bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of control region mitochondrial DNA mutations in cardiovascular disease: stroke and myocardial infarction
Authors: Umbria Miriam , Ramos Amanda , Aluja Maria Pilar , Santos Cristina 
Published: February 2020

AbstractRecent studies associated certain type of cardiovascular disease (CVD) with specific mitochondrial DNA (mtDNA) defects, mainly driven by the central role of mitochondria in cellular metabolism. Considering the importance of the control region (CR) on the regulation of the mtDNA gene expression, the aim of the present study was to investigate the role of mtDNA CR mutations in two CVDs: stroke and myocardial infarction (MI). MtDNA CR mutations (both fixed and in heteroplasmy) were analysed in two demographically-matched case-control samples, using 154 stroke cases, 211 MI cases and their corresponding control individuals. Significant differences were found, reporting mutations m.16145 G > A and m.16311 T > C as potential genetic risk factors for stroke (conditional logistic regression: p = 0.038 and p = 0.018, respectively), whereas the m.72 T > C, m.73 A > G and m.16356 T > C mutations could act as possible beneficial genetic factors for MI (conditional logistic regression: p = 0.001, p = 0.009 and p = 0.016, respectively). Furthermore, our findings also showed a high percentage of point heteroplasmy in MI controls (logistic regression: p = 0.046; OR = 0.209, 95% CI [0.045–0.972]). These results demonstrate the possible role of mtDNA mutations in the CR on the pathogenesis of stroke and MI, and show the importance of including this regulatory region in genetic association studies.
trans-Fatty acids facilitate DNA damage-induced apoptosis through the mitochondrial JNK-Sab-ROS positive feedback loop
Authors: Hirata Yusuke , Inoue Aya , Suzuki Saki , Takahashi Miki , Matsui Ryosuke , Kono Nozomu , Noguchi Takuya , Matsuzawa Atsushi 
Published: February 2020

Abstracttrans-Fatty acids (TFAs) are unsaturated fatty acids that contain one or more carbon-carbon double bonds in trans configuration. Epidemiological evidence has linked TFA consumption with various disorders, including cardiovascular diseases. However, the underlying pathological mechanisms are largely unknown. Here, we show a novel toxic mechanism of TFAs triggered by DNA damage. We found that elaidic acid (EA) and linoelaidic acid, major TFAs produced during industrial food manufacturing (so-called as industrial TFAs), but not their corresponding cis isomers, facilitated apoptosis induced by doxorubicin. Consistently, EA enhanced UV-induced embryonic lethality in C. elegans worms. The pro-apoptotic action of EA was blocked by knocking down Sab, a c-Jun N-terminal kinase (JNK)-interacting protein localizing at mitochondrial outer membrane, which mediates mutual amplification of mitochondrial reactive oxygen species (ROS) generation and JNK activation. EA enhanced doxorubicin-induced mitochondrial ROS generation and JNK activation, both of which were suppressed by Sab knockdown and pharmacological inhibition of either mitochondrial ROS generation, JNK, or Src-homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) as a Sab-associated protein. These results demonstrate that in response to DNA damage, TFAs drive the mitochondrial JNK-Sab-ROS positive feedback loop and ultimately apoptosis, which may provide insight into the common pathogenetic mechanisms of diverse TFA-related disorders.
Muscle Injury Induces Postoperative Cognitive Dysfunction
Authors: Guéniot Lorna , Lepere Victoria , De Medeiros Gabriela Ferreira , Danckaert Anne , Flamant Patricia , Le Dudal Marine , Langeron Olivier , Goossens Pierre L. , Chrétien Fabrice , Jouvion Grégory 
Published: February 2020

