bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of formyl peptide receptors improves the outcome in a mouse model of Alzheimer disease
Authors: Schröder Nicole , Schaffrath Anja , Welter Josua A. , Putzka Tim , Griep Angelika , Ziegler Patrick , Brandt Elisa , Samer Sebastian , Heneka Michael T. , New Hannes Kaddatz , New Jiangshan Zhan , Kipp Eugenia , Pufe Thomas , Tauber Simone C. , Kipp Markus , Brandenburg Lars-Ove
Published: March 2020

Background: An important hallmark of Alzheimer's disease (AD) is the increase of Aβ1-42 burden and its accumulation to senile plaques, leading the reactive gliosis and neurodegeneration. The modulation of glia cell function represent an attractive therapeutic strategy, but is currently limited by an incomplete understanding of its relevance for AD. The chemotactic G-protein coupled formyl peptide receptor (FPR), which is known to modulate Aβ1-42 uptake and signal transduction, might be one candidate molecule regulating glia function in AD. Here, we investigate whether the modulation of FPR exerts beneficial effects in an AD preclinical model.

Methods: To address this question, APP/PS1 double-transgenic AD mice were treated for 20-weeks with either the pro-inflammatory FPR agonist fMLF, the FPR1/2 antagonist Boc2 or the anti-inflammatory FPR2 agonist Ac2-26. Spatial learning and memory were evaluated using a Morris water maze test. Immunohistological staining, gene expression studies and flow cytometry analyses were performed to study neuronal loss, gliosis and Aß-load in the hippocampus and cortex, respectively.

Results: FPR antagonism by Boc2-treatment significantly improved spatial memory performance, reduced neuronal pathology, induced the expression of homeostatic growth factors, and ameliorated microglia, but not astrocyte, reactivity. Furthermore, the elevated levels of amyloid plaques in the hippocampus were reduced by Boc2-treatment, presumably by an induction of amyloid degradation.

Conclusions: We suggest that the modulation of FPR signaling cascades might be considered as a promising therapeutic approach for alleviating the cognitive deficits associated with early AD. Additional studies are now needed to address the downstream effectors as well as the safety profile of Boc2.
Ethylene glycol and glycolic acid production from xylonic acid by Enterobacter cloacae
Authors: Zhang Zhongxi , Yang Yang , Wang Yike , Gu Jinjie , Lu Xiyang , Liao Xianyan , Shi Jiping , Kim Chulho , Lye Gary , Baganz Frank , Hao Jian
Published: March 2020

Background: Biological routes for ethylene glycol production have been developed in recent years by constructing the synthesis pathways in different microorganisms. However, no microorganisms have been reported yet to produce ethylene glycol naturally. Results: Xylonic acid utilizing microorganisms were screened from natural environments, and an Enterobacter cloacae strain was isolated. The major metabolites of this strain were ethylene glycol and glycolic acid. However, the metabolites were switched to 2,3-butanediol, acetoin or acetic acid when this strain was cultured with other carbon sources. The metabolic pathway of ethylene glycol synthesis from xylonic acid in this bacterium was identified. Xylonic acid was converted to 2-dehydro-3-deoxy-D-pentonate catalyzed by D-xylonic acid dehydratase. 2-Dehydro-3-deoxy-D-pentonate was converted to form pyruvate and glycolaldehyde, and this reaction was catalyzed by an aldolase. D-xylonic acid dehydratase and 2-dehydro-3-deoxy-D-pentonate aldolase were encoded by yjhG and yjhH, respectively. The two genes are part of the same operon and are located adjacent on the chromosome. Besides yjhG and yjhH, this operon contains four other genes. However, individually inactivation of these four genes had no effect on either ethylene glycol or glycolic acid production; both formed from glycolaldehyde. YqhD exhibits ethylene glycol dehydrogenase activity in vitro. However, a low level of ethylene glycol was still synthesized by E. cloacae ΔyqhD. Fermentation parameters for ethylene glycol and glycolic acid production by the E. cloacae strain were optimized, and aerobic cultivation at neutral pH were found to be optimal. In fed batch culture, 34 g/L of ethylene glycol and 13 g/L of glycolic acid were produced in 46 hours, with a total conversion ratio of 0.99 mol/mol xylonic acid.Conclusions: A novel route of xylose biorefinery via xylonic acid as an intermediate has been established.
Efficacy of a Single dose versus a Multiple Dose Regimen of Mebendazole against Hookworm Infections among School Children: A Randomized Single-Blinded Trial
Authors: Eshetu Tegegne , Aemero Mulugeta , Jejaw Ayalew
Published: March 2020

