bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative opioid use in patients undergoing shoulder surgery
Authors: Nadarajah Vidushan , Meredith Sean J , Jauregui Julio J , Smuda Michael P , Medina Shaun , Gilotra Mohit N , Hasan S Ashfaq , Henn R Frank
Published: October 2019

Background

Opioids are commonly used to manage pain from acute injury or chronic degenerative diseases. The objective of this study was to assess the prevalence of preoperative opioid use in patients undergoing shoulder surgery and the clinical factors associated with preoperative opioid use.

Methods

This was an analytical cross-sectional study of 175 patients undergoing shoulder surgery at an urban hospital from June 2015 to June 2017. Multivariable regression models were used to determine independent associations.

Results

Fifty-three patients reported preoperative opioid use, which was significantly associated with primary procedure performed (Current Procedural Terminology [CPT]), higher body mass index (BMI), unemployment, lower income, smoking, higher American Society of Anesthesiologists score, greater number of previous surgeries, higher comorbidity burden, and decreased expectations to exercise and do recreational activities (p < 0.05). Preoperative opioid use was independently associated with worse scores on the: Numeric Pain Scale, ASES, IPAQ, and PROMIS domains of Physical Function, Pain Interference, and Social Satisfaction (p < 0.05).

Conclusion

More than one in four patients reported preoperative opioid use. Several health measures, including worse pain, function, and social satisfaction were independently associated with preoperative opioid use. These findings suggest that orthopaedic surgeons need to identify patients using opioids preoperatively in order to effectively establish and execute a plan for pain management, which may include weaning off opioids prior to surgery, managing psychological distress, and optimizing coping strategies. Level of Evidence: III.
Diagnosing and Preventing Hearing Loss in the Genomic Age
Authors: McDermott John H. , Molina-Ramírez Leslie P , Bruce Iain A , Mahaveer Ajit , Turner Mark , Miele Gino , Body Richard , Mahood Rachel , Ulph Fiona , MacLeod Rhona , Harvey Karen , Booth Nicola , Demain Leigh A. M. , Wilson Paul , Black Graeme C. , Morton Cynthia C. , Newman William G
Published: October 2019

Over the past two decades, significant technological advances have facilitated the identification of hundreds of genes associated with hearing loss. Variants in many of these genes result in severe congenital hearing loss with profound implications for the affected individual and their family. This review collates these advances, summarizing the current state of genomic knowledge in childhood hearing loss. We consider how current and emerging genetic technologies have the potential to alter our approach to the management and diagnosis of hearing loss. We review approaches being taken to ensure that these discoveries are used in clinical practice to detect genetic hearing loss as soon as possible to reduce unnecessary investigations, provide information about reproductive risks, and facilitate regular follow-up and early treatment. We also highlight how rapid sequencing technology has the potential to identify children susceptible to antibiotic-induced hearing loss and how this adverse reaction can be avoided.
Racial disparities in treatment patterns and outcomes among patients with multiple myeloma: a SEER-Medicare analysis
Authors: Ailawadhi Sikander , Parikh Kejal , Abouzaid Safiya , Zhou Zhou , Tang Wenxi , Clancy Zoe , Cheung Claudia , Zhou Zheng-Yi , Xie Jipan
Published: October 2019

The objective of the study was to assess racial disparities in the treatment and outcomes among white, African American, and Hispanic patients with multiple myeloma (MM). Patients with an MM diagnosis from the Surveillance Epidemiology and End Results (SEER)–Medicare (2007-2013) database were included. Continuous Medicare enrollment for 6 months before (baseline) and after MM diagnosis was required unless death occurred. Time from MM diagnosis to novel therapy initiation and autologous stem cell transplant (ASCT), overall survival (OS), and MM-specific survival (MSS) was evaluated. Unadjusted and multivariable regressions compared African Americans and Hispanics vs whites. Trends of novel therapy and ASCT use across MM diagnosis years were assessed using linear regression models. The study included 3504 whites, 858 African Americans, and 468 Hispanics. African Americans and Hispanics had a longer time from MM diagnosis to novel therapy initiation vs whites (median: 5.2 and 4.6 vs 2.7 months, respectively). All cohorts had an increasing trend of novel therapy initiation within 6 months of MM diagnosis, particularly whites (all P < .05). Median MSS was significantly longer for African Americans (5.4 years) than whites (4.5 years; P < .05), and was comparable for Hispanics and whites. Median OS was similar overall (2.6-2.8 years). ASCT rate within 1 year of MM diagnosis rose among whites and African Americans (P < .05), but not Hispanics, who were less likely to receive ASCT vs whites. Significant variations in novel therapy and ASCT use were observed among different racial/ethnic groups with MM. Although OS was similar, both African Americans and Hispanics may not be fully benefitting from the introduction of novel therapies, as they receive them later than whites.
BCL2L1 is associated with γ-globin gene expression
Authors: Dai Yan , Shaikho Elmutaz M. , Perez Jessica , Wilson Carolyn A. , Liu Lesley Y. , White Mitchell R. , Farrell John J. , Chui David H. K. , Sebastiani Paola , Steinberg Martin H.
Published: October 2019

Key Points

BCL2L1 is associated with HbF gene activation.
Systems biology and big data in asthma and allergy: recent discoveries and emerging challenges
Authors: Tang Howard H.F. , Sly Peter D. , Holt Patrick G. , Holt Kathryn E. , Inouye Michael
Published: October 2019

Asthma is a common condition caused by immune and respiratory dysfunction, and it is often linked to allergy. A systems perspective may prove helpful in unravelling the complexity of asthma and allergy. Our aim is to give an overview of systems biology approaches used in allergy and asthma research. Specifically, we describe recent “omic”-level findings, and examine how these findings have been systematically integrated to generate further insight.

