bluuebunny/crossref_metadata_2025_split huggingface dataset:
Durable preservation of antiviral antibodies after CD19-directed chimeric antigen receptor T-cell immunotherapy
Authors: Hill Joshua A. , Krantz Elizabeth M. , Hay Kevin A. , Dasgupta Sayan , Stevens-Ayers Terry , Bender Ignacio Rachel A. , Bar Merav , Maalouf Joyce , Cherian Sindhu , Chen Xueyan , Pepper Greg , Riddell Stanley R. , Maloney David G. , Boeckh Michael J. , Turtle Cameron J. 
Published: November 2019

Key Points
Virus-specific IgG levels were stable for up to 1 year after CD19-CARTx in adults with durable complete remission. Preexisting humoral immunity may be preserved in adult recipients of CD19-CARTx.
The biology of pulmonary exacerbations in bronchiectasis
Authors: Amati Francesco , Simonetta Edoardo , Gramegna Andrea , Tarsia Paolo , Contarini Martina , Blasi Francesco , Aliberti Stefano 
Published: November 2019

Bronchiectasis is a heterogeneous chronic disease. Heterogeneity characterises bronchiectasis not only in the stable state but also during exacerbations, despite evidence on clinical and biological aspects of bronchiectasis, exacerbations still remain poorly understood.Although the scientific community recognises that bacterial infection is a cornerstone in the development of bronchiectasis, there is a lack of data regarding other trigger factors for exacerbations. In addition, a huge amount of data suggest a primary role of neutrophils in the stable state and exacerbation of bronchiectasis, but the inflammatory reaction involves many other additional pathways. Cole's vicious cycle hypothesis illustrates how airway dysfunction, airway inflammation, infection and structural damage are linked. The introduction of the concept of a “vicious vortex” stresses the complexity of the relationships between the components of the cycle. In this model of disease, exacerbations work as a catalyst, accelerating the progression of disease. The roles of microbiology and inflammation need to be considered as closely linked and will need to be investigated in different ways to collect samples. Clinical and translational research is of paramount importance to achieve a better comprehension of the pathophysiology of bronchiectasis, microbiology and inflammation both in the stable state and during exacerbations.
Identification of key genes and regulators associated with carotenoid metabolism in apricot (Prunus armeniaca) fruit using weighted gene coexpression network analysis
Authors: Zhang Lina , Zhang Qiuyun , Li Wenhui , Zhang Shikui , Xi Wanpeng 
Published: November 2019

Abstract
Background
Carotenoids are a class of terpenoid pigments that contribute to the color and nutritional value of many fruits. Their biosynthetic pathways have been well established in a number of plant species; however, many details of the regulatory mechanism controlling carotenoid metabolism remain to be elucidated. Apricot is one of the most carotenoid-rich fruits, making it a valuable system for investigating carotenoid metabolism. The purpose of this study was to identify key genes and regulators associated with carotenoid metabolism in apricot fruit based on transcriptome sequencing.

Results
During fruit ripening in the apricot cultivar ‘Luntaixiaobaixing’ (LT), the total carotenoid content of the fruit decreased significantly, as did the levels of the carotenoids β-carotene, lutein and violaxanthin (p < 0.01). RNA sequencing (RNA-Seq) analysis of the fruit resulted in the identification of 44,754 unigenes and 6916 differentially expressed genes (DEGs) during ripening. Among these genes, 33,498 unigenes were annotated using public protein databases. Weighted gene coexpression network analysis (WGCNA) showed that two of the 13 identified modules (‘blue’ and ‘turquoise’) were highly correlated with carotenoid metabolism, and 33 structural genes from the carotenoid biosynthetic pathway were identified. Network visualization revealed 35 intramodular hub genes that putatively control carotenoid metabolism. The expression levels of these candidate genes were determined by quantitative real-time PCR analysis, which showed ripening-associated carotenoid accumulation. This analysis revealed that a range of genes (NCED1, CCD1/4, PIF3/4, HY5, ERF003/5/12, RAP2–12, AP2, AP2-like, BZR1, MADS14, NAC2/25, MYB1R1/44, GLK1/2 and WRKY6/31/69) potentially affect apricot carotenoid metabolism during ripening. Based on deciphering the molecular mechanism involved in ripening, a network model of carotenoid metabolism in apricot fruit was proposed.

