bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-level transcriptome sequencing identifies COL1A1 as a candidate marker in human heart failure progression
Authors: Hua Xiumeng , Wang Yin-Ying , Jia Peilin , Xiong Qing , Hu Yiqing , Chang Yuan , Lai Songqing , Xu Yong , Zhao Zhongming , Song Jiangping 
Published: January 2020

AbstractBackgroundHeart failure (HF) has been recognized as a global pandemic with a high rate of hospitalization, morbidity, and mortality. Although numerous advances have been made, its representative molecular signatures remain largely unknown, especially the role of genes in HF progression. The aim of the present prospective follow-up study was to reveal potential biomarkers associated with the progression of heart failure.MethodsWe generated multi-level transcriptomic data from a cohort of left ventricular heart tissue collected from 21 HF patients and 9 healthy donors. By using Masson staining to calculate the fibrosis percentage for each sample, we applied lasso regression model to identify the genes associated with fibrosis as well as progression. The genes were further validated by immunohistochemistry (IHC) staining in the same cohort and qRT-PCR using another independent cohort (20 HF and 9 healthy donors). Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma level in a validation cohort (139 HF patients) for predicting HF progression.ResultsBased on the multi-level transcriptomic data, we examined differentially expressed genes [mRNAs, microRNAs, and long non-coding RNAs (lncRNAs)] in the study cohort. The follow-up functional annotation and regulatory network analyses revealed their potential roles in regulating extracellular matrix. We further identified several genes that were associated with fibrosis. By using the survival time before transplantation,COL1A1was identified as a potential biomarker for HF progression and its upregulation was confirmed by both IHC and qRT-PCR. Furthermore, COL1A1 content ≥ 256.5 ng/ml in plasma was found to be associated with poor survival within 1 year of heart transplantation from heart failure [hazard ratio (HR) 7.4, 95% confidence interval (CI) 3.5 to 15.8, Log-rankpvalue < 1.0 × 10− 4].ConclusionsOur results suggested that COL1A1 might be a plasma biomarker of HF and associated with HF progression, especially to predict the 1-year survival from HF onset to transplantation.
A systematic review of surgical margins utilized for removal of cutaneous mast cell tumors in dogs
Authors: Selmic Laura E. , Ruple Audrey 
Published: January 2020

Abstract
Background
Traditionally, wide lateral surgical margins of 3 cm and one fascial plane deep have been recommended for resection of canine cutaneous mast cell tumor (MCT). Several studies have been published assessing surgical margins of less than this traditional recommendation. The objective of this systematic review was to determine if resection MCT with lateral surgical margins < 3 cm results in low rates of incomplete resection and local tumor recurrence. Systematic searches of digital bibliographic databases were performed with two authors (AR & LES) screening abstracts to identify relevant scientific articles. Studies regarding surgical treatment of dogs with cutaneous MCT were reviewed. Data abstraction was performed and the quality of individual studies and the strength of the body of evidence for utilization of surgical margins < 3 cm for removal of MCTs was assessed.

Results
From the initial 78 citations identified through the database searches, four articles were retained for data abstraction after both relevance screenings were performed. Two studies were retrospective observational studies, one was a prospective case series and one was a prospective clinical trial. Assessment of the quality level of the body of evidence identified using the GRADE system was low. Excision of MCT at 2 cm and 3 cm was associated with comparably low rates of incomplete excision and recurrence.

Conclusions
Despite the low quality of the overall body of evidence, a recommendation can be made that resection of canine cutaneous MCTs (< 4 cm) of Patnaik grade I and II with 2 cm lateral margins and 1 fascial plane deep results in low rates of incomplete excision and local tumor recurrence.
Melatonin restores Muc2 depletion induced by V. vulnificus VvpM via melatonin receptor 2 coupling with Gαq
Authors: Lee Young-Min , Park Jong Pil , Jung Young Hyun , Lee Hyun Jik , Kim Jun Sung , Choi Gee Euhn , Han Ho Jae , Lee Sei-Jung 
Published: January 2020

Abstract
Background
Melatonin (5-methoxy-N-acetyltryptamine), a hormone produced in the pineal gland, has a variety of biological functions as an antioxidant, but a functional role of melatonin in the regulation of intestinal mucin (Muc) production during bacterial infection has yet to be described in detail. In this study, we investigate the effects of melatonin during Muc2 repression elicited by the Gram-negative bacterium V. vulnificus.