Current research suggests that allergy is driven by genetic and epigenetic factors, in concert with environmental factors such as microbiome and diet, leading to early-life disturbance in immunological development and disruption of balance within key immuno-inflammatory pathways. Variation in inherited susceptibility and exposures causes heterogeneity in manifestations of asthma and other allergic diseases. Machine learning approaches are being used to explore this heterogeneity, and to probe the pathophysiological patterns or “endotypes” that correlate with subphenotypes of asthma and allergy. Mathematical models are being built based on genomic, transcriptomic and proteomic data to predict or discriminate disease phenotypes, and to describe the biomolecular networks behind asthma.

The use of systems biology in allergy and asthma research is rapidly growing, and has so far yielded fruitful results. However, the scale and multidisciplinary nature of this research means that it is accompanied by new challenges. Ultimately, it is hoped that systems medicine, with its integration of omics data into clinical practice, can pave the way to more precise, personalised and effective management of asthma.
Peripheral blood leukocyte telomere length is associated with survival of sepsis patients
Authors: Liu Shuo , Wang Chunxue , Green Gary , Zhuo Hanjing , Liu Kathleen D. , Kangelaris Kirsten N. , Gomez Antonio , Jauregui Alejandra , Vessel Kathryn , Ke Serena , Hendrickson Carolyn , Matthay Michael A. , Calfee Carolyn S. , Ware Lorraine B. , Wolters Paul J.
Published: October 2019

Shorter peripheral blood leukocyte (PBL) telomere length (TL) has been associated with poor outcomes in various chronic lung diseases. Whether PBL-TL is associated with survival from critical illness was tested in this study.

We analysed data from a prospective observational cohort study of 937 critically ill patients at Vanderbilt University Medical Center (VUMC). PBL-TL was measured using quantitative PCR of DNA isolated from PBLs. Findings were validated in an independent cohort of 394 critically ill patients with sepsis admitted to the University of California San Francisco (UCSF).

In the VUMC cohort, shorter PBL-TL was associated with worse 90-day survival (adjusted hazard ratio (aHR) 1.3, 95% CI 1.1–1.6 per 1 kb TL decrease; p=0.004); in subgroup analyses, shorter PBL-TL was associated with worse 90-day survival for patients with sepsis (aHR 1.5, 95% CI 1.2–2.0 per 1 kb TL decrease; p=0.001), but not trauma. Although not associated with development of acute respiratory distress syndrome (ARDS), among ARDS subjects, shorter PBL-TL was associated with more severe ARDS (OR 1.7, 95% CI 1.2–2.5 per 1 kb TL decrease; p=0.006). The associations of PBL-TL with survival (adjusted HR 1.6, 95% CI 1.2–2.1 per 1 kb TL decrease; p=0.003) and risk for developing severe ARDS (OR 2.5, 95% CI 1.1–6.3 per 1 kb TL decrease; p=0.044) were validated in the UCSF cohort.

Short PBL-TL is strongly associated with worse survival and more severe ARDS in critically ill patients, especially patients with sepsis. These findings suggest that telomere dysfunction may contribute to outcomes from critical illness.
Sarcomatoid carcinoma presenting as cancers of unknown primary: a clinicopathological portrait
Authors: Huey Ryan W. , Makawita Shalini , Xiao Lianchun , Matamoros Aurelio , Estrella Jeannelyn S. , Overman Michael J. , Varadhachary Gauri R. , Raghav Kanwal
Published: October 2019

Background

Sarcomatoid carcinoma of unknown primary (SCUP) is a rare entity of either poorly differentiated carcinoma with sarcoma-like differentiation or a true mixed lineage neoplasm. Limited data regarding clinicopathological profile and management exists.

Methods

We retrospectively reviewed the MD Anderson Cancer of Unknown Primary database and tumor registry to identify 48 SCUP patients between 2001 and 2017. Patient characteristics, pathology, molecular diagnostics, treatments, and outcomes were obtained. Kaplan-Meier method was used to estimate overall survival (OS) and compared using log rank test.

Results

Median age at diagnosis was 59 years (range 27–86). Majority of patients were female (58%) and presented with ≥3 metastatic sites (52%), commonly lymph node (50%), bone (42%), lung (27%), and liver (21%). First line treatment included chemotherapy (35%), surgery (27%), and radiation (24%). Gemcitabine and docetaxel (18%) was the most common chemotherapy regimen. Median OS for entire cohort was 11 months (95% CI: 5.6 to 16.4). Poor performance status (PS), > 1 metastatic site, elevated lactate dehydrogenase (LDH), and high neutrophil-to-lymphocyte ratio (NLR) were significantly associated with worse OS on univariate analyses. On multivariate analyses, poor PS (HR 8.7; 95%CI: 3.0–25.0; p <  0.001) and high NLR (HR 3.4; 95%CI: 1.3–8.8; p = 0.011) emerged as independent prognostic factors for OS.

