bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arrhythmogenic left atrial roof vein
Authors: Fukaya Hidehira , Niwano Shinichi , Nakamura Hironori , Igarashi Tazuru , Fujiishi Tamami , Ishizue Naruya , Satoh Akira , Kishihara Jun , Ako Junya 
Published: May 2017

AbstractA seventy year‐old male was referred to our hospital to undergo radiofrequency catheter ablation (RFCA) for drug‐refractory paroxysmal atrial fibrillation (AF). Pre‐operative three‐dimensional computed tomography revealed a unique left atrial (LA) roof vein. Electrophysiological findings showed expansion of the myocardial sleeve and local firing in the LA roof vein. We performed isolation of this arrhythmogenic abnormal vein concomitant with general pulmonary vein isolation in this case, and AF did not recur after the procedure.
Independent and additive interaction between polymorphisms of tumor necrosis factor α−308 and lymphotoxin α+252 on risk of hepatocellular carcinoma related to hepatitis B
Authors: Tsai Jung‐Fa , Chen Shinn‐Chern , Lin Zu‐Yau , Dai Chia‐Yen , Huang Jee‐Fu , Yu Min‐Lung , Chuang Wan‐Long 
Published: May 2017

AbstractThis case–control study was aimed to assess the effect of genetic variants of tumor necrosis factor (TNF) α−308 and lymphotoxin (LT) α+252 on development of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC). Their gene–gene interaction was also investigated. We enrolled 200 pairs of age‐ and sex‐matched patients with cirrhotic HBV‐HCC and unrelated patients with HBV‐cirrhosis alone. Polymorphisms of TNFα−308 and LTα+252 were genotyped. Synergy index was used to calculate interaction between the variant genotypes. The results indicated that the frequency distribution of the variant genotypes (TNFα−308 G/A and LTα+252 G/G) in patients with HCC were significantly higher than those in patients with cirrhosis alone. Multivariate analysis indicated that TNFα−308 G/A (odds ratio [OR], 2.34) and LTα+252 G/G (OR, 2.04) were independent risk factors for HCC. By the clinical characteristics of study population, multivariate analysis demonstrated that independent factors associated with harboring the variant genotypes included cirrhosis with Child‐Pugh C (OR = 6.47 in cases and OR = 11.56 in controls) and thrombocytopenia (OR = 8.86 in cases and OR = 7.74 in controls). Calculation of synergy index (SI) indicated that there are additive interaction between TNFα−308 G/A and LTα+252 G/G on risk of HCC (SI = 1.29). In conclusion: There are independent and additive interactions between TNFα−308 G/A and LTα+252 G/G on risk for HBV‐HCC. They correlated with advanced hepatic fibrosis and severe liver damage, which might contribute to a higher risk for HCC.
The association between pain characteristics, pain catastrophizing and health care use – Baseline results from the SWEPAIN cohort
Authors: Jöud Anna , Björk Jonas , Gerdle Björn , Grimby-Ekman Anna , Larsson Britt 
Published: May 2017

Abstract

Background and aim
Pain is common and adds to the global burden of disease. However, individuals suffering from pain are a heterogeneous group in terms of pain spreading, intensity and duration. While pain influences overall health care consultation not everyone with pain consult health care. To be able to provide health care matching the patients’ needs increased knowledge about what factors determines the decision to consult health care is essential. The aim of this study was to explore the combined importance of pain spreading, intensity, duration and pain catastrophizing for consulting health care.

Methods
In this cross-sectional study we used population based survey data from southeast Sweden (SWEPAIN) including 7792 individuals’ aged 16–85 reporting pain. We used Modified Poisson regressions to analyse factors of importance related to the decision to consult health care.

Results
High and moderate pain intensity, as compared to low, increases the probability of consulting health care (High PR = 1.7 [95% CI 1.51–1.88], moderate PR = 1.2 [1.15–1.41]). Having widespread pain, as compared to localised pain, increased the probability of consulting health (PR = 1.2 [1.03–1.36). Pain duration was not associated with increased probability of consulting health care (PR = 1.0 CI0.88–1.07). However an interaction (p = 0.05) between pain duration and pain catastrophizing beliefs was seen indicating a combined importance of the two when consulting health care.

