bluuebunny/crossref_metadata_2025_split huggingface dataset:
Canine adenovirus type 1 causing neurological signs in a 5-week-old puppy
Authors: Hornsey Samuel J. , Philibert Hélène , Godson Dale L. , Snead Elisabeth C. R. 
Published: November 2019

Abstract
Background
Infectious canine hepatitis is a rarely encountered disease, that is caused by Canine Adenovirus-1. Clinical signs can vary dramatically, and neurological signs are rarely seen. Neurological manifestation of this disease is rarely reported in the veterinary literature.

Case presentation
A 5-week-old, male entire Husky cross puppy presented for a one-day history of abnormal neurological behaviour (circling, ataxia, vocalization and obtund mentation). The puppy was euthanized shortly after presentation due to rapid deterioration. Histopathology raised concerns for Canine Adenovirus 1 (CAdV-1) based on vasculitis in the brain and intranuclear inclusion bodies in endothelial cell and hepatocytes; immunohistochemistry on brain tissue confirmed CAdV-1 infection.

Conclusions
This report discusses possible routes of infection and manifestations of adenovirus infections causing neurologic signs. It also provides a timely reminder that CAdV-1 should be considered a differential in unvaccinated dogs that present with neurological signs. Further studies are required to better understand the neurotrophic tendencies of this virus.
Analysis of key clinical features for achieving complete remission in stage III and IV non-small cell lung cancer patients
Authors: Aoki Takuya , Akiba Takeshi , Nishiyama Jun , Tajiri Sakurako , Hayama Naoki , Takahashi Genki , Tanaka Jun , Sato Masako , Takiguchi Hiroto , Tomomatsu Hiromi , Tomomatsu Katsuyoshi , Takihara Takahisa , Niimi Kyoko , Oguma Tsuyoshi , Kohno Mitsutomo , Masuda Ryota , Urano Tetsuya , Itoh Hitoshi , Kajiwara Hiroshi , Nakamura Naoya , Kunieda Etsuo , Matsumae Mitsunori , Iwazaki Masayuki , Asano Koichiro 
Published: November 2019

AbstractBackgroundAlthough development of immune checkpoint inhibitors and various molecular target agents has extended overall survival time (OS) in advanced non-small cell lung cancer (NSCLC), a complete cure remains rare. We aimed to identify features and treatment modalities of complete remission (CR) cases in stages III and IV NSCLC by analyzing long-term survivors whose OS exceeded 3 years.MethodsFrom our hospital database, 1,699 patients, registered as lung cancer between 1stMar 2004 and 30thApr 2011, were retrospectively examined. Stage III or IV histologically or cytologically confirmed NSCLC patients with chemotherapy initiated during this period were enrolled. A Cox proportion hazards regression model was used. Data collection was closed on 13thFeb 2017.ResultsThere were 164 stage III and 279 stage IV patients, including 37 (22.6%) and 51 (18.3%) long-term survivors and 12 (7.3%) and 5 (1.8%) CR patients, respectively. The long-term survivors were divided into three groups: 3 ≤ OS < 5 years, 5 years ≤ OS with tumor, and 5 years ≤ OS without tumor (CR). The median OS of these groups were 1,405, 2,238, and 2,876 days in stage III and 1,368, 2,503, and 2,643 days in stage IV, respectively. The mean chemotherapy cycle numbers were 16, 20, and 10 in stage III and 24, 25, and 5 in stage IV, respectively. In the stage III CR group, all patients received chemoradiation, all oligometastases were controlled by radiation, and none had brain metastases. Compared with non-CR patients, the stage IV CR patients had smaller primary tumors and fewer metastases, which were independent prognostic factors for OS among long-term survivors. The 80% stage IV CR patients received radiation or surgery for controlling primary tumors, and the surgery rate for oligometastases was high. Pathological findings in the stage IV CR patients revealed that numerous inflammatory cells existed around and inside resected lung and brain tumors, indicating strong immune response.ConclusionsMultiple line chemotherapies with primary and oligometastatic controls by surgery and/or radiation might achieve cure in certain advanced NSCLC. Cure strategies must be changed according to stage III or IV.This study was retrospectively registered on 16thJun 2019 in UMIN Clinical Trials Registry (number UMIN000037078).
Strategies for measuring airway mucus and mucins
Authors: Atanasova Kalina R. , Reznikov Leah R. 
Published: November 2019