Conclusions

SCUP is a rare presentation with an aggressive clinical course and limited survival. Diagnosis is difficult to make and requires careful review and synthesis of histology, immunohistochemistry, and molecular diagnostics. Chemotherapy resistance remains a challenge. Early mutational profiling is warranted, and clinical trial participation should be encouraged for this subset.
Detection of large rearrangements in a hereditary pan-cancer panel using next-generation sequencing
Authors: Mancini-DiNardo Debora , Judkins Thaddeus , Kidd John , Bernhisel Ryan , Daniels Courtney , Brown Krystal , Meek Kirsten , Craft Jonathan , Holladay Jayson , Morris Brian , Roa Benjamin B.
Published: October 2019

Background

Healthcare providers increasingly use information about pathogenic variants in cancer predisposition genes, including sequence variants and large rearrangements (LRs), in medical management decisions. While sequence variant detection is typically robust, LRs can be difficult to detect and characterize and may be underreported as a cause for hereditary cancer risk. This report describes the outcomes of hereditary cancer genetic testing using a comprehensive strategy that employs next-generation sequencing (NGS) for LR detection, coupled with LR confirmation using repeat hybrid capture NGS, microarray comparative genomic hybridization (microarray-CGH), and/or multiplex ligation-dependent probe amplification (MLPA).

Methods

Sequencing and LR analysis were conducted in a consecutive series of 376,159 individuals who received clinical testing with a hereditary pan-cancer gene panel from September 2013 through May 2017. NGS dosage analysis was used to evaluate potential deletions or duplications, with controls in place to exclude pseudogene reads. Samples positive for a putative LR based on NGS were confirmed using a comprehensive approach that included targeted microarray-CGH and/or MLPA analysis, with further examination as needed to ascertain the nature of the LR.

Results

A total of 3461 LRs were identified and classified as a deleterious mutation (DM), suspected deleterious mutation (SDM) or variant of uncertain significance. Pathogenic LRs (DM/SDM) accounted for the majority of LRs (67.7%), the largest proportion of which were deletions (86.1%), followed by duplications (11.3%), insertions (1.8%), triplications (0.5%), and inversions (0.3%). Several cases presented illustrate that the laboratory approach employed here can ensure consistent identification and accurate characterization of LRs. In the absence of this comprehensive testing strategy, 9% of LRs identified in this testing population might have been missed, potentially leading to inappropriate medical management in as many as 210 individuals referred for hereditary cancer testing.

Conclusions

These data show that copy number analysis using NGS coupled with confirmatory testing reliably detects and characterizes LRs. Further, LRs comprise a substantial proportion (7.2%) of pathogenic variants identified by the test. A robust and accurate LR identification strategy is an essential component of a high-quality genetic testing program, enabling clinicians to optimize patient medical management decisions.
Protein phosphatase 2A (PP2A): a key phosphatase in the progression of chronic obstructive pulmonary disease (COPD) to lung cancer
Authors: Nader Cassandra P. , Cidem Aylin , Verrills Nicole M. , Ammit Alaina J.
Published: October 2019

Lung cancer (LC) has the highest relative risk of development as a comorbidity of chronic obstructive pulmonary disease (COPD). The molecular mechanisms that mediate chronic inflammation and lung function impairment in COPD have been identified in LC. This suggests the two diseases are more linked than once thought. Emerging data in relation to a key phosphatase, protein phosphatase 2A (PP2A), and its regulatory role in inflammatory and tumour suppression in both disease settings suggests that it may be critical in the progression of COPD to LC. In this review, we uncover the importance of the functional and active PP2A holoenzyme in the context of both diseases. We describe PP2A inactivation via direct and indirect means and explore the actions of two key PP2A endogenous inhibitors, cancerous inhibitor of PP2A (CIP2A) and inhibitor 2 of PP2A (SET), and the role they play in COPD and LC. We explain how dysregulation of PP2A in COPD creates a favourable inflammatory micro-environment and promotes the initiation and progression of tumour pathogenesis. Finally, we highlight PP2A as a druggable target in the treatment of COPD and LC and demonstrate the potential of PP2A re-activation as a strategy to halt COPD disease progression to LC. Although further studies are required to elucidate if PP2A activity in COPD is a causal link for LC progression, studies focused on the potential of PP2A reactivating agents to reduce the risk of LC formation in COPD patients will be pivotal in improving clinical outcomes for both COPD and LC patients in the future.
Induction of LEF1 by MYC activates the WNT pathway and maintains cell proliferation
Authors: Hao Yi-Heng , Lafita-Navarro M. Carmen , Zacharias Lauren , Borenstein-Auerbach Nofit , Kim Min , Barnes Spencer , Kim Jiwoong , Shay Jerry , DeBerardinis Ralph J. , Conacci-Sorrell Maralice
Published: October 2019

Background

While regulated WNT activity is required for normal development and stem cell maintenance, mutations that lead to constitutive activation of the WNT pathway cause cellular transformation and drive colorectal cancer. Activation of the WNT pathway ultimately leads to the nuclear translocation of β-catenin which, in complex with TCF/LEF factors, promotes the transcription of genes necessary for growth. The proto-oncogene MYC is one of the most critical genes activated downstream the WNT pathway in colon cancer. Here, we investigate the converse regulation of the WNT pathway by MYC.

Methods

We performed RNA-seq analyses to identify genes regulated in cells expressing MYC. We validated the regulation of genes in the WNT pathway including LEF1 by MYC using RT-qPCR, Western blotting, and ChIP-seq. We investigated the importance of LEF1 for the viability of MYC-expressing cells in in fibroblasts, epithelial cells, and colon cells. Bioinformatic analyses were utilized to define the expression of MYC-regulated genes in human colon cancer and metabolomics analyses were used to identify pathways regulated by LEF1 in MYC expressing cells.