Conclusions
Overall, our work provides new insights into the carotenoid metabolism of apricot and other species, which will facilitate future apricot functional studies and quality breeding through molecular design.
Infection and RNA-seq analysis of a zebrafish tlr2 mutant shows a broad function of this toll-like receptor in transcriptional and metabolic control and defense to Mycobacterium marinum infection
Authors: Hu Wanbin , Yang Shuxin , Shimada Yasuhito , Münch Magnus , Marín-Juez Rubén , Meijer Annemarie H. , Spaink Herman P. 
Published: November 2019

Abstract
Background
The function of Toll-like receptor 2 (TLR2) in host defense against pathogens, especially Mycobacterium tuberculosis (Mtb) is poorly understood. To investigate the role of TLR2 during mycobacterial infection, we analyzed the response of tlr2 zebrafish mutant larvae to infection with Mycobacterium marinum (Mm), a close relative to Mtb, as a model for tuberculosis. We measured infection phenotypes and transcriptome responses using RNA deep sequencing in mutant and control larvae.

Results
tlr2 mutant embryos at 2 dpf do not show differences in numbers of macrophages and neutrophils compared to control embryos. However, we found substantial changes in gene expression in these mutants, particularly in metabolic pathways, when compared with the heterozygote tlr2+/− control. At 4 days after Mm infection, the total bacterial burden and the presence of extracellular bacteria were higher in tlr2−/− larvae than in tlr2+/−, or tlr2+/+ larvae, whereas granuloma numbers were reduced, showing a function of Tlr2 in zebrafish host defense. RNAseq analysis of infected tlr2−/− versus tlr2+/− shows that the number of up-regulated and down-regulated genes in response to infection was greatly diminished in tlr2 mutants by at least 2 fold and 10 fold, respectively. Analysis of the transcriptome data and qPCR validation shows that Mm infection of tlr2 mutants leads to decreased mRNA levels of genes involved in inflammation and immune responses, including il1b, tnfb, cxcl11aa/ac, fosl1a, and cebpb. Furthermore, RNAseq analyses revealed that the expression of genes for Maf family transcription factors, vitamin D receptors, and Dicps proteins is altered in tlr2 mutants with or without infection. In addition, the data indicate a function of Tlr2 in the control of induction of cytokines and chemokines, such as the CXCR3-CXCL11 signaling axis.

Conclusion
The transcriptome and infection burden analyses show a function of Tlr2 as a protective factor against mycobacteria. Transcriptome analysis revealed tlr2-specific pathways involved in Mm infection, which are related to responses to Mtb infection in human macrophages. Considering its dominant function in control of transcriptional processes that govern defense responses and metabolism, the TLR2 protein can be expected to be also of importance for other infectious diseases and interactions with the microbiome.
Coordination of care for multimorbid patients from the perspective of general practitioners – a qualitative study
Authors: Stumm Judith , Thierbach Cornelia , Peter Lisa , Schnitzer Susanne , Dini Lorena , Heintze Christoph , Döpfmer Susanne 
Published: November 2019

Abstract
Background
In Germany, a decreasing number of general practitioners (GPs) face a growing number of patients with multimorbidity. Whilst care for patients with multimorbidity involves various healthcare providers, the coordination of this care is one of the many responsibilities of GPs. The aims of this study are to identify the barriers to the successful coordination of multimorbid patient care and these patients’ complex needs, and to explore the support needed by GPs in the care of multimorbid patients. Interviewees were asked for their opinion on concepts which involve the support by additional employees within the practice or, alternatively, external health care professionals, providing patient navigation.

Methods
Thirty-two semi-structured, qualitative interviews were conducted with 16 GPs and 16 medical practice assistants (MPAs) from 16 different practices in Berlin. A MPA is a qualified non-physician practice employee. He or she undergoes a three years vocational training which qualifies him or her to provide administrative and clinical support.
The interviews were digitally recorded, transcribed and analysed using the framework analysis methodology.