AbstractMucus secretion and mucociliary transport are essential defense mechanisms of the airways. Deviations in mucus composition and secretion can impede mucociliary transport and elicit airway obstruction. As such, mucus abnormalities are hallmark features of many respiratory diseases, including asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD). Studying mucus composition and its physical properties has therefore been of significant interest both clinically and scientifically. Yet, measuring mucus production, output, composition and transport presents several challenges. Here we summarize and discuss the advantages and limitations of several techniques from five broadly characterized strategies used to measure mucus secretion, composition and mucociliary transport, with an emphasis on the gel-forming mucins. Further, we summarize advances in the field, as well as suggest potential areas of improvement moving forward.
Infective endocarditis according to type 2 diabetes mellitus status: an observational study in Spain, 2001–2015
Authors: de Miguel-Yanes José M. , Jiménez-García Rodrigo , Hernández-Barrera Valentín , de Miguel-Díez Javier , Méndez-Bailón Manuel , Muñoz-Rivas Nuria , Pérez-Farinós Napoleón , López-de-Andrés Ana 
Published: November 2019

Abstract
Background
The main aims of this study were to describe trends and outcomes during admission for infective endocarditis (IE) in people ≥ 40 years old with or without type 2 diabetes distributed in five time-periods (2001–2003; 2004–2006; 2007–2009; 2010–2012 and 2013–2015), using Spanish national hospital discharge data.

Methods
We estimated admission rates by diabetes status. We analyzed comorbidity, therapeutic procedures, and outcomes. We built Poisson regression models to compare the adjusted time-trends in admission rates. Type 2 diabetes cases were matched with controls using propensity score matching (PSM). We tested in-hospital mortality (IHM) in logistic regression analyses.

Results
We identified 16,626 hospitalizations in patients aged ≥ 40 years for IE in Spain, 2001–2015. The incidence of IE increased significantly from 6.0/100,000 per year to 13.1/100,000 per year (p < 0.001) in the population with type 2 diabetes, and from 3.9/100,000 per year to 5.5/100,000 per year (p < 0.001) in the population without diabetes, over the study period. The adjusted incidence of IE was 2.2-times higher among patients with diabetes than among those without diabetes (IRR = 2.2; 95% CI 2.1–2.3). People with type 2 diabetes less often underwent heart valve surgery than people without diabetes (13.9% vs. 17.3%; p < 0.001). Although IHM decreased significantly in both groups over time, it represented 20.8% of IE cases among diabetes patients and 19.9% among PSM matched controls (p = 0.337). Type 2 diabetes was not associated with a higher IHM in people admitted to the hospital for IE (OR = 1.1; 95% CI 0.9–1.2).

Conclusion
Incidence rates of IE in Spain, among those with and without T2DM, have increased during the period 2001–2015 with significantly higher incidence rates in the T2DM population. In our population based study and after PSM we found that T2DM was not a predictor of IHM in IE.
LncRNA-LET inhibits cell growth of clear cell renal cell carcinoma by regulating miR-373-3p
Authors: Ye Zhuo , Duan Jiachen , Wang Lihui , Ji Yanli , Qiao Baoping 
Published: November 2019

Abstract
Background
Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma subtype with a poor prognosis. LncRNA-LET is a long non-coding RNA (lncRNA) that is down-regulated in ccRCC tissues. However, its role in ccRCC development and progress is unclear.

Methods
LncRNA-LET expression was detected in ccRCC tissues and ccRCC cells using quantitative real-time PCR. The overexpression and knockdown experiments were performed in ccRCC cells and xenograft mouse model to evaluate role of lncRNA-LET. Cell cycle, apoptosis and JC-1 assays were conducted via flow cytometer. The protein levels were measured through western blot analysis and the interaction between lncRNA-LET and miR-373-3p was identified via luciferase reporter assay.