Results

MYC regulates the levels of numerous WNT-related genes, including the β-catenin co-transcription factor LEF1. MYC activates the transcription of LEF1 and is required for LEF1 expression in colon cancer cells and in primary colonic cells transformed by APC loss of function, a common mutation in colon cancer patients. LEF1 caused the retention of β-catenin in the nucleus, leading to the activation of the WNT pathway in MYC-expressing cells. Consequently, MYC-expressing cells were sensitive to LEF1 inhibition. Moreover, we describe two examples of genes induced in MYC-expressing cells that require LEF1 activity: the peroxisome proliferator activated receptor delta (PPARδ) and the Acyl CoA dehydrogenase 9 (ACAD9).

Conclusions

We demonstrated that MYC is a transcriptional regulator of LEF1 in colonic cells. Our work proposes a novel pathway by which MYC regulates proliferation through activating LEF1 expression which in turn activates the WNT pathway.

Graphical Abstract
Lack of hepatic apoE does not influence early Aβ deposition: observations from a new APOE knock-in model
Authors: Huynh Tien-Phat V. , Wang Chao , Tran Ainsley C. , Tabor G. Travis , Mahan Thomas E. , Francis Caroline M. , Finn Mary Beth , Spellman Rebecca , Manis Melissa , Tanzi Rudolph E. , Ulrich Jason D. , Holtzman David M.
Published: October 2019

Background

The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer disease (AD). ApoE is produced by both astrocytes and microglia in the brain, whereas hepatocytes produce the majority of apoE found in the periphery. Studies usingAPOEknock-in and transgenic mice have demonstrated a strong isoform-dependent effect of apoE on the accumulation of amyloid-β (Aβ) deposition in the brain in the form of both Aβ-containing amyloid plaques and cerebral amyloid angiopathy. However, the specific contributions of different apoE pools to AD pathogenesis remain unknown.

Methods

We have begun to address these questions by generating new lines ofAPOEknock-in (APOE-KI) mice (ε2/ε2, ε3/ε3, and ε4/ε4) where the exons in the coding region ofAPOEare flanked by loxP sites, allowing for cell type-specific manipulation of gene expression. We assessed these mice both alone and after crossing them with mice with amyloid deposition in the brain. Using biochemical and histological methods. We also investigated how removal ofAPOEexpression from hepatocytes affected cerebral amyloid deposition.

Results

As in otherAPOEknock-in mice, apoE protein was present predominantly in astrocytes in the brain under basal conditions and was also detected in reactive microglia surrounding amyloid plaques. Primary cultured astrocytes and microglia from theAPOE-KI mice secreted apoE in lipoprotein particles of distinct size distribution upon native gel analysis with microglial particles being substantially smaller than the HDL-like particles secreted by astrocytes. Crossing of APP/PS1 transgenic mice to the differentAPOE-KI mice recapitulated the previously described isoform-specific effect (ε4 > ε3) on amyloid plaque and Aβ accumulation. Deletion ofAPOEin hepatocytes did not alter brain apoE levels but did lead to a marked decrease in plasma apoE levels and changes in plasma lipid profile. Despite these changes in peripheral apoE and on plasma lipids, cerebral accumulation of amyloid plaques in APP/PS1 mice was not affected.

Conclusions

Altogether, these new knock-in strains offer a novel and dynamic tool to study the role ofAPOEin AD pathogenesis in a spatially and temporally controlled manner.
MEIS2C and MEIS2D promote tumor progression via Wnt/β-catenin and hippo/YAP signaling in hepatocellular carcinoma
Authors: Guan Lei , Li Ting , Ai Nanping , Wang Wei , He Bing , Bai Yanxia , Yu Zhaocai , Li Mingyue , Dong Shanshan , Zhu Qingge , Ding Xiao Xiao , Zhang Shiming , li Ming , Tang Guangbo , Xia Xiaochun , Zhao Jing , lin Song , yao Shi , zhang Lei , chen Geng , Liu Fang-E , Li Xinyuan , Zhang Huqin
Published: October 2019

Background

MEIS2 has been identified as one of the key transcription factors in the gene regulatory network in the development and pathogenesis of human cancers. Our study aims to identify the regulatory mechanisms of MEIS2 in hepatocellular carcinoma (HCC), which could be targeted to develop new therapeutic strategies.

Methods

The variation of MEIS2 levels were assayed in a cohort of HCC patients. The proliferation, clone-formation, migration, and invasion abilities of HCC cells were measured to analyze the effects of MEIS2C and MEIS2D (MEIS2C/D) knockdown with small hairpin RNAs in vitro and in vivo. Chromatin immunoprecipitation (ChIP) was performed to identify MEIS2 binding site. Immunoprecipitation and immunofluorescence assays were employed to detect proteins regulated by MEIS2.

Results

The expression of MEIS2C/D was increased in the HCC specimens when compared with the adjacent noncancerous liver (ANL) tissues. Moreover, MEIS2C/D expression negatively correlated with the prognosis of HCC patients. On the other hand, knockdown of MEIS2C/D could inhibit proliferation and diminish migration and invasion of hepatoma cells in vitro and in vivo. Mechanistically, MESI2C activated Wnt/β-catenin pathway in cooperation with Parafibromin (CDC73), while MEIS2D suppressed Hippo pathway by promoting YAP nuclear translocation via miR-1307-3p/LATS1 axis. Notably, CDC73 could directly either interact with MEIS2C/β-catenin or MEIS2D/YAP complex, depending on its tyrosine-phosphorylation status.

