bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of predictors of pain response in patients with bone metastasis undergoing palliative radiotherapy: Does age matter?
Authors: Cacicedo Jon , Gómez‐Iturriaga Alfonso , Navarro Arturo , Morillo Virginia , Willisch Patricia , Lopez‐Guerra Jose Luis , Illescas Ana , Casquero Francisco , Del Hoyo Olga , Ciervide Raquel , Martinez‐Indart Lorea , Bilbao Pedro , Rades Dirk 
Published: May 2018

AbstractIntroductionTo evaluate whether age is a predictor of pain response after radiotherapy for painful bone metastasis (BM).MethodsBetween June 2010 and June 2014, 204 patients with BM undergoing palliative radiotherapy participated in a multicentre prospective study. Patients completed the Brief Pain Inventory (BPI) to rate the intensity pain (from 0 to 10) at baseline and 4 weeks after radiotherapy. To determine which variables predicted pain response and particularly whether age is a predictor, logistic regression analysis was used. Baseline variables considered were: age (≤65/66–75/>75 years), sex, Eastern Cooperative Oncology Group performance status (0–1/≥2), pretreatment pain score (≤4/5–7/≥8), radiotherapy (single/multiple fraction), primary tumour location, visceral metastases (yes/no), concomitant systemic chemotherapy and bisphosphonate use (yes/no).ResultsPain response was assessed in the 128 patients who completed BPI pretreatment and at 4 weeks after radiotherapy. According to univariate analysis, pain response was better in over 75‐year‐olds than younger patients: (OR, 3.2; 95% CI, 1.1–9.1; P = 0.031). Response was better in patients receiving multiple fractions rather than a single fraction of 8 Gy (OR, 2.8; 95% CI, 1.2–6.1; P = 0.01), and in patients with a pretreatment pain score ≥8 vs ≤7 (OR, 2.4; 95% CI, 1.1–5.0; P = 0.017). No other variables were significant. Multivariate analysis showed that treatment schedule (OR, 3.4; 95% CI 1.4–7.9; P = 0.004) and pre‐radiotherapy pain score (OR, 2.8; 95% CI 1.3–6.3; P = 0.009) were the only independent predictors of pain response.ConclusionAll patients with painful bone metastasis should be referred for palliative radiotherapy to relieve the pain regardless of age. Therefore, an older age should not be a reason to withhold palliative radiation treatment.
Noncoding RNAs as therapeutic targets in atherosclerosis with diabetes mellitus
Authors: Tang Ningning , Jiang Shaoyan , Yang Yanyan , Liu Shaoyan , Ponnusamy Murugavel , Xin Hui , Yu Tao 
Published: May 2018

SummaryAtherosclerosis is one of the major macrovascular complications of diabetes mellitus (DM), and it is the main cause of death from clinical observation. Among various cell types involved in this disorder, endothelial cells, vascular smooth muscle cells (VSMCs), and macrophages play a crucial role in the occurrence and development of this disease. The regulation and stabilization of these cells are a key therapeutic strategy for DM‐associated atherosclerosis. An increasing number of evidences implicate that various types of noncoding RNAs (ncRNAs) play a vital role in many cellular responses as well as in physiological and pathological processes of atherosclerosis and DM that drive atherogenic/antiatherogenic processes in those cells. Encouragingly, many ncRNAs have already been tested in animal experiments or clinical trials showing good performance. In this review, we summarize recent progresses in research on functional regulatory role of ncRNAs in atherosclerosis with DM. More importantly, we illustrate new thoughts and findings relevant to ncRNAs as potential therapeutic targets or biomarkers for atherosclerosis with DM.
Apolipoprotein E region molecular signatures of Alzheimer's disease
Authors: Kulminski Alexander M. , Huang Jian , Wang Jiayi , He Liang , Loika Yury , Culminskaya Irina 
Published: May 2018