Conclusion
Our result suggests that pain intensity, pain spreading and pain catastrophizing independently influence the decision to consult health care while there is an interaction effect between pain duration and pain catastrophizing beliefs where the importance of pain catastrophizing believes differ with pain duration; the importance of pain catastrophizing believes differ with pain duration.

Implications
Treatment and rehabilitation strategies should incorporate this finding in order to meet the individual’s needs focusing on the biopsychosocial model within health care focusing not only on actual pain reliefs but also on for example acceptance and behavioural changes.
Alzheimer's disease drug development pipeline: 2017
Authors: Cummings Jeffrey , Lee Garam , Mortsdorf Travis , Ritter Aaron , Zhong Kate 
Published: May 2017

AbstractIntroductionThere is an urgent need to develop new treatments for Alzheimer's disease (AD) and to understand the drug development process for new AD therapies.MethodsWe assessed the agents in the AD pipeline as documented in clinicaltrials.gov for phase I, phase II, and phase III, accessed 1/5/2017.ResultsThere are 105 agents in the AD treatment development pipeline, of which 25 agents are in 29 trials in phase I, 52 agents are in 68 trials in phase II, and 28 agents are in 42 trials in phase III. Seventy percent of drugs in the AD pipeline are disease‐modifying therapies (DMTs). Fourteen percent are symptomatic cognitive enhancers, and 13% are symptomatic agents addressing neuropsychiatric and behavioral changes (2% have undisclosed mechanisms). Most trials are sponsored by the biopharmaceutical industry. Trials include patients with preclinical AD (cognitively normal with biomarker evidence of AD), prodromal AD (mild cognitive symptoms and biomarker evidence of AD), and AD dementia. Biomarkers are included in many drug development programs particularly those for DMTs. Thirteen of 46 phase II DMT trials have amyloid imaging as an entry criterion, and 10 of 28 phase III trials incorporate amyloid imaging for diagnosis and entry. A large number of participants are needed for AD clinical trials; in total, 54,073 participants are required for trials spanning preclinical AD to AD dementia. When compared with the 2016 pipeline, there are eight new agents in phase I, 16 in phase II, and five in phase III.DiscussionThe AD drug development pipeline has 105 agents divided among phase I, phase II, and phase III. The trials include a wide range of clinical trial populations, many mechanisms of action, and require a substantial number of clinical trial participants. Biomarkers are increasingly used in patient identification and as outcome measures, particularly in trials of DMTs.
The Eyjafjallajökull AD 2010 eruption and the preservation of medium-sized eruptions in marine surface sediment offshore southern Iceland
Authors: Bonanati Christina , Wehrmann Heidi , Portnyagin Maxim , Hoernle Kaj 
Published: May 2017

AbstractThe recent volcanic eruptions of Eyjafjallajökull 2010 and Grímsvötn 2011 demonstrated the risks that mediumsized explosive Icelandic eruptions pose to the North Atlantic region. Using the Eyjafjallajökull 2010 eruption as a case study, we assess how traceable such eruptions are in the marine sedimentary record at medial distances from the source and investigate which factors have affected the particle transport to the marine sedimentary archive. During R/VPoseidoncruise 457, we recovered 13 box cores at 100–1600 m water depths and distances of 18–180 km southwest, south, and east of Iceland. Volcanic glass shards from the uppermost surface sediment were analyzed for their major element composition by electron microprobe and assigned to their eruptive source by geochemical fingerprinting. The predominantly basaltic particles are mostly derived from the Katla, Grímsvötn-Lakagígar, and Bárðarbunga-Veiðivötn volcanic systems. We also identified rhyolitic particles from the Askja 1875 and Öræfajökull 1362 eruptions. Only three out of almost 900 analyzed glass shards are derived from the recent Eyjafjallajökull 2010 eruption, suggesting that medium-sized eruptions are only poorly preserved in marine sediments located at medial distances southwest to east of Iceland. We conclude that the frequency of past medium-sized eruptions is likely higher than detectable in this archive.
One thousand seven hundred years of interaction between glacial activity and flood frequency in proglacial Lake Muzelle (western French Alps)
Authors: Fouinat Laurent , Sabatier Pierre , Poulenard Jérôme , Etienne David , Crouzet Christian , Develle Anne-Lise , Doyen Elise , Malet Emmanuel , Reyss Jean-Louis , Sagot Clotilde , Bonet Richard , Arnaud Fabien 
Published: May 2017