Background : Despite the existence of population-based control program using single dose albendazole or mebendazole as a preventive chemotherapy, Hookworm disease transmissions remains high. It causes a negative impact on the growth and school performance of children. In connection to this preventive chemotherapy, different studies produced conflicting results. This study evaluated the efficacy of single (500mg) versus multiple doses (100mg twice a day during three consecutive days) of mebendazole against Hookworm infections among school aged children.
Methods : This randomized single-blinded clinical trial took place among school-aged children (6-14 years old) in Burie and Debre Elias towns, Northwest Ethiopia. Using simple randomization, eligible Hookworm positive children were allocated (1:1) to either a single or multiple doses treatment arm. Stool samples were collected and processed using McMaster method at baseline and follow-up period (14-21 days after treatment).
Main outcome measures : The cure rate against Hookworm and egg reduction rate for determining the changes in infection intensity were the main outcome measures after 14-21 days following dosing. An independent t-test was used to compare group means, and logistic regression was used to calculate odds ratio (OR). P-value < 0.05 at 95% CI was considered statistically significant.
Result: 109 children were participated in both treatment arms. Cure rate against Hookworm was significantly higher in the multiple dose (96.1%) than in the single dose (30.8%) with (OR=55.125; 95% CI: 11.92-254.9; P < 0.001). The egg reduction rate in the multiple dose treatment arm (99.5%) was also significantly higher than in the single dose arm (68.9%) with difference (t (101) =5.38; 95% CI 230.95-505.36; P < 0.001).
Conclusion : The single dose regimen of mebendazole for the treatment of Hookworm infection showed poor efficacy, while the multiple dose revealed satisfactory efficacy. Moreover, infection intensity reduction was not achieved following single dosing. Therefore, we strongly recommend replacing the single dose mebendazole regimen with multiple dose regimen during deworming program in hookworm endemic areas.
Trial registration : This trial is registered in www.pactr.org , # PACTR201911466695052
Increased resistance of a methicillin-resistant Staphylococcus aureus Δagr mutant with modified control in fatty acid metabolism
Authors: Song Hun-Suk , Choi Tae-Rim , Han Yeong-Hoon , Park Ye-Lim , Park Jun Young , Yang Soo-Yeon , Bhatia Shashi Kant , Gurav Ranjit , Kim Yun-Gon , Kim Jae-Seok , Joo Hwang-Soo , Yang Yung-hun
Published: March 2020

Methicillin-resistant Staphylococcus aureus (MRSA) strains are distinct from general Staphylococcus strains with respect to the composition of the membrane, ability to form a thicker biofilm, and, importantly, ability to modify the target of antibiotics to evade their activity. The agr gene is an accessory global regulator of gram-positive bacteria that governs virulence or resistant mechanisms and therefore an important target for the control of resistant strains. However, the mechanism by which agr impacts resistance to β-lactam antibiotics remains unclear. In the present study, we found the Δagr mutant strain having higher resistance to high concentrations of b-lactam antibiotics such as oxacillin and ampicillin. To determine the influence of variation in the microenvironment of cells between the parental and mutant strains, fatty acid analysis of the supernatant, total lipids, and phospholipid fatty acids were compared. The Δagr mutant strain tended to produce fewer fatty acids and retained lower amounts of C16, C18 fatty acids in the supernatant. Phospholipid analysis showed a dramatic increase in the hydrophobic longer-chain fatty acids in the membrane. To target membrane, we applied several surfactants and found that sorbitan monolaurate (Span20) had a synergistic effect with oxacillin by decreasing biofilm formation and growth. These findings indicate that agr deletion allows for MRSA to resist antibiotics via several changes including constant expression of mecA, fatty acid metabolism, and biofilm thickening.
Characterization of clinical and genetic spectrum of Chinese patients with cystic fibrosis
Authors: Liu Keqiang , Xu Wenshuai , xiao Meng , Zhao Xinyue , New Chun Bian , Zhang Qianli , Song Jiaxing , Chen Keqi , Tian Xinlun , Liu Yaping , Xu Kai-Feng , Zhang Xue
Published: March 2020

Background

Cystic fibrosis (CF) is a rare autosomal recessive disorder caused by biallelic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The clinical features and mutation spectrum of CF have been well characterized in Caucasians, while limited studies were conducted in Chinese patients.

Subjects and methods

A total of 20 individuals from 19 families were diagnosed with CF in this study. We analyzed the clinical features and screened all coding exons of CFTR using a combination of Sanger sequencing and multiplex ligation-dependent probe amplification analysis.

Results

The median age at onset was 9.3 years in our cohort, while the median age at diagnosis was 19 years. The respiratory system was most frequently affected in this study: all patients (100%, 19/19) presented diffuse bronchiectasis and 61.1% (11/18) of patients showed a forced expiratory volume in 1 s below 80% predicted. Six patients (6/20, 30%) exhibited allergic bronchopulmonary aspergillosis (ABPA). Only 4 (4/20, 20%) patients presented pancreatic exocrine insufficiency (PI). Three adult male patients receiving examinations for congenital bilateral absence of the vas deferens were all found positive for the condition. A total of 22 distinct mutations were detected in this cohort, with the variant p.G970D as the most common variant (12/38 alleles, 31.6%). Four variants (p.Y109D, p.I203F, p.D572E, and exon 2-3 deletion) were novel, which expanded the mutation spectrum of Chinese CF patients.

Conclusions

Chinese CF patients showed different clinical features and a distinct CFTR mutation spectrum compared with Caucasians. There is a significant diagnosis delay, suggesting the current underdiagnosis of CF in China.
TIMP-2*IGFBP7 as an auxiliary identification of successful discontinuation CRRT and prediction of renal recovery in critically ill patients: a case control study
Authors: xie yuanyuan , Zarbock Alexander , Brendolan Alessandra , Martino Francesca , Samoni Sara , Marchionna Nicola , fan Weixuan , Rosa Silvia De , Giavarina Davide , Romero-González Gregorio , Ronco Claudio
Published: March 2020