SummaryAlthough the APOE region is the strongest genetic risk factor for Alzheimer's diseases (ADs), its pathogenic role remains poorly understood. Elucidating genetic predisposition to ADs, a subset of age‐related diseases characteristic for postreproductive period, is hampered by the undefined role of evolution in establishing molecular mechanisms of such diseases. This uncertainty is inevitable source of natural‐selection–free genetic heterogeneity in predisposition to ADs. We performed first large‐scale analysis of linkage disequilibrium (LD) structures characterized by 30 polymorphisms from five genes in the APOE 19q13.3 region (BCAM, NECTIN2, TOMM40, APOE, and APOC1) in 2,673 AD‐affected and 16,246 unaffected individuals from five cohorts. Consistent with the undefined role of evolution in age‐related diseases, we found that these structures, being highly heterogeneous, are significantly different in subjects with and without ADs. The pattern of the difference represents molecular signature of AD comprised of single nucleotide polymorphisms (SNPs) from all five genes in the APOE region. Significant differences in LD in subjects with and without ADs indicate SNPs from different genes likely involved in AD pathogenesis. Significant and highly heterogeneous molecular signatures of ADs provide unprecedented insight into complex polygenetic predisposition to ADs in the APOE region. These findings are more consistent with a complex haplotype than with a single genetic variant origin of ADs in this region.
Concomitant drug abuse of opioid dependent patients in maintenance treatment detected with a multi‐target screening of oral fluid
Authors: Wagner Elias , Raabe Florian , Martin Gabriele , Winter Catja , Plörer Diana , Krause Daniela L. , Adorjan Kristina , Koller Gabriele , Pogarell Oliver 
Published: May 2018

Background and ObjectivesNumbers of drug‐related deaths have been growing in Europe and the USA, especially those attributable to mixed drug consumption. Overdose deaths account for about one third up to one half of all illicit drug deaths worldwide. In most cases opioids are involved. Opioid maintenance treatment (OMT) is a well‐established therapy option among people with opioid dependence. The aim of this study was to assess concomitant substance abuse in opioid‐dependent patients under OMT in two centers in Munich, Germany.MethodsOral fluid samples of opioid‐dependent patients (n = 388) in OMT were randomly collected and analyzed by a multi‐drug screening covering a wide range of psychotropic agents with UPLC‐MS/MS techniques.ResultsFifty‐one percent of the patients had concomitant substance abuse of at least one non‐prescribed substance, 32% were positive for substances that were not tested in routine urine diagnostics, especially pregabalin. Fifty‐seven percent received take‐home opioid medication, and 26% had contact with underage children. Among the take‐home subgroup, a concomitant substance abuse of 43.5% was detected. Furthermore 52.5% of the patients with contact to underaged children exhibited concomitant substance abuse.ConclusionsConcomitant substance abuse is a serious issue among OMT patients. Screening for a broader range of substances than usually analyzed, reveals additional relevant abuse among OMT patients, including pregabalin—an anticonvulsant.Scientific SignificanceOur study underscores the importance of monitoring a broad range of substances including others than usually screened in opioid‐dependent patients in OMT. (Am J Addict 2018;27:407–412)
Long‐term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy
Authors: Sandborn W. J. , Rutgeerts P. , Gasink C. , Jacobstein D. , Zou B. , Johanns J. , Sands B. E. , Hanauer S. B. , Targan S. , Ghosh S. , de Villiers W. J. S. , Colombel J.‐F. , Feagan B. G. 
Published: May 2018

SummaryBackgroundIn Phase 3 studies of ustekinumab, a fully human monoclonal IL‐12/23p40 antibody approved for moderate‐to‐severe Crohn's disease, patients entered a long‐term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment. Efficacy through 92 weeks and safety through 96 weeks of IM‐UNITI maintenance are reported.MethodsUNITI‐1 (TNF‐antagonist failures) and UNITI‐2 (conventional therapy failures) patients (N = 1281) entered IM‐UNITI, including 397 ustekinumab intravenous induction responders randomised to subcutaneous ustekinumab 90 mg every 12 weeks, every 8 weeks, or placebo and 884 nonrandomised patients. Dose‐adjustment to 90 mg every 8 weeks occurred in patients randomised to 90 mg every 12 weeks and placebo patients with loss of response (Weeks 8–32). All Week 44 completers could enter the long‐term extension without further dose adjustment. Placebo patients discontinued following study unblinding.ResultsA total of 718 patients (all treated) entered the long‐term extension (298 randomised and 420 not randomised). Overall, 86.5% (621/718) completed Week 96. The proportions of randomised patients in clinical remission were generally maintained from Week 44 through 92 in ustekinumab 90 mg every 12 weeks (77.4% to 72.6%), every 8 weeks (84.1% to 74.4%), and prior dose adjustment groups (63.4% to 53.5%). At Week 92, the proportions of patients in clinical remission were similar in the ustekinumab 90 mg every 12 weeks and every 8 weeks groups and lower in patients with prior dose adjustment. Proportions of patients in clinical remission at Week 92 for all treated every 8 weeks (64.4%) and every 12 weeks (64.3%) groups were lower than randomised every 8 weeks (74.4%) and every 12 weeks (72.6%) groups, but similarly maintained. Safety events (per hundred patient‐years) were similar among all placebo and ustekinumab patients (Week 0‐96), including adverse events (484.39 vs 447.76), serious adverse events (19.24 vs 18.82), and serious infections (4.09 vs 4.02). No dose effect was observed.ConclusionsSubcutaneous ustekinumab maintained clinical response and remission through Week 92. No new safety signals were observed. ClinicalTrials.gov number NCT01369355.
Effectiveness, treatment completion and safety of sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir + dasabuvir in patients with chronic kidney disease: an ERCHIVES study
Authors: Butt A. A. , Ren Y. , Puenpatom A. , Arduino J. M. , Kumar R. , Abou‐Samra A‐B. 
Published: May 2018