AbstractLocal glacial fluctuations and flood occurrences were investigated in the sediment sequence of proglacial Lake Muzelle. Based on geochemical analysis and organic matter content established using loss on ignition and reflectance spectroscopy, we identified six periods of increased glacial activity over the last 1700 yr. Each is in accordance with records from reference glaciers in the Alps. A total of 255 graded layers were identified and interpreted as flood deposits. Most of these occurred during glacial advances such as the Little Ice Age period and exhibit thicker deposits characterized by an increase in the fine grain-size fraction. Fine sediment produced by glacial activity is transported to the proglacial lake during heavy rainfall events. The excess of glacial flour during these periods seems to increase the watershed’s tendency to produce flood deposits in the lake sediment, suggesting a strong influence of the glacier on flood reconstruction records. Thus, both flood frequency and intensity, which is estimated based on layer thickness as a proxy, cannot be used in reconstruction of past extreme events because of their variability. There is a need to take into account changes in sediment supply in proglacial areas that could preclude satisfactory interpretation of floods in terms of past climate variability.
Evaluating the impact ofHomo-carnivore competition in European human settlements during the early to middle Pleistocene
Authors: Rodríguez-Gómez Guillermo , Rodríguez Jesús , Martín-González Jesús A. , Mateos Ana 
Published: May 2017

AbstractFossil remains and the technological complexes recorded in archaeological sites suggest that the human presence in Europe late in the early and middle Pleistocene was discontinuous. Moreover, competition for meat with other secondary consumers could have delayed the human dispersal through Europe. However, evaluation of the extent competition intensity among secondary consumers suggests this influenced the discontinuity of the human settlement of Europe between 1.1 and 0.2 Ma. Using a mathematical model, we estimate the amount of biomass available in a community for secondary consumers. The amount of available biomass is subsequently distributed among the guild of secondary consumers according to their requirements and prey preferences. Indexes that quantify the competition intensity among secondary consumers to compare the conditions in different paleoecosystems show that the competition intensity late in the early Pleistocene, early in the middle Pleistocene, and late in the middle Pleistocene does not support the view that an increase in competition intensity constrained the expansion of human populations early in the middle Pleistocene. Somewhat paradoxically, the lowest competition intensity is estimated to have occurred early in the middle Pleistocene, most likely because of an increase in the number of large herbivore species and a decrease in the number of secondary consumers. The early Pleistocene paleoecosystems supported higher competition intensity than the middle Pleistocene ecosystems, likely because of the different configuration in the food webs of these two periods (the early and middle Pleistocene).
Double aortic arch presenting with a foreign object in the oesophagus: a case report and imaging diagnosis
Authors: Yang Xiuzhen , Ye Jingjing , Gao Zhan 
Published: May 2017

AbstractIn this article, we report a rare case of double aortic arch. The case presented initially with a foreign object in the oesophagus. The patient was a 2-year-old boy, who was referred with primary symptoms of tussis (15 days) and emesis (2 days). He had a history of ingesting a coin. Routine chest X-ray indicated a rounded, metal foreign object in the upper oesophagus. A half-Yuan coin was removed by gastroduodenoscopy. Echocardiographic imaging suggested that the patient had double aortic arch, which was subsequently diagnosed by CT angiography with three-dimensional reconstruction. The right subclavian artery arose from the right loop of the double aortic arch. The left subclavian artery as well as left and right common carotid arteries had distinct origins from the left aortic arch. Imaging also indicated atresia of the distal left arch. The patient underwent corrective surgery and made a full recovery. Despite the rarity, double aortic arch should be considered when patients present with a foreign object in the oesophagus. Echocardiography and CT angiography can inform the diagnosis.
Does metformin protect against osteoarthritis? An electronic health record cohort study
Authors: Barnett Lauren A. , Jordan Kelvin P. , Edwards John J. , van der Windt Danielle A. 
Published: May 2017

Background
Obesity is a major risk factor for osteoarthritis (OA) whilst there is some evidence that diabetes also increases risk. Metformin is a common oral treatment for those with diabetes.

Objective
The aim is to investigate whether metformin reduces the risk of OA.

