bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intra-bone marrow co-transplantation of umbilical cord mesenchymal stem cells promotes the engraftment of umbilical cord blood stem cells in iron overload NOD/SCID mice
Authors: Huang Zhi , Xiao Yuhua , Chen Xiaomin , Li Huiping , Gao Jingyu , Zhang Xinyao , Feng Xiaoqin 
Published: May 2020

Abstract
Background: Iron overload aggravates the difficulty of umbilical cord blood stem cell engraftment and reduces the survival of patients undergoing hematopoietic stem cells (HSC) transplantation. Mesenchymal stem cells (MSC) have been implicated in playing a significant role in HSC engraftment. This study aimed to determine the effect of intra-bone marrow (IBM) co-transplantation of umbilical cord blood mononuclear cells (UCB-MNC) and mesenchymal stem cells (UC-MSC) on the engraftment and hematopoietic recovery in an iron overload hematopoietic microenvironment. Methods: The iron overload model was established by dose-escalation intraperitoneal injection of iron dextran in NOD/SCID mice. Iron deposition in the bone marrow, heart, and liver was examined using H&E staining. Serum levels of ferritin and iron status in the liver were measured. The iron overload NOD/SCID mice were sublethally irradiated and divided into four groups for transplantation: (1) control group, (2) IBM MSC+ group: IBM injection of combined UCB-MNC/UC-MSC, (3) IBM group: IBM injection of only UCB-MNC, and (4) IV group: intravenous injection of UCB-MNC. Six weeks after transplantation, the human CD45 + cells in the bone marrow were analyzed by flow cytometry. The semi-quantitative analysis of vascular endothelial growth factor (VEGF-a), osteopontin (OPN), and stromal cell-derived factor-1a (SDF-1a) were examined by immunohistochemistry staining (IHC). Results: The survival rate and the percentages of human CD45 + cells in bone marrow were highest in the IBM MSC+ group with statistical significance. In addition, the levels of VEGF-a, OPN, and SDF-1a in bone marrow were all significantly higher in the IBM MSC+ group than the other groups. Conclusion: IBM co-transplantation of UC-MSC might improve the engraftment of UCB-MNC in iron overload NOD/SCID mice. The increased expression of VEGF-a, OPN, and SDF-1a in the bone marrow may be involved in improving the hematopoietic microenvironment and promoting the implantation of human umbilical cord blood stem cells in the bone marrow with iron overload.
Clinical and molecular characteristics of mucosal signet-ring cell carcinoma in Helicobacter pylori-uninfected stomach
Authors: Kiso Mariko , Urabe Yuji , Ito Masanori , Masuda Kazuhiko , Boda Tomoyuki , Kotachi Takahiro , Hata Kosaku , Yorita Naoki , Nagasaki Naoko , Abduwali Madina , Hiyama Yuich , Oka Shiro , Tanaka Shinji , Chayama Kazuaki 
Published: May 2020

Abstract
Background: Gastric cancer develops even in Helicobacter pylori-uninfected patients and its typical histological feature is signet ring cell carcinoma (SRCC) within the mucosal layer. However, the biological characteristics of SRCC remain unclear. We aimed to clarify the pathological and genetic features of SRCC in Helicobacter pylori -uninfected patients.Methods: Seventeen Helicobacter pylori-uninfected patients with mucosal SRCCs were enrolled and their clinicopathological characteristics were compared with those of Helicobacter pylori-infected patients with mucosal SRCCs. Seven SRCCs without Helicobacter pylori infection, including two invasive SRCCs, and seven Helicobacter pylori-positive SRCCs were subjected to a genetic analysis using next-generation sequencing. Results: Helicobacter pylori-uninfected patients with mucosal SRCCs revealed male dominancy and a significantly higher prevalence of smokers among them as compared with the Helicobacter pylori-infected patients with SRCC. A CDH1 mutation (frame shift indel) was detected in one Helicobacter pylori-uninfected cancer not only in the mucosal SRCC but also in the invasive portion. A TP53 mutation was detected in one SRCC without Helicobacter pylori infection. In the control group, ARID1A and TP53 mutations were detected in one SRCC each. The C to A mutation, which is a characteristic smoking-induced mutation, was not found in any of the samples.Conclusions: Some SRCCs in Helicobacter pylori-uninfected patients may have a malignant potential similar to that of SRCCs in Helicobacter pylori-infected patients. Smoking is not a main carcinogenic factor for the development of SRCCs.
Characteristics of symptom in patients with hepatic cirrhosis of different etiologies
Authors: Guan Xin , Xing Fei , Wang Mengchun , Li Yan 
Published: May 2020

