bluuebunny/crossref_metadata_2025_split huggingface dataset:
SDA: a semi-parametric differential abundance analysis method for metabolomics and proteomics data
Authors: Li Yuntong , Fan Teresa W.M. , Lane Andrew N. , Kang Woo-Young , Arnold Susanne M. , Stromberg Arnold J. , Wang Chi , Chen Li 
Published: October 2019

Abstract

Background
Identifying differentially abundant features between different experimental groups is a common goal for many metabolomics and proteomics studies. However, analyzing data from mass spectrometry (MS) is difficult because the data may not be normally distributed and there is often a large fraction of zero values. Although several statistical methods have been proposed, they either require the data normality assumption or are inefficient.

Results
We propose a new semi-parametric differential abundance analysis (SDA) method for metabolomics and proteomics data from MS. The method considers a two-part model, a logistic regression for the zero proportion and a semi-parametric log-linear model for the possibly non-normally distributed non-zero values, to characterize data from each feature. A kernel-smoothed likelihood method is developed to estimate model coefficients and a likelihood ratio test is constructed for differential abundant analysis. The method has been implemented into an R package, SDAMS, which is available at https://www.bioconductor.org/packages/release/bioc/html/SDAMS.html.

Conclusion
By introducing the two-part semi-parametric model, SDA is able to handle both non-normally distributed data and large fraction of zero values in a MS dataset. It also allows for adjustment of covariates. Simulations and real data analyses demonstrate that SDA outperforms existing methods.
Genome-wide identification, expression profiles and regulatory network of MAPK cascade gene family in barley
Authors: Cui Licao , Yang Guang , Yan Jiali , Pan Yan , Nie Xiaojun 
Published: October 2019

Abstract

Background
Mitogen-activated protein kinase (MAPK) cascade is a conserved and universal signal transduction module in organisms. Although it has been well characterized in many plants, no systematic analysis has been conducted in barley.

Results
Here, we identified 20 MAPKs, 6 MAPKKs and 156 MAPKKKs in barley through a genome-wide search against the updated reference genome. Then, phylogenetic relationship, gene structure and conserved protein motifs organization of them were systematically analyzed and results supported the predictions. Gene duplication analysis revealed that segmental and tandem duplication events contributed to the expansion of barley MAPK cascade genes and the duplicated gene pairs were found to undergone strong purifying selection. Expression profiles of them were further investigated in different organs and under diverse abiotic stresses using the available 173 RNA-seq datasets, and then the tissue-specific and stress-responsive candidates were found. Finally, co-expression regulatory network of MAPK cascade genes was constructed by WGCNA tool, resulting in a complicated network composed of a total of 72 branches containing 46 HvMAPK cascade genes and 46 miRNAs.

Conclusion
This study provides the targets for further functional study and also contribute to better understand the MAPK cascade regulatory network in barley and beyond.
Genome-wide identification of small heat-shock protein (HSP20) gene family in grape and expression profile during berry development
Authors: Ji Xiao-Ru , Yu Yi-He , Ni Pei-Yi , Zhang Guo-Hai , Guo Da-Long 
Published: October 2019

Abstract

Background
Studies have shown that HSP20 (heat-shock protein 20) genes play important roles in regulating plant growth, development, and stress response. However, the grape HSP20 gene family has not been well studied.