Results
LncRNA-LET expression was lower in ccRCC tissues than that in the matched adjacent non-tumor tissues (n = 16). In vitro, lncRNA-LET overexpression induced cell cycle arrest, promoted apoptosis and impaired mitochondrial membrane potential, whereas its knockdown exerted opposite effects. Moreover, we noted that lncRNA-LET may act as a target for oncomiR miR-373-3p. In contrast to lncRNA-LET, miR-373-3p expression was higher in ccRCC tissues. The binding between lncRNA-LET and miR-373-3p was validated. Two downstream targets of miR-373-3p, Dickkopf-1 (DKK1) and tissue inhibitor of metalloproteinase-2 (TIMP2), were positively regulated by lncRNA-LET in ccRCC cells. MiR-373-3p mimics reduced lncRNA-LET-induced up-regulation of DKK1 and TIMP2 levels, and attenuated lncRNA-LET-mediated anti-tumor effects in ccRCC cells. In vivo, lncRNA-LET suppressed the growth of ccRCC xenograft tumors.

Conclusion
These findings indicate that lncRNA-LET plays a tumor suppressive role in ccRCC by regulating miR-373-3p.
MicroRNA-1269 promotes cell proliferation via the AKT signaling pathway by targeting RASSF9 in human gastric cancer
Authors: Liu Wen-Li , Wang Hu-xia , Shi Cheng-xin , Shi Fei-yu , Zhao Ling-yu , Zhao Wei , Wang Guang-hui 
Published: November 2019

Abstract
Background
MicroRNAs (miRNAs) play key roles in tumorigenesis and progression of gastric cancer (GC). miR-1269 has been reported to be upregulated in several cancers and plays a crucial role in carcinogenesis and cancer progression. However, the biological function of miR-1269 in human GC and its mechanism remain unclear and need to be further elucidated.

Methods
The expression of miR-1269 in GC tissues and cell lines was detected by quantitative real-time PCR (qRT-PCR). Target prediction programs (TargetScanHuman 7.2 and miRBase) and a dual-luciferase reporter assay were used to confirm that Ras-association domain family 9 (RASSF9) is a target gene of miR-1269. The expression of RASSF9 was measured by qRT-PCR and Western blotting in GC tissues. MTT and cell counting assays were used to explore the effect of miR-1269 on GC cell proliferation. The cell cycle and apoptosis were measured by flow cytometry. RASSF9 knockdown and overexpression were used to further verify the function of the target gene.

Results
We found that miR-1269 expression was upregulated in human GC tissues and cell lines. The overexpression of miR-1269 promoted GC cell proliferation and cell cycle G1-S transition and suppressed apoptosis. The inhibition of miR-1269 inhibited cell growth and G1-S transition and induced apoptosis. miR-1269 expression was inversely correlated with RASSF9 expression in GC tissues. RASSF9 was verified to be a direct target of miR-1269 by using a luciferase reporter assay. The overexpression of miR-1269 decreased RASSF9 expression at both the mRNA and protein levels, and the inhibition of miR-1269 increased RASSF9 expression. Importantly, silencing RASSF9 resulted in the same biological effects in GC cells as those induced by overexpression of miR-1269. Overexpression of RASSF9 reversed the effects of miR-1269 overexpression on GC cells. Both miR-1269 overexpression and RASSF9 silencing activated the AKT signaling pathway, which modulated cell cycle regulators (Cyclin D1 and CDK2). In contrast, inhibition of miR-1269 and RASSF9 overexpression inhibited the AKT signaling pathway. Moreover, miR-1269 and RASSF9 also regulated the Bax/Bcl-2 signaling pathway.