Abstract
Backgrounds: The complications of hepatic cirrhosis are responsible for death and hospitalization. We aimed to analyze the clinical characteristics in cirrhotic symptom according to etiology.Methods: A total of 1,573 admissions of decompensated hepatic cirrhosis in the hospital were enrolled between September 2014 and August 2019. We described the relationships between major symptoms and cirrhotic etiologies. We assessed the secondary hepatic encephalopathy for each cirrhotic etiology.Results: Among all complications, the constituent ratio of gastrointestinal hemorrhage was 37.87%, followed by ascites and jaundice with 23.70% and 11.40%, respectively. Gastrointestinal hemorrhage was more presented in hepatitis B and hepatitis C than in alcoholic cirrhosis (57.59%, 47.86% and 42.19%, p < 0.05). No significant difference was found between hepatitis B and hepatitis C for all symptoms. Jaundice was the major symptom in primary biliary cirrhosis and autoimmune cirrhosis. Alcoholic cirrhotic patients had a higher rate to develop secondary encephalopathy than other etiologies (13.51%, p < 0.05).Conclusions: Gastrointestinal hemorrhage was the main symptom for hospitalization in decompensated cirrhotic patients. Patients of hepatitis cirrhosis were more likely to have gastrointestinal hemorrhage than those of alcohol cirrhosis. Patients of alcohol cirrhosis were likely to develop a secondary encephalopathy following the presentation of other symptoms.
Dose- and time-dependent effects of hyaluronidase on structural cells and the extracellular matrix of the skin
Authors: Buhren Bettina Alexandra , Schrumpf Holger , Gorges Katharina , Reiners Oliver , Boelke Edwin , Fischer Jens W , Homey Bernhard , Gerber Peter Arne 
Published: May 2020

Abstract
BACKGROUNDHyaluronic acid (hyaluronan; HA) is an essential component of the extracellular matrix (ECM) of the skin. The HA-degrading enzyme hyaluronidase (HYAL) is critically involved in the HA-metabolism. Yet, only little information is available regarding the skin´s HA-HYAL interactions on the molecular and cellular levels.To analyze the dose- and time-dependent molecular and cellular effects of HYAL on structural cells and the HA-metabolism in the skin.METHODSChip-based, genome-wide expression analyses (Affymetrix® GeneChip PrimeView™ Human Gene Expression Array), quantitative real-time PCR analyses, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (DAB), and in vitro wound healing assays were performed to assess dose-dependent and time-kinetic effects of HA and HYAL (bovine hyaluronidase, Hylase Dessau) on normal human dermal fibroblasts (NHDF), primary human keratinocytes in vitro and human skin samples ex vivo.RESULTSGenome-wide expression analyses revealed an upregulation of HA synthases (HAS) up to 1.8-fold change in HA- and HYAL-treated NHDF. HA and HYAL significantly accelerated wound closure in an in vitro model for cutaneous wound healing. HYAL induced HAS1 and HAS2 mRNA gene expression in NHDF. Interestingly, low concentrations of HYAL (0.015 U/ml) resulted in a significantly higher induction of HAS compared to moderate (0.15 and 1.5 U/ml) and high concentrations (15 U/ml) of HYAL. This observation corresponded to increased concentrations of HA measured by ELISA in conditioned supernatants of HYAL-treated NHDF with the highest concentrations observed for 0.015 U/ml of HYAL. Finally, immunohistochemical analysis of human skin samples incubated with HYAL for up to 48 hrs ex vivo demonstrated that low concentrations of HYAL (0.015 U/ml) led to a pronounced accumulation of HA, whereas high concentrations of HYAL (15 U/ml) reduced dermal HA-levels.CONCLUSIONSHYAL is a bioactive enzyme that exerts multiple effects on the HA-metabolism as well as on the structural cells of the skin. Our results indicate that HYAL promotes wound healing and exerts a dose-dependent induction of HA-synthesis in structural cells of the skin. Herein, interestingly the most significant induction of HAS and HA were observed for the lowest concentration of HYAL.
Transcriptional Profiles in Ischemia/Reperfusion-Injured Murine Kidneys Synergistically Protected by Erythropoietin Derived Peptide CHBP and Caspase-3 siRNA
Authors: Wu Yuanyuan , Chen Weiwei , Zhang Yufang , Liu Aifen , Yang Cheng , Wang Hui , Zhu Tongyu , Fan Yaping , Yang Bin 
Published: May 2020