Methods
Mucus-secreting human HT29-MTX cells were used to study the functional role of melatonin during Muc2 depletion induced by the recombinant protein (r) VvpM produced by V. vulnificus. The regulatory effects of melatonin coupling with melatonin receptor 2 (MT2) on the production of reactive oxygen species (ROS), the activation of PKCδ and ERK, and the hypermethylation of the Muc2 promoter as induced by rVvpM were examined. Experimental mouse models of V. vulnificus infection were used to study the role of melatonin and how it neutralizes the bacterial toxin activity related to Muc2 repression.

Results
Recombinant protein (r) VvpM significantly reduced the level of Muc2 in HT29-MTX cells. The repression of Muc2 induced by rVvpM was significantly restored upon a treatment with melatonin (1 μM), which had been inhibited by the knockdown of MT2 coupling with Gαq and the NADPH oxidase subunit p47 phox. Melatonin inhibited the ROS-mediated phosphorylation of PKCδ and ERK responsible for region-specific hypermethylation in the Muc2 promoter in rVvpM-treated HT29-MTX cells. In the mouse models of V. vulnificus infection, treatment with melatonin maintained the level of Muc2 expression in the intestine. In addition, the mutation of the VvpM gene from V. vulnificus exhibited an effect similar to that of melatonin.

Conclusions
These results demonstrate that melatonin acting on MT2 inhibits the hypermethylation of the Muc2 promoter to restore the level of Muc2 production in intestinal epithelial cells infected with V. vulnificus.
Up-regulation of circ_LARP4 suppresses cell proliferation and migration in ovarian cancer by regulating miR-513b-5p/LARP4 axis
Authors: Lin Wumei , Ye Haiyan , You Keli , Chen Le 
Published: January 2020

Abstract
Background
Ovarian cancer (OC) is a common fatal malignant tumor of female reproductive system worldwide. Growing studies have proofed that circular RNAs (circRNAs) engage in the regulation of various types of cancers. However, the underlying biological functions and effect mechanism of circular RNA_LARP4 (circ_LARP4) in OC have not been explored.

Methods
Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to detect the expression of circ_LARP4 in OC cells. The function of circ_LARP4 was measured by cell counting kit-8 (CCK-8), colony formation assay and transwell assay. RNA immunoprecipitation (RIP) assay and luciferase reporter assays assessed the binding correlation between miR-513b-5p and circ_LARP4 (or LARP4).

Results
The expression of circ_LARP4 in OC cells was much lower than that in human normal ovarian epithelial cells. Overexpressing circ_LARP4 impaired cell proliferation, invasion and migration abilities. Circ_LARP4 worked as a competing endogenous RNA (ceRNA) to sponge miR-513b-5p. Furthermore, LARP4 was indirectly modulated by circ_LARP4 as the downstream target of miR-513b-5p, as well as the host gene of circ_LARP4.

Conclusion
Circ_LARP4 could hamper cell proliferation and migration by sponging miR-513b-5p to regulate the expression of LARP4. This research may provide some referential value to OC treatment.
Ras isoforms: signaling specificities in CD40 pathway
Authors: Nair Arathi , Chakraborty Sushmita , Banerji Late Anirban , Srivastava Ankita , Navare Charudutta , Saha Bhaskar 
Published: January 2020