Conclusions
Our results demonstrate that miR-1269 promotes GC cell proliferation and cell cycle G1-S transition by activating the AKT signaling pathway and inhibiting cell apoptosis via regulation of the Bax/Bcl-2 signaling pathway by targeting RASSF9. Our findings indicate an oncogenic role of miR-1269 in GC pathogenesis and the potential use of miR-1269 in GC therapy.
Description of Plasmodium falciparum infections in central Gabon demonstrating high parasite densities among symptomatic adolescents and adults
Authors: Zoleko Manego Rella , Koehne Erik , Kreidenweiss Andrea , Nzigou Mombo Brice , Adegbite Bayode Romeo , Dimessa Mbadinga Lia Betty , Akinosho Malik , Matthewman Julian , Adegnika Ayola Akim , Ramharter Michael , Mombo-Ngoma Ghyslain 
Published: November 2019

Abstract
Background
Malaria remains a public health issue, particularly in sub-Saharan Africa with special features of seriousness in young children and pregnant women. Adolescents and adults are reported to have acquired a semi-immune status and, therefore, present with low parasitaemia. Children are understood to present with a much higher parasitaemia and severe malaria. It is a concern that effective malaria control programmes targeting young children may lead to a delay in the acquisition of acquired immunity and, therefore, causing a shift in the epidemiology of malaria. Prevalence and parasitaemia were explored in adolescents and adults with Plasmodium falciparum infections compared to young children in the area of Lambaréné, Gabon as an indicator for semi-immunity.

Methods
A cross-sectional study was conducted at the Centre de Recherches Médicales de Lambaréné (CERMEL) during a 6-month period in 2018. Symptomatic patients, of all ages were screened for malaria at health facilities in Lambaréné and Fougamou and their respective surrounding villages in the central region of Gabon. Plasmodium falciparum infections were determined either by rapid diagnostic test (RDT) or by microscopy. Descriptive analysis of data on parasite densities, anaemia, and fever are presented.

Results
1589 individuals screened were included in this analysis, including 731 (46%) adolescents and adults. Out of 1377 assessed, the proportion of P. falciparum positive RDTs was high among adolescents (68%) and adults (44%), compared to young children (55%) and school children (72%). Out of 274 participants assessed for malaria by microscopy, 45 (16%) had a parasite count above 10,000/µl of which 9 (20%) were adults.

Conclusion
This study shows a high rate of P. falciparum infections in adolescents and adults associated with high-level parasitaemia similar to that of young children. Adolescents and adults seem to be an at-risk population, suggesting that malaria programmes should consider adolescents and adults during the implementation of malaria prevention and case management programmes with continuous care, since they also act as reservoirs for P. falciparum.
Ongoing challenges in access to diabetes care among the indigenous population: perspectives of individuals living in rural Guatemala
Authors: Nieblas-Bedolla Edwin , Bream Kent D. W. , Rollins Allison , Barg Frances K. 
Published: November 2019

AbstractBackgroundIndigenous persons living in Latin America suffer from a higher prevalence of type 2 diabetes compared to their non-indigenous counterparts. This difference has been attributed to a wide range of factors. Future interventions could be influenced by a deeper understanding of the challenges that impact care in rural regions and in other low-income settings.MethodsThis study was conducted using a modified grounded theory approach. Extended observations and fifteen interviews were performed with adult male and female residents of three rural Mayan towns in Sololá Department, Guatemala using purposive sampling. Questions focused on the perceptions of individuals living with type 2 diabetes and their caregivers regarding disease and treatment.ResultsAcross interviews the most common themes that emerged included mistreatment by healthcare providers, mental health comorbidity, and medication affordability. These perceptions were in part influenced by indigeneity, poverty, and/or gender.ConclusionsBoth structural and cultural barriers continue to impact diabetes care for indigenous communities in rural Guatemala. The interviews in this study suggest that indigenous people experience mistrust in the health care system, unreliable access to care, and mental health comorbidity in the context of type 2 diabetes care. These experiences are shaped by the complex relationship among poverty, gender, and indigeneity in this region. Targeted interventions that are conscious of these factors may increase their chances of success when attempting to address similar health disparities in comparable populations.
Transcriptome-wide analysis of changes in the fetal placenta associated with prenatal arsenic exposure in the New Hampshire Birth Cohort Study
Authors: Winterbottom Emily F. , Ban Yuguang , Sun Xiaodian , Capobianco Anthony J. , Marsit Carmen J. , Chen Xi , Wang Lily , Karagas Margaret R. , Robbins David J. 
Published: November 2019

