bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering Pichia pastoris with surface-display minicellulosome for carboxymethyl cellulose hydrolysis and ethanol production
Authors: Dong Ce , Qiao Jie , Wang Xinping , Sun Wenli , Chen Lixia , Li Shuntang , Ma Lixin , liu yi 
Published: February 2020

Abstract
Backgrounds: Engineering yeast with cell surface immobilized cellulosome is a promising strategy for consolidated bioprocessing (CBP) to produce bioethanol from the conversion of cellulose. However, previous studies mostly focused on utilization of Saccharomyces cerevisiae , which was able to directly convert phosphoric acid-swollen cellulose (PASC) or microcrystalline cellulose (Avicel) but not carboxymethyl cellulose (CMC) to ethanol, with an average titer below 2 g/L. Results: Harnessing an ultra-high-affinity IM7/CL7 protein pair, here we describe a method to engineer Pichia pastoris with minicellulosome through in vitro assembly of various recombinant cellulases on the cell surface. For the first time, the yeast can efficiently convert CMC to bioethanol, achieving an impressive ethanol titer of 5.1 g/L. Further, the engineered yeasts were lyophilized to powders that can be utilized as compound cellulases. Conclusions: This research promotes the application of P. pastoris as CBP cell factory in cellulosic ethanol production and provides a promising platform for screening optimal cellulase species and ratios to construct celluosome on the yeast cell surface.
LAIR-1 overexpression inhibits osteosarcoma epithelial-mesenchymal transition via GLUT1-related energy metabolism
Authors: Zhang Jinxue , Zhang Yuan , Liu Yongming , Yi Xin , Cheng Shiyang , Jiang Dongxu , Ding Yong , Zhuang Ran 
Published: February 2020

Abstract
Background: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a collagen receptor belonging to the immunoglobulin superfamily. Although prior studies have evaluated the biological role of LAIR in solid tumors, the precise mechanisms underlying LAIR-1 functions as a regulator of tumor biological functions remains unclear.
Methods: LAIR-1 expression was evaluated using an osteosarcoma (OS) tissue microarray by immunohistochemical analysis. Wound healing and Transwell assays were performed to evaluate tumor cell migration. Quantitative PCR and western blotting were conducted to detect the expression of epithelial-mesenchymal transition (EMT)-related molecules. RNA-sequencing (RNA-seq) was conducted to evaluate the mRNA expression profiles after overexpressing LAIR-1 in OS cells. Glucose uptake and glucose transporter (Glut) 1 expression in OS cells in vitro were evaluated by flow cytometry and western blotting.
Results: LAIR-1 expression significantly differed between the T1 and T2 stages of OS tumors, and LAIR-1 overexpression inhibited OS cell migration. LAIR-1 expression was inversely correlated with the expression of EMT-associated transcription factors via the Forkhead box O1/Twist1 signal transduction pathway. Furthermore, RNA-seq and quantitative PCR demonstrated that EMT energy metabolism-related molecules were significantly reduced after LAIR-1 overexpression.
Conclusions: Notably, overexpression of LAIR-1 in OS cells decreased Glut1 expression. These findings provide insight into the molecular mechanism underlying OS progression.
Impact of 3-dimensional genome organization, guided by cohesin and CTCF looping, on sex-biased chromatin interactions and gene expression in mouse liver
Authors: Matthews Bryan J , Waxman David J 
Published: February 2020