Results
A total of 48 VvHSP20 genes were identified from the grape genome, which were divided into 11 subfamilies (CI, CII, CIII, CV, CVI, CVII, MI, MII, ER, CP and PX/Po) based on a phylogenetic analysis and subcellular localization. Further structural analysis showed that most of the VvHSP20 genes (93.8%) had no intron or only one intron, while genes that clustered together based on a phylogenetic tree had similar motifs and evolutionarily conserved structures. The HSP20s share a conservedα-crystalline domain (ACD) and the different components of the ACD domain suggest the functional diversity of VvHSP20s. In addition, the 48 VvHSP20 genes were distributed on 12 grape chromosomes and the majority of VvHSP20 genes were located at the proximal or distal ends of chromosomes. Chromosome mapping indicated that four groups of VvHSP20 genes were identified as tandem duplication genes. Phytohormone responsive, abiotic and biotic stress-responsive, and plant development-related cis-elements were identified from the cis-regulatory elements analysis of VvHSP20s. The expression profiles of VvHSP20s genes (VvHSP20–1, 11, 14, 17, 18, 19, 20, 24, 25, 28, 31, 39, 42, and 43) were largely similar between RNA-Seq and qRT-PCR analysis after hydrogen peroxide (H2O2) treatment. The results showed that most VvHSP20s were down-regulated by H2O2 treatment during fruit development. VvHSP20s genes were indeed found to be involved in the grape berry development and differences in their transcriptional levels may be the result of functional differentiation during evolution.

Conclusions
Our results provide valuable information on the evolutionary relationship of genes in the VvHSP20 family, which is useful for future studies on the functional characteristics of VvHSP20 genes in grape.
Evaluation of the surveillance system for invasive meningococcal disease (IMD) in the Netherlands, 2004–2016
Authors: Brandwagt Diederik A. H. , van der Ende Arie , Ruijs Wilhelmina L. M. , de Melker Hester E. , Knol Mirjam J. 
Published: October 2019

Abstract

Background
Enhanced surveillance for confirmed cases of invasive meningococcal disease (IMD) was introduced in the Netherlands in 2003, in which reference laboratory data (NRLBM) are linked with notification data (OSIRIS). The quality of surveillance information is important for public health decision making. Our objective was to describe the system and evaluate it for data completeness and timeliness.

Methods
Cases reported in the surveillance system from 2004 to 2016 were included. For the notification data, we used information on serogroup, vaccination status, mortality, and country of infection as indicators for record completeness. Notification times to regional and national level were calculated using the reported dates available in the notification database.

Results
A total of 2123 cases were reported in the years 2004–2016, of which 1.968 (93%) were reported by the reference laboratory and 1.995 (94%) in the notification system. Of all cases, 1.840 cases (87%) were reported in both systems and could be linked. The serogroup was known in 86% of the notified cases, and was significantly higher (94%) in the years 2013–2016. Information on vaccination status, mortality and country of infection was available in 88, 99 and 97% of notified cases, respectively. Regional notification of cases occurred within one working day for 86% of cases and 98% were notified nationally within three days.

Conclusions
A well performing IMD surveillance system was demonstrated and serogroup completeness has improved over the years. Underlining the need for reporting to both the clinical and laboratory surveillance system remains important to further improve the overall performance in supporting public health response and vaccination policy.
Factors associated with successful vaginal birth after a cesarean section: a systematic review and meta-analysis
Authors: Wu Yanxin , Kataria Yachana , Wang Zilian , Ming Wai-Kit , Ellervik Christina 
Published: October 2019

Abstract

Background
Evidence for the relationship between maternal and perinatal factors and the success of vaginal birth after cesarean section (VBAC) is conflicting. We aimed to systematically analyze published data on maternal and fetal factors for successful VBAC.

Methods
A comprehensive search of Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature, from each database’s inception to March 16, 2018. Observational studies, identifying women with a trial of labor after one previous low-transverse cesarean section were included. Two reviewers independently abstracted the data. Meta-analysis was performed using the random-effects model. Risk of bias was assessed by the Newcastle-Ottawa Scale.

Results
We included 94 eligible observational studies (239,006 pregnant women with 163,502 VBAC). Factors were associated with successful VBAC with the following odds ratios (OR;95%CI): age (0.92;0.86–0.98), obesity (0.50;0.39–0.64), diabetes (0.50;0.42–0.60), hypertensive disorders complicating pregnancy (HDCP) (0.54;0.44–0.67), Bishop score (3.77;2.17–6.53), labor induction (0.58;0.50–0.67), macrosomia (0.56;0.50–0.64), white race (1.39;1.26–1.54), previous vaginal birth before cesarean section (3.14;2.62–3.77), previous VBAC (4.71;4.33–5.12), the indications for the previous cesarean section (cephalopelvic disproportion (0.54;0.36–0.80), dystocia or failure to progress (0.54;0.41–0.70), failed induction (0.56;0.37–0.85), and fetal malpresentation (1.66;1.38–2.01)). Adjusted ORs were similar.