Results
The results of this paper predominantly focus on GPs’ perspectives of coordination within and external to general practice. Coordination in the context of care for multimorbid patients consists of a wide range of different tasks. Organisational and administrative obstacles under the regulatory framework of the German healthcare system, and insufficient communication with other healthcare providers constitute barriers described by the interviewed GPs and MPAs. In order to ensure optimal care for patients with multimorbidity, GPs may have to delegate responsibilities associated with coordinating tasks. GPs consider the deployment of an additional specifically qualified employee inside the general practice to take on coordinative and social and legal duties to be a viable option.

Conclusions
The cross-sectoral cooperation between all involved key players working within the healthcare system, as well as the coordination of the whole care process, is seemingly challenging for GPs within the complex care system of multimorbid patients. GPs are generally open to the assignment of a person to support them in coordination tasks, preferably situated within the practice team.
Estimating extra length of stay and risk factors of mortality attributable to healthcare-associated infection at a Chinese university hospital: a multi-state model
Authors: Zhou Qian , Fan Lili , Lai Xiaoquan , Tan Li , Zhang Xinping 
Published: November 2019

Abstract
Background
The current evidence of extra length of stay (LOS) attributable to healthcare-associated infection (HCAI) scarcely takes time-dependent bias into consideration. Plus, limited evidences were from developing countries. We aim to estimate the extra LOS and risk factors of mortality attributable to HCAI for inpatients.

Methods
Multi-state model (MSM) was adopted to estimate the extra LOS attributable to HCAI of each type and subgroup. COX regression model was used to examine the risk of mortality.

Results
A total of 51,691 inpatients were included and 1709 (3.31%) among them developed HCAI. Lower respiratory tract infection and Acinetobacter baumannii were the most prevalent HCAI and causative pathogen in surveyed institute. Generally, the expected extra LOS attributable to HCAI was 2.56 days (95% confidence interval: 2.54–2.61). Patients below 65 had extra LOS attributable to HCAI longer about 2 days than those above. The extra LOS attributable to HCAI of male patients was 1.33 days longer than female. Meanwhile, age above 65 years old and HCAI were the risk factors of mortality for inpatients.

Conclusions
HCAI contributes to an increase in extra LOS of inpatients in China. The effect of HCAI on extra LOS is different among subgroups, with the age below 65, male and medicine department more sensitive.
MRI-based radiomics of rectal cancer: preoperative assessment of the pathological features
Authors: Ma Xiaolu , Shen Fu , Jia Yan , Xia Yuwei , Li Qihua , Lu Jianping 
Published: November 2019

Abstract

Background
This study aimed to evaluate the significance of MRI-based radiomics model derived from high-resolution T2-weighted images (T2WIs) in predicting tumor pathological features of rectal cancer.

Methods
A total of 152 patients with rectal cancer who underwent surgery without any neoadjuvant therapy between March 2017 and September 2018 were included retrospectively. The patients were scanned using a 3-T magnetic resonance imaging, and high-resolution T2WIs were obtained. Lesions were delineated, and 1029 radiomics features were extracted. Least absolute shrinkage and selection operator was used to select features, and multilayer perceptron (MLP), logistic regression (LR), support vector machine (SVM), decision tree (DT), random forest (RF), and K-nearest neighbor (KNN) were trained using fivefold cross-validation to build a prediction model. The diagnostic performance of the prediction models was assessed using the receiver operating characteristic curves.

Results
A total of 1029 features were extracted, and 15, 11, and 11 features were selected to predict the degree of differentiation, T stage, and N stage, respectively. The best performance of the radiomics model for the degree of differentiation, T stage, and N stage was obtained by SVM [area under the curve (AUC), 0.862; 95% confidence interval (CI), 0.750–0.967; sensitivity, 83.3%; specificity, 85.0%], MLP (AUC, 0.809; 95% CI, 0.690–0.905; sensitivity, 76.2%; specificity, 74.1%), and RF (AUC, 0.746; 95% CI, 0.622-0.872; sensitivity, 79.3%; specificity, 72.2%).