AbstractPostoperative cognitive dysfunction (POCD) is a major complication affecting patients of any age undergoing surgery. This syndrome impacts everyday life up to months after hospital discharge, and its pathophysiology still remains unclear. Translational research focusing on POCD is based on a wide variety of rodent models, such as the murine tibial fracture, whose severity can limit mouse locomotion and proper behavioral assessment. Besides, influence of skeletal muscle injury, a lesion encountered in a wide range of surgeries, has not been explored in POCD occurrence. We propose a physical model of muscle injury in CX3CR1GFP/+ mice (displaying green fluorescent microglial cells) to study POCD, with morphological, behavioral and molecular approaches. We highlighted: alteration of short- and long-term memory after muscle regeneration, wide microglial reactivity in the brain, including hippocampus area, 24 hours after muscle injury, and an alteration of central brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) balance, 28 days after muscle injury. Our results suggest for the first time that muscle injury can have early as well as late impacts on the brain. Our CX3CR1GFP/+ model can also facilitate microglial investigation, more specifically their pivotal role in neuroinflammation and synaptic plasticity, in the pathophysiology of POCD.
Incidence of diabetes mellitus in Spain as results of the nation-wide cohort di@bet.es study
Authors: Rojo-Martínez G. , Valdés S. , Soriguer F. , Vendrell J. , Urrutia I. , Pérez V. , Ortega E. , Ocón P. , Montanya E. , Menéndez E. , Lago-Sampedro A. , González- Frutos T. , Gomis R. , Goday A. , García-Serrano S. , García-Escobar E. , Galán-García J. L. , Castell C. , Badía-Guillén R. , Aguilera-Venegas G. , Girbés J. , Gaztambide S. , Franch-Nadal J. , Delgado E. , Chaves F. J. , Castaño L. , Calle-Pascual A. 
Published: February 2020

AbstractOur aim was to determine the incidence of type 2 diabetes mellitus in a nation-wide population based cohort from Spain (di@bet.es study). The target was the Spanish population. In total 5072 people older than 18 years,were randomly selected from all over Spain). Socio-demographic and clinical data, survey on habits (physical activity and food consumption) and weight, height, waist, hip and blood pressure were recorder. A fasting blood draw and an oral glucose tolerance test were performed. Determinations of serum glucose were made. In the follow-up the same variables were collected and HbA1c was determined. A total of 2408 subjects participated in the follow-up. In total, 154 people developed diabetes (6.4% cumulative incidence in 7.5 years of follow-up). The incidence of diabetes adjusted for the structure of age and sex of the Spanish population was 11.6 cases/1000 person-years (IC95% = 11.1–12.1). The incidence of known diabetes was 3.7 cases/1000 person-years (IC95% = 2.8–4.6). The main risk factors for developing diabetes were the presence of prediabetes in cross-sectional study, age, male sex, obesity, central obesity, increase in weight, and family history of diabetes. This work provides data about population-based incidence rates of diabetes and associated risk factors in a nation-wide cohort of Spanish population.
5-Nitrouracil stabilizes the plasma concentration values of 5-FU in colorectal cancer patients receiving capecitabine
Authors: Yoshida Yoichiro , Hashimoto Yasuhiro , Miyazaki Makoto , Aisu Naoya , Yamada Teppei , Kajitani Ryuji , Munechika Taro , Matsumoto Yoshiko , Nagano Hideki , Shimaoka Hideki , Komono Akira , Sakamoto Ryohei , Yoshimatsu Gumpei , Yoshimura Fumihiro , Kiyomi Fumiaki , Hasegawa Suguru 
Published: February 2020