Background Cell cycle arrest biomarkers as TIMP-2*IGFBP7 are elevated in the Acute Kidney Stress and can predict the probability of developing Acute Kidney Injury (AKI). Approximately 25% of those patients with AKI deteriorate clinically and are unable to maintain adequate homeostasis, eventually requiring continuous renal replacement therapy. However, when clinical improvement occurs, the ideal mode of weaning patients from CRRT is an unmet medical need.
Methods We performed a prospective single-center study of AKI patients treated with CRRT between October 2017 to April 2019 in a multidisciplinary ICU of an Italian hospital. All patients admitted to ICU requiring CRRT were enrolled. Urine samples for measuring urinary TIMP-2*IGFBP7 levels were collected immediately upon enrollment and at the moment when CRRT was discontinued. The primary endpoint was independence from RRT for at least 7 days after CRRT discontinuation. Renal recovery, which was defined as serum creatinine (SCr) level <1.5 times the baseline value at ICU discharge or day 28, was the secondary endpoint.
Results 73 patients were enrolled of whom 45 patients effectively discontinued CRRT (61.6%). The patients with a TIMP-2*IGFBP7 concentration >2(ng/ml) 2 /1000 at enrollment were longer CRRT-dependent. The ROC-AUC values for the prediction of successful discontinuation with TIMP-2*IGFBP7 concentrations at enrollment, at discontinuation of CRRT and with the final model were 0.828, 0.814 and 0.882, respectively. The risk for CRRT discontinuation failure was nearly 5 times higher patients with a positive biomarker at CRRT discontinuation (OR 4.879, P=0.043), and 3.5 times higher in patients with a TIMP-2*IGFBP7 concentration >2(ng/ml) 2 /1000 at patient enrollment (OR 3.515, P=0.016). Multivariate Cox regression analysis showed a significant association between successful discontinuation of CRRT and TIMP-2*IGFBP7-negative patients at CRRT discontinuation (RR 0.436, 95% CI 0.202-0.939, P=0.034). Kaplan-Meier curves revealed that TIMP-2*IGFBP7 concentration <2 (ng/ml) 2 /1000 at enrollment and TIMP-2*IGFBP7 turning negative were positively related to high renal recovery rate.
Conclusions Urinary TIMP-2*IGFBP7 can serve as a biomarker for identifying successful discontinuation CRRT and predicting renal recovery in critically ill patients.
Mining hub genes correlated with immune infiltrating level across multiple tumors microenvironment
Authors: Zhao Ning , Wu Liang , Zhou Zili , Zhang Xudan , Han Shengbo , Bao Haijun , Shu Xiaogang
Published: March 2020

Background: Previous studies revealed that cancer-associated differentially expressed genes (DEGs) in an independent cancer type are rarely related to the tumorigenesis and metastasis, while the common DEGs across multiple types of cancer may be proved as potential oncogenes or tumor suppressors. Although tumor-infiltrating immune cells have been reported to be associated with prognosis in multiple types of cancer, the hub genes regulating immune cells function in different cancer types remain unclear.
Methods: To screen for the hub genes regulating immune infiltrating level across multiple tumors microenvironment, the raw data containing RNA sequencing and clinical information from TCGA database and immune scores from ESTIMATE website across 25 cancer types were obtained.
Results: Based on the immune scores, all cases were categorized into high-score and low-score groups. Kaplan–Meier survival analysis demonstrated that a strong correlation between immune infiltrating level and survival prognosis was found in six cancer types. The functional enrichment analysis of common DEGs revealed that infection and immune response are the most prominent biological characteristics. Subsequently, the twelve common DEGs with prognostic value were identified as candidate hub genes and were adopted to construct the PPI network. Because of highly interconnected with other hub genes, protein tyrosine phosphatase non-receptor type 6 (PTPN6) was selected as the real hub gene across the six immune-specific tumors. Finally, a significant correlation between PTPN6 and immune inﬁltrating level, and immune marker sets of various immune cells were observed.
Conclusion: PTPN6 may play a vital role in regulating immune response for tumor development, due to its significant correlation with tumor-infiltrating immune cells in multiple cancers.
The general movements assessment in term and late-preterm infants diagnosed with neonatal encephalopathy, as a predictive tool of cerebral palsy by two years of age: a scoping review protocol.
Authors: Seesahai Judy , Luther Maureen , Rhoden Carmen Cindy , Church Paige Terrien , Asztalos Elizabeth , Banihani Rudaina
Published: March 2020

Background Prediction of long-term neurodevelopmental outcomes remains an elusive goal for neonatology. Clinical and socioeconomic markers have not proven to be adequately reliable. The limitation in prognostication includes those term and late-preterm infants born with neonatal encephalopathy. The General Movements Assessment tool by Prechtl has demonstrated reliability for identifying infants at risk for neuromotor impairment. This tool is non-invasive and cost-effective. The purpose of this study is to identify the published literature on how this tool applies to the prediction of cerebral palsy in term and late-preterm infants diagnosed with neonatal encephalopathy and so detect the research gaps. Methods We will conduct a systematic scoping review for data on sensitivity, specificity, positive and negative predictive value and describe the strengths and limitations of the results. This review will consider studies that included infants more than or equal to 34+0 weeks gestational age, diagnosed with neonatal encephalopathy, with a General Movements Assessment done between birth to six months of life and an assessment for cerebral palsy by at least two years of age. Experimental and quasi-experimental study designs including randomized controlled trials, non-randomized controlled trials, before and after studies, interrupted time-series studies and systematic reviews will be considered. Case reports, case series, case control and cross-sectional studies will be included. Text, opinion papers and animal studies will not be considered for inclusion in this scoping review as this is a highly specific and medical topic. Studies in the English language only will be considered. Studies published from at least 1970 will be included as this is around the time when the General Movements Assessment was first introduced in neonatology as a potential predictor of neuromotor outcomes. We will search five databases (MEDLINE, Embase, PsychINFO, Scopus and CINAHL). Two reviewers will conduct all screening and data extraction independently. The articles will be categorized according key findings and a critical appraisal performed. Discussion The results of this review will guide future research to improve early identification and timely intervention in infants with neonatal encephalopathy at risk of neuromotor impairment.
Transcriptome analysis of the hypothalamus and pituitary of turkey hens with low and high egg production
Authors: Brady Kristen , Liu Hsiao-Ching , Hicks Julie , Long Julie A , Porter Tom E
Published: March 2020

