bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensive immunochemotherapy improves prognosis of young patients with double-expressor lymphoma comparison to non-double-expressor lymphoma: a single-center retrospective cohort study
Authors: Zhan Jing , Zhang Wei , Zhou Daobin , Zhang Yan , Wang Wei , Wei Chong 
Published: February 2020

Abstract
Background Double-expressor lymphoma (DEL), defined as cases with concurrent MYC and BCL2 proteins overexpression, is associated with poor prognosis when treated with R-CHOP alone. Prognostic data on DEL treated with intensive treatment are limited and controversial.Methods We retrospectively report our experiences about 221 consecutive de-novo diffuse large B cell lymphoma patients and analyze the role of intensive therapies for 65 patients with DEL.Results No significant difference in clinical characteristics and survival outcomes between DEL and non-DEL was observed. Overall, 32 (76.2%) and 20 (87.0%) patients with DEL received R-CHOP and intensive treatment achieved partial response or complete response, respectively. Intensive therapies may improve the prognosis over R-CHOP in patients with DEL (P = 0.029 for PFS, P = 0.026 for OS). Subgroup analysis according to clinical characteristics showed intensive therapies resulted in better prognosis than R-CHOP regimen in DEL patients aged under 60 years (P = 0.004 for PFS; P =0.090 for OS), whereas no significant superiority was found in DEL patients aged over 60 years (P = 0.646 for PFS; P = 0.361 for OS).Conclusions This second Chinese cohort study suggests that intensive immunochemotherapy may have the ability to improve the prognosis of young patients with DEL.
Screening and Quantification of Antiquorum-Sensing Activity of Actinobacteria Isolates Against Gram-Positive and Gram-Negative Biofilm Associated Bacteria
Authors: Wijaya Marco , Delicia Dea , Waturangi Diana Elizabeth 
Published: February 2020

Abstract
Objectives: The purpose of the study is to screen antiquorum sensing activity compound from actinobacteria using Chromobacterium violaceum as indicator and quantify the antibiofilm activity against several biofilm-forming pathogenic bacteria, such as Staphylococcus aureus ATCC 29213, Bacillus cereus ATCC 14579, Enterococcus faecalis ATCC 33186, Vibrio cholerae , Salmonella typhimurium , Pseudomonas aeruginosa ATCC 27853.Results: Crude extracts from marine actinobacteria isolated from Indonesia were promising for treating biofilm-related diseases. Out of 40 isolates 10 were found to have great quorum quenching activity against C. violaceum. Moreover, these isolates were able to inhibit biofim formation by Gram positive and Gram negative pathogenic bacteria. Quorum quenching agents in extracts of 1AC, 14PM, 16PM, 18PM, and CW17 isolates were predicted as proteins or enzymes.
Nationwide survey on the use of local antibiotics during anterior cruciate ligament reconstruction in Norway
Authors: Sailer Monica Alessandria , Skråmm Inge , Sivertsen Einar Andreas , Lygre Stein Håkon , Årøen Asbjørn 
Published: February 2020

Abstract
Objective: The use of local antibiotics in surgical reconstruction of the anterior cruciate ligament (ACLR) in Europe and Scandinavia is increasing.We wanted to survey the scope of this practice in Norway. In cooperation with the Norwegian cruciate ligament registry we contacted all institutions in Norway performing ACLR to find out.Results: The results showed that the practice of local antibiotics in ACLR is not widely used in Norway.
Anti- Toxoplasma gondii&nbsp;effect of Lumefantrine in vitro and in vivo
Authors: Wang Dawei , Xing Mengen , El-Ashram Saeed , Ding Yingying , Sang Xiaoyu , Feng Ying , Chen Ran , Wang Xinyi , Jiang Ning , Chen Qijun , Yang Na 
Published: February 2020