AbstractCapecitabine is selectively converted from 5′-DFUR to 5-fluorouracil (5-FU) in tumours by thymidine phosphorylase (TP). We investigated the addition of 5-nitrouracil (5-NU), a TP inhibitor, into blood samples for precise measurements of plasma 5-FU concentrations. The plasma concentration of 5-FU was measured after capecitabine administration. Two samples were obtained at 1 or 2 h after capecitabine administration and 5-NU was added to one of each pair. Samples were stored at room temperature or 4 °C and 5-FU concentrations were measured immediately or 1.5 or 3 h later. The mean plasma 5-FU concentration was significantly higher at room temperature than at 4 °C (p < 0.001). The 5-FU concentration was significantly increased in the absence of 5-NU than in the presence of 5-NU (p < 0.001). The 5-FU change in concentration was greater in the absence of 5-NU, and reached 190% of the maximum compared with baseline. A significant interaction was found between temperature and 5-NU conditions (p < 0.001). Differences between the presence or absence of 5-NU were greater at room temperature than under refrigerated conditions. 5-FU plasma concentrations after capecitabine administration varied with time, temperature, and the presence or absence of 5-NU. This indicates that plasma concentrations of 5-FU change dependent on storage conditions after blood collection.
The integrated effect of salinity, organic amendments, phosphorus fertilizers, and deficit irrigation on soil properties, phosphorus fractionation and wheat productivity
Authors: Ding Zheli , Kheir Ahmed M. S. , Ali Marwa G. M. , Ali Osama A. M. , Abdelaal Aly I. N. , Lin Xin’e , Zhou Zhaoxi , Wang Bizun , Liu Beibei , He Zhenli 
Published: February 2020

AbstractSoil degradation due to global warming, water scarcity and diminishing natural resources negatively impacts food security. Soil fertility deterioration, particularly phosphorus (P) deficiency, remains a challenge in the arid and semi-arid regions. In this study, field experiments were conducted in different geographical locations to investigate the effects of organic amendments coupled with P fertilization and irrigation on soil physical-chemical properties, and the growth, yield and quality of wheat. Application of P fertilizers combined with organic amendments mitigated soil salinity, increased organic matter content, available water, hydraulic conductivity and available macronutrients, but decreased soil bulk density. Application of organic amendments slightly increased total Cd, Ni and Pb in soil, but Cd and Ni concentration was below allowable limits whilst Pb reached a hazardous level. Soil P fractions were significantly increased with the combined application of mineral P and organic amendments irrespective of salinity and irrigation. Crop growth yield and quality of wheat improved significantly in response to the integrated application of mineral P and organic amendments. In conclusion, the combination of mineral P sources with organic amendments could be successfully used as a cost-effective management practice to enhance soil fertility and crop production in the arid and semi-arid regions stressed with water scarcity and natural resource constraints.
Homologous recombination deficiency status-based classification of high-grade serous ovarian carcinoma
Authors: Takaya Hisamitsu , Nakai Hidekatsu , Takamatsu Shiro , Mandai Masaki , Matsumura Noriomi 
Published: February 2020

AbstractHomologous recombination repair (HRR) pathway deficiency (HRD) is involved in the tumorigenesis and progression of high-grade serous ovarian carcinoma (HGSOC) as well as in the sensitivity to platinum chemotherapy drugs. In this study, we obtained data from The Cancer Genome Atlas (TCGA) on HGSOC and identified scores for the loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions, and calculated the HRD score. We then investigated the relationships among the score, genetic/epigenetic alterations in HRR-related genes, and the clinical data. We found that BRCA1/2 mutations were enriched in the group with HRD scores ≥63. Compared with the groups with scores ≤62, this group had a good prognosis; we thus considered HRD scores ≥63 to be the best cutoff point for identifying HRD cases in HGSOC. Classification of HGSOC cases by the HRD status revealed a better prognosis for HRD cases caused by genetic alterations (genetic HRD) than those caused by epigenetic changes and those caused by undetermined reasons (p = 0.0002). Among cases without macroscopic residual tumors after primary debulking surgery, 11 of 12 genetic HRD cases survived after the median observation period of 6.6 years, showing remarkably high survival rates (p = 0.0059). In conclusion, HGSOC can be classified into subtypes with different prognoses according to HRD status. This classification could be useful for personalized HGSOC treatment.
Genomic insights into the lifestyles, functional capacities and oleagenicity of members of the fungal family Trichosporonaceae
Authors: Aliyu Habibu , Gorte Olga , de Maayer Pieter , Neumann Anke , Ochsenreither Katrin 
Published: February 2020