Methods
This was a cohort study set within the Consultations in Primary Care Archive, with 3217 patients with type 2 diabetes. Patients at 13 general practices with recorded type 2 diabetes in the baseline period (2002–2003) and no prior record of OA were identified. Exposure was a prescription for metformin. Outcome was an OA record during follow up. Cox proportional hazard models with Gamma frailty term were fitted: adjusted for age, gender, deprivation, and comorbidity.

Results
There was no association between prescribed metformin treatment at baseline and OA (adjusted HR: 1.02, 95% CI: 0.91, 1.15). A similar non- significant association was found when allowing exposure status of prescription of metformin to vary over time.
Niche pork: Comparing pig performance and understanding producer benefits, barriers and labeling interest
Authors: Picardy Jamie A. , Pietrosemoli Silvana , Griffin Timothy S. , Peters Christian J. 
Published: May 2017

AbstractOpportunities for alternative swine production and marketing are emerging across the value chain. Given the developing nature of the differentiated pork industry, measurements of niche performance and success are not yet fully known. For this reason, the objectives of this study were to determine performance metrics across all major life phases for niche pork production and compare such metrics with national averages of conventional commodity pork production. Additionally, this study aimed to quantify producers’ reasoning and barriers to successfully raising niche swine. Niche meat producers in the USA self-identified for this study (n = 176); their swine production had alternative characteristics that included small- to mid-sized farms, farrow-to-finish operations, heritage breeds, housing with bedding and outdoor or pasture access, no use of antibiotics (sub-therapeutic for growth promotion or no antibiotics ever), vegetarian feed, diverse agricultural enterprises and alternative marketing avenues. This study focused on the metric categories regarding reproduction, mortality, culling and growth characteristics. The niche system produced approximately 15% fewer weaned piglets per bred sow per year than the conventional system due to fewer breeding cycles, smaller litters and higher piglet mortality in alternative production. Similarly, niche production finished 12% fewer hogs per bred sow per year than conventional production. Regarding age benchmarks of finishing and breeding, the niche system averaged 18 additional days to finish hogs at a standardized market weight of 124 kg. Likewise, niche production gilts were first bred at 283 days, whereas conventional production breeds gilts at 225 days. All directly comparable metrics were found to be statistically significant with 95% confidence for the one-sample test of means. Regarding farmer attitudes toward niche pork, survey participants shared personal reasons for raising swine and barriers to successful niche production. Choosing niche over commodity swine, participants’ reasons were grouped into three intra-related categories: (1) farm and producer viability, (2) animal and environmental welfare, and (3) consumer preference and taste. Despite these benefits, participants were faced with numerous challenges, which were organized into four intra-related categories: (1) alternative production requirements, restrictions and knowledge; (2) access and affordability of credit and inputs; (3) alternative supply chain for processing, marketing and customers; and (4) non-niche production competition and governmental policies. In sum, the success of these niche pork operations equates to high welfare for the pigs, economic viability for the operation, personal enjoyment for the farmer, customer satisfaction with meat flavor and quality, and responsible environmental practices, inclusive of many components of an alternative food system.
Regulator of G protein signaling 2 is a key regulator of pancreatic β-cell mass and function
Authors: Dong H , Zhang Y , Wang J , Kim D S , Wu H , Sjögren B , Gao W , Luttrell L , Wang H 
Published: May 2017