Abstract
Background: Toxoplasma gondii is an obligate intracellular protozoan parasite, which can infect almost all warm-blooded animals, including humans, leading to toxoplasmosis. Currently, the effective treatment for human toxoplasmosis is the combination of sulfadiazine and pyrimethamine. However, both drugs have serious side effects and toxicity in the host. Therefore, there is an urgent need for the discovery of new anti-Toxoplasma drugs with high potency and less or no side-effects. Methods: The cytotoxicity of sulfadiazine and lumefantrine to Vero cells was evaluated by the methyl thiazolyl tetrazolium (MTT) assay. And MTT assay was also used to detect the inhibitory effects of lumefantrine on parasites invasion and proliferation. Flow cytometry was conducted to further verify parasites proliferation. qPCR was performed to evaluate the parasite load in the mice after lumefantrine treatment. In order to determine whether lumefantrine treatment enhances Th1 or Th2 cytokine response, IFN-γ, IL-4, and IL-10 levels in the serum of mice were determined. Results: Our findings suggest that lumefantrine exerts activity against T. gondii by inhibiting its replication and invasion of Vero cells in vitro without being toxic to the cells. Furthermore, lumefantrine protected mice with acute toxoplasmosis from death to a certain extent and reduced the parasite burden in mouse tissues in vivo. In addition, a significant increase in IFN-γ production was observed in high dose lumefantrine-treated mice while IL-10 and IL-4 levels increased in low dose lumefantrine-treated mice. Conclusions: The results of this study demonstrated that lumefantrine may be a promising agent to treat toxoplamosis, and more experiments on the protective mechanism of lumefantrine should be undertaken in further studies.Key words: Toxoplasma gondii, Lumefantrine, anti-Toxoplasma gondii, Invasion, Proliferation
Factors affecting perioperative ∆ALB and short term complications in pediatric patients undergoing major gastroenterology surgery
Authors: Gao Kai , Liu Qingshuang , guo chunbao 
Published: February 2020

Abstract
Background: Albumin is considered a negative acute-phase protein because its concentration decreases during injury and sepsis. The decrease in serum albumin might be important for perioperative morbidity, even in patients with normal preoperative levels in pediatric population. We here intend to determine the perioperative factors associated with the reduction in serum albumin within 2 postoperative days compared with the preoperative level (∆ALB) and its influence on the perioperative outcome in a pediatric general surgical cohort. Methods: This single-center retrospective review included 939 patients who underwent Roux-en-Y hepaticojejunostomy between August 2010 and Aug 2019. Based on the median ∆ALB (14.6%), patients were separated into two groups, including a high ∆ALB group (≥14.6%) and a low ∆ALB group (<14.6%). Multivariable logistic regression analyses were performed to determine the independent risk factors for the reduction in serum albumin. Propensity score matching was performed to adjust for any potential selection bios for the two groups. In 366 matched patients, influences of operating time on perioperative outcomes, including postoperative recovery, complications measurement, length of hospital stay between the two groups were analyzed. Results: For all 996 patients reviewed, 939 patient records were enrolled into the final analysis. Controlling for other factors, multivariate analysis showed that the high CRP on POD 3 or 4 (OR =2.36 [95% CI, 1.51-3.86]; p =0.007), presence of Charcot's triad (OR=1.73[95% CI, 1.05-2.83]; p = 0.031), the longer operating time (OR=1.18[95% CI, 1.00 -1.53]; p=0.014) were factors that predicted the high ∆ALB level. The high ∆ALB level was associated with postoperative gastrointestinal functional recovery, reflected by the first defecation (p= 0.013) and first bowel movement (p=0.019) and the high occurrence of postoperative complications (16.1% vs 10.9%, RR, 1.57; 95 %CI, 1.02-2.41, P=0.0026). The mean length of postoperative stay was longer than that of patients with ∆ALB < 14.0% group, although no statistic significant was stained (p=0.057). Conclusions: We showed that change in albumins was associated with postoperative outcomes. The risk factors for ∆ALB could be intervened in the perioperative period to permit patients gain a safe recovery and discharge after major abdominal operations
Early targeted DNA methylation profiling of CD04+/CD08+ T cells reveals pathogenic mechanisms in different stages of impaired glucose homeostasis Cardiovascular Diabetology
Authors: Benincasa Giuditta , Franzese Monica , Schiano Concetta , Marfella Raffaele , Miceli Marco , Infante Teresa , Mura Nunzia Della , Luongo Marco , Sardu Celestino , Zanfardino Mario , Affinito Ornella , Mansueto Gelsomina , Sommese Linda , Nicoletti Giovanni Francesco , Salvatore Marco , Paolisso Giuseppe , Napoli Claudio 
Published: February 2020

