bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relative Abundance of Integrant-Derived Viral RNAs in Infected Tissues Harvested from Chronic Hepatitis B Virus Carriers
Authors: Freitas Natalia , Lukash Tetyana , Gunewardena Sumedha , Chappell Benjamin , Slagle Betty L. , Gudima Severin O. 
Published: February 2018

ABSTRACT
Five matching sets of nonmalignant liver tissues and hepatocellular carcinoma (HCC) samples from individuals chronically infected with hepatitis B virus (HBV) were examined. The HBV genomic sequences were determined by using overlapping PCR amplicons covering the entire viral genome. Four pairs of tissues were infected with HBV genotype C, while one pair was infected with HBV genotype B. HBV replication markers were found in all tissues. In the majority of HCC samples, the levels of pregenomic/precore RNA (pgRNA) and covalently closed circular DNA (cccDNA) were lower than those in liver tissue counterparts. Regardless of the presence of HBV replication markers, (i) integrant-derived HBV RNAs (id-RNAs) were found in all tissues by reverse transcription-PCR (RT-PCR) analysis and were considerably abundant or predominant in 6/10 tissue samples (2 liver and 4 HCC samples), (ii) RNAs that were polyadenylated using the cryptic HBV polyadenylation signal and therefore could be produced by HBV replication or derived from integrated HBV DNA were found in 5/10 samples (3 liver and 2 HCC samples) and were considerably abundant species in 3/10 tissues (2 livers and 1 HCC), and (iii) cccDNA-transcribed RNAs polyadenylated near position 1931 were not abundant in 7/10 tissues (2 liver and 5 HCC samples) and were predominant in only two liver samples. Subsequent RNA sequencing analysis of selected liver/HCC samples also showed relative abundance of id-RNAs in most of the examined tissues. Our findings suggesting that id-RNAs could represent a significant source of HBV envelope proteins, which is independent of viral replication, are discussed in the context of the possible contribution of id-RNAs to the HBV life cycle.

IMPORTANCE
The relative abundance of integrant-derived HBV RNAs (id-RNAs) in chronically infected tissues suggest that id-RNAs coding for the envelope proteins may facilitate the production of a considerable fraction of surface antigens (HBsAg) in infected cells bearing HBV integrants. If the same cells support HBV replication, then a significant fraction of assembled HBV virions could bear id-RNA-derived HBsAg as a major component of their envelopes. Therefore, the infectivity of these HBV virions and their ability to facilitate virus cell-to-cell spread could be determined mainly by the properties of id-RNA-derived envelope proteins and not by the properties of replication-derived HBsAg. These interpretations suggest that id-RNAs may play a role in the maintenance of chronic HBV infection and therefore contribute to the HBV life cycle. Furthermore, the production of HBsAg from id-RNAs independently of viral replication may explain at least in part why treatment with interferon or nucleos(t)ides in most cases fails to achieve a loss of serum HBsAg.
Predictive risk modelling under different data access scenarios: who is identified as high risk and for how long?
Authors: Johnson Tracy L , Kaldor Jill , Falster Michael O , Sutherland Kim , Humphries Jacob , Jorm Louisa R , Levesque Jean-Frederic 
Published: February 2018