SummaryBackgroundChronic kidney disease (CKD) was a relative contraindication to hepatitis C virus (HCV) treatment in the interferon/ribavirin era.AimTo determine the efficacy, tolerability and safety of sofosbuvir/ledipasvir (SOF/LDV) and paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens in persons with CKD.MethodsWe identified persons initiated on a SOF/LDV or PrOD regimen from October 30, 2014 to April 30, 2016. We excluded those with missing HCV genotype or eGFR values. We determined treatment completion and sustained virologic response (SVR) rates, and proportion developing worsening renal function or grade 3/4 haematologic toxicity.ResultsAmong 13 663 persons on SOF/LDV±ribavirin, 14% and 1% persons had CKD Stage 3 and 4‐5 respectively, 67.8% completed treatment, 98.2% achieved SVR. Treatment completion or SVR rates did not decline with advanced CKD or ribavirin administration. Among 3961 persons on PrOD±ribavirin, 9% and 3% persons had CKD Stage 3 and 4‐5, respectively, 74.0% completed treatment and 98.2% achieved SVR. A decrease in treatment completion rates was seen in CKD stage 4‐5 and those on ribavirin, but this did not impact SVR rates. A >10 mL/min/1.73 m2 drop in eGFR from baseline was observed in 30%‐38% of persons with baseline eGFR ≥60 mL/min/1.73 m2, but in only 0%‐6% with CKD4‐5. Grade 3/4 anaemia was more frequent in persons with CKD4‐5, but ribavirin co‐administration did not appear to affect this.ConclusionsSOF/LDV and PrOD achieved high SVR rates in CKD population. Treatment completion rates were lower than expected. A decline in eGFR and development of anaemia were observed in a substantial proportion of persons, but the clinical implications remain unclear.
Anti‐viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus‐related hepatocellular carcinoma: real‐world east and west experience
Authors: Chen V. L. , Yeh M.‐L. , Le A. K. , Jun M. , Saeed W. K. , Yang J. D. , Huang C.‐F. , Lee H. Y. , Tsai P.‐C. , Lee M.‐H. , Giama N. , Kim N. G. , Nguyen P. P. , Dang H. , Ali H. A. , Zhang N. , Huang J.‐F. , Dai C.‐Y. , Chuang W.‐L. , Roberts L. R. , Jun D. W. , Lim Y.‐S. , Yu M.‐L. , Nguyen M. H. 
Published: May 2018

SummaryBackgroundHepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti‐viral therapy affects survival after HCC diagnosis.MethodsThis was an international multicentre cohort study of 2518 HBV‐related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti‐viral therapy and cirrhosis on patients' risk of death.ResultsApproximately, 48% of patients received anti‐viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti‐viral therapy would have been indicated for >60% of the patients not on anti‐viral therapy based on American criteria. Patients with cirrhosis had lower 5‐year survival (34% vs 46%; P < 0.001) while patients receiving anti‐viral therapy had increased 5‐year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti‐viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001).ConclusionsAnti‐viral therapy improved overall survival in patients with HBV‐related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti‐viral therapy in HBV‐related HCC and better linkage‐to‐care for HBV patients are needed.
Physical deconditioning is the common denominator in both obese and overweight subjects with nonalcoholic steatohepatitis
Authors: Argo C. K. , Stine J. G. , Henry Z. H. , Lackner C. , Patrie J. T. , Weltman A. L. , Caldwell S. H. 
Published: May 2018