Abstract
Background: Despite current intensive treatments, hyperglycemic patients have an unfavorable prognosis due to severe CHD and development of complications. The interplay between hyperglycemia and systemic inflammation can modify patterns of gene expression mainly affecting DNA methylation in promoter regions and, thus, endothelial damage. However, DNA methylome of CD04+ and CD08+ T cells, which play a relevant role in endothelial dysfunction has not been studied, especially during increasing hyperglycemia.Purpose: To identify differentially methylated regions (DRMs) in CD04 + and CD08 + T cells by comparing healthy subjects (HS) to Pre-Diab and type 2 (T2D) patients. This approach would investigate possible biomarkers useful to identify vascular damage already at Pre-Diab state.Methods: In this pilot study, we enrolled a subgroup of patients from our ongoing PIRAMIDE clinical trial (NCT03792607) including a total of 14 individuals classified in HS (n=2), Pre-Diab (n=6), and T2D (n=6). The DMRs were identified by using the reduced representation bisulfite sequencing platform (RRBS) which captures the majority of promoters and CpG islands. Big data analysis was performed by using the R package and ChromHMM algorithms.Results: Most of the total DMRs (30-35%) were in the promoter regions in increasing hyperglycemia vs HS. A global analysis of DMR-related genes overlapping between Pre-Diab and T2D patients showed a prevalence of DNA hypermethylation in both T cells. Interestingly, the secreted protein acidic and cysteine rich (SPARC) gene was annotated to the most hypomethylated-DMR in Pre-Diab and its methylation level gradually decreased in T2D patients.Conclusions: Preliminary data indicated that hypomethylation of the SPARC promoter may be a useful biomarker of vascular complications in Pre-Diab patients with a possible role for primary prevention. However, larger multicenter trials are needed to validate our epigenetic data in the clinical arena.
Deficiency in interleukin-18 ameliorated glial activation and neuroinflammation after traumatic brain injury in mice
Authors: Dong Wenwen , Wang Linlin , Chen Ziyuan , Guo Xiangshen , Wang Pengfei , Cheng Hao , Zhang Fuyuan , Yang Bei , Wang Shuaibo , Qi Ruiqun , Wang Jiawen , Guan Dawei , Zhao Rui 
Published: February 2020

Abstract
Background: Neuroinflammation is recognized as one of the main pathological mechanisms of secondary injury caused by traumatic brain injury (TBI). It has been reported that interleukin (IL)-18 is expressed in glial cells and involved in the regulation of neuroinflammation. Further studies have revealed that IL-18 expression is upregulated and may contribute to pathogenesis in the later phases of TBI; however, the mechanism underlying the effect of IL-18 on TBI remains unclear. Our present study assessed the roles of IL-18 in inflammatory and neurodegenerative pathology in mice subjected to TBI.Methods: A controlled cortical impact (CCI) injury model was conducted to mimic TBI, and brains were collected at 3 and 7 days post TBI (dpi). The levels of IL-18 were detected by qRT-PCR and immunofluorescence staining. In addition, neurological severity score (NSS) was used to assess neurological deficits after TBI. Furthermore, neuronal cell death, glial activation, and inflammatory cytokine and chemokine secretion were evaluated in wild-type ( WT ) and Il18-knockout ( Il18 -KO) mice to explore the role of IL-18 in TBI.Results: IL-18 levels were upregulated post TBI, accompanied by reactive glial activation. Il-18 deficiency significantly ameliorated glial activation and improved neuronal cell death and neurological deficits. In addition, Il-18 deficiency reduced the TBI-induced M1-like microglia frequency. Interestingly, the levels of all pro- and anti-inflammatory cytokines, including IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p40, IL-12p70, IL-13, IL17A, G-CSF, GM-CSF, IFN-γ, and TNF-α, were downregulated in Il18 -KO mice. The deletion of Il-18 attenuated the levels of most chemokines induced by TBI, including CCL2, CCL3, CCL4, CCL5, CCL7, CCL12, CCL20, CXCL1, CXCL2, CXCL10, CXCL12, CXCL13, and CXCL16.Conclusions: These data demonstrated that IL-18 is involved in TBI induced neuroinflammation, which suggests that IL-18 is important for the development of secondary injury induced by TBI.
cGAS-STING signaling regulates control of microglia polarization in cerebral ischemic stroke
Authors: Jiang Guoliang , Yang Xinglong , Zhou Houjun , Long Jiang , Zhang Linming , Lu Di 
Published: February 2020