Conclusions

Our studies indicate that MEISC/D promote HCC development via Wnt/β-catenin and Hippo/YAP signaling pathways, highlighting the complex molecular network of MEIS2C/D in HCC pathogenesis. These results suggest that MEISC/D may serve as a potential novel therapeutic target for HCC.
Improvement of corn stover fuel properties via hydrothermal carbonization combined with surfactant
Authors: Tu Ren , Sun Yan , Wu Yujian , Fan Xudong , Wang Jiamin , Cheng Shuchao , Jia Zhiwen , Jiang Enchen , Xu Xiwei
Published: October 2019

Background

Biomass fuel has been used to supply heat or crude materials in industry to replace the traditional fossil fuel which was one of the chief causes of climate warming. However, the large-scale utilization of biomass fuel was restricted due to the low density and high hydrophilicity of biomass, which causes the problem of transportation and storage. Therefore, pelletization of biomass was used to improve its fuel density. At present, the biomass pellet was widely used to supply heat, gas or electricity generation via gasification, which supplied clean and sustainable energy for industry. However, the energy consumption during pelletization and high hydrophilicity of pellets were still the problem for the large-scale application of biomass pellet. In this study, hydrothermal carbonization and surfactant played the role of permeation, adsorption and wetting in the solution, which was expected to improve the fuel properties and pelletization effectivity of corn stover.

Results

In the article, surfactant (PEG400, Span80, SDBS) was chosen to be combined with wet torrefaction to overcome the drawbacks and improve the pelletization and combustion properties of Corn stover (CS). Especially, hydrothermal carbonization (HTC) combined with surfactant improves the yield of solid products and reduces the ash content of solid product, which was beneficial for reducing the ashes of furnace during gasification. Meanwhile, surfactant promotes the formation of pseudo-lignin and the absorption for oil with low O and high C during HTC, which improves the energy density of solid product. Furthermore, the oil in solid product plays the role of lubricant and binder, which reduces the negative effect of high energy consumption, low bulk density and weak pellets strength caused by HTC during pelletization. HTC combined with surfactant improved the hydrophobicity of pellet as well as grindability due to the modification of solid product. Moreover, surfactant combined with HTC improved the combustion characteristic of solid product such as ignition and burning temperature as well as kinetic parameters due to the bio-oil absorbed and the improvement of surface and porosity.

Conclusions

The study supplied a new, less-energy intensive and effective method to improve the pelletization and combustion properties of corn stover via hydrothermal carbonization combined with surfactant, and provided a promising alternative fuel from corn stover .
Catalytic valorization of hardwood for enhanced xylose-hydrolysate recovery and cellulose enzymatic efficiency via synergistic effect of Fe3+ and acetic acid
Authors: Huang Kaixuan , Das Lalitendu , Guo Jianming , Xu Yong
Published: October 2019

Background

Poplars are considered suitable dedicated energy crops, with abundant cellulose and hemicellulose, and huge surplus biomass potential in China. Xylan, the major hemicellulosic component, contributes to the structural stability of wood and represents a tremendous quantity of biobased chemicals for fuel production. Monomeric xylose conversion to value-added chemicals such as furfural, xylitol, and xylonic acid could greatly improve the economics of pulp-paper industry and biorefinery. Acetic acid (HAc) is used as a friendly and recyclable selective catalyst amenable to xylan degradation and xylooligosaccharides production from lignocellulosic materials. However, HAc catalyst usually works much feebly at inert woods than agricultural straws. In this study, effects of different iron species in HAc media on poplar xylan degradation were systematically compared, and a preferable Fe3+-assisted HAc hydrolysis process was proposed for comparable xylose-hydrolysate recovery (XHR) and enzymatic saccharification of cellulose.

Results

In presence of 6.5% HAc with 0.17–0.25 wt% Fe3+, xylose yield ranged between 72.5 and 73.9%. Additionally, pretreatment was effective in poplar delignification, with a lignin yield falling between 38.6 and 42.5%. Under similar conditions, saccharification efficiency varied between 60.3 and 65.9%. Starting with 100 g poplar biomass, a total amount of 12.7–12.8 g of xylose and 18.8–22.8 g of glucose were harvested from liquid streams during the whole process of Fe3+-HAc hydrolysis coupled with enzymatic saccharification. Furthermore, the enhancement mechanism of Fe3+ coupled with HAc was investigated after proof-of-concept experiments. Beechwood xylan and xylose were treated under the same condition as poplar sawdust fractionation, giving understanding of the effect of catalysts on the hydrolysis pathway from wood xylan to xylose and furfural by Fe3+-HAc.

Conclusions

The Fe3+-assisted HAc hydrolysis process was demonstrated as an effective approach to the wood xylose and other monosaccharides production. Synergistic effect of Lewis acid site and aqueous acetic acid provided a promising strategy for catalytic valorization of poplar biomass.
Hemimethylation of CpG dyads is characteristic of secondary DMRs associated with imprinted loci and correlates with 5-hydroxymethylcytosine at paternally methylated sequences
Authors: Nechin Julianna , Tunstall Emma , Raymond Naideline , Hamagami Nicole , Pathmanabhan Chris , Forestier Samantha , Davis Tamara L.
Published: October 2019

Background

In mammals, the regulation of imprinted genes is controlled by differential methylation at imprinting control regions which acquire parent of origin-specific methylation patterns during gametogenesis and retain differences in allelic methylation status throughout fertilization and subsequent somatic cell divisions. In addition, many imprinted genes acquire differential methylation during post-implantation development; these secondary differentially methylated regions appear necessary to maintain the imprinted expression state of individual genes. Despite the requirement for both types of differentially methylated sequence elements to achieve proper expression across imprinting clusters, methylation patterns are more labile at secondary differentially methylated regions. To understand the nature of this variability, we analyzed CpG dyad methylation patterns at both paternally and maternally methylated imprinted loci within multiple imprinting clusters.