SummaryBackgroundObesity and decreased physical activity mirror increasing prevalence of nonalcoholic fatty liver disease (NAFLD).AimWe aimed to investigate associations between aerobic fitness, anthropometrics and disease parameters in patients with nonalcoholic steatohepatitis (NASH). We hypothesised that NASH subjects have lower aerobic power and capacity than untrained, sedentary, normal subjects.MethodsForty subjects (60% obese, 40% overweight) with biopsy‐confirmed NASH and NAFLD activity score (NAS) ≥4 were enrolled in a clinical trial where anthropometrics, laboratories, liver fat content by MRI, activity, and aerobic fitness by cycle ergometry data were obtained.ResultsNASH subjects were significantly deconditioned compared to 148 untrained, sedentary, healthy subjects from our laboratory in aerobic power (VO2peak) (NASH 16.8 ± 6.6 vs control 28.4 ± 10.6 mL/kg/min, P < 0.0001) and capacity (VO2 at lactate threshold [LT]) (NASH 8.3 ± 2.5 vs control 14.1 ± 5.9 mL/kg/min, P < 0.0001). NASH subjects' fitness was comparable to the “least fit” tertile of controls: VO2peak [NASH 16.8 ± 6.6 vs “least fit” 17.3 ± 3.3, P = 0.64]) and VO2 at LT (NASH 8.3 ± 2.5 vs “least fit” 9.3 ± 2.1, P = 0.31). Fitness was similar in obese compared to overweight subjects (adjusted for gender) and was not correlated with visceral adiposity or NAS. Engaging in dedicated cardiovascular activity correlated with higher VO2peak and VO2peak at LT.ConclusionsAerobic deconditioning was universally present in NASH subjects. NASH subjects' fitness was similar to our laboratory's “least fit” untrained, sedentary control subjects. Further research investigating NASH patients' ability to improve low baseline aerobic fitness is warranted.
Maize‐dominated crop sequences in northern Germany: Reaction of the weed species communities
Authors: von Redwitz Christoph , Gerowitt Bärbel 
Published: May 2018

AbstractQuestionsDoes the mere introduction of maize into the crop sequence change the weed species community? Does a growing share of maize cropping lead to a more problematic weed species community? Do we generally have to expect problematic weed species communities when maize is continuously cultivated?LocationNorthern Germany.MethodsWeeds in 224 maize fields were surveyed in 3 years and management data of these fields collected for the previous ten cropping years. We arranged seven parameters describing maize cropping patterns and used them as constraining variables in redundancy analysis.ResultsThe weed species community was immediately altered by the introduction of maize into the crop sequence. Of those weed species known to be adapted to maize, in our study Echinochloa crus‐galli and to a lesser extent Setaria spp. were strongly related to dense maize cropping patterns, other summer annuals were much less affected.ConclusionsThe spatial growth of areas dedicated to maize cropping will change the weed species communities and, in turn, the arable landscape. E. crus‐galli deserves particular attention due to its tendency to develop herbicide resistance and its positive reaction to dense maize cropping patterns.
Effect of endocannabinoid signalling on cell fate: life, death, differentiation and proliferation of brain cells
Authors: Garcia‐Arencibia Moises , Molina-Holgado Eduardo , Molina‐Holgado Francisco 
Published: May 2018

Cell fate events are regulated by different endogenous developmental factors such as the cell micro‐environment, external or remote signals and epigenetic factors. Among the many regulatory factors, endocannabinoid‐associated signalling pathways are known to conduct several of these events in the developing nervous system and in the adult brain. Interestingly, endocannabinoids exert modulatory actions in both physiological and pathological conditions. Endocannabinoid signalling can promote cell survival by acting on non‐transformed brain cells (neurons, astrocytes or oligodendrocytes) and can have either a protumoural or antitumoural effect on transformed cells. Moreover, endocannabinoids are able to attenuate the detrimental effects on neurogenesis and neuroinflammation associated with ageing. Thus, the endocannabinoid system emerges as an important regulator of cell fate, controlling cell survival/cell death decisions depending on the cell type and its environment.Linked ArticlesThis article is part of a themed section on 8thEuropean Workshop on Cannabinoid Research. To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc
Refining area of occupancy to address the modifiable areal unit problem in ecology and conservation
Authors: Moat Justin , Bachman Steven P. , Field Richard , Boyd Doreen S. 
Published: May 2018