ObjectiveThis observational study critically explored the performance of different predictive risk models simulating three data access scenarios, comparing: (1) sociodemographic and clinical profiles; (2) consistency in high-risk designation across models; and (3) persistence of high-risk status over time.MethodsCross-sectional health survey data (2006–2009) for more than 260 000 Australian adults 45+ years were linked to longitudinal individual hospital, primary care, pharmacy and mortality data. Three risk models predicting acute emergency hospitalisations were explored, simulating conditions where data are accessed through primary care practice management systems, or through hospital-based electronic records, or through a hypothetical ‘full’ model using a wider array of linked data. High-risk patients were identified using different risk score thresholds. Models were reapplied monthly for 24 months to assess persistence in high-risk categorisation.ResultsThe three models displayed similar statistical performance. Three-quarters of patients in the high-risk quintile from the ‘full’ model were also identified using the primary care or hospital-based models, with the remaining patients differing according to age, frailty, multimorbidity, self-rated health, polypharmacy, prior hospitalisations and imminent mortality. The use of higher risk prediction thresholds resulted in lower levels of agreement in high-risk designation across models and greater morbidity and mortality in identified patient populations. Persistence of high-risk status varied across approaches according to updated information on utilisation history, with up to 25% of patients reassessed as lower risk within 1 year.Conclusion/implicationsSmall differences in risk predictors or risk thresholds resulted in comparatively large differences in who was classified as high risk and for how long. Pragmatic predictive risk modelling design decisions based on data availability or projected high-risk patient numbers may therefore influence individuals identified as high-risk, overall case mix and risk persistence. Routine data linkage would enable greater flexibility in developing and optimising predictive risk models appropriate to both case-finding and performance measurement applications.
Improving cardiometabolic and mental health in women with gestational diabetes mellitus and their offspring: study protocol forMySweetHeart Trial, a randomised controlled trial
Authors: Horsch Antje , Gilbert Leah , Lanzi Stefano , Gross Justine , Kayser Bengt , Vial Yvan , Simeoni Umberto , Hans Didier , Berney Alexandre , Scholz Urte , Barakat Ruben , Puder Jardena J 
Published: February 2018

IntroductionGestational diabetes mellitus (GDM) carries prenatal and perinatal risk for the mother and her offspring as well as longer-term risks for both the mother (obesity, diabetes, cardiovascular disease) and her child (obesity, type 2 diabetes). Compared with women without GDM, women with GDM are twice as likely to develop perinatal or postpartum depression. Lifestyle interventions for GDM are generally limited to physical activity and/or nutrition, often focus separately on the mother or the child and take place either during or after pregnancy, while their results are inconsistent. To increase efficacy of intervention, the multifactorial origins of GDM and the tight link between mental and metabolic as well as maternal and child health need to be heeded. This calls for an interdisciplinary transgenerational approach starting in, but continuing beyond pregnancy.Methods and analysisThis randomised controlled trial will assess the effect of a multidimensional interdisciplinary lifestyle and psychosocial intervention aimed at improving the metabolic and mental health of 200 women with GDM and their offspring. Women with GDM at 24–32 weeks gestational age who understand French or English, and their offspring and partners can participate. The intervention components will be delivered on top of usual care during pregnancy and the first year postpartum. Metabolic and mental health outcomes will be measured at 24–32 weeks of pregnancy, shortly after birth and at 6–8 weeks and 1 year after childbirth. Data will be analysed using intention-to-treat analyses. TheMySweetHeart Trialis linked to theMySweetHeart Cohort(clinicaltrials.gov/ct2/show/NCT02872974).Ethics and disseminationWe will disseminate the findings through regional, national and international conferences and through peer-reviewed journals.Trial registration numberNCT02890693; Pre-results.
Hypoadrenocorticism in an aged cat
Authors: Fowlie Samuel J , McKenzie Jennifer , Ramsey Ian 
Published: February 2018

A 13‐year‐old, female, neutered, domestic longhair cat was referred to the hospital with a two‐month history of fluctuating weakness, lethargy, inappetence and intermittently soft stools. Physical examination noted variable mentation, mild tachycardia with poor pulse quality and a body condition score of 1/9. In‐house haematology and biochemistry abnormalities included a mild neutrophilia, hyponatraemia, and decreased Na:K ratio of 24 and isosthenuric urine (1.012). The cat was admitted to the hospital for intravenous fluid therapy and management of its electrolyte abnormalities. A low basal cortisol (36 nmol/l) was found on analysis of a stored serum sample, and further investigations confirmed the diagnosis of hypoadrenocorticism. Treatment was implemented initially with hydrocortisone and dexamethasone and continued long term with desoxycorticosterone pivalate and oral prednisolone. More than one year since diagnosis, the cat is clinically well and stable on treatment.
Outbreak of clostridial abomasitis in dairy calves
Authors: Melendez Pedro , Poock Scott 
Published: February 2018