Abstract
Background: Target-specific treatment is not available for acute kidney injury (AKI). A novel erythropoietin-derived cyclic helix B surface peptide (CHBP) protects kidneys against AKI subjected to different causes. Herein, we investigated the transcriptional profile of renoprotection induced by CHBP and its potential synergistic effects with caspase-3 siRNA (CASP3siRNA) on ischemia/reperfusion (IR) injury associated AKI. Methods: A mouse renal IR model was established by clamping bilateral pedicles for 30 min and reperfusion for 48 h. 0.03 mg/kg of CASP3siRNA/negative control (NCsiRNA) was injected via tail vein 2 h pre-surgery, with/without 24 nmol/kg of CHBP administered to peritoneal cavity at 15 min post reperfusion. The transcriptomic profile in kidneys was assessed by affymetrix gene chips, along with renal function, histology, active caspase-3 and HMGB1.Results: CHBP or CASP3siRNA significantly improved renal function and structure, with decreased caspase-3 and HMGB1 in IR kidneys. Combined treatment of CHBP and CASP3siRNA further preserved kidney structure, and reduced active caspase-3 and HMGB1. Furthermore, fold change > 1.414 and P < 0.05 were used to identify differentially expressed genes (DEGs). In IR kidneys, 281 DEGs induced by CHBP were mainly involved in promoting cell division and improving cellular function and metabolism (up-regulated STAT5B and SLC22A7). The additional administration of CASP3siRNA caused 504 and 418 DEGs in IR + CHBP kidneys with or without NCsiRNA, with 37 genes in common. These DEGs were associated with modulated apoptosis and inflammation (up-regulated BCL6，SLPI and SERPINA3M), and immunity, injury and microvascular homeostasis (up-regulated CFH and GREM1, and down-regulated ANGPTL2). Conclusions: This proof-of-effect study indicated that the synergistic renoprotection of CHBP and CASP3siRNA at the early stage of IR-induced AKI. Underlying genes, BCL6, SLPI, SERPINA3M, GREM1 and ANGPTL2, might be potential new biomarkers for clinical applications.
Multi-factorial Barriers and Facilitators to High Adherence to Lung Protective Ventilation Using a Computerized Protocol: A Mixed Methods Study
Authors: Knighton Andrew J , Kean Jacob , Wolfe Doug , Allen Lauren , Jacobs Jason , Carpenter Lori , Winberg Carrie , Berry Jay G , Peltan Ithan , Grissom Colin K , Srivast Raj 
Published: May 2020

Abstract
Background
Lung-protective ventilation (LPV) improves outcomes for patients with acute respiratory distress syndrome (ARDS) through administration of low tidal volumes (≤ 6.5 ml/kg predicted body weight [PBW]) with co-titration of positive end-expiratory pressure and fraction of inspired oxygen. Many patients with ARDS, however, are not managed with LPV. The purpose of this study was to understand implementation barriers and facilitators to the use of LPV and a computerized LPV clinical decision support (CDS) tool in intensive care units (ICUs) in preparation for a pilot hybrid implementation-effectiveness clinical trial.
Methods
We performed an explanatory sequential mixed methods study from June 2018 – March 2019 to evaluate variation in LPV adherence across 17 ICUs in an integrated healthcare system with > 4,000 mechanically-ventilated patients annually. We analyzed 47 key informant interviews of ICU physicians, respiratory therapists (RTs) and nurses in 3 of the ICUs using a qualitative content analysis paradigm to investigate site variation as defined by adherence level (low, medium, high) and identify barriers and facilitators to LPV and LPV CDS tool use.
Results
Forty-two percent of patients had an initial set tidal volume ≤ 6.5 ml/kg PBW during the measurement period (site range: 21–80%). LPV CDS tool use was 28% (site range: 6%-91%). This study’s main findings revealed multi-factorial facilitators and barriers to use that varied by ICU site adherence level. The primary facilitator was that LPV and the LPV CDS tool could be used on all mechanically-ventilated patients. Barriers included a persistent gap between clinician attitudes regarding the use of LPV and actual use; the perceived loss of autonomy associated with using a computerized protocol; the nature of physician-RT interaction in ventilation management; and the lack of clear organization measures of success.
Conclusions
Variation in adherence to LPV persists in ICUs within a healthcare delivery system that was an early adopter of LPV. Strategies to increase adherence to LPV for ARDS patients should include initiating low tidal ventilation on all mechanically ventilated patients, establishing and measuring adherence measures, and focused education addressing the physician-RT interaction. These strategies represent a blueprint for a future hybrid implementation-effectiveness trial.
Why do pregnant women prefer cesarean delivery?: a qualitative study in a tertiary care center in Southern Thailand
Authors: Suwanrath Chitkasaem , Chunuan Sopen , Matemanosak Phawat , Pinjaroen Sutham 
Published: May 2020