Results

We determined that both paternally and maternally methylated secondary differentially methylated regions associated with imprinted genes display high levels of hemimethylation, 29–49%, in comparison to imprinting control regions which exhibited 8–12% hemimethylation. To explore how hemimethylation could arise, we assessed the differentially methylated regions for the presence of 5-hydroxymethylcytosine which could cause methylation to be lost via either passive and/or active demethylation mechanisms. We found enrichment of 5-hydroxymethylcytosine at paternally methylated secondary differentially methylated regions, but not at the maternally methylated sites we analyzed in this study.

Conclusions

We found high levels of hemimethylation to be a generalizable characteristic of secondary differentially methylated regions associated with imprinted genes. We propose that 5-hydroxymethylcytosine enrichment may be responsible for the variability in methylation status at paternally methylated secondary differentially methylated regions associated with imprinted genes. We further suggest that the high incidence of hemimethylation at secondary differentially methylated regions must be counteracted by continuous methylation acquisition at these loci.
Ultrasound-guided peripheral venous cannulation in critically ill patients: a practical guideline
Authors: Blanco Pablo
Published: October 2019

Background

Up to one-third of critically ill patients have difficult intravenous access (DIVA). This occurs often in obese patients, those with generalized edemas or in patients with previous venous cannulations. In DIVA patients, the conventional technique often fails. In contrast, ultrasound-guided cannulation has demonstrated a high success rate, improving patient satisfaction and even a reduction in the need of central venous lines. However, a high rate of premature catheter failure has been shown in cannulations performed by ultrasound guidance and thus a comprehensive knowledge of several aspects related to this procedure is mandatory to improve cannulation success, avoid complications and lengthen the survival of the catheter.

Main text

Several practical issues related to peripheral venous cannulation are described: peripheral venous anatomy, vein size and catheter selection, distance from skin to vein, insertion angle and selection of the catheter length, cannulation technique itself (out-of-plane or in-plane) and checking catheter position.

Conclusion

Key concepts regarding ultrasound-guided peripheral vein cannulation should be well known for practitioners, aiding in improving cannulation success and catheter dwell time, and avoiding complications.
Osteogenic potential of induced pluripotent stem cells from human adipose-derived stem cells
Authors: Mao Shih-Hsuan , Chen Chih-Hao , Chen Chien-Tzung
Published: October 2019

Background

Bone regeneration is a crucial and challenging issue in clinical practice. Bone tissue engineering (BTE) with an optimal cell source may provide an ideal strategy for the reconstruction of bone defects. This study examined whether induced pluripotent stem cells (iPSCs) derived from adipose-derived stem cells (ASCs) could act as an osteogenic substitute and whether these ASC-iPSCs yield more new bone formation than ASCs in hydrogel scaffolds.

Methods

ASC-iPSCs were reprogrammed from ASCs through a retroviral system. ASCs were harvested and isolated from adipose tissue of humans. An aliquot of cell suspension (1 × 106 cells/mL) was seeded directly onto the nHAP-gelatin cryogel scaffolds. Nude mice back implantation of cell-seeded scaffolds was designed for in vivo comparison of osteogenic potentials between ASCs and ASC-iPSCs. Samples were harvested 4 and 8 weeks after implantation for further analysis based on histology and RT-PCR.

Results

ASC-iPSCs were successfully obtained from human adipose-derived stem cells. PCR results also showed that specific genes of iPSCs with the ability to cause the differentiation of cells into the three germ layers were expressed. In our in vivo experiments, iPSCs were subcutaneously injected into nude mice to induce teratoma formation. The morphology of the three germ layers was confirmed by histological staining. ASC is an essential cell source for BTE with benefits of high volume and less-invasive acquisition. With additional transforming Yamanaka factors, ASC-iPSCs showed higher osteogenic differentiation and elevated expression of collagen type I (Col I), osteocalcin (OCN), alkaline phosphate (ALP), and runt-related transcription factor 2 (RunX-2).

Conclusions

This report suggests that ASC-iPSCs could be a superior cell source in BTE with better osteogenic differentiation efficacy for future clinical applications.
Antioxidants inhibit cell senescence and preserve stemness of adipose tissue-derived stem cells by reducing ROS generation during long-term in vitro expansion
Authors: Liao Naishun , Shi Yingjun , Zhang Cuilin , Zheng Youshi , Wang Yingchao , Zhao Bixing , Zeng Yongyi , Liu Xiaolong , Liu Jingfeng
Published: October 2019

Background

Adipose tissue-derived mesenchymal stem cells (ADSCs) are promising candidates for regenerative medicine. However, long-term in vitro passaging leads to stemness loss and cell senescence of ADSCs, resulting in failure of ADSC-based therapy.

Methods

In this study, ADSCs were treated with low dose of antioxidants (reduced glutathione and melatonin) with anti-aging and stem cell protection properties in the in vitro passaging, and the cell functions including stem cell senescence, cell migration, cell multidirectional differentiation potential, and ROS content were carefully analyzed.