An outbreak of clostridial abomasitis was diagnosed and described on a Missouri, USA, dairy farm with seasonal parturitions during the fall of 2016. The outbreak comprised 9 fatality cases and 11 clinical cases in calves 4–12 days old. The epidemic event began 10 days after the calving season started. Postmortem examination results reported clostridial abomasitis. Clinical cases were characterised by anorexia, depression, bloat, abdominal distension and yellow‐greenish haemorrhagic pre‐stomach contents. The outbreak was resolved in a period of 11 days and was handled by consistently reinforcing and monitoring standard operation procedures of the entire calf operation. Factors such as proper methods of milk replacer preparation and delivery, quality and temperature of water, osmolality, hygiene, tool disinfection and stress proved to be critical in controlling the outbreak in the calf operation.
Deriving relationships between diapir spacing and salt-layer thickness in the Southern North Sea
Authors: Hernandez Karina , Mitchell Neil C. , Huuse Mads 
Published: February 2018

Abstract
In analytical models of salt diapirism, the initial salt-layer thickness and the post-deformation spacing of salt structures are key parameters. Here, 3D seismic data from The Netherlands offshore has enabled these parameters to be measured over large areas which can then be compared with model predictions. Estimates of the original salt-layer thickness were obtained by spatially filtering present thickness, using filters with varied spatial scales that remove local effects. Loss of evaporite minerals by dissolution or erosion during exposure, cannot be ruled out and, as such, thicknesses are minima. Spacing estimates were derived in two dimensions by locating the minimum separation of lines representing ridgelines of diapirs/walls. Because the length scale of spatial filtering was chosen based on the dependent variable, diapir spacing, the results are non-unique. Nevertheless, choosing an apparently optimal filter length of 50 km, a ratio between diapir spacing and original thickness from 12 to 20 is defined. This ratio is greater than has been reported for the pillow province of the UK North Sea Quadrant 44, which is as expected if pillows evolve into diapirs with progressive halokinetic deformation. This work is key to understanding the evolution of salt displacement, a necessity for unlocking remaining hydrocarbon resources.
Nigericin Exerts Anticancer Effects on Human Colorectal Cancer Cells by Inhibiting Wnt/β-catenin Signaling Pathway
Authors: Liu Fei , Li Wei , Hua Shangbo , Han Ye , Xu Zhihua , Wan Daiwei , Wang Yilin , Chen Weichang , Kuang Yuting , Shi Jianming , Zhi Qiaoming 
Published: February 2018

Abstract
Nigericin, an antibiotic derived from Streptomyces hygroscopicus, which works by acting as an H+, K+, and Pb2+ ionophore, has exhibited promising anticancer activity. The main purpose of this study is to investigate its inhibitory effects on Wnt/β-catenin signaling pathway in colorectal cancer cells and clarify the underlying mechanism. We exposed two colorectal cancer lines (SW620 and KM12) to increasing concentrations of nigericin for different time periods and the 50% inhibiting concentration (IC50) values were evaluated. Our data showed that nigericin treatment significantly reduced tumor cell proliferation in dose- and time-dependent manners in colorectal cancer cells. The subsequent experiments in vitro and in vivo implied that nigericin could significantly suppress the tumor growth, migration, and invasion, and induce the apoptosis of colorectal cancer cells. Our results of Western blot and immunofluorescence assay showed that nigericin could suppress the Wnt/β-catenin signaling pathway in colorectal cancer cells with dose-dependent increased expressions of downstream effectors and target proteins. To further elucidate the inhibitory effects of nigericin via a β-catenin–dependent signaling mechanism, we established the stably β-catenin overexpression colorectal cancer cells. Western blot, SuperTOPFlash luciferase reporter, and immunoprecipitation assays all confirmed β-catenin as a critical intermediary and player in Wnt/β-catenin pathway, and nigericin exerted anticancer effects on colorectal cancer cells by directly targeting the β-catenin destruction complex. These results suggested that Wnt/β-catenin signaling might have an essential role in colorectal cancer progression. Nigericin targeting Wnt/β-catenin signaling might provide new insight into the molecular mechanism of nigericin toward cancer cells, and suggest possible clinical application in colorectal cancer. Mol Cancer Ther; 17(5); 952–65. ©2018 AACR.
Sustained Persistence of IL2 Signaling Enhances the Antitumor Effect of Peptide Vaccines through T-cell Expansion and Preventing PD-1 Inhibition
Authors: Sultan Hussein , Kumai Takumi , Fesenkova Valentyna I. , Fan Aaron E. , Wu Juan , Cho Hyun-Il , Kobayashi Hiroya , Harabuchi Yasuaki , Celis Esteban 
Published: February 2018