Abstract
Background
The increasing worldwide rate of cesarean sections is of global concern, and in recent years, cesarean deliveries upon maternal request have become both an interesting and debated issue. Hence, this study aimed to explore the maternal reasons for cesarean preference without medical indications.
Methods
A descriptive qualitative study was conducted, using an in-depth interview, with 27 pregnant women, attending antenatal care at Songklanagarind Hospital from September, 2018 to June, 2019, who preferred cesarean delivery. Data were analyzed using content analysis.
Results
Maternal reasons for cesarean preference were classified into 6 main categories including: fear of childbirth, safety concerns related to health risk perception, negative birth experience, a positive attitude toward cesarean delivery, access to biased information resources and superstitious belief in auspicious birth dates. Most women had more than one reason for choosing cesarean delivery.
Conclusion
Several reasons for cesarean delivery preference emerging from pregnant women have been elucidated. One striking reason was a superstitious belief in auspicious birth dates, which was challengeable for an obstetrician to approach. Obstetricians should explore the exact reasons why women request cesarean delivery, so as to prevent or diminish unnecessary cesarean sections.
Establishment of Agrobacterium-mediated genetic transformation and application of CRISPR/Cas9 gene-editing system to Chinese cabbage (Brassica rapa L. ssp. pekinensis)
Authors: Li Xiaonan , Li Haiyan , Zhao Yuzhu , Zong Peixuan , Zhan Zongxiang , Piao Zhongyun 
Published: May 2020

Abstract
Background: Chinese cabbage, belonging to Brassica rapa species, is an important vegetable in Eastern Asia. It is well known that Chinese cabbage is quite recalcitrant to genetic transformation and the transgenic frequency is generally low. The lack of an efficient and stable genetic transformation system for Chinese cabbage has largely limited related gene functional studies.Results: In this study, we firstly developed a regeneration system for Chinese cabbage by optimizing numerous factors, with 93.50% regeneration rate. Based on this, a simple and efficient Agrobacterium-mediated genetic transformation method was established, without a pre-culture procedure and concentration adjustment of hormone and AgNO3 in co-cultivation and selection media. Using this system, transformants could be obtained within 3.5 to 4.0 months. Average transformation frequency is up to 10.83%. Furthermore, using this transformation system, the CRISPR/Cas9 technology was successfully applied in Chinese cabbage by knocking out a self-incompatibility-related gene SRK. Gene sequencing analysis in the positive transgenic lines revealed various mutations, including deletions, insertions, and substitutions. Conclusion: A simple, stable and efficient genetic transformation method was established for Chinese cabbage and successfully applied to the CRISPR/Cas9 system. The results of this study pave the way for further gene functional studies and genome editing in Chinese cabbage.
Activation and enhancement of Caerulomycin A biosynthesis in marine-derived Actinoalloteichus sp. AHMU CJ021 by combinatorial genome mining strategies
Authors: Xie Yunchang , Chen Jiawen , Wang Bo , Chen Tai , Chen Junyu , Zhang Yuan , Liu Xiaoying , Chen Qi 
Published: May 2020