AbstractPancreatic β-cell death and dysfunction contributes to the pathogenesis of both type 1 and type 2 diabetes. We aimed to examine whether the regulator of G protein signaling protein 2 (RGS2), a multifunctional inhibitor of G protein-coupled receptor (GPCR) signaling, impacts β-cell death and function. Metabolic phenotypes, β-cell secretory function, and glucose and insulin tolerance were measured in RGS2 knockout (RGS2−/−) mice and their wild-type (RGS2+/+) littermate controls. β-Cell death was evaluated in RGS2-knockdown and -overexpressing β cells and RGS2−/− islets by flow cytometry, western blot, ELISA, TUNEL staining, and apoptosis RT2 profiler PCR array analysis. β-Cell mass was evaluated in pancreases from RGS2−/− and RGS2+/+ mice at 1 day, 4 weeks, and 25 weeks of age. Our data show that RGS2−/− islets secreted more insulin than RGS2+/+ islets when challenged with glucose or exendin-4. RGS2-knockdown cells are susceptible to hypoxia induced cell death while RGS2-overexpressing cells are protected from cell death. Depletion of RGS2 in islets alters expression of apoptosis-related genes and RGS2−/− islets are prone to apoptosis compared with RGS2+/+ islets. Ultimately, excessive insulin secretion and increased β-cell apoptosis contributed to a 70% reduction in pancreatic β-cell mass in RGS2−/− mice compared with RGS2+/+ mice at 25 weeks of age. RGS2 has critical roles in maintaining pancreatic β-cell mass via modulating β-cell function and apoptosis. It may serve as a druggable target to help prevent pancreatic β-cell loss in the treatment of diabetes.
TRIM45 functions as a tumor suppressor in the brain via its E3 ligase activity by stabilizing p53 through K63-linked ubiquitination
Authors: Zhang Jindong , Zhang Chuanxia , Cui Jun , Ou Jiayu , Han Jing , Qin Yunfei , Zhi Feng , Wang Rong-Fu 
Published: May 2017

AbstractTripartite motif-containing protein 45 (TRIM45) belongs to a large family of RING-finger-containing E3 ligases, which are highly expressed in the brain. However, little is known regarding the role of TRIM45 in cancer biology, especially in human glioma. Here, we report that TRIM45 expression is significantly reduced in glioma tissue samples. Overexpression of TRIM45 suppresses proliferation and tumorigenicity in glioblastoma cells in vitro and in vivo. In addition, CRISPR/Cas9-mediated knockout of TRIM45 promotes proliferation and inhibits apoptosis in glioblastoma cells. Further mechanistic analyses show that TRIM45 interacts with and stabilizes p53. TRIM45 conjugates K63-linked polyubiquitin chain to the C-terminal six lysine residues of p53, thereby inhibiting the availability of these residues to the K48-linked polyubiquitination that targets p53 for degradation. These findings suggest that TRIM45 is a novel tumor suppressor that stabilizes and activates p53 in glioma.
DT-13 synergistically enhanced vinorelbine-mediated mitotic arrest through inhibition of FOXM1-BICD2 axis in non-small-cell lung cancer cells
Authors: Li Hongyang , Sun Li , Li Hang , Lv Xiaodan , Semukunzi Herve , Li Ruiming , Yu Jun , Yuan Shengtao , Lin Sensen 
Published: May 2017

AbstractNon-small-cell lung cancer (NSCLC) is the most commonly diagnosed malignant disease with the leading cause of cancer-related death. Combination treatment remains the major strategy in the clinical therapy of NSCLC. Vinorelbine (NVB), a semi-synthetic vinca alkaloid, is used for advanced and metastatic NSCLC by destabilizing microtubule formation to induce mitotic arrest and cell death. However, the side effect of NVB heavily affected its effectiveness in clinical therapy. Hence, it is of great significance to develop new agents to synergize with NVB and decrease the adverse effect. In our study, we found that the saponin monomer 13 of the dwarf lilyturf tuber, DT-13, exhibiting anti-angiogenesis and anti-metastasis effect, synergized with NVB to inhibit cell proliferation in NSCLC cells. The synergistic interaction of DT-13 and NVB was confirmed by combination Index values. Also, DT-13 and NVB act in concert to inhibit the long-term colony formation. Furthermore, DT-13/NVB co-treatment cooperated to induce mitotic arrest and subsequent apoptosis. Mechanistically, we found that nuclear expression of transcription factors forkhead box M1 (FOXM1) and levels of motor adaptor bicaudal D2 (BICD2) were dramatically reduced by combination treatment. Importantly, oncogene FOXM1 was identified as the crucial regulator of BICD2, which played critical roles in NVB-induced mitotic spindle defects. Moreover, overexpression of FOXM1 and BICD2 significantly reversed mitotic arrest induced by DT-13/NVB co-treatment, and siRNAs against both genes greatly increased the combinational effects. In addition, in vivo study revealed that DT-13 combined with NVB significantly suppressed tumor growth in nude mice xenograft model, and downregulated the expression of FOXM1 and BICD2 in tumor tissues, which was consistent with in vitro study. In conclusion, DT-13 might provide a novel strategy for the chemosensitization of NVB in NSCLC therapy.