AbstractTrichosporonaceae incorporates six genera of physiologically and ecologically diverse fungi including both human pathogenic taxa as well as yeasts of biotechnological interest, especially those oleagenic taxa that accumulate large amounts of single cell oils (SCOs). Here, we have undertaken comparative genomic analysis of thirty-three members of the family with a view to gain insight into the molecular determinants underlying their lifestyles and niche specializations. Phylogenomic analysis revealed potential misidentification of three strains which could impact subsequent analyses. Evaluation of the predicted proteins coding sequences showed that the free-living members of the family harbour greater numbers of carbohydrate active enzymes (CAZYmes), metallo- and serine peptidases compared to their host-associated counterparts. Phylogenies of selected lipid biosynthetic enzymes encoded in the genomes of the studied strains revealed disparate evolutionary histories for some proteins inconsistent with the core genome phylogeny. However, the documented oleagenic members distinctly cluster based on the constitution of the upstream regulatory regions of genes encoding acetyl-CoA carboxylase (ACC), ATP-citrate synthase (ACS) and isocitrate dehydrogenase [NADP] (ICDH), which are among the major proteins in the lipid biosynthetic pathway of these yeasts, suggesting a possible pattern in the regulation of these genes.
PDCD4 controls the G1/S-phase transition in a telomerase-immortalized epithelial cell line and affects the expression level and translation of multiple mRNAs
Authors: Haas Astrid , Nilges Benedikt S. , Leidel Sebastian A. , Klempnauer Karl-Heinz 
Published: February 2020

AbstractPDCD4, the protein encoded by the tumor suppressor gene PDCD4 (programmed cell death 4) has been implicated in the control of cellular transcription and translation by modulating the activity of specific transcription factors and suppressing the translation of mRNAs with structured 5′-UTRs. Most studies of human PDCD4 have employed tumor cell lines, possibly resulting in a biased picture of its role in normal cells. Here, we have studied the function of PDCD4 in a telomerase-immortalized human epithelial cell line. We show for the first time that PDCD4 is required for the G1/S-transition, demonstrating its crucial role in the cell cycle. Inhibition of p53-dependent activation of p21WAF1/CIP1 overrides the requirement for PDCD4 for the G1/S-transition, suggesting that PDCD4 counteracts basal p53 activity to prevent activation of the G1/S checkpoint by p53. Transcriptome and ribosome profiling data show that silencing of PDCD4 changes the expression levels and translation of many mRNAs, providing an unbiased view of the cellular processes that are affected by PDCD4 in an epithelial cell line. Our data identify PDCD4 as a key regulator of cell cycle- and DNA-related functions that are inhibited when it is silenced, suggesting that decreased expression of PDCD4 might contribute to tumor development by compromising genomic integrity.
One-pot synthesis of sweetening syrup from lactose
Authors: Cheng Shouyun , Metzger Lloyd E. , Martínez-Monteagudo Sergio I. 
Published: February 2020

AbstractLactose has become the main byproduct of many dairy products and ingredients. Current applications of lactose are insufficient to use the recovered lactose from manufacturing operations. Here we exemplified a new process for converting aqueous lactose into a sweeting syrup via one-pot synthesis. The synthesis consisted of two-steps: (1) enzymatic hydrolysis of lactose and (2) catalytic isomerization over MgO/SiO2. The hydrolysis of lactose over β-galactosidase converted 95.77 ± 0.67% of lactose into glucose and galactose. The catalytic isomerization was performed over MgO/SiO2 with different MgO loadings (10–40 wt.%). A battery of tests was conducted to characterize the different catalysts, including surface properties, basicity, and microstructure. The one-pot synthesis, enzymatic hydrolysis and catalytic isomerization over 20%-MgO/SiO2, converted 99.3% of lactose into a sweetening syrup made of glucose (30.48%), galactose (33.51%), fructose (16.92%), D-tagatose (10.54%), and lactulose (3.62%). The outcomes of this research present an opportunity for expanding the utilization of lactose.
Effects of glucose metabolism pathways on nuclear and cytoplasmic maturation of pig oocytes
Authors: Wen Jing , Wang Guo-Liang , Yuan Hong-Jie , Zhang Jie , Xie Hong-Li , Gong Shuai , Han Xiao , Tan Jing-He 
Published: February 2020