AbstractBackgroundRas are small cellular GTPases which regulate diverse cellular processes. It has three isoforms: H-Ras, K-Ras, and N-Ras. Owing to the N-terminus (1–165 residues) sequence homology these isoforms were thought to be functionally redundant. However, only K-Ras-deficient mice but not H-Ras- and N-Ras-deficient mice show embryonic lethality. Similarly, mutations in a given Ras isoform are associated with a particular type of cancer. Moreover, we have previously reported that Ras isoforms perform unique functions inLeishmania majorinfection. Thus, Ras isoforms are implicated to have signaling and functional specificity but the mechanism remains to be elucidated.ResultUsing CD40 as a model receptor, we showed that depending on the strength of signaling, specific Ras isoforms are activated. Weak CD40 signal activates N-Ras, whereas strong signal activates H-Ras and K-Ras. Additionally, we showed that suppression of N-Ras expression reduced CD40-induced extracellular signal–regulated kinase-1/2 (ERK-1/2) activation and Interleukin (IL)-10 production; whereas suppression of H-Ras or K-Ras reduced CD40-induced p38 mitogen-activated protein kinase (p38MAPK) activation and IL-12 production. Furthermore, we showed that Ras isoforms have activator (GEF) specificity as weak CD40 signal-activated N-Ras requires Sos-1/2 whereas strong CD40 signal-activated H-Ras/K-Ras requires Ras-GRP as the guanine-nucleotide exchange factor (GEF) inducing ERK-1/2- or p38MAPK-mediated IL-10 or IL-12 productions, respectively, in macrophages. Silencing of syk reduced CD40-induced N-Ras activation but silencing of lyn inhibited H-Ras and K-Ras activation. In CD40 signaling, Ras isoforms also showed effector specificity; while H-Ras and K-Ras showed specificity for phosphatidyl inositol-3 kinase activation at high dose of CD40 stimulation, N-Ras primarily associated with Raf-1 at low dose of CD40 stimulation. Moreover, fractal analysis showed that functional site surface roughness for H-Ras (SurfaceFD = 2.39) and K-Ras (SurfaceFD = 2.39) are similar but significantly different from N-Ras (SurfaceFD = 2.25).ConclusionThe activator and effector specificities of Ras isoforms in CD40 signaling indicated their differential involvement in CD40 pathway and in maintaining the reciprocity. Our observations reveal Ras-regulated signaling outcome and its potential for developing Ras isoform-targeted immunotherapy and prophylaxis.Graphical abstract
Rapid diagnosis and comprehensive bacteria profiling of sepsis based on cell-free DNA
Authors: Chen Pei , Li Shuo , Li Wenyuan , Ren Jie , Sun Fengzhu , Liu Rui , Zhou Xianghong Jasmine 
Published: January 2020

Abstract
Background
Sepsis remains a major challenge in intensive care units, causing unacceptably high mortality rates due to the lack of rapid diagnostic tools with sufficient sensitivity. Therefore, there is an urgent need to replace time-consuming blood cultures with a new method. Ideally, such a method also provides comprehensive profiling of pathogenic bacteria to facilitate the treatment decision.

Methods
We developed a Random Forest with balanced subsampling to screen for pathogenic bacteria and diagnose sepsis based on cell-free DNA (cfDNA) sequencing data in a small blood sample. In addition, we constructed a bacterial co-occurrence network, based on a set of normal and sepsis samples, to infer unobserved bacteria.

Results
Based solely on cfDNA sequencing information from three independent datasets of sepsis, we distinguish sepsis from healthy samples with a satisfactory performance. This strategy also provides comprehensive bacteria profiling, permitting doctors to choose the best treatment strategy for a sepsis case.

Conclusions
The combination of sepsis identification and bacteria-inferring strategies is a success for noninvasive cfDNA-based diagnosis, which has the potential to greatly enhance efficiency in disease detection and provide a comprehensive understanding of pathogens. For comparison, where a culture-based analysis of pathogens takes up to 5 days and is effective for only a third to a half of patients, cfDNA sequencing can be completed in just 1 day and our method can identify the majority of pathogens in all patients.
Assessing and measuring financial sustainability model of the Spanish HIV HGM BioBank
Authors: Fernández Irene Consuegra , Merino Isabel García , Muñoz-Fernández María Ángeles 
Published: January 2020

Abstract
Background
The Spanish HIV HGM BioBank is of great relevance for basic and clinical investigation, and for those groups trying to establish large networks focused on investigation on specific clinical problems. The collection of different types of samples from HIV-infected individuals is the beginning of the chain of translational investigation, starting in 2004 a prospective national HIV BioBank that expanded in 2009 a local node (HGM: Hospital Gregorio Marañón) for diverse pathologies and clinical networks, not only in adults but also in paediatric patients, becoming the Spanish HIV HGM BioBank. Our main objective is to find a general criteria and analytical tools to widespread its economic management to assure their sustainability and the future exploitation of the extreme high valuable biomaterial they custody.