Results

We found that GSH and melatonin could maintain ADSC cell functions through reducing cell senescence and promoting cell migration, as well as by preserving stemness and multidirectional differentiation potential, through inhibiting ROS generation during long-term expansion of ADSCs.

Conclusions

Our results suggested that antioxidant treatment could efficiently prevent the dysfunction and preserve cell functions of ADSCs after long-term passaging, providing a practical strategy to facilitate ADSC-based therapy.
Anti-inflammatory and vasculogenic conditioning of peripheral blood mononuclear cells reinforces their therapeutic potential for radiation-injured salivary glands
Authors: I Takashi , Sumita Yoshinori , Yoshida Takako , Honma Ryo , Iwatake Mayumi , Raudales Jorge Luis Montenegro , Shizuno Tomoko , Kuroshima Shinichiro , Masuda Haruchika , Seki Makoto , Tran Simon D. , Asahara Takayuki , Asahina Izumi
Published: October 2019

Background

There are currently no effective treatments available for patients with irreversible loss of salivary gland (SG) function caused by radiation therapy for head and neck cancer. In this study, we have developed an effective culture method to enhance the anti-inflammatory and vasculogenic phenotypes of peripheral blood mononuclear cells (PBMNCs) and investigated whether such effectively conditioned PBMNCs (E-MNCs) could regenerate radiation-injured SGs and ameliorate salivary secretory function in mice.

Methods

Mouse PBMNCs were expanded in primary serum-free culture with five vasculogenic proteins for 5 days, and then the resulting cells (E-MNCs) were analyzed for their characteristics. Subsequently, 5 × 104 E-MNCs (labeled with EGFP in some experiments) were injected intra-glandularly into a mouse model of radiation-injured atrophic submandibular glands. After 2–3 weeks, the submandibular glands were harvested, and then the injected E-MNCs were tracked. Four, 8, and 12 weeks after irradiation (IR), salivary outputs were measured to evaluate the recovery of secretory function, and the gland tissues were harvested for histological and gene expression analyses to clarify the effects of cell transplantation.

Results

The resulting E-MNCs contained an enriched population of definitive CD11b/CD206-positive (M2 macrophage-like) cells and showed anti-inflammatory and vasculogenic characteristics. Salivary secretory function in E-MNC-transplanted mice gradually recovered after 4 weeks post-irradiation (post-IR) and reached 3.8-fold higher than that of non-transplanted mice at 12 weeks. EGFP-expressing E-MNCs were detected in a portion of the vascular endothelium and perivascular gland tissues at 2 weeks post-IR, but mainly in some microvessels at 3 weeks. Between 4 and 12 weeks post-IR, mRNA expression and histological analyses revealed that E-MNC transplantation reduced the expression of inflammatory genes and increased the level of tissue-regenerative activities such as stem cell markers, cell proliferation, and blood vessel formation. At 12 weeks post-IR, the areas of acinar and ductal cells regenerated, and the glands had less fibrosis.

Conclusions

This effective conditioning of PBMNCs is a simple, rapid, and efficient method that provides a non-invasive source of therapeutic cells for regenerating radiation-injured atrophic SGs.
Towards the understanding of the enzymatic cleavage of polyisoprene by the dihaem-dioxygenase RoxA
Authors: Schmitt Georg , Birke Jakob , Jendrossek Dieter
Published: October 2019

Utilization of polyisoprene (natural rubber) as a carbon source bySteroidobacter cummioxidans35Y (previouslyXanthomonassp. strain 35Y) depends on the formation and secretion of rubber oxygenase A (RoxA). RoxA is a dioxygenase that cleaves polyisoprene to 12-oxo-4,8-dimethyl-trideca-4,8-diene-1-al (ODTD), a suitable growth substrate forS. cummioxidans. RoxA harbours two non-equivalent, spectroscopically distinguishable haem centres. A dioxygen molecule is bound to the N-terminal haem of RoxA and identifies this haem as the active site. In this study, we provide insights into the nature of this unusually stable dioxygen-haem coordination of RoxA by a re-evaluation of previously published together with newly obtained biophysical data on the cleavage of polyisoprene by RoxA. In combination with the meanwhile available structure of RoxA we are now able to explain several uncommon and previously not fully understood features of RoxA, the prototype of rubber oxygenases in Gram-negative rubber-degrading bacteria.
Sources and reservoirs of Staphylococcus capitis NRCS-A inside a NICU
Authors: Butin Marine , Dumont Yann , Monteix Alice , Raphard Aurane , Roques Christine , Martins Simoes Patricia , Picaud Jean-Charles , Laurent Frédéric
Published: October 2019

Background

The methicillin-resistant clone Staphylococcus capitis NRCS-A, involved in sepsis in neonatal intensive care units (NICUs) worldwide, is able to persist and spread in NICUs, suggesting the presence of reservoirs inside each setting. The purpose of the present study was to identify these reservoirs and to investigate the cycle of transmission of NRCS-A in one NICU.

Methods

In a single institution study, NRCS-A was sought in 106 consecutive vaginal samples of pregnant women to identify a potential source of NRCS-A importation into the NICU. Additionally NICU caregivers and environmental including incubators were tested to identify putative secondary reservoirs. Finally, the efficacy of disinfection procedure in the elimination of NRCS-A from incubators was evaluated.

Results

No S. capitis was isolated from vaginal samples of pregnant women. Three of the 21 tested caregivers (14%) carried S. capitis on their hands, but none remain positive after a five-day wash-out period outside NICU. Moreover, the clone NRCS-A persisted during six consecutive weeks in the NICU environment, but none of the sampled sites was constantly contaminated. Finally in our before/after disinfection study, all of 16 incubators were colonized before disinfection and 10 (62%) incubators remained colonized with NRCS-A after the disinfection procedure.