AbstractThe developmental competence of IVM porcine oocytes is still low compared with that in their in vivo counterparts. Although many studies reported effects of glucose metabolism (GM) on oocyte nuclear maturation, few reported on cytoplasmic maturation. Previous studies could not differentiate whether GM of cumulus cells (CCs) or that of cumulus-denuded oocytes (DOs) supported oocyte maturation. Furthermore, species differences in oocyte GM are largely unknown. Our aim was to address these issues by using enzyme activity inhibitors, RNAi gene silencing and special media that could support nuclear but not cytoplasmic maturation when GM was inhibited. The results showed that GM in CCs promoted pig oocyte maturation by releasing metabolites from both pentose phosphate pathway and glycolysis. Both pyruvate and lactate were transferred into pig DOs by monocarboxylate transporter and pyruvate was further delivered into mitochondria by mitochondrial pyruvate carrier in both pig DOs and CCs. In both pig DOs and CCs, pyruvate and lactate were utilized through mitochondrial electron transport and LDH-catalyzed oxidation to pyruvate, respectively. Pig and mouse DOs differed in their CC dependency for glucose, pyruvate and lactate utilization. While mouse DOs could not, pig DOs could use the lactate-derived pyruvate.
Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population
Authors: Dang Anh-Thu Huynh , Tran Vu-Uyen , Tran Thanh-Truong , Thi Pham Hong-Anh , Le Dinh-Thong , Nguyen Lam , Nguyen Ngoc-Vu , Thi Nguyen Thai-Hoa , Nguyen Chu Van , Le Ha Thu , Thi Nguyen Mai-Lan , Le Vu Thuong , Nguyen Phuc Huu , Vo Binh Thanh , Thi Dao Hong-Thuy , Nguyen Luan Thanh , Van Nguyen Thien-Chi , Bui Quynh-Tram Nguyen , Nguyen Long Hung , Nguyen Nguyen Huu , Thi Nguyen Quynh-Tho , Le Truong Xuan , Do Thanh-Thuy Thi , Dinh Kiet Truong , Do Han Ngoc , Phan Minh-Duy , Nguyen Hoai-Nghia , Tran Le Son , Giang Hoa 
Published: February 2020

AbstractComprehensive profiling of actionable mutations in non-small cell lung cancer (NSCLC) is vital to guide targeted therapy, thereby improving the survival rate of patients. Despite the high incidence and mortality rate of NSCLC in Vietnam, the actionable mutation profiles of Vietnamese patients have not been thoroughly examined. Here, we employed massively parallel sequencing to identify alterations in major driver genes (EGFR, KRAS, NRAS, BRAF, ALK and ROS1) in 350 Vietnamese NSCLC patients. We showed that the Vietnamese NSCLC patients exhibited mutations most frequently in EGFR (35.4%) and KRAS (22.6%), followed by ALK (6.6%), ROS1 (3.1%), BRAF (2.3%) and NRAS (0.6%). Interestingly, the cohort of Vietnamese patients with advanced adenocarcinoma had higher prevalence of EGFR mutations than the Caucasian MSK-IMPACT cohort. Compared to the East Asian cohort, it had lower EGFR but higher KRAS mutation prevalence. We found that KRAS mutations were more commonly detected in male patients while EGFR mutations was more frequently found in female. Moreover, younger patients (<61 years) had higher genetic rearrangements in ALK or ROS1. In conclusions, our study revealed mutation profiles of 6 driver genes in the largest cohort of NSCLC patients in Vietnam to date, highlighting significant differences in mutation prevalence to other cohorts.
Molecular characterization of Extended-spectrum β lactamase- producing E. coli recovered from community-acquired urinary tract infections in Upper Egypt
Authors: Hassuna Noha A. , Khairalla Ahmed S. , Farahat Eman M. , Hammad Adel M. , Abdel-Fattah Medhat 
Published: February 2020