Abstract
Background Cerebral ischemic stroke is a highly debilitating disease, in which inflammation is well document to play a pivotal role in its pathophysiology. Microglia are the the major immuncompetent cells of the brain involved in different neuropathologies. Recent discovery of cyclic GMP-AMP synthase(cGAS) activation and its induction of the downstream signaling protein stimulator of interferon genes (STING) is increasingly recognized as a crucial determinant of neuropathophysiology. Although cGAS-STING pathway has been reported to play an important role in inflammatory response in myocardial infarction (MI), its mechanism in inflammatory response in ischemic stroke (IS) has remained to be fully explored.Methods In light of the above, this study sought to explore the roles of cGAS-STING pathway in inflammatory reaction in IS. It is hoped that the results would provide new insights for designing of therapeutic strategies targeting at IS. We used HT22 cells to establish an oxygen-glucose deprivation (OGD) cell model. The supernatant derived from this and which contained OGD-induced DAMPs(OIDs) was used to stimulate the BV2 microglia. Additionally, we used siRNA technology to interfere with cGAS gene expression to observe changes in downstream cytokines. Furthermore, we established middle cerebral artery occlusion (MCAO) mouse model and performed cGAS-siRNA lentivirus infection to further elucidate the mechanism of cGAS-STING pathway in vivo.Results We show here that OIDs strongly activated the cGAS-STING pathway and triggered accumulation of a plethora of proinflammatory factors in activated Microglia. Of note, the cascade reaction was successfully inhibited by cGAS-siRNA. Furthermore, we extended the study of cGAS-STING in a mouse MCAO model, which showed that inhibiting cGAS-STING pathway can effectively diminish MIDs(MCAO-induced DAMPs)-induced neuronal apoptosis and ultimately functional improvement.Conclusion The present results have shown GAS-STING signaling pathway controls the polarity transformation of microglia. The underlying mechanisms of cGAS-STING triggering microglial inflammatory response is now better clarified which made the pathway a potential therapeutic target of IS.
TRPM7 ameliorates the blue light-induced apoptosis of RPE cells involving PKC/ERK
Authors: Hu Luping , Xu Guoxing 
Published: February 2020

Abstract
Background Blue light triggers apoptosis of retinal pigment epithelium (RPE) cells and causes retinal damage. The aim of this study was to elucidate the protective role of TRPM7 in photo-damaged RPE cells. Methods RPE cells isolated from Sprague-Dawley (SD) rats were cultured in vitro , and exposed to varying intensities of blue light (500-5000 Lux). Cell proliferation and viability were respectively assessed by BrdU incorporation and MTT assays. Real-time PCR and Western blotting were used to analyze the mRNA and protein expression levels of TRPM7, PKC, ERK and Bax/Bcl-2. The cells were transfected with TRPM7 siRNA to knockdown its mRNA levels, or transduced with TRPM7–overexpressing lentiviruses. Pigment epithelium-derived factor (PEDF) was used in combination to detect the anti apoptosis effect. Results Blue light inhibited the proliferation and viability of RPE cells in an intensity-de pendent manner when compared to non-irradiated controls ( P <0.05). Compared to the control, photo-damaged RPE cells showed decreased levels of TRPM7, PKC, ERK and Bax, increased in Bcl-2 ( P <0.01) . Forced expression of TRPM7 partially ameliorated the reduction of proliferation and viability of RPE cells( P <0.01), alleviated the downregulation of TRPM7, PKC, ERK and Bax expression levels( P <0.01), induced by blue light irradiation, while TRPM7 knockdown had opposite effects( P <0.01). TRPM7 and PEDF synergistically alleviated the damaging effects of blue light. Conclusions The apoptosis of RPE cells induced by blue light was positively correlated with the expression of TRPM7. Forced expression of TRPM7 partially attenuated the deleterious effects of blue-light-demaged RPE cells and showed a synergistic protective effect with PEDF, involving PKC/ERK signaling pathway.
Co-expression of CMTM6 and PD-L1: a novel prognostic indicator of gastric cancer
Authors: Zhang Chao , An Wen , Tan Yuen , Xu Huimian 
Published: February 2020