AbstractBackgroundIncreasing evidence suggests that prenatal exposure to arsenic, even at common environmental levels, adversely affects child health. These adverse effects include impaired fetal growth, which can carry serious health implications lifelong. However, the mechanisms by which arsenic affects fetal health and development remain unclear.MethodsWe addressed this question using a group of 46 pregnant women selected from the New Hampshire Birth Cohort Study (NHBCS), a US cohort exposed to low-to-moderate arsenic levels in drinking water through the use of unregulated private wells. Prenatal arsenic exposure was assessed using maternal urine samples taken at mid-gestation. Samples of the fetal portion of the placenta were taken from the base of the umbilical cord insertion at the time of delivery, stored in RNAlater and frozen. We used RNA sequencing to analyze changes in global gene expression in the fetal placenta associated with in utero arsenic exposure, adjusting for maternal age. Gene set enrichment analysis and enrichment mapping were then used to identify biological processes represented by the differentially expressed genes. Since our previous analyses have identified considerable sex differences in placental gene expression associated with arsenic exposure, we analyzed male and female samples separately.ResultsAt FDR < 0.05, no genes were differentially expressed in female placenta, while 606 genes were differentially expressed in males. Genes showing the most significant associations with arsenic exposure in females wereLEMD1andUPK3B(fold changes 2.51 and 2.48), and in males,FIBINandRANBP3L(fold changes 0.14 and 0.15). In gene set enrichment analyses, at FDR < 0.05, a total of 211 gene sets were enriched with differentially expressed genes in female placenta, and 154 in male placenta. In female but not male placenta, 103 of these gene sets were also associated with reduced birth weight.ConclusionsOur results reveal multiple biological functions in the fetal placenta that are potentially affected by increased arsenic exposure, a subset of which is sex-dependent. Further, our data suggest that in female infants, the mechanisms underlying the arsenic-induced reduction of birth weight may involve activation of stress response pathways.
Wrangling environmental exposure data: guidance for getting the best information from your laboratory measurements
Authors: Udesky Julia O. , Dodson Robin E. , Perovich Laura J. , Rudel Ruthann A. 
Published: November 2019

Abstract
Background
Environmental health and exposure researchers can improve the quality and interpretation of their chemical measurement data, avoid spurious results, and improve analytical protocols for new chemicals by closely examining lab and field quality control (QC) data. Reporting QC data along with chemical measurements in biological and environmental samples allows readers to evaluate data quality and appropriate uses of the data (e.g., for comparison to other exposure studies, association with health outcomes, use in regulatory decision-making). However many studies do not adequately describe or interpret QC assessments in publications, leaving readers uncertain about the level of confidence in the reported data. One potential barrier to both QC implementation and reporting is that guidance on how to integrate and interpret QC assessments is often fragmented and difficult to find, with no centralized repository or summary. In addition, existing documents are typically written for regulatory scientists rather than environmental health researchers, who may have little or no experience in analytical chemistry.

Objectives
We discuss approaches for implementing quality assurance/quality control (QA/QC) in environmental exposure measurement projects and describe our process for interpreting QC results and drawing conclusions about data validity.

Discussion
Our methods build upon existing guidance and years of practical experience collecting exposure data and analyzing it in collaboration with contract and university laboratories, as well as the Centers for Disease Control and Prevention. With real examples from our data, we demonstrate problems that would not have come to light had we not engaged with our QC data and incorporated field QC samples in our study design. Our approach focuses on descriptive analyses and data visualizations that have been compatible with diverse exposure studies with sample sizes ranging from tens to hundreds of samples. Future work could incorporate additional statistically grounded methods for larger datasets with more QC samples.

Conclusions
This guidance, along with example table shells, graphics, and some sample R code, provides a useful set of tools for getting the best information from valuable environmental exposure datasets and enabling valid comparison and synthesis of exposure data across studies.