AbstractTreatment of community urinary tract infections (UTIs) caused by extended-spectrum β lactamase (ESBL)- producing Escherichia coli (E. coli) is more expensive than treating ESBL-negative opposites. Evaluation of the prevalence of ESBL-production among urinary E. coli isolates is crucial due to its great impact on the choice of proper antimicrobials. Accordingly, the aim of this work was to detect and characterize ESBL-producing E. coli isolated from outpatients with signs of UTIs in Upper Egypt. Urinary E. coli isolates were identified by 16S rRNA and their ESBL-production was confirmed by Modified Double Disc Synergy Test (MDDST) and ESBL- CHROMagar media. Isolates were then subjected to Polymerase Chain Reaction (PCR) for new Clermont phylogrouping, ESBL genes detection and CTX-M typing. The study enrolled 583 patients with clinically diagnosed UTIs. Uropathogens were found in 400 urine samples (68.6%) out of which 134 E. coli isolates were identified. Among the examined uropathogenic E. coli (UPEC), 80 (59.7%) were recognized as ESBL-producers. Greater than half of the ESBL-producers were multi-drug resistant (MDR) (62%). All of them were susceptible to meropenem. Most of the E. coli isolates were distributed in 4 phylogenetic groups: B2 = 42 (52.5%), F = 17 (21.25%) and Clade I or II = 10 (12.5%). The predominant gene types were TEM 60 (75%) and CTX-M gene 45 (56.25%). The CTX-M-1 group was the most prevalent (62.2%), including the CTX-M-15 enzyme, followed by the CTX-M-2 group, CTX-M-8 group and CTX-M-9 group. In conclusion, the results present alarming evidence of a serious spread of ESBL genes in Egypt, especially the epidemiological CTX-M 15, with the potential for the dissemination of MDR UPEC strains in the community.
Efficacy of red yeast rice extract on myocardial infarction patients with borderline hypercholesterolemia: A meta-analysis of randomized controlled trials
Authors: Sungthong Bunleu , Yoothaekool Chenchira , Promphamorn Sornsalak , Phimarn Wiraphol 
Published: February 2020

AbstractRed yeast rice (RYR) extract is widely used for improving cardiovascular outcomes and lipid profiles. However, RYR efficacy on cardiovascular outcomes in myocardial infarction (MI) patients remains unclear. This meta-analysis assessed efficacy of RYR extract in MI patients with borderline hypercholesterolemia. PubMed, CENTRAL, CINAHL, Scopus, Web of Science, and Clinicaltrials.gov were systematically searched from inception through May 2019 for relevant publications. Seven studies with 10,699 MI patients diagnosed with borderline hypercholesterolemia were included. Follow-up periods ranged from 4 weeks – 4.5 years and the studies were overall of high quality with low risk of bias. RYR extract (1,200 mg/day) reduced nonfatal MI (risk ratio (RR) = 0.42, 95% CI 0.34 to 0.52), revascularization (RR = 0.58, 95% CI 0.48 to 0.71), and sudden death (RR = 0.71, 95% CI 0.53 to 0.94). RYR extract also lowered LDL (weighted mean difference (WMD) = −20.70 mg/dL, 95% CI −24.51 to −16.90), TC (WMD = −26.61 mg/dL, 95% CI −31.65 to −21.58), TG (WMD = − 24.69 mg/dL, 95% CI −34.36 to −15.03), and increased HDL levels (WMD = 2.71 mg/dL, 95% CI 1.24 to 4.17). This meta-analysis indicated that RYR extract in MI patients with borderline hypercholesterolemia is associated with improved cardiovascular outcomes and lipid profiles.