bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cross-sectional study of environmental, dog, and human-related risk factors for positive canine leptospirosis PCR test results in the United States, 2009 to 2016
Authors: Smith Amanda M. , Arruda Andréia Gonçalves , Evason Michelle D. , Weese J. S. , Wittum Thomas E. , Szlosek Donald , Stull Jason W. 
Published: November 2019

AbstractBackgroundCanine leptospirosis is a reemerging zoonotic disease concern in North America, and a better understanding of its epidemiology is needed. Wide-scale use and subsequent analyses of polymerase chain reaction (PCR) testing may provide additional insight into leptospirosis. This study aimed to describe temporal trends, to descriptively map, and to identify environmental, dog, and human-level factors associated with positive canine leptospirosis PCR test results in the United States.ResultsData obtained from IDEXX Laboratories, Inc. on 40,118 canine leptospirosis PCR tests run in the United States between 2009 and 2016 were evaluated. Climate and socioeconomic (e.g. urban influence, income) data were obtained from public databases. Choropleth maps were created to identify high test-positive proportion areas and a cross-sectional analysis was completed with generalized (univariable, followed by multivariable) mixed logistic regression models accounting for county within state to identify significant predictors for a positive test. Overall test-positive proportion was 5.4% across the United States, with the regional point estimate highest in the southwest (8.1%). In the final multivariable model, the odds of a positive test were greater for male dogs (Odds Ratio [OR] = 1.28) and dogs 0–4 years of age (ORs ranged from 0.35–0.71 for the other age groups). The odds of a positive test were greater for dogs living in areas with wet environmental conditions (OR = 1.24). Season and temperature, as well as the interaction between them, were significant predictors of a positive test. Dogs had a greater probability of testing positive during cool temperatures (< 4 °C) compared to the other temperature categories in the fall season.ConclusionsThese findings based on PCR testing allow for an improved understanding of factors influencing a positive canine leptospirosis PCR test and will assist targeted education and prevention efforts.
Classification of glioma based on prognostic alternative splicing
Authors: Li Yaomin , Ren Zhonglu , Peng Yuping , Li Kaishu , Wang Xiran , Huang Guanglong , Qi Songtao , Liu Yawei 
Published: November 2019

Abstract
Background
Previously developed classifications of glioma have provided enormous advantages for the diagnosis and treatment of glioma. Although the role of alternative splicing (AS) in cancer, especially in glioma, has been validated, a comprehensive analysis of AS in glioma has not yet been conducted. In this study, we aimed at classifying glioma based on prognostic AS.

Methods
Using the TCGA glioblastoma (GBM) and low-grade glioma (LGG) datasets, we analyzed prognostic splicing events. Consensus clustering analysis was conducted to classified glioma samples and correlation analysis was conducted to characterize regulatory network of splicing factors and splicing events.

Results
We analyzed prognostic splicing events and proposed novel splicing classifications across pan-glioma samples (labeled pST1–7) and across GBM samples (labeled ST1–3). Distinct splicing profiles between GBM and LGG were observed, and the primary discriminator for the pan-glioma splicing classification was tumor grade. Subtype-specific splicing events were identified; one example is AS of zinc finger proteins, which is involved in glioma prognosis. Furthermore, correlation analysis of splicing factors and splicing events identified SNRPB and CELF2 as hub splicing factors that upregulated and downregulated oncogenic AS, respectively.

Conclusion
A comprehensive analysis of AS in glioma was conducted in this study, shedding new light on glioma heterogeneity and providing new insights into glioma diagnosis and treatment.
Diabetes mellitus and other cardiovascular risk factors in lower-extremity peripheral artery disease versus coronary artery disease: an analysis of 1,121,359 cases from the nationwide databases
Authors:   the J-EVT and J-PCI investigators, Takahara Mitsuyoshi , Iida Osamu , Kohsaka Shun , Soga Yoshimitsu , Fujihara Masahiko , Shinke Toshiro , Amano Tetsuya , Ikari Yuji 
Published: November 2019

Abstract
Background
Lower-extremity peripheral artery disease (LE-PAD) and coronary artery disease (CAD) are both pathologically rooted in atherosclerosis, and their shared clinical features regarding the exposure to cardiovascular risk factors have been emphasized. However, comparative data of the two cardiovascular diseases (CVDs) were so far lacking. The purpose of this study was to directly compare the clinical profile between cases undergoing endovascular therapy (EVT) for LE-PAD and those undergoing percutaneous coronary intervention (PCI).