Abstract
Peptide vaccines can be a successful and cost-effective way of generating T-cell responses against defined tumor antigens, especially when combined with immune adjuvants such as poly-IC. However, strong immune adjuvants can induce a collateral increase in numbers of irrelevant, nonspecific T cells, which limits the effectiveness of the peptide vaccines. Here, we report that providing prolonged IL2 signaling in the form of either IL2/anti-IL2 complexes or pegylated IL2 overcomes the competitive suppressive effect of irrelevant T cells, allowing the preferential expansion of antigen-specific T cells. In addition to increasing the number of tumor-reactive T cells, sustained IL2 enhanced the ability of T cells to resist PD-1–induced negative signals, increasing the therapeutic effectiveness of the vaccines against established tumors. This vaccination strategy using peptides and sustained IL2 could be taken into the clinic for the treatment of cancer. Cancer Immunol Res; 6(5); 617–27. ©2018 AACR.
Urinary Leukotriene E4 Levels in Children with Sleep‐Disordered Breathing
Authors: Biyani Sneh , Benson M. Jedorah , DeShields Sarah C. , Cunningham Tina D. , Baldassari Cristina M. 
Published: February 2018

ObjectiveDue to limitations of polysomnography (PSG), novel ways to evaluate pediatric obstructive sleep apnea (OSA) are needed. Urinary leukotriene E4 (LTE4), an inflammatory marker, has been identified as a potential biomarker for pediatric OSA. The objective of the study was to assess whether urinary LTE4 levels correlate with OSA severity, as determined by obstructive apnea‐hypopnea index (AHI) and nadir oxygen saturation.Study DesignProspective trial.SettingTertiary care children's hospital.Subjects and MethodsChildren (age, 3‐16 years) with sleep‐disordered breathing (SDB) who were referred for PSG were included. Urine samples were obtained the morning following PSG, and urinary LTE4 levels were quantified with enzyme‐linked immunoassay kits.ResultsA total of 113 children were enrolled, and the mean age was 7.3 years. Thirty‐nine percent (n = 44) were obese, and the majority were white (53%, n = 58). Seventy‐eight percent (n = 88) were diagnosed with OSA (AHI >1), with 27% (n = 30) having severe disease (AHI >10). The mean urinary LTE4 level was 91.3 ng/mM. Urinary LTE4 levels did not correlate with AHI (P =. 77) or nadir oxygen saturation (P =. 64). There was a significant difference in urinary LTE4 levels between patients with mild SDB and those with moderate to severe OSA (P =. 03).ConclusionUrinary LTE4 levels do not correlate with AHI in children with SDB. Compared with children with severe OSA, children with mild SDB have higher urinary LTE4 levels. Further research is needed determine whether urinary LTE4 is a satisfactory biomarker for pediatric OSA.
Music Appreciation after Cochlear Implantation in Adult Patients: A Systematic Review
Authors: Riley Phoebe E. , Ruhl Douglas S. , Camacho Macario , Tolisano Anthony M. 
Published: February 2018

ObjectiveThe cochlear implant (CI) improves quality of life for people who are severely and profoundly deafened, allowing implantees to perceive speech at levels similar to those of individuals with normal hearing. However, patients with CIs generally report a reduced appreciation of music after implantation. We aimed to systematically review the English‐language literature for studies evaluating music enjoyment and perception among adult patients with CIs.Data SourcesA systematic review of PubMed/MEDLINE, Scopus, Embase, and the Cochrane Library.Review MethodsThe PRISMA statement was utilized to identify English‐language studies reporting music appreciation among adults with CIs. Two independent reviewers performed searches through May 2017. Included studies investigated parameters related to music enjoyment and music perception, including (1) pitch and timbre perception, (2) noise‐canceling algorithms, and (3) the presence of dissonant chords, lyrics, or visual cues.ResultsA total of 508 articles were screened for relevance. Forty‐one full‐text articles were evaluated, and 18 met final inclusion criteria. Studies used heterogeneous methods of outcome measurement for identifying music appreciation. The outcome measures suggest that rhythm and lyrics are important components of enjoyment. Patients with CIs had difficulty with pitch and timbre perception.ConclusionThe heterogeneous outcome measures identified in this systematic review suggest that rhythm and lyrics are important components of enjoyment, while patients with CIs had difficulty with pitch and timbre perception. Because there is no standardized reporting metric for music appreciation among adult patients with CIs, a standardized validated outcome‐measuring tool is warranted.
Percutaneous kyphoplasty for the treatment of distal lumbosacral pain caused by osteoporotic thoracolumbar vertebral fracture
Authors: Niu Junjie , Song Dawei , Gan Minfeng , Liu Bin , Tan Chenglong , Yang Huilin , Meng Bin 
Published: February 2018