Methods
The Spanish HIV HGM BioBank was created with the aim of contributing to advance understanding of different pathologies through the transfer, management, register, processing, cryopreservation and cession of biological material from patients, always for research purposes and under conditions that guarantee its usefulness in current studies and future research that may appear as knowledge evolves. In this study, we have developed a policy for financial control and recovery costs of the Spanish HIV HGM BioBank.

Results
Actually, Spanish HIV HGM BioBank guards 413,747 vials of 46,594 samples from 16,210 donors with various prospective longitudinal study type of samples. Interestingly, more than 7907 of these samples are now used in 28 national and international investigation projects and clinical trials. One of the objectives of this study is to develop an economic plan that you get future projects, design of acceptance or rejection keys, have internal investment limits, minimum recovery needs in short/medium term, deviation detection system and a register of capital recovery by period and type of service for the Spanish HIV HGM BioBank.

Conclusion
Our model can help BioBanks that do not have a costs recovery model to design it, as well as to detect improves and functional revisions to those experienced in this field.
Scaling up breastfeeding policy and programs in Samoa: application of the Becoming Breastfeeding Friendly initiative
Authors:   on behalf of BBF Samoa Committee, Soti-Ulberg Christina , Hromi-Fiedler Amber , Hawley Nicola L. , Naseri Take , Manuele-Magele Analosa , Ah-Ching John , Pérez-Escamilla Rafael 
Published: January 2020

AbstractBackgroundBreastfeeding is a critical, evidence-based intervention that addresses malnutrition, improves early childhood development outcomes, and influences long-term maternal and infant health by reducing the non-communicable disease risk. Scaling up breastfeeding is an indisputably strong action countries can take to prevent suboptimal maternal and infant health outcomes. The Becoming Breastfeeding Friendly (BBF) initiative assists countries with scaling up breastfeeding policy and programs. BBF has been successfully implemented within Latin America, Africa, Europe and South-East Asian regions. This study assessed its application in Samoa.MethodsIn 2018, BBF was implemented in Samoa by a 20 member committee of breastfeeding experts who participated in collecting and utilizing national level data to score the degree of friendliness of Samoa’s breastfeeding environment, identify gaps, and propose policy recommendations to address those gaps. This eight-month process resulted in a public event where priority recommendations were widely disseminated to decision makers and actions agreed upon.ResultsThe total BBF Index score for Samoa was 1.6 out of 3.0, indicating a moderate breastfeeding friendly environment for scaling up policies and programs that protect, promote, and support breastfeeding. Gear total scores indicated that seven of the eight gears were moderately strong within Samoa, while the eighth gear, funding and resources, was weakest in strength. Six prioritized recommendations emerged: 1) development and implementation of a National Breastfeeding Policy and Strategic Action Plan; 2) strengthening monitoring and evaluation of all breastfeeding activities; 3) ratifying the International Labour Organization’s Maternity Protection Convention 2000 (No 183); 4) identifying high-level advocates to champion and serve as role models for breastfeeding; 5) creation of a national budget line for breastfeeding activities; and 6) hiring of a national breastfeeding coordinator and trainer. Decision makers demonstrated commitment by signing the breastfeeding policy for hospitals ahead of the BBF dissemination meeting and electing to move forward with establishing lactation rooms within government ministries.ConclusionImplementation of BBF in Samoa yielded important policy recommendations that will address current gaps in national level breastfeeding support. The BBF consultation process can be successfully applied to other countries within the Western Pacific region in order to strengthen their breastfeeding programs.
The sustainability of public health interventions in schools: a systematic review
Authors: Herlitz Lauren , MacIntyre Helen , Osborn Tom , Bonell Chris 
Published: January 2020

Abstract
Background
The sustainability of school-based health interventions after external funds and/or other resources end has been relatively unexplored in comparison to health care. If effective interventions discontinue, new practices cannot reach wider student populations and investment in implementation is wasted. This review asked: What evidence exists about the sustainability of school-based public health interventions? Do schools sustain public health interventions once start-up funds end? What are the barriers and facilitators affecting the sustainability of public health interventions in schools in high-income countries?