Methods
Data were extracted from the nationwide procedural databases of EVT and PCI in Japan (J-EVT and J-PCI) between 2012 and 2017. A total of 1,121,359 cases (103,887 EVT cases for critical limb ischemia [CLI] or intermittent claudication and 1,017,472 PCI cases for acute coronary syndrome [ACS] or stable angina) were analyzed. Heterogeneity in clinical profile between CVDs was evaluated using the C statistic of the logistic regression model for which dependent variable was one CVD versus another, and explanatory variables were clinical profile. When two CVDs were completely discriminated from each other by the developed model, the C statistic (discrimination ability) of the model would be equal to 1, indicating that the two CVDs were completely different in clinical profile. On the other hand, when two CVDs were identical in clinical profile, the developed model would not discriminate them at all, with the C statistic equal to 0.5.

Results
Mean age was 73.5 ± 9.3 years in LE-PAD patients versus 70.0 ± 11.2 years in CAD patients (P < 0.001). The prevalence of diabetes mellitus and end-stage renal disease was 1.96- and 6.39-times higher in LE-PAD patients than in CAD patients (both P < 0.001). The higher prevalence was observed irrespective of age group. The exposure to other cardiovascular risk factors and the likelihood of cardiovascular risk clustering also varied between the diseases. The between-disease heterogeneity in patient profile was particularly evident between CLI and ACS, with the C statistic equal to 0.833 (95% CI 0.831–0.836).

Conclusions
The current study, an analysis based on nationwide procedural databases, confirmed that patient profiles were not identical but rather considerably different between clinically significant LE-PAD and CAD warranting revascularization.
Phosphorylation of NFATC1 at PIM1 target sites is essential for its ability to promote prostate cancer cell migration and invasion
Authors: Eerola Sini K. , Santio Niina M. , Rinne Sanni , Kouvonen Petri , Corthals Garry L. , Scaravilli Mauro , Scala Giovanni , Serra Angela , Greco Dario , Ruusuvuori Pekka , Latonen Leena , Rainio Eeva-Marja , Visakorpi Tapio , Koskinen Päivi J. 
Published: November 2019

Abstract
Background
Progression of prostate cancer from benign local tumors to metastatic carcinomas is a multistep process. Here we have investigated the signaling pathways that support migration and invasion of prostate cancer cells, focusing on the role of the NFATC1 transcription factor and its post-translational modifications. We have previously identified NFATC1 as a substrate for the PIM1 kinase and shown that PIM1-dependent phosphorylation increases NFATC1 activity without affecting its subcellular localization. Both PIM kinases and NFATC1 have been reported to promote cancer cell migration, invasion and angiogenesis, but it has remained unclear whether the effects of NFATC1 are phosphorylation-dependent and which downstream targets are involved.

Methods
We used mass spectrometry to identify PIM1 phosphorylation target sites in NFATC1, and analysed their functional roles in three prostate cancer cell lines by comparing phosphodeficient mutants to wild-type NFATC1. We used luciferase assays to determine effects of phosphorylation on NFAT-dependent transcriptional activity, and migration and invasion assays to evaluate effects on cell motility. We also performed a microarray analysis to identify novel PIM1/NFATC1 targets, and validated one of them with both cellular expression analyses and in silico in clinical prostate cancer data sets.

Results
Here we have identified ten PIM1 target sites in NFATC1 and found that prevention of their phosphorylation significantly decreases the transcriptional activity as well as the pro-migratory and pro-invasive effects of NFATC1 in prostate cancer cells. We observed that also PIM2 and PIM3 can phosphorylate NFATC1, and identified several novel putative PIM1/NFATC1 target genes. These include the ITGA5 integrin, which is differentially expressed in the presence of wild-type versus phosphorylation-deficient NFATC1, and which is coexpressed with PIM1 and NFATC1 in clinical prostate cancer specimens.

Conclusions
Based on our data, phosphorylation of PIM1 target sites stimulates NFATC1 activity and enhances its ability to promote prostate cancer cell migration and invasion. Therefore, inhibition of the interplay between PIM kinases and NFATC1 may have therapeutic implications for patients with metastatic forms of cancer.