Abstract
Background: Sex differences in the transcriptome and epigenome are widespread in mouse liver and are associated with sex-bias in liver disease. Several thousand sex-differential distal enhancers have been identified; however, their links to sex-biased genes and the impact of any sex-differences in nuclear organization, DNA looping, and chromatin interactions are unknown.Results: To address these issues, we first characterized 1,847 mouse liver genomic regions showing significant sex differential occupancy by cohesin and CTCF, two key 3D nuclear organizing factors. These sex-differential binding sites were largely distal to sex-biased genes, but rarely generated sex-differential TAD (topologically associating domain) or intra-TAD loop anchors. A substantial subset of the sex-biased cohesin-non-CTCF binding sites, but not the sex-biased cohesin-and-CTCF binding sites, overlapped sex-biased enhancers. Cohesin depletion reduced the expression of male-biased genes with distal, but not proximal, sex-biased enhancers by >10-fold, implicating cohesin in long-range enhancer interactions regulating sex-biased genes. Using circularized chromosome conformation capture-based sequencing (4C-seq), we showed that sex differences in distal sex-biased enhancer-promoter interactions are common. Sex-differential chromatin interactions involving sex-biased gene promoters, enhancers, and lncRNAs were associated with sex-biased binding of cohesin and/or CTCF. Furthermore, intra-TAD loops with sex-independent cohesin-and-CTCF anchors conferred sex specificity to chromatin interactions indirectly, by insulating sex-biased enhancer-promoter contacts and by bringing sex-biased genes into closer proximity to sex-biased enhancers.Conclusions: These findings elucidate how 3-dimensional genome organization contributes to sex differences in gene expression in a non-reproductive tissue through both direct and indirect effects of cohesin and CTCF looping on distal enhancer interactions with sex-differentially expressed genes.
A risk score based on pediatric sequential organ failure assessment predicts 90-day mortality in children with Klebsiella pneumoniae bloodstream infection
Authors: Li Shuang , Liu Jingxian , Chen Feng , Cai Kang , Tan Jintong , Xie Wei , Qian Rong , Liu Xiaoqin , Zhang Wenhong , Liu Ying , Huang Lisu 
Published: February 2020

Abstract
Background: Klebsiella pneumoniae bloodstream infection (Kp-BSI) is a serious threat to pediatric patients. The objective of this study was to explore the risk factors for mortality, validate the prediction efficiency of pediatric sequential organ failure assessment (SOFA) and establish better specific early predictors. Methods: All children diagnosed with Kp-BSI were included in this retrospective cohort study from January 2009 to June 2019. Basic characteristics, symptoms and physical examinations, laboratory statistics, and SOFA at the onset of Kp-BSI were recorded. The Cox proportional hazard model and the receiver operating characteristic curves were used to assess the association of the variables with the 90-day mortality and their predictive values. The DeLong's test of receiver operating characteristic curves and integrated discrimination improvement index were calculated to investigate predictive improvement of the modified SOFA models. A predictive score was developed using multivariate logistic regression. Results: Of the 146 children enrolled, 33 (22.6%) died within 90 days. Hospitalization within the previous six months, intra-abdominal source of bloodstream infection, presence of organ failures, and blood biomarkers including the C-reactive protein, albumin, and lactate were identified as significant risk factors for the 90-day mortality. The area under the curve (AUC) of SOFA for predicting 90-day mortality was 0.80 (95% CI 0.71–0.89). We further found a better combined model when adding hospitalization within the previous six months and intra-abdominal source of bloodstream infection into the SOFA score (AUC = 0.89, 95% CI 0.82–0.96, sensitivity = 0.86, specificity = 0.84). According to this novel risk model, we defined three statistically different groups: low-risk, medium-risk and high-risk groups, with an observed 90-day mortality of 5.4%, 35.7%, and 72.0%, respectively. With the reference of the low-risk group, the medium-risk and high-risk groups had a higher mortality, with hazard ratios of 8.36 (95% CI 3.60–27.83) and 20.27 (95% CI 7.47–54.95), respectively. Conclusions: The modified SOFA model may better predict the 90-day mortality of Kp-BSI. Future perspective studies will be required to validate this novel scoring system in external cohorts.
Bone Metastases in Newly Diagnosed Colorectal Cancer by Tumor Location: a Population-based Study
Authors: Yang Lin , Liu Shousheng , Xie Qiankun , He Wenzhuo , Jiang Chang , Zhang Bei , Xia Liangping 
Published: February 2020