Background: High egg producing hens ( HEPH ) show increased hypothalamic and pituitary gene expression related to hypothalamo-pituitary-gonadal ( HPG ) axis stimulation as well as increased in vitro responsiveness to gonadotropin releasing hormone ( GnRH ) stimulation in the pituitary when compared to low egg producing hens ( LEPH ). Transcriptome analysis was performed on hypothalamus and pituitary samples from LEPH and HEPH to identify novel regulators of HPG axis function. Results: In the hypothalamus and pituitary, 4644 differentially expressed genes ( DEGs ) were identified between LEPH and HEPH, with 2021 genes up-regulated in LEPH and 2623 genes up-regulated in HEPH. In LEPH, up-regulated genes showed enrichment of the hypothalamo-pituitary-thyroid ( HPT ) axis. Beta-estradiol was identified as an upstream regulator regardless of tissue. When LEPH and HEPH samples were compared, beta-estradiol was activated in HEPH in 3 of the 4 comparisons, which correlated to the number of beta-estradiol target genes up-regulated in HEPH. In in vitro pituitary cell cultures from LEPH and HEPH, thyroid hormone pretreatment negatively impacted gonadotropin subunit mRNA levels in cells from both LEPH and HEPH, with the effect being more prominent in HEPH cells. Additionally, the effect of estradiol pretreatment on gonadotropin subunit mRNA levels in HEPH cells was negative, whereas estradiol pretreatment increased gonadotropin subunit mRNA levels in LEPH cells. Conclusions: Up-regulation of the HPT axis in LEPH and upstream beta-estradiol activation in HEPH may play a role in regulating HPG axis function, and ultimately ovulation rates. Thyroid hormone and estradiol pretreatment impacted gonadotropin mRNA levels following GnRH stimulation, with the inhibitory effects of thyroid hormone more detrimental in HEPH and estradiol stimulatory effects more prominent in LEPH. Responsiveness to thyroid hormone and estradiol may be due to desensitization to thyroid hormone and estradiol in LEPH and HEPH, respectively, due to up-regulation of the HPT axis in LEPH and of the HPG axis in HEPH. Further studies will be necessary to identify possible target gene desensitization mechanisms and elicit the regulatory role of the HPT axis and beta-estradiol on ovulation rates in turkey hens.
Circulating heat shock protein 27 as a novel marker of subclinical atherosclerosis in type 2 diabetes: a cross-sectional community-based study
Authors: Wang Xinru , Shi Jie , Lu Bin , Zhang Weiwei , Yang Yehong , Wen Jie , Hu Renming , Yang Zhen , Wang Xuanchun
Published: March 2020

Background

Heat shock protein 27 (HSP27) has been proposed as a vital protective factor in atherosclerosis. The objective of the present study was to evaluate the association between circulating HSP27 and intima–media thickness (IMT) of the common carotid artery in individuals with type 2 diabetes and to determine whether HSP27 represents an independent marker for subclinical atherosclerosis in this patient population.

Methods

We performed a cross-sectional community-based study consisting in 186 Chinese subjects with a median duration of diabetes of 8.2 years who underwent carotid ultrasound IMT measurement. Serum HSP27 levels were assessed by ELISA.

Results

Serum HSP27 levels were significantly higher in the IMT (+, >1.0 mm) group than in the IMT (-, ≤1.0 mm) group, with the median value of 8.80 ng/mL (5.62–12.25) and 6.93 ng/mL (4.23–9.60), respectively ( P =0.006). The discriminative value of HSP27 to evaluate IMT was 7.16 ng/mL and the area under the curve was 0.72 (95%CI=0.64–0.80, P=0.0065). Spearman's rank correlation analysis demonstrated that the concentrations of circulating HSP27 were positively correlated with carotid IMT ( r =0.198, P =0.007) and blood urea nitrogen ( r =0.170, P <0.05). Furthermore, in the logistic model, serum HSP27 levels were found to be independent predictors of carotid IMT in type 2 diabetic patients after adjustment for onset age of diabetes, blood pressure, total cholesterol and C-reactive protein. (OR=1.085, P =0.022).

Conclusions

Circulating HSP27 level, positively correlates with carotid IMT, is an independent predictor for early atherosclerotic changes in diabetes, and may represent a novel marker of subclinical atherosclerosis in type 2 diabetes.
Association between Aminotransferase/alanine Aminotransferase Ratio and Cardiovascular Disease mortality in Patients on Peritoneal Dialysis: A Multi-center Retrospective Study
Authors: Feng Xiaoran , Wen Yueqiang , Peng FenFen , Wang Niansong , Zhan Xiaojiang , Wu Xianfeng
Published: March 2020