Abstract
Background CKLF Like MARVEL Transmembrane Domain Containing 6 (CMTM6) is involved in the epigenetic regulation of genes and tumorigenesis. Programmed cell death ligand 1 (PD-L1) is closely related to the prognosis of some human cancers. CMTM6 is a key regulator of PD-L1 in many cancers. The purpose of this study was to investigate the expressions of these proteins in gastric cancer and the correlations with clinicopathological features and survival. Methods The expression levels of CMTM6 and PD-L1 were examined in 185 gastric cancer specimens by immunohistochemistry. Chi-square test was used to analyze the relationship between CMTM6 and PD-L1 expressions and clinicopathological characteristics. Kaplan-Meier method and log-rank test were used to analyze the survival data of patients.Results The positive expression rates of CMTM6 and PD-L1 were 78.38% (145/185) and 75.68% (140/185), respectively. High expression of CMTM6 and PD-L1 was correlated with Borrmann type ( P < 0.001), N stage ( P = 0.002), peritoneal metastasis ( P = 0.007) and TNM stage ( P = 0.038). The expression of CMTM6 and PD-L1 in gastric cancer tissues was positively correlated (Pearson's coefficient test, r = 0.260; P < 0.001). High expression of CMTM6 was correlated with poor prognosis (HR = 1.668; 95% CI = 1.032–2.695; P = 0.037). High expression of both CMTM6 and PD-L1 could be used as an independent factor for overall survival (HR = 1.554; 95% CI = 1.011–2.389; P = 0.044). Conclusions The combined detection of CMTM6 and PD-L1 may be used as an indicator for judging the prognosis of gastric cancer.
Clinical characteristics and predictors of mortality in critically ill influenza adult patients
Authors: Hsu Jui-Chi , Lee Ing-Kit , Huang Wen-Chi , Chen Yi-Chun , Tsai Ching-Yen 
Published: February 2020

Abstract

Background Severe influenza is associated with high morbidity and mortality. The aim of this study was to investigate the factors affecting the clinical outcomes of critically ill influenza patients. Methods In this retrospective study, we enrolled critically ill adult patients with influenza at the Kaohsiung Chang Gung Memorial Hospital in Taiwan. We evaluated the demographic, clinical, and laboratory findings and examined whether any of these measurements correlated with mortality. We then created an event-based algorithm as a simple predictive tool using 2 variables with statistically significant associations with mortality. Results Between 2015 and 2018, 102 critically ill influenza patients (median age, 62 years) were assessed; among them, 41 (40.1%) patients died. Of the 94 patients who received oseltamivir therapy, 68 (72.3%) began taking oseltamivir 48 hours after the onset of illness. Of the 102 patients, the major influenza-associated complications were respiratory failure (97%), pneumonia (94.1%), acute kidney injury (65.7%), adult respiratory distress syndrome (ARDS) (51%), gastrointestinal bleeding (35.3%), and bacteremia (16.7%). In the multivariate regression model, high lactate levels, ARDS, acute kidney injury, and gastrointestinal bleeding were independent predictors of mortality in critically ill influenza patients. The optimal lactate level cutoff for predicting mortality was 33 mg/dL with an area under curve of 0.728. We constructed an event-associated algorithm that included lactate and ARDS. Fifteen (75%) of 20 patients with lactate levels ≥33 mg/dL and ARDS died, compared with only 1 (7.7%) of 13 patients with normal lactate levels and without ARDS. Conclusions We identified clinical and laboratory predictors of mortality at hospital admission that could aid in the care of critically ill influenza patients. Identification of these prognostic markers could be improved to prioritize key examinations that might be useful in determining patient outcomes.
Maternal 25-hydroxyvitamin D correlates with weight gain and bone metabolism during pregnancy
Authors: Luo Lianmei , Wu Nan , Xu Dan , Wang Lijiao , Zhang Jun , Yang Dong 
Published: February 2020

Abstract
Background: Vitamin D is involved in the regulation of 3% of the human genome, which encode proteins affecting bone health, immune system and other systems. The status of maternal vitamin D may program neonatal skeletal development. Besides, vitamin D is associated with obesity during pregnancy. Obesity has a detrimental effect on bone metabolism and the level of several hormones related to bone metabolism．Methods: This cross-sectional study recruited 103 families who visited Anzhen Hospital from January 2017 to June 2017. The age of included pregnant women ranged from 21 to 42 years old. Patients were assigned to different groups according to their body mass index (BMI) and weight gain during pregnancy. The level of 25-hydroxyvitamin D (25-(OH)D) in serum, parathyroid hormone (PTH), total procollagen type 1 N-terminal propeptide (P1NP), osteocalcin (OC), and C-terminal telopeptides type I collagen (CTX) from mothers and neonates were compared.Results: The results showed that the average level of 25-(OH) D in serum from mothers was 15.09ng/ml during pregnancy and 16.23ng/ml in the umbilical cord. The maternal P1NP increased significantly when the weight gain increased during pregnancy (P<0.01), as well as the fetal weight (P<0.05).Conclusions: Vitamin D deficiency is prevalent during pregnancy and led to more weight gain during pregnancy, also influence the fetal bone health. Obesity negatively correlates with 25-(OH)D level in serum and has a detrimental effect on bone metabolism.