Abstract
Purpose Bone metastasis (BM) in colorectal cancer (CRC) is rare and data on population-based incidence is lacking. We aimed to evaluate the incidence of BM and the risk factors for BM in CRC. Methods The Surveillance, Epidemiology, and End Results (SEER) database was interrogated as part of the analysis. We used multivariable logistic and Cox regression analyses to determine predictors for the presence of BM at diagnosis, and the elements associated with poor survival. Kaplan–Meier analysis was used to estimate the survival difference among subgroups. Results A total of 166,388 adult patients were identified between 2010 and 2013 as being diagnosed with CRC. Of these, 1,659 patients developed BM representing 1% of the entire CRC cohort and 5.5% of patients had metastatic disease. The median survival period of patients with BM was merely 11.3 months. We found that extracranial metastases number and tumor site were associated with BM at CRC diagnosis and these parameters were also associated with poorer survival in the BM cohort. Unlike other solid tumors, patients with bone metastasis had poorer survival and the median survival time (MST) was significantly shortened for single metastasis disease or when lung and liver metastasis were present.Conclusions The findings of this study clearly reveal the incidence and prognosis for patients with BM at time of CRC diagnosis. Our findings lend support for positive treatment of BM without other organ metastasis.
Identification of therapeutic targets and prognostic biomarkers among STAT family in glioblastoma
Authors: Li Chenglin , Zhou Yanfei , Deng Hanshun , Ye Yuanshen , Zhao Shuizhen , Liang Shangnan , Cai Shirong , Lin Jincai , Tang Yaolong , Wu Yanyu 
Published: February 2020

Abstract
Background: Glioblastoma (GBM) is the most common and aggressive primary brain malignancies with high incidence and mortality. The aberrant activation of STAT signaling was confirmed to result in tumor pathogenesis and progress by regulating cell cycle, cell survival, and immune response.
Methods: The clinical significance of and regulation network of STAT family in GBM were explored with several web applications or database.
Results: The level of STAT1/3/5A/5B/6 were increased in GBM while STAT4 level was decreased. GBM patients with high expression of STAT1/2/3/5A/6 and low expression of STAT4/5B had a worse overall survival. Among the STAT family, STAT 4 and STAT6 were the top two frequently mutated genes. Correlation suggested a low to moderate correlation among STAT family. STAT family were also involved in the activation or inhibition of the famous cancer related pathways. Immune infiltrates analysis suggested that STAT5A level showed significantly correlated with the abundance of immune cells and the level of immune gene biomarkers. GO functions and KEGG pathways analysis revealed that STAT5A was involved in immune response-regulating signaling pathway, neutrophil and lymphocyte mediated immunity, single-stranded DNA binding, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, NF-kappa B signaling pathway, and TNF signaling pathway. Moreover, we also identified several Kinase and transcription factor targets of STAT5A in GBM.
Conclusions: Our results revealed the therapeutic targets, prognostic biomarkers and regulation network of STAT family in GBM, laying the foundation for further studies about STAT family in therapy and prognosis of GBM.
Differentiation and localization of interneurons in the developing spinal cord depends on DOT1L expression
Authors: de Cristoforis Angelica Gray , Ferrari Francesco , Clotman Frédéric , Vogel Tanja 
Published: February 2020

Abstract
Genetic and epigenetic factors contribute to the development of the spinal cord. Failure in correct exertion of the developmental programs, including neurulation, neural tube closure and neurogenesis of the diverse spinal cord neuronal subtypes results in clinical phenotypes with variable severity. The histone methyltransferase Disruptor of Telomeric 1 Like (DOT1L), which mediates histone H3 lysine 79 (H3K79) methylation, is fundamental for proper development of the cerebral cortex and cerebellum, and here we report on its essential role for development of the spinal cord. Conditional inactivation of DOT1L using Wnt1-cre as driver in the developing murine spinal cord did not result in neural tube closure defect (NTCD). Transcriptome analysis revealed that DOT1L deficiency favored differentiation over progenitor proliferation. Dot1l -cKO mainly decreased the numbers of dI1 interneurons expressing Lhx2 . Loss of DOT1L affected localization but not generation of dI2, dI3, and dI5 interneurons. The resulting derailed interneuron patterns might be responsible for increased cell death that occurred at the late developmental stage E18.5. Together our data indicate that DOT1L is essential for subtype- specific neurogenesis, migration and localization of interneurons in the developing spinal cord, in part by regulating transcriptional activation of Lhx2 .
Evaluation of a Ketogenic Diet for Improvement of Neurological Recovery in Individuals with Acute Spinal Cord Injury: study protocol for a randomized controlled trial
Authors: DEMIREL Aynur , LI Jia , MORROW Casey , BARNES Stephen , JANSEN Jan , GOWER Barbara , KIRKSEY Keneshia , REDDEN David , Yarar-Fisher Ceren 
Published: February 2020