Objectives: Elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio is an independent risk factor for cardiovascular disease (CVD) among the general population. However, an association between AST/ALT ratio and CVD mortality in patients on peritoneal dialysis (PD) has received little attention.Methods: A total of 2224 incident PD patients from multi-centers were enrolled from November 1, 2005, to June 30, 2017, in this retrospective cohort study. The primary endpoint was CVD mortality. Eligible patients were divided into high and normal groups according to the AST/ALT ratio cut-off for CVD mortality with the receiver operating characteristic (ROC) curve. The associations between the AST/ALT ratio and CVD mortality were evaluated by the Cox regression model.Results: Of eligible 1579 patients with a mean age of 49.3±14.6 years, 55.4% of patients were male, 18.1% of patients had diabetes, and 64.2% of patients had hypertension. The prevalence of a high AST/ALT ratio was 76.6% in the cohort population. During a follow-up period with 4659.6 patient-years, 316 patients died, of which 193 (61.1%) deaths were caused by CVD episodes. The incidence of CVD mortality in the high group was significantly higher than that in the normal group (13.1% versus 9.2%, P=0.024). Cumulative CVD mortality rates were significantly different between the two groups by Kaplan-Meier analysis [hazards ratio (HR)=1.50, 95% confidence index (CI) 1.09-2.07, P=0.014]. After adjusting for confounding factors, a higher AST/ALT ratio was independently associated with an increased risk of CVD mortality compared with their counterparts (HR=1.43, 95%CI 1.08-2.41, P=0.002). Conclusions: PD patients with high baseline AST/ALT ratio levels may be at a significant risk of CVD mortality.
Chromosomal instability in untreated primary prostate cancer as an indicator of metastatic potential
Authors: Miller Eric T , You Sungyong , Cadaneanu Radu M , Kim Minhyung , Yoon Junhee , Liu Sandy T , Li Xinmin , Kwan Lorna , Hodge Jennelle , Quist Michael J , Grasso Catherine S , Lewis Michael S. , Knudsen Beatrice S , Freeman Michael R , Garraway Isla P
Published: March 2020

Background: Metastatic prostate cancer (PC) is highly lethal. The ability to identify primary tumors capable of dissemination is an unmet need in the quest to understand lethal biology and improve patient outcomes. Previous studies have linked chromosomal instability (CIN), which generates aneuploidy following chromosomal missegregation during mitosis, to PC progression. Evidence of CIN includes broad copy number alterations (CNAs) spanning >300 base pairs of DNA, which may also be measured via RNA expression signatures associated with CNA frequency. Signatures of CIN in metastatic PC, however, have not been interrogated or well defined. We examined a published 70-gene CIN signature (CIN70) in untreated and castration-resistant prostate cancer (CRPC) cohorts from The Cancer Genome Atlas (TCGA) and previously published reports. We also performed transcriptome and CNA analysis in a unique cohort of untreated primary tumors collected from diagnostic prostate needle biopsies (PNBX) of localized (M0) and metastatic (M1) cases to determine if CIN was linked to clinical stage and outcome.
Methods: PNBX were collected from 99 patients treated in the VA Greater Los Angeles (GLA-VA) Healthcare System between 2000-2016. Total RNA was extracted from high-grade cancer areas in PNBX cores, followed by RNA sequencing and/or copy number analysis using OncoScan. Multivariate logistic regression analyses permitted calculation of odds ratios for CIN status (high versus low) in an expanded GLA-VA PNBX cohort (n = 121).
Results: The CIN70 signature was significantly enriched in primary tumors and CRPC metastases from M1 PC cases. An intersection of gene signatures comprised of differentially expressed genes (DEGs) generated through comparison of M1 versus M0 PNBX and primary CRPC tumors versus metastases revealed a 157-gene "metastasis" signature that was further distilled to 7-genes (PC-CIN) regulating centrosomes, chromosomal segregation, and mitotic spindle assembly. High PC-CIN scores correlated with CRPC, PC-death and all-cause mortality in the expanded GLA-VA PNBX cohort. Interestingly, approximately 1/3 of M1 PNBX cases exhibited low CIN, illuminating differential pathways of lethal PC progression.
Conclusions: Measuring CIN in PNBX by transcriptome profiling is feasible, and the PC-CIN signature may identify patients with a high risk of lethal progression at the time of diagnosis.
How to recover from a bad start: size at metamorphosis affects growth and survival in a tropical amphibian
Authors: Szekely Diana , Cogalniceanu Dan , Szekely Paul , Armijos-Ojeda Diego , Espinosa-Mogrovejo Valentina , Denoel Mathieu
Published: March 2020

Background:
In species with complex life cycles, size at metamorphosis is a key life-history trait which reflects the complex interactions between costs and benefits of life in the aquatic and terrestrial environments. Whereas the effects of a deteriorating larval habitat (e.g. pond desiccation) on triggering an early metamorphosis have been extensively investigated in amphibians, the consequences of the resulting reduced size at metamorphosis on fitness in the post-metamorphic terrestrial stage remain poorly understood. We tested the hypothesis that a smaller size at metamorphosis negatively affects performance and survival in the ensuing terrestrial stage. Using as model a tropical amphibian ( Ceratophrys stolzmanni ) showing a large phenotypic plasticity in metamorphosing traits, we evaluated the effects of size at metamorphosis on fitness-related trophic and locomotor performance traits, as well as on growth and survival rates.
Results:
Our results support the hypothesis that a larger size at metamorphosis is correlated with better survival and performance. The survival rate of large metamorphosing individuals was 95%, compared to 60% for those completing metamorphosis at a small size. Locomotor performance and gape size were positively correlated with body size, larger animals being more mobile and capable to ingest larger prey. However, smaller individuals achieved higher growth rates, thus reducing the size gap.
Conclusions:
Overall, size at metamorphosis affected profoundly the chances of survival in the short term, but smaller surviving individuals partly compensated their initial disadvantages by increasing growth rates.
Rickettsia spp. in rodent-attached ticks and first evidence of Spotted fever Group Rickettsia species Candidatus Rickettsia uralica in Europe.
Authors: Vikentjeva Maria , Geller Julia , Remm Jaanus , Golovljova Irina
Published: March 2020

BACKGROUND

Rickettsia spp. are human pathogens that cause a number of diseases and are transmitted by arthropods, including ixodid ticks. Estonia contributes a region, where the distribution area of two exophilic tick species of known medical importance, Ixodes persulcatus and I. ricinus, overlap. The presence of the nidicolous rodent-associated I. trianguliceps has recently been shown for Estonia. Although there is no Estonian data available on human disease caused by tick-borne Rickettsia spp., the presence of three Rickettsia species in non-nidicolous ticks, albiet at very dissimilar rates, was also previously reported. The aim of this studywas to screen, identify and characterize Rickettsia species in nidicolous and non-nidicolous ticks attached to rodents.