Conclusions

The partial ineffectiveness of incubators’ disinfection procedures is responsible for persistence of NRCS-A inside a NICU, and the passive hand contamination of caregivers could be involved in the inter-patient transmission of S. capitis.
HIF-1α contributes to Ang II-induced inflammatory cytokine production in podocytes
Authors: Huang Hao , Fan Yanqin , Gao Zhao , Wang Wei , Shao Ning , Zhang Lu , Yang Yingjie , Zhu Weifang , Chen Zhaowei , Hu Jijia , Ding Guohua
Published: October 2019

Background

Studies have indicated that changed expression of hypoxia-inducible factor-1α (HIF-1α) in epithelial cells from the kidney could affect the renal function in chronic kidney disease (CKD). As Angiotensin II (Ang II) is a critical active effector in the renin-angiotensin system (RAS) and was proved to be closely related to the inflammatory injury. Meanwhile, researchers found that Ang II could alter the expression of HIF-1α in the kidney. However, whether HIF-1α is involved in mediating Ang II-induced inflammatory injury in podocytes is not clear.

Methods

Ang II perfusion animal model were established to assess the potential role of HIF-1α in renal injury in vivo. Ang II stimulated podocytes to observe the corresponding between HIF-1α and inflammatory factors in vitro.

Results

The expression of inflammatory cytokines such as MCP-1 and TNF-α was increased in the glomeruli from rats treated with Ang II infusion compared with control rats. Increased HIF-1α expression in the glomeruli was also observed in Ang II-infused rats. In vitro, Ang II upregulated the expression of HIF-1α in podocytes. Furthermore, knockdown of HIF-1α by siRNA decreased the expression of MCP-1 and TNF-α. Moreover, HIF-1α siRNA significantly diminished the Ang II-induced overexpression of HIF-1α.

Conclusion

Collectively, our results suggest that HIF-1α participates in the inflammatory response process caused by Ang II and that downregulation of HIF-1α may be able to partially protect or reverse inflammatory injury in podocytes.
An analytical study of information extraction from unstructured and multidimensional big data
Authors: Adnan Kiran , Akbar Rehan
Published: October 2019

Process of information extraction (IE) is used to extract useful information from unstructured or semi-structured data. Big data arise new challenges for IE techniques with the rapid growth of multifaceted also called as multidimensional unstructured data. Traditional IE systems are inefficient to deal with this huge deluge of unstructured big data. The volume and variety of big data demand to improve the computational capabilities of these IE systems. It is necessary to understand the competency and limitations of the existing IE techniques related to data pre-processing, data extraction and transformation, and representations for huge volumes of multidimensional unstructured data. Numerous studies have been conducted on IE, addressing the challenges and issues for different data types such as text, image, audio and video. Very limited consolidated research work have been conducted to investigate the task-dependent and task-independent limitations of IE covering all data types in a single study. This research work address this limitation and present a systematic literature review of state-of-the-art techniques for a variety of big data, consolidating all data types. Recent challenges of IE are also identified and summarized. Potential solutions are proposed giving future research directions in big data IE. The research is significant in terms of recent trends and challenges related to big data analytics. The outcome of the research and recommendations will help to improve the big data analytics by making it more productive.
Impacts of fire severity and cattle grazing on early plant dynamics in old-growth Araucaria-Nothofagus forests
Authors: Arroyo-Vargas Paola , Fuentes-Ramírez Andres , Muys Bart , Pauchard Aníbal
Published: October 2019

Background

Fire has historically shaped the dynamics of Araucaria araucana-Nothofagus pumilio forests in the Andean region of South America. Nevertheless, human disturbances and stronger drought events have resulted in increased occurrence and severity of wildfires. Regardless of their conservation relevance, the initial response to fire of Araucaria-Nothofagus forests has not been well documented. Through this research we tested the hypothesis that plant composition of Araucaria-Nothofagus forest after fire will initially differ in its recovery depending on fire severity, but over time, plant similarity will increase among areas with different levels of fire severity. The study was carried out in old-growth Araucaria-Nothofagus forests in south-central Chile (38°S) that were burned in 2015. We studied vegetation response to three levels of fire severity (low (LS), moderate (MS) and high (HS) severity), also including an adjacent unburned forest (UN), which were assessed one, two and three years after fire. We also evaluated the impact of cattle on plant recovery after fire. We measured species richness, abundance, plant diversity and origin of all vascular plant species.

Results

Species richness and plant abundance responded differently to fire severity. Time-since-fire had a significant effect on plant richness and abundance. Plant composition within LS areas was similar to UN areas, but MS and HS areas were significantly less diverse compared to UN and LS. In absence of other major disturbances, similarity in plant composition tended to increase over time across the different levels of fire severity, becoming more similar to UN. We also found a synergetic effect of cattle and fire on species richness. This interaction promotes the establishment of non-native species and limits the recovery of native species following fire.

Conclusions

Fire severity had a significant impact on the plant community of old-growth Araucaria-Nothofagus forests, especially in areas of high fire severity, where the native tree N. pumilio was completely absent. Nevertheless, plant communities can recover gradually, depending on fire severity, time-since-fire, and the absence of cattle grazing. Management actions should include the exclusion of cattle within fire-affected areas and afforestation with N. pumilio in areas high fire severity due to its unsuccessful recruitment after fire.