Graphical abstract
GPR110 (ADGRF1) mediates anti-inflammatory effects of N-docosahexaenoylethanolamine
Authors: Park Taeyeop , Chen Huazhen , Kim Hee-Yong 
Published: November 2019

Abstract
Background
Neuroinflammation is a widely accepted underlying condition for various pathological processes in the brain. In a recent study, synaptamide, an endogenous metabolite derived from docosahexaenoic acid (DHA, 22:6n-3), was identified as a specific ligand to orphan adhesion G-protein-coupled receptor 110 (GPR110, ADGRF1). Synaptamide has been shown to suppress lipopolysaccharide (LPS)-induced neuroinflammation in mice, but involvement of GPR110 in this process has not been established. In this study, we investigated the possible immune regulatory role of GPR110 in mediating the anti-neuroinflammatory effects of synaptamide under a systemic inflammatory condition.

Methods
For in vitro studies, we assessed the role of GPR110 in synaptamide effects on LPS-induced inflammatory responses in adult primary mouse microglia, immortalized murine microglial cells (BV2), primary neutrophil, and peritoneal macrophage by using quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) as well as neutrophil migration and ROS production assays. To evaluate in vivo effects, wild-type (WT) and GPR110 knock-out (KO) mice were injected with LPS intraperitoneally (i.p.) or TNF intravenously (i.v.) followed by synaptamide (i.p.), and expression of proinflammatory mediators was measured by qPCR, ELISA, and western blot analysis. Activated microglia in the brain and NF-kB activation in cells were examined microscopically after immunostaining for Iba-1 and RelA, respectively.

Results
Intraperitoneal (i.p.) administration of LPS increased TNF and IL-1β in the blood and induced pro-inflammatory cytokine expression in the brain. Subsequent i.p. injection of the GPR110 ligand synaptamide significantly reduced LPS-induced inflammatory responses in wild-type (WT) but not in GPR110 knock-out (KO) mice. In cultured microglia, synaptamide increased cAMP and inhibited LPS-induced proinflammatory cytokine expression by inhibiting the translocation of NF-κB subunit RelA into the nucleus. These effects were abolished by blocking synaptamide binding to GPR110 using an N-terminal targeting antibody. GPR110 expression was found to be high in neutrophils and macrophages where synaptamide also caused a GPR110-dependent increase in cAMP and inhibition of LPS-induced pro-inflammatory mediator expression. Intravenous injection of TNF, a pro-inflammatory cytokine that increases in the circulation after LPS treatment, elicited inflammatory responses in the brain which were dampened by the subsequent injection (i.p.) of synaptamide in a GPR110-dependent manner.

Conclusion
Our study demonstrates the immune-regulatory function of GPR110 in both brain and periphery, collectively contributing to the anti-neuroinflammatory effects of synaptamide under a systemic inflammatory condition. We suggest GPR110 activation as a novel therapeutic strategy to ameliorate inflammation in the brain as well as periphery.
Long-term follow-up outcomes for patients undergoing primary total hip arthroplasty with uncemented versus cemented femoral components: a retrospective observational study with a 5-year minimum follow-up
Authors: Liu Tiejian , Hua Xiaoxiao , Yu Weiguang , Lin Jinluan , Zhao Mingdong , Liu Jun , Zeng Xianshang 
Published: November 2019

Abstract
Background
This retrospective analysis compared the long-term outcomes for patients with a femoral neck fracture (AO/OTA type 31B) treated with a primary unilateral total hip arthroplasty with uncemented or cemented femoral components (UTHA or CTHA, respectively).

Methods
We conducted a retrospective cohort study using the South China Hip Arthroplasty Database. We identified 422 patients with femoral neck fracture (AO/OTA type 31B) who were previously treated with primary unilateral UTHA or CTHA between 2007 and 2015, with follow-up until 2019. Follow-up occurred 1, 3, 6 and 12 months postoperatively and yearly thereafter. The primary outcome was the Harris hip score (HHS). The secondary outcome was the orthopaedic complication rate.