Abstract
Background: Therapies that significantly improve the neurological and functional recovery of individuals with spinal cord injury (SCI) are still urgently needed. The ketogenic diet (KD) has been shown to improve forelimb motor function in a rat model of SCI, likely by reducing inflammation and cell death in the spinal cord. Furthermore, our recent pilot study in patients with SCI showed that, compared with a standard hospital diet (SD), 5 weeks of KD, started during acute care, improved upper extremity motor function and reduced serum levels of a neuroinflammatory blood protein. The primary goals of our proposed study are to 1) show the safety and feasibility of administering a KD during acute care for SCI; 2) determine if consuming 5 weeks of a KD significantly improves motor and sensory function, functional independence, and glycemic control; and 3) quantify serum biomarkers that are linked to improvements in neurological recovery and functional independence via targeted proteomics.Methods/Design: In a single-masked, longitudinal, randomized parallel controlled study design, 60 participants with acute SCI will be randomly assigned to KD or SD in a 1:1 ratio. We intend to recruit 24 participants for each group with traumatic SCI (C5–T12, American Spinal Injury Association impairment scale A–C, and aged 18–60 years). Patients will be taken to acute care after their injury. Neurological and functional examinations, resting energy expenditure, blood, urine, stool collection and protein analyses related to neuro recovery will be done within 72 h of injury, as baseline measures. Patients received five weeks of KD or SD according to their allocation. The KD is a high-fat, low-carbohydrate diet (3:1 ratio of fat: carbohydrate + protein) that includes ~75% total energy as fat, ~20% as protein, and ~5% as carbohydrate and fiber. The SD includes ~45-50% total energy as carbohydrate and fiber, ~30% total energy as fat, and ~20% total energy as protein. All baseline examinations will be repeated at discharge from the hospital at week 5 (discharge measure). Discussion: The proposed diet intervention is practical and safe and is expected to translate into efficacious early nutritional interventions. Intervention with a more neuroprotective diet during acute care of SCI can be implemented anywhere in the world at low cost and without major regulatory hurdles. Better functional recovery will lead to a better quality of life and long-term health outcomes in individuals with SCI. While this study targets SCI, if successful it has the potential to improve neurological outcomes for individuals with various traumatic injuries such as traumatic brain injury and stroke.
Using electroacupuncture to recover muscle strength in knee osteoarthritic patients after total knee arthroplasty: a study protocol for a double-blinded, randomized and placebo-controlled trial
Authors: Xu Hui , Kang Bingxin , Li Yulin , Xie Jun , Sun Songtao , Zhong Sheng , Gao Chenxin , Xu Xirui , Zhao Chi , Qiu Guowei , Xiao Lianbo 
Published: February 2020

Abstract
Background: Total knee arthroplasty (TKA) has recently become an almost irreplaceable and effective means to relieve pain, reconstruct knee motor function and improve the quality of life of patients with end-stage knee osteoarthritis (KOA). However, the muscle strength after TKA is usually difficult to recover. Although electroacupuncture (EA) can enhance the muscle strength of lower extremity, there is hardly any literature on the effect of EA on the muscle strength of lower extremity in patients after TKA. To address this problem, this trial is intended to evaluate the efficacy of EA after TKA for recovering the muscle strength of lower extremity, esp. in the early post-TKA period.Methods/design: This is a double-blinded, randomized and controlled trial. It will be conducted between January, 2020 and June, 2020. A total of 94 participants with KOA will have undergone unilateral TKA and they will then be randomized into a treatment group and a control group, viz. the EA group and the sham EA group. The former will receive EA at acupuncture points of ST37, ST36, SP10 and SP9. The latter, the control group will receive sham EA at sham locations for the acupuncture points of ST37, ST36, SP10 and SP9. The participants will be given 5 sessions of treatment per day for 2 weeks. The primary outcomes include a change in the amount of muscle strength and the Hospital for Special Surgery (HSS) score at the second week from a baseline (POD 3). The secondary outcomes include a 6-minute walking test, Numerical rating scale (NRS), the Hamilton Anxiety Scale and additional use of analgesia. The additional outcomes include incidence of analgesia-related side effects and rate of participant satisfaction. Blinding of the participants will also be assessed. The participants will be asked to guess whether they have received EA after the latest intervention. Adverse events of EA will be documented and assessed throughout the trial.Discussion: EA is helpful for the recovery and enhancement of muscle strength of the lower limb after TKA.
The effect of using awake craniotomy combined with multimodal techniques intraoperative on survival of patients with glioblastoma: a single-center experience
Authors: Yang Li , Lu Ming , Deng Xinqing , Yang Mingming , zhou hui 
Published: February 2020