Conclusion
This study demonstrated that the high-resolution T2WI–based radiomics model could serve as pretreatment biomarkers in predicting pathological features of rectal cancer.
Public-private partnerships and the politics of alcohol policy in England: the Coalition Government’s Public Health ‘Responsibility Deal’
Authors: Hawkins Benjamin , McCambridge Jim 
Published: November 2019

Abstract

Background
The 2010–2015 Conservative-led Coalition Government launched their flagship Public Health Responsibility Deal (PHRD) for England in 2011; a year before their alcohol strategy. This co-regulatory regime placed alcohol industry actors at the heart of policy-making, but was viewed with scepticism by public health actors. This article examines the ways in which the PHRD structured the alcohol policy environment throughout this period, which included the rejection of evidence-based policies such as minimum unit pricing.

Methods
This article draws on 26 semi-structured interviews with policy actors (parliamentarians, civil servants, civil society actors and academics) in 2018. Respondents were identified and recruited using purposive sampling. Interviews were recorded, transcribed and analysed using thematic coding.

Results
The PHRD shaped the context of alcohol policy development at Westminster throughout this period. It circumscribed the policy space by taking evidence-based measures not amenable to industry partnership off the agenda. While the PHRD created important opportunities for industry engagement with policy-makers, it undermined public health actors’ access to government, particularly following their withdrawal from the process. Moreover, the PHRD demonstrates the enduring appeal of partnership as a policy idea for governments, despite a lack of evidence of their effectiveness.

Conclusions
This study of the PHRD demonstrates the ways in which industry actors are able to influence policy through long-term relationship building and partnership working on policy decision-making. Whilst such partnership approaches may appear to have the potential to mitigate some of alcohol harms, they create fundamental conflicts of interest, and may undermine the very causes they seek to further.
Increased lactic acid content associated with extracellular matrix depletion in a porcine disc degeneration induced by superficial annular lesion
Authors: Shi Jinhui , Zhou Xichao , Wang Zhen , Kurra Swamy , Niu Junjie , Yang Huilin 
Published: November 2019

Abstract
Background
Degenerative intervertebral disc (IVD) disease can cause lower back pain. However, the change of lactic acid content during disc degeneration process still unclear. The objective of this study was to investigate whether the change of the content of lactic acid is associated with depletion of degenerative intervertebral disc extracellular matrix.

Methods
A total of 18 miniature pigs were equally divided into annular lesion surgery (AL) and sham group. The lateral superficial annulus fibrosus (AF) of T12-L4 discs in AL group were penetrated by 3.5 mm trepan with the depth of 3 mm, the same IVD were only exposed without any injury in the sham group. At 4, 8 and 12 weeks after surgery, the degree of intervertebral disc degeneration was evaluated by magnetic resonance, histological and biochemical analysis.

Results
No obvious degeneration was found in sham group. However, disc degeneration was found and gradually worsened in AL group after surgery. Histological analysis showed that the AF was rupture and disorder, the number of cells in nucleus pulposus (NP) was decreased in AL group. Compared with the sham group, the extent of type II collagen (Col-II) and aggrecan in NP tissue was dramatically decreased in AL group, consistent with the results of Col -II immunohistochemistry staining and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Besides, the gene expression of matrix metallopeptidase 3 and 13 also continuous increased in AL group. The amount of lactic acid and nerve growth factor in NP tissue was gradually increased after operation in AL group.