Results
In total, 324 patients (UTHA n = 160, mean age 68.61 ± 7.49 years; CTHA n = 164, mean age 68.75 ± 7.04 years) were evaluated for study eligibility. The median follow-up was 73.3 months (range, 11.6–89.2 months). At the final follow-up, HHS was 74.09 ± 6.23 vs 79.01 ± 10.21 (UTHA vs CTHA, p = 0.012). Significant differences were detected in the incidence of prosthetic revision, loosening, and periprosthetic fracture between the UTHA and CTHA groups (7.5% for UTHA vs 1.8% for CTHA, p = 0.015; 17.5% for UTHA vs 8.5% for CTHA, p = 0.016; 11.9% for UTHA vs 4.9% for CTHA, p = 0.021, respectively).

Conclusion
In this setting, CTHA demonstrated superiority to UTHA by improving functional outcomes and decreasing complication rates.
Multilevel instrumented posterolateral lumbar spine fusion with an allogeneic cellular bone graft
Authors: Hall John F. , McLean Julie B. , Jones Savannah M. , Moore Mark A. , Nicholson Michelle D. , Dorsch Kimberly A. 
Published: November 2019

Abstract
Background
Low back pain (LBP) is the leading cause of absence from work, disability, and impaired quality of life. Fusion surgery may be indicated when non-operative treatments have failed to provide relief. Surgery may include the use of fusion-enhancing implants, such as cellular bone allografts (CBAs). The purpose of this retrospective study was to evaluate efficacy and safety of one CBA (V-CBA) in patients who underwent instrumented posterolateral fusion (IPLF).

Methods
Retrospective data were collected from 150 consecutive patients who had undergone IPLF surgery between January 1, 2015, and March 31, 2018, in which V-CBA was used. All surgeries were performed by one surgeon. V-CBA was mixed with local autograft bone. Patient diagnoses included degenerative disc disease, spondylosis, spondylolisthesis, or spondylolysis with or without stenosis. Standing anteroposterior (AP) and lateral images were collected prior to surgery and again at the terminal visit, which took place between 6 and 33 months post-operatively. De-identified images were assessed radiologically. Adverse events were documented. The primary composite endpoint of fusion status was dependent upon two main criteria: bridging bone per the Lenke scale (classified as “A” definitely solid or “B” possibly solid) and posterior hardware status (intact). Lenke scale C or D were categorized as pseudarthrosis.

Results
Eighty-seven male and 63 female patients (613 levels total) underwent IPLF in which V-CBA was implanted. An average of 4.1 levels was treated, with 59.3% of patients having undergone treatment for more than 3 levels. Twenty-nine percent of patients had diabetes. Fifty-two percent of patients had previously used nicotine products, and 12% were current smokers. Sixteen serious adverse events were recorded and included lumbar seroma, cerebrospinal fluid leak, wound dehiscence, pneumonia, urinary tract infection, and myocardial infarction. Successful fusion (Lenke scale “A” or “B”) was recorded in 148 out of 150 patients (98.7%), or 608 out of 613 levels. The total pseudarthrosis rate was 0.8%.

Conclusions
The use of V-CBA combined with local autograft in multilevel IPLF resulted in successful fusions in 98.7% of patients. These results are particularly robust given the complex nature of many of these cases: 89 patients had 4 or more surgical levels, and many patients had multiple comorbidities.

Level of evidence
IV
A meta-analysis comparing tenotomy or tenodesis for lesions of the long head of the biceps tendon with concomitant reparable rotator cuff tears
Authors: Na Yuyan , Zhu Yong , Shi Yuting , Ren Yizhong , Zhang Ting , Liu Wanlin , Han Changxu 
Published: November 2019

Abstract
Background
The best treatment for lesions of the long head of the biceps tendon (LHBT) with concomitant reparable rotator cuff tears is still controversial. The purpose of the meta-analysis was to compare clinical outcomes of biceps tenotomy and tenodesis for LHBT lesions.

Methods
A literature retrieval was conducted in MEDLINE, Embase, and Cochrane Library from 1979 to March 2018. Comparative studies (level of evidence I or II) comparing tenotomy and tenodesis for LHBT lesions with concomitant reparable rotator cuff tears were included. Risk of bias for all included studies was assessed using the Cochrane Collaboration’s risk of bias tool. Clinical outcomes compared were Popeye sign, Constant score, VAS pain score, cramping pain, elbow flexion and forearm supination strength, and re-tear of the rotator cuff.