Abstract
Background:We analysed outcomes of cerebral glioblastoma patients undergoing awake craniotomies combined with multimodal techniques for tumour resection, with regards to the extent of resection, functional preservation, and prognosis.Methods:A retrospective analysis was conducted on adult glioblastoma patients who underwent an awake craniotomy from September 2010 to August 2018 under anaesthesia combined with multimodal techniques. Results:In total, 81 glioblastoma patient charts were analysed. The most common lesion sites were the frontal lobe (n=36), temporal lobe (n=17), and parietal lobe (n=6). The main symptoms were headache (n=51), dyskinesia (n=11), speech disorder (n=9), and epilepsy (n=10). The extent of resection was gross total for 91.36% patients, subtotal for 7.41%, and partial for 1.23%. No deaths occurred 30 days post-operation. Intracranial haemorrhage occurred in 2 patients, seizures in 5 patients, and intracranial infections in 3 patients. There was no significant difference between preoperative and postoperative Karnofsky Performance Status scores (P>0.05). There were no significant changes in postoperative neurological function in 50 patients. Symptoms improved in 24 patients. Three patients exhibited motor dysfunction, 2 exhibited speech deficits, and 2 exhibited sensory deficits. The average duration of hospitalization was 6.89±2.66 days. The shortest survival time was 4 months, the longest survival time was 26 months, and the median survival time was 12 months.Conclusions: Awake craniotomy using multimodal techniques such as neuronavigation, intraoperative ultrasound, electrophysiology, and tumour fluorescence during an operation can maximize safety during the cerebral glioblastoma resection, thus protecting brain function and improving surgical efficacy and patients’ postoperative quality of life.
Skeletal muscle loss in the postoperative acute phase after esophageal cancer surgery as a new prognostic factor
Authors: Maeda Naoaki , Shirakawa Yasuhiro , Tanabe Shunsuke , Sakurama Kazufumi , Noma Kazuhiro , Fujiwara Toshiyoshi 
Published: February 2020

Abstract
Background: The postoperative survival rate of patients with esophageal squamous cell carcinoma (ESCC) remains poor compared with other gastrointestinal cancers. We hypothesized that skeletal muscle loss (SML) in the postoperative acute phase might be a new predictor for long-term prognosis after highly invasive surgery such as ESCC surgery.Methods: The following items were retrospectively investigated. First, whether SML occurred in the postoperative acute phase of ESCC was verified. Second, the preoperative and intraoperative factors involved in SML in the postoperative acute phase of ESCC were investigated. Then, whether SML in the postoperative acute phase affected long-term prognosis was examined. The medical records of consecutive patients who underwent radical esophagectomy for ESCC were retrospectively reviewed; 72 cases were eligible for this study.Results: There was already a significant difference between the total psoas major muscle mass index (TPI) of the acute phase up to 3 days after surgery and the preoperative baseline TPI. The psoas muscle loss index (PMLI) was significantly milder in cases with less blood loss during surgery and in cases that underwent thoracoscopic esophagectomy than in cases that underwent open esophagectomy. The three-year overall survival rate was significantly different between the PMLI severe group and the PMLI mild group.Conclusion: SML occurred even in the postoperative acute phase. Furthermore, it is very significant that SML in the postoperative acute phase of ESCC surgery is involved in the long-term prognosis.