Abstract
Backgrounds: Activation of silent biosynthetic gene clusters (BGCs) in marine-derived actinomycete strains is a feasible strategy to discover bioactive natural products. Actinoalloteichus sp. AHMU CJ021, isolated from the seashore, was shown to contain an intact but silent caerulomycin A (CRM A) BGC-cam in its genome. Thus, a genome mining work was preformed to activate the strain’s bioproduction of CRM A, an immunosuppressive drug lead with diverse bioactivities.Results: To well activate the expression of cam, ribosomal engineering was adopted to treat the wild type Actinoalloteichus sp. AHMU CJ021. The initial mutant strain XC-11G with gentamycin resistance and CRM A bioproduction titer of 42.51 ± 4.22 mg/L was selected from all generated mutant strains by gene expression comparison of the essential biosynthetic gene-camE. The titer of CRM A bioproduction was then improved by two strain breeding methods via UV mutagenesis and cofactor engineering-directed increasing of intracellular riboflavin, which finally generated the optimal mutant strain XC-11GUR with a CRM A bioproduction titer of 113.91 ± 7.58 mg/L. Subsequently, this titer of strain XC-11GUR was improved to 618.61 ± 16.29 mg/L through medium optimization together with further adjustment derived from response surface methodology. In terms of this 14.7 folds increase in the titer of CRM A compared to the initial value, strain XC-GUR could be a well alternative strain for CRM A development.Conclusions: Our results have constructed an ideal CRM A producer. More importantly, our efforts also have demonstrated the effectiveness of abovementioned combinatorial strategies, which is applicable to the genome mining of bioactive natural products from abundant actinomycetes strains.
Memantine ameliorates motor impairments and pathologies in a mouse model of neuromyelitis optica spectrum disorders.
Authors: Yick Leung-Wah , Tang Chi-Ho , Ma Oscar Ka-Fai , Kwan Jason Shing-Cheong , CHAN Koon Ho 
Published: May 2020

Abstract
Background: Neuromyelitis optica spectrum disorders (NMOSD) are central nervous system (CNS) autoimmune inflammatory demyelinating diseases characterized by recurrent episodes of acute optic neuritis and transverse myelitis. Aquaporin-4 immunoglobulin G (AQP4-IgG) autoantibodies, which target the water channel aquaporin-4 (AQP4) on astrocytic membrane, are pathogenic in NMOSD. Glutamate excitotoxicity, which is triggered by internalization of AQP4-glutamate transporter complex after AQP4-IgG binding to astrocytes, is involved in early NMOSD pathophysiologies. We studied the effects of memantine, a N-methyl-D-aspartate (NMDA) receptor antagonist, on motor impairments and spinal cord pathologies in mice which received human AQP4-IgG. Methods: Purified IgG from AQP4-IgG-seropositive NMOSD patients were passively transferred to adult C57BL/6 mice with disrupted blood-brain barrier. Memantine was administered by oral gavage. Motor impairments of the mice were assessed by beam walking test. Spinal cords of the mice were assessed by immunofluorescence and ELISA. Results: Oral administration of memantine ameliorated the motor impairments induced by AQP4-IgG, no matter the treatment was initiated before (preventive) or after (therapeutic) disease flare. Memantine profoundly reduced AQP4 and astrocyte loss, and attenuated demyelination and axonal loss in the spinal cord of mice which had received AQP4-IgG. The protective effects of memantine were associated with inhibition of apoptosis and suppression of neuroinflammation, with decrease in microglia activation and neutrophil infiltration and reduction of increase in levels of proinflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α). In addition, memantine elevated growth factors including brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF) in the spinal cord. Conclusions: Our findings support that glutamate excitotoxicity and neuroinflammation plays important roles in complement-independent pathophysiology during early development of NMOSD lesions, and highlight the potential of oral memantine as a therapeutic agent in NMOSD acute attacks.
Ferrans and Powers Quality of Life Index for Spinal Cord Injury: to adapt in local language
Authors: Divyalasya TVS , Kumar A Kiran , Bhat NR Sahana , Jahnavi M , Jena Ranjan Kumar , Lakhan Ram , Subrahmanyam B. V. , Agrawal Amit 
Published: May 2020

Abstract
Objective

To translate and culturally adapt Telugu version of Quality of Life tool among Spinal Cord Injury patients.

Method

It’s a prospective cross sectional study conducted at tertiary neuro centre care hospital. The English version was translated into Telugu by two expert medical professionals and cross checked by three experts in Telugu vocabulary. Nursing students who had good proficiency in reading and writing in English and Telugu languages were chosen for checking tool reliability. Initially English language was administered on satisfaction domain followed by importance domain with one month apart. After two months Telugu version was administered in same way as English version. The reliability analysis was done.

Results

The tool was administered on 50 nursing students. The Cronbach’s alpha for satisfaction domain was 0.97 and importance domain was 0.91, indicating excellent reliability.

Conclusion

The Telugu version of QOL tool had excellent reliability. Therefore it can be administered in Telugu language for evaluating the quality of life of people with spinal cord injury.