile, antimicrobial activity, and leaf anatomy of Adenophyllum porophyllum var. cancellatum
Authors: Aguilar-Rodríguez Silvia , López-Villafranco Ma. Edith , Jácquez-Ríos María Patricia , Hernández-Delgado Claudia Tzasna , Mata-Pimentel María Fernanda , Estrella-Parra Edgar Antonio , Espinosa-González Adriana Montserrat , Nolasco-Ontiveros Erick , Avila-Acevedo José Guillermo , García-Bores Ana María 
Published: October 2022

Adenophyllum porophyllum var. cancellatum, known as “árnica del monte” in Mexico, is an aromatic annual plant belonging to the Asteraceae family that grows from southern Arizona to central Mexico. The aerial parts of the plant are used in traditional medicine to treat skin diseases such as irritations, infections, and wounds. In this study, the essential oil of this plant was characterized, and its antimicrobial activity was evaluated. This species has large glands in its leaves; therefore, for quality control purposes, an anatomical study of the leaves was performed. The essential oil was isolated from the aerial parts of the plant through hydro-distillation and analyzed using a gas chromatography/mass spectrometry (GC/MS) system. Its anti-yeast activity was evaluated against three Candida species and ten bacterial strains using the disk diffusion technique. The minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and minimum bactericidal concentration (MBC) were determined using broth microdilution. Anatomical study was performed on the middle part of the leaf. A yield of 0.5% of the essential oil was obtained from the herb, and Eighteen compounds in the essential oil were identified, within them trans pinocamphone (29.5%), limonene (24.7%), pinocarvone (21.8%), and cis pinocamphone (8.0%) were the main components. The inhibition zones were between 10 mm and 20 mm, and the MIC and MFC against the three Candida species ranged from 60 to 500 μg/ml. The leaf anatomy showed anisocytic stomata, simple and glandular trichomes of different types, and large and elliptical-shaped lysigenous glands, which can be used for taxonomic identification. The A. porophyllum var. cancellatum essential oil can serve as an alternative source of natural antimicrobial agents as an affordable approach to control infectious diseases. This is the first study that reports the chemical composition and antimicrobial activity of the essential oil, as well as the leaf anatomy of this species.