Conclusions
Diabetes, HDCP, Bishop score, labor induction, macrosomia, age, obesity, previous vaginal birth, and the indications for the previous CS should be considered as the factors affecting the success of VBAC.
Case report of oxalate nephropathy in a patient with pancreatic metastases from renal carcinoma
Authors: Purshouse Karin , Chamberlain Sarah , Soares Maria , Tuthill Mark , Protheroe Andrew , Mole David R. 
Published: October 2019

Abstract

Background
Patients with metastatic renal carcinoma frequently have pre-existing renal impairment and not infrequently develop worsening renal function as a complication of their treatment. The presence of pancreatic metastases in patients with metastatic renal carcinoma, often confers a more favourable prognosis and as a consequence this patient group may be exposed to such treatments for more prolonged periods of time. However, the development of renal failure may also be a consequence of the cancer itself rather than its treatment.

Case presentation
We present an 84-year-old patient receiving the tyrosine kinase inhibitor (TKI) pazopanib for metastatic renal carcinoma who developed oxalate nephropathy as a consequence of pancreatic exocrine insufficiency resulting from pancreatic metastases.

Conclusions
This case demonstrates the importance of investigating unexpected toxicities and highlights the potential consequences of pancreatic insufficiency and its sequelae in patients with pancreatic metastases.
Development of interventions for an intelligent and individualized mobile health care system to promote healthy diet and physical activity: using an intervention mapping framework
Authors: Chen Yuling , Wu Fangqin , Wu Ying , Li Jia , Yue Peng , Deng Ying , Lamb Karen V. , Fong Simon , Liu Yisi , Zhang Yan 
Published: October 2019

Abstract

Background
The mortality of coronary heart disease can be largely reduced by modifying unhealthy lifestyles. However, the long-term effectiveness of interventions for modifying unhealthy diet and physical inactivity of patients with coronary heart disease remain unsatisfactory worldwide. This study aims to systematically design a set of theory-based and evidence-based, individualized, and intelligent interventions for promoting the adoption and maintenance of a healthy diet and physical activity level in patients with coronary heart disease.

Methods
The interventions will be delivered by a mobile health care system called Individualized, Intelligent and Integrated Cardiovascular Application for Risk Elimination. Three steps of the intervention mapping framework were used to systematically develop the interventions. Step 1: needs assessment, which was carried out by a literature review, in-depth interviews and focus group discussions. Step 2: development of objective matrix for diet and physical activity changes, based on the intersection of objectives and determinants from the Contemplation-Action-Maintenance behavior change model. Step 3: formulation of evidence-based methods and strategies, and practical applications, through a systematic review of existing literature, research team discussions, and consultation with multidisciplinary expert panels.

Results
Three needs relevant to content of the intervention, one need relevant to presentation modes of the intervention, and four needs relevant to functional features of the application were identified. The objective matrix includes three performance objectives, and 24 proximal performance objectives. The evidence-based and theory-based interventions include 31 strategies, 61 evidence-based methods, and 393 practical applications.

Conclusions
This article describes the development of theory-based and evidence-based interventions of the mobile health care system for promoting the adoption and maintenance of a healthy diet and physical activity level in a structured format. The results will provide a theoretical and methodological basis to explore the application of intervention mapping in developing effective behavioral mobile health interventions for patients with coronary heart disease.