RESULTS

Nymphs and larvae of I. ricinus ( n = 1004), I . persulcatus ( n = 75) and I. trianguliceps ( n = 117) attached to rodents and shrews caught in different parts of Estonia were studied for the presence of Rickettsia spp. by nested PCR. Ticks were removed from 314 small animals of 5 species (bank voles Myodes glareolus , yellow necked mice Apodemus flavicollis , striped field mice A. agrarius, pine voles M. subterranius and common shrews S. araneus) . Rickettsial DNA was detected in 8,7% (103/1186) studied ticks. In addition to R. helvetica, previously found in questing ticks, this study reports the first identification of the recently described I. trianguliceps- associated Candidatus R. uralica in west of the Ural.
Prevalence of hypertension and its risk factor among cotton textile workers in low-and-middle-income countries: A systematic review protocol
Authors: Ali Naureen , Feroz Anam
Published: March 2020

Background: Cotton workers are exposed to various hazards in the textile industry that might result in different ailments including hypertension (HTN). However, few attempts have been made to systematically review the prevalence of hypertension and its risk factor among cotton textile workers in low-and-middle-income countries (LMICs). This review aims to identify the factors and burden of hypertension; considering that modifiable factors can be prevented in this high risk population. Methods: We will carry out the systematic literature search on the major electronic databases including PubMed, CINAHL Plus, Science Direct, and Cochrane between January 2000 and December 2019, to identify the prevalence and incidence along with risk factors of hypertension in adults’ cotton textile workers in LMIC. Two researchers will independently search the databases. The search strategy will be piloted to ensure sufficient specificity and sensitivity. We will limit the search findings to human studies conducted in the adult workers. Discussion: This review will highlight the proportion of hypertension along with its risk factor among cotton textile workers in LMICs. Given that, some of the factors can be prevented in this high-risk population, we will call on health, experts to prioritize policies and commission and conduct programs to support the improvement in their health. The findings of this review will be made publicly available and the results will be disseminated via presentations and peer-reviewed publications Conclusion: The review provides detailed information about the prevalence and risk factors of hypertension that will help to progress the health of cotton workers in LMICs.
Determination of ephedrine, pseudoephedrine, sinapine thiocyanate, tetrahydropalmatine and amygdalin by HPLC-MS/MS after oral administration of extracts of Majie cataplasm in rabbits plasma: Application to a pharmacokinetic study
Authors: Li Changxiang , Shi Hanfen , Cheng Fafeng , Zhu Wenxiang , Liu Yuanjun , Ji Wenting , Zhang Qianyi , Du Xilei , Feng Tianyi , Wang Xueqian
Published: March 2020

BackgroundThis study aimed to develop HPLC-MS/MS method for quantification of ephedrine, pseudoephedrine, sinapine thiocyanate, tetrahydropalmatine and amygdalin of extracts of Majie cataplasm after oral administration in rabbits plasma and describe the pharmacokinetics of this five components.MethodsThe qualitative detection of the five compounds was accomplished by two methods. One method for the simultaneous determination of ephedrine, pseudoephedrine, sinapine thiocyanate and tetrahydropalmatine was developed and validated for the first time, while the other method was for amygdalin. Chromatographic separations were achieved on a C18 column using gradient elution with the mobile phase consisting of acetonitrile and water (containing 0.1% formic acid and 5mM ammonium formate) for ephedrine, pseudoephedrine, sinapine thiocyanate and tetrahydropalmatine, while acetonitrile and water for amygdalin, at a flow rate of 0.4 mL/min. The initial gradient was extended in order to isolate ephedrine and pseudoephedrine better. The detection was performed in multiple-reaction monitoring (MRM) mode using electrospray ionization (ESI).ResultsAll calibration curves showed good linearity (r2＞0.996) within the test ranges. The lower limit of quantification was 0.01 ng/mL for all five analytes. Reproducibility for five analytes ranged from 0.79 to 2.3% (Ephedrine), 0.51 to 3.4% (pseudoephedrine), 2.8 to 5.0% (Sinapine thiocyanate), 2.6 to 6.3% (Tetrahydropalmatine) and 1.1—2.5% (amygdalin) respectively. The extraction recoveries were within the acceptable range.ConclusionThe two methods were successfully applied to pharmacokinetic study of rabbits after oral administration. The two methods has several advantages including good chromatographic resolution, specific and reproducibility and superior minimum detection limit. The results provided a basis for further study on the bioactivity of Majie cataplasm.
Rates, predictors and mortality of sepsis-induced acute kidney injury: systematic review and meta-analysis
Authors: Liu Jie feng , Xie Hebin , ye ziwei , Wang Lesan
Published: March 2020

Objective

The incidence and mortality of sepsis-induced acute kidney injury is high. Many studies have explored the causes of sepsis-induced acute kidney injury (AKI). However, its predictors are still uncertain; additionally, a complete overview is missing. A systematic review and a meta-analysis were performed to determine the predisposing factors for sepsis-induced AKI.