Methods
Seven bibliographic databases and 15 websites were searched. References and citations of included studies were searched, and experts and authors were contacted to identify relevant studies. We included reports published from 1996 onwards. References were screened on title/abstract, and those included were screened on full report. We conducted data extraction and appraisal using an existing tool. Extracted data were qualitatively synthesised for common themes, using May’s General Theory of Implementation (2013) as a conceptual framework.

Results
Of the 9677 unique references identified through database searching and other search strategies, 24 studies of 18 interventions were included in the review. No interventions were sustained in their entirety; all had some components that were sustained by some schools or staff, bar one that was completely discontinued. No discernible relationship was found between evidence of effectiveness and sustainability. Key facilitators included commitment/support from senior leaders, staff observing a positive impact on students’ engagement and wellbeing, and staff confidence in delivering health promotion and belief in its value. Important contextual barriers emerged: the norm of prioritising educational outcomes under time and resource constraints, insufficient funding/resources, staff turnover and a lack of ongoing training. Adaptation of the intervention to existing routines and changing contexts appeared to be part of the sustainability process.

Conclusions
Existing evidence suggests that sustainability depends upon schools developing and retaining senior leaders and staff that are knowledgeable, skilled and motivated to continue delivering health promotion through ever-changing circumstances. Evidence of effectiveness did not appear to be an influential factor. However, methodologically stronger primary research, informed by theory, is needed.

Trial registration
The review was registered on PROSPERO: CRD42017076320, Sep. 2017.
Mid-term results after proximal humeral fractures following angular stable plate fixation in elderly patients—which scores can be evaluated by a telephone-based assessment?
Authors: Ziegler Patrick , Stierand Kim , Bahrs Christian , Ahrend Marc-Daniel 
Published: January 2020

Abstract
Background
The aim was to evaluate postsurgical outcome in elderly patients (> 70 years) after open reduction and internal fixation (ORIF) of proximal humeral fractures and compare the test-retest agreement of scores which are frequently used to assess the outcome of upper extremity disorders.

Methods
Ninety patients (78.1 ± 5.2 years) with a minimum follow-up of 2 years (3.7 ± 0.9 years) following angular stable plate fixation of a proximal humeral fracture (2-part: 34, 3-part: 41, 4-part: 12) were enrolled. Two telephone-based interviews assessed Disabilities of the Arm, Shoulder and Hand Score (DASH), Oxford Shoulder Score (OSS), and Constant Score adjusted for interview assessment (CS) by two independent interviewers. Correlations, Bland-Altman analyses, Cross tabulation, and weighted Kappa measure of agreement (k) were calculated to assess differences and the test-retest agreement between the categories of each score.

Results
In the first and second interview, we could state fair outcomes: CS 91 (range 40–100) and 65.5 (23–86), DASH 12.5 (0–64.2) and 18.3 (0–66.7), and OSS 58 (33–60) and 55 (25–60) points.
The test-retest correlations were r = 0.67, r = 0.77, and r = 0.71 for CS, DASH, and OSS. Bland-Altman analyses showed absolute mean individual score differences of − 22.3, 4.9, and − 3.0 for CS, DASH, and OSS. Limits of agreement represented possible differences of 21.6%, 15.5%, and 9.0% of CS, DASH, and OSS. The category agreements were medium to high: CS 55.9% (k = 0.08), DASH 87.2% (k = 0.62), and OSS 99.3% (k = 0.74).

Conclusion
Patients showed good subjective outcomes. The test-retest agreement of the interview-adjusted CS was low, but telephone-based assessment of OSS and DASH present as an alternative to collect outcomes in elderly patients.

Trial registration
(250/2011BO2).