Results
Two randomized controlled trials (RCTs) and five prospective cohort studies (PCS) with 288 biceps tenotomy patients and 303 biceps tenodesis patients were included in this review. Tenotomy resulted in significantly greater rates of Popeye sign (RR, 2.70 [95% CI, 1.80 to 4.04]; P < 0.01) and a less favorable Constant score (MD, − 1.09 [95% CI, − 1.90 to − 0.28]; P < 0.01) compared to tenodesis. No significant heterogeneity was found between the two groups across all parameters except forearm supination strength.

Conclusions
The current evidence indicates that biceps tenodesis for LHBT lesions with concomitant reparable rotator cuff tears results in decreased rate of Popeye sign and improved Constant score compared to biceps tenotomy.

Trial registration
PROSPERO, CRD42018105504. Registered on 13 August 2018.
Incidence of acquired thrombotic thrombocytopenic purpura in Germany: a hospital level study
Authors: Miesbach Wolfgang , Menne Jan , Bommer Martin , Schönermarck Ulf , Feldkamp Thorsten , Nitschke Martin , Westhoff Timm H. , Seibert Felix S. , Woitas Rainer , Sousa Rui , Wolf Michael , Walzer Stefan , Schwander Björn 
Published: November 2019

Abstract
Background
Acquired thrombotic thrombocytopenic Purpura (aTTP) is a life-threatening ultra-orphan disease with a reported annual incidence between 1.5 and 6.0 cases per million in Europe and mainly affecting otherwise young and healthy adults aged 40 years on average. The goal of this study was to assess the incidence of aTTP in Germany.

Methods
A systematic review was performed to determine the published evidence on the aTTP epidemiology in Germany. To obtain additional evidence on the proportion of aTTP cases within the national Thrombotic Microangiopathy (TMA) population a hospital-level study was performed, using a retrospective data collection approach. Diagnosis of aTTP was confirmed if ADAMTS13 level were < 10% and/or the medical records explicitly mentioned aTTP diagnosis. The aggregated hospital data were then projected to the national level using logistic regression techniques.

Results
The systematic literature search did not provide incidence estimates of aTTP in Germany. Eight centers (≈27% of the top 30 TMA hospitals) delivered data according to a predefined data collection form. On average (year 2014–2016) a total number of 172 aTTP episodes per year was projected (95% confidence interval [95%CI]: 132–212). The majority were newly diagnosed aTTP cases (n = 121; 95%CI: 105–129), and 51 were recurrent aTTP cases (95%CI: 27–84). The average annual projected incidence (year 2014–2016) of aTTP episodes was 2.10 per million inhabitants in Germany (95%CI: 1.60–2.58).

Conclusions
The determined annual incidence of newly diagnosed aTTP cases and the overall annual incidence of aTTP episodes in Germany confirm the ultra-orphan character of aTTP. An external validation against international registries (France, UK and USA) shows that our findings are quite comparable with those international incidence rates.
Socio-cultural change in conflict and post conflict settings: five decades of giving birth in Cambodia
Authors: Ros Bandeth , Lê Gillian , Fustukian Suzanne , McPake Barbara 
Published: November 2019

Abstract
Background
This paper explores the changing experience of giving birth in Cambodia over a 53-year period. During this time, Cambodian people experienced armed conflict, extreme privation, foreign invasion, and civil unrest.

Methods
An historical perspective was used to explore the changing place and nature of birth assistance given to Cambodian women between 1950 and 2013. Twenty-four life histories of poor and non-poor Cambodians aged 40–74 were gathered and analysed using a grounded thematic approach.

Results
In the early lives of the respondents, almost all births occurred at home and were assisted by Traditional Birth Attendants. In modern times, towards the end of their lives, the respondents’ grand-children and great grand-children are almost universally born in institutions in which skilled birth attendants are available. Respondents recognise that this is partly due to the availability of modern health care facilities but also describe the process by which attitudes to institutional and homebirth changed over time. Interviews can also chart the increasing awareness of the risks of homebirth, somewhat influenced by the success of health education messages transmitted by public health authorities.

Conclusions
The life histories provide insight into the factors driving the underlying cultural change: a modernising supply side; improving transport and communications infrastructure. In addition, a step-change occurred in the aftermath of the conflict with significant influence of extensive contact with the Vietnamese recognised.

Trial registration
None.