Method

A systematic literature search was performed in the Medline, Embase, Cochrane Library, PubMed and Web of Science databases, with an end date parameter of May 25, 2019. Valid data were retrieved in compliance with the inclusion and exclusion criteria.

Result

Forty-seven observational studies were included for analysis. A cumulative number of 55911sepsis patients were evaluated. The incidence of AKI caused by septic shock is the highest. 30 possible risk factors were included in the meta-analysis. The results showed that 20 factors were found to be significant. The odds ratio(OR),95% confidence interval (CI) and Prevalence of the most prevalent predisposing factors for sepsis-induced AKI were as the following: Septic shock[2.88(2.36-3.52), 60.47%], Hypertension[1.43(1.20-1.70),38.39%), Diabetes mellitus[1.59(1.47-1.71),27.57%],Abdominal infection[1.44(1.32-1.58),30.87%], Vasopressors use[2.95(1.67-5.22),64.61%],vasoactive drugs use [3.85(1.89-7.87),63.22%], Mechanical ventilation[1.64(1.24-2.16),68.00%), Positive blood culture[1.60(1.35-1.89), 41.19%], Smoke history[1.60(1.09-2.36),43.09%]. Other risk factors include cardiovascular, coronary artery disease, liver disease, unknow infection, diuretics use, ACEI or ARB, gram-negative bacteria and organ transplant.

Conclusion

A large number of factors are associated with AKI development in sepsis patients. Our review can guide risk-reducing interventions, clinical prediction rules, and patient-specific treatment and management strategies for sepsis-induced acute kidney injury.
Does Atorvastatin Help Prevent Classic Migraine Attacks? A Triple-Blind Controlled Clinical Trial
Authors: Ganji Reza , Majdinasab Nastaran , Hesam Saeed , Rostami Nazanin , Sayyah Mehdi , Sahebnasagh Adeleh
Published: March 2020

Background: Migraine is a painful and disabling nervous disorder which negatively affects the quality of life. Migraineurs may suffer from a generalized vasomotor dysfunction. Statins improve vasomotor and vascular function, with their pleiotropic effects. We aimed to assess efficacy and safety of adding Atorvastatin to prophylactic regimen in better control of classic migraine.Methods: This triple-blind controlled clinical trial was on 68 consecutive patients with history of classic migraine. An interval of at least one month was given to evaluate vitamin D3 level and eligibility. In patients with vitamin D3 deficiency, the correction was provided by administration of soft gelatin capsule of vitamin D supplementation. The patients were randomly assigned to receive atorvastatin 20mg plus sodium valproate 500mg or placebo plus sodium valproate 500mg once a day for two months. The patients were evaluated based for the number of attacks and pain severity based on Visual Analogue Scale. Results: There was a significant (p = 0.0001) improvement in severity of pain and number of migraine attacks by adding Atorvastin to the prophylactic regimen of patients. After controlling for variable parameters, the differences between two arms of the study was yet statistically significant (p = 0.0001). A significant number of participants in intervention group were satisfied by their treatment (p = 0.001). There was no remarkable difference in two arms of the study in terms of possible side effects (P =0.315).Conclusions: The results of present study suggested that adding atorvastatin to migraine preventive regimen may help reduce the number of acute attacks and pain severity. This modality did not cause considerable side effects and led to a better patient satisfaction.
Modeling Survival Time to Recovery from COVID-19: A Case Study on Singapore
Authors: Mollazehi Monira , Mollazehi Mohammad , Abdel-Salam Abdel-Salam G.
Published: March 2020

Background

Novel coronavirus (COVID-19) is a new strain of viruses that originated in China. In December 2019, a strange case of pneumonia was reported in Wuhan, which then was diagnosed to be COVID-19. In Singapore, the first positive case was reported on January 23, 2020.

Aim

This study aims to study the recovery time from COVID-19 in Singapore between January 23 and March 13, 2020.

Methods

It's a retrospective study from January 23 until March 13, 2020 for 187 cases with COVID-19 infection. Data of the instances were collected to identify the factors affecting the recovery time from COVID-19. Several parametric models were fitted and the best predictor model was selected using the Bayesian information criterion (BIC).

Results

Out of 187 patients, 96 (51.34%) were cured. The mean (±standard deviation) survival time was 9.40±7.17 days. Based on BIC, the exponential regression model was the weakest and the Weibull model was the best for fitting to data. According to the Weibull model, age (HR=1.01) and nationality (HR=0.76) had significant statistical effects (α=0.05) on patient recovery time.

Conclusion

According to the findings of the study, younger patients recover faster compared to elderly patients, and the Singaporean patients cure more quickly than non-Singaporean patients.
Development of a TB vaccine trial site in Africa and lessons from the Ebola experience.
Authors: Kaguthi Grace , Nduba Videlis , Rabuogi Prisca , Okelloh Douglas , Ouma Samuel G. , Blatner Gretta , Gelderbloem Sebastian J. , Mitchell Ellen M.H. , Scott Cherise P. , Verver Suzanne , Hawkridge Anthony , de Steenwinkel Jurriaan E.M , Laserson Kayla F. , Richardus Jan Hendrik
Published: March 2020