AbstractThe modifiable areal unit problem is prevalent across many aspects of spatial analysis within ecology and conservation. The problem is particularly manifested when calculating metrics for extinction risk estimation, for example, area of occupancy (AOO). Although embedded in the International Union for the Conservation of Nature (IUCN) Red List criteria, AOO is often not used or is poorly applied. We evaluated new and existing methods for calculating AOO from occurrence records and devised a method for determining the minimum AOO with a uniform grid. We evaluated the grid cell shape, origin, and rotation with real‐world and simulated data and reviewed the effects on AOO values and possible impacts for species already assessed on the IUCN Red List. The AOO varied by up to 80%, and a ratio of cells to points of 1:1.21 yielded the maximum variation in the number of occupied cells. These findings potentially impact 3% of existing species on the IUCN Red List and species not yet assessed. Our new method combined grid rotation and moving grid origin and gave fast, robust, and reproducible results and, in the majority of cases, achieved the minimum AOO. As well as determining minimum AOO, our method yielded a confidence interval that should be incorporated into existing tools that support species risk assessment. We recommend when recording AOO and other areal measurements that the methods; summary statistics across multiple iterations; angle and origin of the minimum grid; map projection; and datum be recorded, this will lead to more robust species risk assessments.
Constitutive plasma membrane monoamine transporter (PMAT, Slc29a4) deficiency subtly affects anxiety‐like and coping behaviours
Authors: Gilman T. Lee , George Christina M. , Vitela Melissa , Herrera‐Rosales Myrna , Basiouny Mohamed S. , Koek Wouter , Daws Lynette C. 
Published: May 2018

AbstractOriginally, uptake‐mediated termination of monoamine (e.g., serotonin and dopamine) signalling was believed to only occur via high‐affinity, low‐capacity transporters (“uptake1”) such as the serotonin or dopamine transporters, respectively. Now, the important contribution of a second low‐affinity, high‐capacity class of biogenic amine transporters has been recognised, particularly in circumstances when uptake1 transporter function is reduced (e.g., antidepressant treatment). Pharmacologic or genetic reductions in uptake1 function can change locomotor, anxiety‐like or stress‐coping behaviours. Comparable behavioural investigations into reduced low‐affinity, high‐capacity transporter function are lacking, in part, due to a current dearth of drugs that selectively target particular low‐affinity, high‐capacity transporters, such as the plasma membrane monoamine transporter. Therefore, the most direct approach involves constitutive genetic knockout of these transporters. Other groups have reported that knockout of the low‐affinity, high‐capacity organic cation transporters 2 or 3 alters anxiety‐like and stress‐coping behaviours, but none have assessed behaviours in plasma membrane monoamine transporter knockout mice. Here, we evaluated adult male and female plasma membrane monoamine transporter wild‐type, heterozygous and knockout mice in locomotor, anxiety‐like and stress‐coping behavioural tests. A mild enhancement of anxiety‐related behaviour was noted in heterozygous mice. Active‐coping behaviour was modestly and selectively increased in female knockout mice. These subtle behavioural changes support a supplemental role of plasma membrane monoamine transporter in serotonin and dopamine uptake, and suggest sex differences in transporter function should be examined more closely in future investigations.
Ferulic acid reduced histamine levels in the smoked horsemeat sausage
Authors: Zhao Lili , Xue Linlin , Li Binbin , Wang Qingling , Li Baokun , Lu Shiling , Fan Qinglu 
Published: May 2018

SummaryThis study assessed the effect of ferulic acid on the accumulation of histamine in traditional Xinjiang smoked horsemeat sausage. The dynamics of histamine‐producing microorganisms were monitored by PCR‐denaturing gradient gel electrophoresis (DGGE) with specific primer pairs, and histidine and histamine levels were measured by high‐performance liquid chromatography (HPLC). Relative parameters including microbiological growth, pH and moisture content were also evaluated. PCR‐DGGE provided a rapid and convenient method for detecting and identifying histamine‐producing bacteria. The results showed that ferulic acid reduced the histamine concentration and inhibited the growth of histamine‐producing bacteria during fermentation and ripening. Additionally, the inhibitory effect of ferulic acid was stronger than that of the starter culture. Therefore, ferulic acid appears to be a useful additive for manufacturing fermented sausages.