Trial registration
Chinese Clinical Trial Registry: ChiCTR-INR-16010242. Registered 24 December 2016. http://www.chictr.org.cn/index.aspx
Utilizing a user-centered approach to develop and assess pharmacogenomic clinical decision support for thiopurine methyltransferase
Authors: Nguyen Khoa A. , Patel Himalaya , Haggstrom David A. , Zillich Alan J. , Imperiale Thomas F. , Russ Alissa L. 
Published: October 2019

AbstractBackgroundA pharmacogenomic clinical decision support tool (PGx-CDS) for thiopurine medications can help physicians incorporate pharmacogenomic results into prescribing decisions by providing up-to-date, real-time decision support. However, the PGx-CDS user interface may introduce errors and promote alert fatigue. The objective of this study was to develop and evaluate a prototype of a PGx-CDS user interface for thiopurine medications with user-centered design methods.MethodsThis study had two phases: In phase I, we conducted qualitative interviews to assess providers’ information needs. Interview transcripts were analyzed through a combination of inductive and deductive qualitative analysis to develop design requirements for a PGx-CDS user interface. Using these requirements, we developed a user interface prototype and evaluated its usability (phase II).ResultsIn total, 14 providers participated: 10 were interviewed in phase I, and seven providers completed usability testing in phase II (3 providers participated in both phases). Most (90%) participants were interested in PGx-CDS systems to help improve medication efficacy and patient safety. Interviews yielded 11 themes sorted into two main categories: 1) health care providers’ views on PGx-CDS and 2) important design features for PGx-CDS. We organized these findings into guidance for PGx-CDS content and display. Usability testing of the PGx-CDS prototype showed high provider satisfaction.ConclusionThis is one of the first studies to utilize a user-centered design approach to develop and assess a PGx-CDS interface prototype for Thiopurine Methyltransferase (TPMT). This study provides guidance for the development of a PGx-CDS, and particularly for biomarkers such as TPMT.
Economic barriers, evidentiary gaps, and ethical conundrums: a qualitative study of physicians’ challenges recommending HPV vaccination to older gay, bisexual, and other men who have sex with men
Authors: Grace Daniel , Gaspar Mark , Rosenes Ron , Grewal Ramandip , Burchell Ann N. , Grennan Troy , Salit Irving E. 
Published: October 2019

Abstract

Background
The human papillomavirus (HPV) is the most common sexually transmitted infection (STI) worldwide. Gay, bisexual, and other men who have sex with men (GBM), and GBM living with HIV in particular, are disproportionately impacted by HPV-associated cancers. The HPV vaccine, given early enough in life, may markedly reduce the likelihood of such cancers. In Canada, most provincial insurance programs only cover HPV vaccination for GBM up to the age of 26. Our objective was to understand physicians’ everyday experiences and challenges in recommending HPV vaccination to older GBM patients.

Methods
As part of the HPV Screening and Vaccine Evaluation (HPV-SAVE) Study, we conducted semi-structured interviews with 25 HIV-positive GBM patients who had received anal cancer screening and 15 service providers, including 13 physicians, who had arranged for anal cancer screening in the Canadian provinces of Ontario and British Columbia. In this analysis, we draw upon the 13 physician interviews, which were coded following Grounded Theory.

Results
Physicians strongly supported the HPV vaccine for all GBM and considered it to be important for the management of HIV-related care. However, the overall support for HPV vaccination among physicians did not translate into consistent recommendation practices. There were two overarching factors that limited the strength/frequency of physicians’ vaccine recommendation practices. First, cost/insurance coverage for some older patients impacted if and how the HPV vaccine was discussed. Second, physicians had diverse perspectives on both the prevention and therapeutic benefits of vaccinating older GBM and the reality that national guidelines are incongruent with publicly funded vaccine programs for vaccinating patients over 26 years old. These two interrelated factors have co-produced an apparent economic-evidentiary conundrum for many physicians regarding how and for whom to offer HPV vaccination.