Tuberculosis is the deadliest infection of our time. In contrast, about 11,000 people died of Ebola between 2014 and 2016. Despite this manifest difference in mortality, there is now a vaccine licensed in the United States and by the European Medicines Agency, with up to 100% efficacy against Ebola. The developments that led to the trialing of the Ebola vaccine were historic and unprecedented. The single licensed TB vaccine (BCG) has limited efficacy. There is a dire need for a more efficacious TB vaccine. To deploy such vaccines, trials are needed in sites that combine high disease incidence and research infrastructure. We describe our twelve-year experience building a TB vaccine trial site in contrast to the process in the recent Ebola outbreak. There are additional differences. Relative to the Ebola pipeline, TB vaccines have fewer trials and a paucity of government and industry led trials. While pathogens have varying levels of difficulty in the development of new vaccine candidates, there yet appears to be greater interest in funding and coordinating Ebola interventions. TB is a global threat that requires similar concerted effort for elimination.
Quantitative comparison of clinical outcomes and decompression parameters between extreme lateral lumbar interbody fusion and transforaminal lumbar interbody fusion in treating lumbar spinal stenosis: a 3-year retrospective cohort study
Authors: Xing Junchao , Cheng Peng , Xu Jianzhong , Lu Hongwei , He Qingyi
Published: March 2020

Background This retrospective cohort study was conducted to compare the clinical efficacy and decompression parameters of extreme lateral lumbar interbody fusion (XLIF) with transforaminal lumbar interbody fusion (TLIF) in treating lumbar spinal stenosis (LSS). Methods From January 2012 to June 2016, 1455 patients with LSS who underwent surgery were reviewed and 83 cases were included (40 cases for XLIF and 43 cases for TLIF). The operative time, blood loss, accumulated fluoroscopy time, visual analogue scale (VAS), Oswestry Disability Index (ODI), fusion rate and complications were evaluated. Moreover, decompression parameters were compared, including the sagittal disc height (DH), the foraminal height (FH) and area (FA), the lumbar lordosis (LL), the transverse area of the dural sac (DS), as well as the rate of change loss of these parameters. Results The baseline was consistent between two groups. The mean follow-up time was 36.9 months. Both of XLIF and TLIF yielded clinical improvements. XLIF had advantages over TLIF in blood loss, operative time, hospital stay and complication. The fusion rate, postoperative VAS and ODI scores were comparable. Particularly, XLIF showed analogous, or even better, capacity of ameliorating decompression parameters to TLIF, especially regarding DH, LL and the maintenance of decompression. Conclusions Compared with TLIF, XLIF is advantageous to avoid blood loss, shorten the operative time, hospital stay and maintain the decompressive effect in treating LSS.
A Comprehensive Data Analysis of Differentially Regulated Genes in Melanoma
Authors: Han Yanjie , Li Xinxin , Yan Jiliang , Ma Chunyan , Wang Xin , Pan Hong , Zheng Xiaoli , Zhang Zhen , Gao Biao , JI Xin-Ying
Published: March 2020

Background: Melanoma is the most deadly tumor in skin tumors and is prone to distant metastases. The incidence of melanoma has increased rapidly in the past few decades, and current trends indicate that this growth is continuing. This study was aimed to explore the molecular mechanisms of melanoma pathogenesis and discover underlying pathways and genes associated with melanoma.Methods: We used high-throughput expression data to study differential expression profiles of related genes in melanoma. The differentially expressed genes (DEGs) of melanoma in GSE15605, GSE46517, GSE7553 and the Cancer Genome Atlas (TCGA) datasets were analyzed. Differentially expressed genes (DEGs) were identified by paired t-test. Then the DEGs were performed cluster and principal component analyses and protein–protein interaction (PPI) network construction. After that, we analyzed the differential genes through bioinformatics and got hub genes. Finally, the expression of hub genes was confirmed in the TCGA databases and collected patient tissue samples.Results: Total 144 up-regulated DEGs and 16 down-regulated DEGs were identified. A total of 17 gene ontology analysis (GO) terms and 11 pathways were closely related to melanoma. Pathway of pathways in cancer was enriched in 8 DEGs, such as junction plakoglobin (JUP) and epidermal growth factor receptor (EGFR). In the PPI networks, 9 hub genes were obtained, such as loricrin (LOR), filaggrin (FLG), keratin 5 (KRT5), corneodesmosin (CDSN), desmoglein 1 (DSG1), desmoglein 3 (DSG3), keratin 1 (KRT1), involucrin (IVL) and EGFR. The pathway of pathways in cancer and its enriched DEGs may play important roles in the process of melanoma. The hub genes of DEGs may become promising melanoma candidate genes. Five key genes FLG, DSG1, DSG3, IVL and EGFR were identified in the TCGA database and melanoma tissues.Conclusions: The results suggested that FLG, DSG1, DSG3, IVL and EGFR might play important roles and potentially be valuable in the prognosis and treatment of melanoma.
Small repeating earthquake catalog for the Japanese Islands
Authors: Igarashi Toshihiro
Published: March 2020

Groups of repeating earthquakes, which occur in approximately the same location and possess a similar focal mechanism, have been extracted in various tectonic environments worldwide. Their recurrence interval has been used to estimate the spatiotemporal evolution of aseismic slip along major tectonic boundaries. Furthermore, slight changes between the waveforms of repeating earthquakes have been analyzed to delineate temporal changes in the local seismic velocity structure. Here we construct a long-term catalog of small repeating earthquakes throughout the Japanese Islands since 2001 (2001–2019) based on waveform similarity and relative source locations. Most of the long-duration sequences are located near the strongly coupled areas of the Philippine Sea and Pacific plates as they subduct from the Ryukyu-Nankai-Sagami and Kuril–Japan trenches, respectively. Many of the repeating sequences that occur in shallow crustal environments are short-lived. This repeating earthquake catalog allows us to estimate the slip history along each tectonic boundary. We believe that this and similar catalogs will be useful for future investigations of source processes, temporal slip and stress changes along faults, and local velocity structures, thereby providing new insights into earthquake generation mechanisms.