Conclusions
The content of lactic acid gradually increased after annular lesion, associated with the damage of AF structural and the decrease of Col -II and aggrecan in NP tissue, which leading to the disc degeneration. Depletion of extracellular matrix is consistent with lactic acid accumulation inside of IVD.
Diagnostic criteria of periprosthetic joint infection: a prospective study protocol to validate the feasibility of the 2018 new definition for Chinese patients
Authors: Guan Haitao , Xu Chi , Fu Jun , Ni Ming , Li Xiang , Chai Wei , Hao Libo , Zhou Yonggang , Chen Jiying 
Published: November 2019

Abstract
Background
Periprosthetic joint infection (PJI) is a challenging complication following total joint arthroplasty (TJA), and the diagnostic criteria remains controversial. The 2018 new definition proposed in May 2018 consists of new diagnostic criteria for PJI. We conducted a retrospective study and demonstrated that the new definition could improve the diagnostic efficiency in Chinese patients. However, missing data led to bias in the previous retrospective study. Therefore, this prospective study is designed to further validate the feasibility of 2018 new definition (and its modified version) for Chinese patients.

Methods/design
This is a single-centre, prospective diagnostic study with 1 year of follow-up. The patients enrolled in the trial will be divided into a PJI group and an Aseptic group based on the eligibility criteria. We will recruit at least 70 patients for each group from October 2019 to October 2020. Blood samples, synovial fluid samples and intraoperative variables of all the included patients will be collected to assess various indicators. We will integrate the results of the various tests and examine the diagnostic efficiency (sensitivity and specificity) of five diagnostic criteria.

Discussion
We design the prospective study in the hope of reducing the bias caused by missing data. Therefore, the prospective study will further support the conclusion of our preceding retrospective study. The results of this study will be submitted to a peer-reviewed journal for publication.

Conclusion
Through this prospective study, we will validate the feasibility of the 2018 new PJI definition (and its modified version) for Chinese patients and determine the optimal method of PJI diagnosis.

Trial registration
Chinese Clinical Trial Registry, ChiCTR1900025395. Registered on 25 August 2019.
Towards improved health service quality in Tanzania: contribution of a supportive supervision approach to increased quality of primary healthcare
Authors: Renggli Sabine , Mayumana Iddy , Mboya Dominick , Charles Christopher , Mshana Christopher , Kessy Flora , Glass Tracy R. , Lengeler Christian , Schulze Alexander , Aerts Ann , Pfeiffer Constanze 
Published: November 2019

Abstract
Background
Universal Health Coverage only leads to the desired health outcomes if quality of health services is ensured. In Tanzania, quality has been a major concern for many years, including the problem of ineffective and inadequate routine supportive supervision of healthcare providers by council health management teams. To address this, we developed and assessed an approach to improve quality of primary healthcare through enhanced routine supportive supervision.

Methods
Mixed methods were used, combining trends of quantitative quality of care measurements with qualitative data mainly collected through in-depth interviews. The former allowed for identification of drivers of quality improvements and the latter investigated the perceived contribution of the new supportive supervision approach to these improvements.

Results
The results showed that the new approach managed to address quality issues that could be solved either solely by the healthcare provider, or in collaboration with the council. The new approach was able to improve and maintain crucial primary healthcare quality standards across different health facility level and owner categories in various contexts.

Conclusion
Together with other findings reported in companion papers, we could show that the new supportive supervision approach not only served to assess quality of primary healthcare, but also to improve and maintain crucial primary healthcare quality standards. The new approach therefore presents a powerful tool to support, guide and drive quality improvement measures within council. It can thus be considered a suitable option to make routine supportive supervision more effective and adequate.
Nasal epithelial cells to assess in vitro immune responses to respiratory virus infection in pregnant women with asthma
Authors: Vanders Rebecca L. , Hsu Alan , Gibson Peter G. , Murphy Vanessa E. , Wark Peter A. B. 
Published: November 2019

AbstractRespiratory virus-induced asthma exacerbations occur frequently during pregnancy and are associated with adverse outcomes for mother and child. Primary nasal epithelial cells (pNECs) provide a useful method to study immune responses in pregnancy. pNECs were obtained by nasal brushings from pregnant and non-pregnant women with and without asthma. pNECS were infected in vitro with major group Rhinovirus 43 (RV43) and seasonal influenza (H3N2). Following infection, pNECs showed measurable quantities of interferon (IFN)-λ, IL-1β, IL-8, IP-10 and MIP1-α. pNECs provide a safe and effective method for studying respiratory epithelial cell responses during pregnancy.