Conclusion
Economic barriers coupled with evidentiary and guideline gaps have created clinical practice challenges for physicians and has resulted in different messages being communicated to some older GBM patients about how important HPV vaccination is for their health.
Doxorubicin-polyglycerol-nanodiamond conjugate is a cytostatic agent that evades chemoresistance and reverses cancer-induced immunosuppression in triple-negative breast cancer
Authors: Yuan Shen-Jun , Xu Yong-Hong , Wang Chao , An Hui-Chao , Xu Hua-Zhen , Li Ke , Komatsu Naoki , Zhao Li , Chen Xiao 
Published: October 2019

Abstract

Background
Triple negative breast cancer (TNBC) has the poorest prognosis of all breast cancer subtypes and is one of the most fatal diseases for women. Combining cytotoxic chemotherapy with immunotherapy has shown great promise for TNBC treatment. However, chemotherapy often leads to the development of chemoresistance and severe systemic toxicity compromising the immune functions that are crucial to anti-TNBC immune therapy. Tumor-induced immunosuppression also poses a great hindrance to efficacious anti-TNBC immunotherapy. Nanomedicine holds great promise to overcome these hurdles.

Results
Doxorubicin-polyglycerol-nanodiamond conjugate (Nano-DOX) was firstly found to be a cytostatic agent to the 4T1 cells and displayed a lower apparent therapeutic potency than DOX. However, the tumor-bearing animals, particularly some key immune cells thereof, showed good tolerance of Nano-DOX as opposed to the severe toxicity of DOX. Next, Nano-DOX did not induce significant upregulation of P-gp and IL-6, which were demonstrated to be key mediators of chemoresistance to DOX in the 4T1 cells. Then, Nano-DOX was shown to downregulate tumor-derived granulocyte-colony stimulating factor (G-CSF) and suppresses the induction and tissue filtration of myeloid-derived suppressor cells (MDSCs) that are the principal effectors of cancer-associated systemic immunosuppression. Nano-DOX also alleviated the phenotype of MDSCs induced by 4T1 cells. Finally, Nano-DOX induced the 4T1 cells to emit damage associated molecular patterns (DAMPs) that stimulated the tumor immune microenvironment through activating key immune effector cells involved in anti-tumor immunity, such as macrophages, dendritic cells and lymphocytes in the tumor tissue.

Conclusions
Nano-DOX is a cytostatic agent with good host tolerance which is capable of evading chemoresistance and reversing cancer-induced immunosuppression both at the systemic level and in the tumor microenvironment in TNBC. Our work presents Nano-DOX as an interesting example that a chemotherapeutic agent in nano-form may possess distinct biochemical properties from its free form, which can be exploited to join chemotherapy with immunotherapy for better treatment of cancer.
pH-triggered endosomal escape of pore-forming Listeriolysin O toxin-coated gold nanoparticles
Authors: Plaza-GA Ismael , Manzaneda-González Vanesa , Kisovec Matic , Almendro-Vedia Víctor , Muñoz-Úbeda Mónica , Anderluh Gregor , Guerrero-Martínez Andrés , Natale Paolo , López Montero Iván 
Published: October 2019

AbstractBackgroundA major bottleneck in drug delivery is the breakdown and degradation of the delivery system through the endosomal/lysosomal network of the host cell, hampering the correct delivery of the drug of interest. In nature, the bacterial pathogenListeria monocytogeneshas developed a strategy to secrete Listeriolysin O (LLO) toxin as a tool to escape the eukaryotic lysosomal system upon infection, allowing it to grow and proliferate unharmed inside the host cell.ResultsAs a “proof of concept”, we present here the use of purified His-LLO H311A mutant protein and its conjugation on the surface of gold nanoparticles to promote the lysosomal escape of 40 nm-sized nanoparticles in mouse embryonic fibroblasts. Surface immobilization of LLO was achieved after specific functionalization of the nanoparticles with nitrile acetic acid, enabling the specific binding of histidine-tagged proteins.ConclusionsEndosomal acidification leads to release of the LLO protein from the nanoparticle surface and its self-assembly into a 300 Å pore that perforates the endosomal/lysosomal membrane, enabling the escape of nanoparticles.