Background Kyphoplasty has been demonstrated to be minimally invasive and effective in treating osteoporotic vertebral fracture patients with back pain over the level of the fractured vertebrae. Rare studies have reported on thoracolumbar vertebral fracture patients presenting with distal lumbosacral pain (DLP). Whether kyphoplasty had a favorable therapeutic benefit for these patients remains unclear. Purpose To evaluate the therapeutic efficacy of kyphoplasty in treating osteoporotic thoracolumbar vertebral fracture (OTVF) patients with DLP and assess the clinical significance of focal tenderness to palpation in these patients. Material and Methods Thirty-two OTVF patients who only complained of DLP were treated by kyphoplasty. The vertebral heights, local kyphotic angle, Visual Analogue Scale (VAS), and Oswestry Disability Index (ODI) scores were assessed preoperatively, one day after surgery, and at last follow-up. All patients were evaluated regarding their degree of satisfaction with kyphoplasty. In addition, we compared the therapeutic efficacy of kyphoplasty in patients with and without focal tenderness to palpation. Results All patients successfully underwent kyphoplasty without complications. The vertebral heights, local kyphotic angles, VAS, and ODI scores were all significantly improved after kyphoplasty and maintained at last follow-up in our patients ( P < 0.001). At last follow-up, all patients expressed satisfaction with kyphoplasty. No significant differences in these parameters were detected between patients with and without focal tenderness. Conclusion The possibility of thoracolumbar vertebral fractures in elderly patients complaining of DLP should not be neglected. Kyphoplasty presents a superior benefit in treating OTVF patients with DLP. The absence of focal tenderness does not influence the clinical efficacy in these patients.
Malignant Mesothelioma of the Pleuraand Other Malignancies in the Same Patient
Authors: Bianchi Claudio , Bianchi Tommaso , Ramani Lucia 
Published: February 2018

Aims and background The co-existence of mesothelioma, mostly asbestos-related, and other primary malignancies has repeatedly been reported. The present study evaluated the frequency of such an occurrence. Methods In the period October 1979-June 2002, 215 cases of malignant pleural mesothelioma were diagnosed at the Hospital of Monfalcone, Italy. All the cases of the above series, examined at necropsy (169), were included in the study. Occupational histories had been obtained from the patients or from their relatives by personal or telephone interviews. In 132 cases, asbestos bodies were isolated after chemical digestion of lung samples. The thoracic cavities were examined for pleural plaques. Results Additional malignancies were observed in 32 cases (18.9%). Multiple tumors were synchronous in 22 cases, metachronous in 8 cases, and synchronous and metachronous in 2. Four different tumors were found in 2 cases, 3 malignancies were detected in 6 patients, and 2 malignancies in the remaining 24. The most frequent additional malignancies were prostate adenocarcinoma (7 cases), non-Hodgkin lymphoma or chronic lymphocytic leukaemia (5 cases), bladder carcinoma (4 cases), kidney carcinoma (4 cases), large bowel carcinoma (4 cases), and liver cell carcinoma (4 cases). All the patients had histories of exposure to asbestos, mostly in shipbuilding. Lung asbestos body burdens ranged between 60 and 230,000 per gram of dried tissue. Pleural plaques were found in 26 cases. Conclusions In contrast with other series of the literature, in the present cases the co-existence of mesothelioma and other malignancies appeared as a relatively frequent event. The lack of a control group does not allow definite conclusions about the meaning of the occurrence. However, the co-existence of certain tumors with asbestos-related mesothelioma suggests that mesothelioma and associated malignancies might share some etiologic factors (asbestos and others).