bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of a cytomegalovirus serology dual‐testing strategy in hematopoietic stem cell transplant recipients
Authors: Perry D.A. , Hakki M. 
Published: August 2016

AbstractBackgroundAccurate determination of recipient cytomegalovirus (CMV) serostatus before allogeneic hematopoietic stem cell transplantation (HSCT) is critical, as it is the most important predictor of post‐transplant CMV infection and remains associated with non‐relapse mortality. The purpose of this study was to assess a recipient dual‐testing strategy before HSCT.MethodsCMV serologic testing was performed before allogeneic HSCT using 2 different assays: reference laboratory (RL) and American Red Cross (ARC). In all cases, blood samples were obtained for RL testing either before ARC testing (median 130 days before HSCT [range 12–2594]) or at the same time (median 25 days before HSCT [range 8–129]). The results of serologic testing were correlated with CMV viremia post HSCT.ResultsOf 287 recipients evaluated, 76 (26.5%) had discordant results, of which 74 (97.4%) tested RL−/ARC+. Ten had RL and ARC testing performed on simultaneously obtained samples, 3 of which (30%) were discordant (3 [100%] RL−/ARC+). Acute myeloid leukemia and receipt of blood product transfusion in the interval between testing were associated with RL−/ARC+ discordance. Correlation with viremia after HSCT suggested that RL−/ARC+ discordance was caused by detection of anti‐CMV immunoglobulin transferred in transfused blood products and reduced specificity of the ARC assay.ConclusionCMV‐seronegative hematopoietic stem cell transplant recipients may be misclassified as seropositive if testing is performed after receipt of blood products or when using assays optimized for sensitivity at the expense of specificity. This misclassification may negatively affect post‐HSCT outcomes for individual patients and studies that rely on accurate CMV serology reporting.
Nicotiana alata Defensin Chimeras Reveal Differences in the Mechanism of Fungal and Tumor Cell Killing and an Enhanced Antifungal Variant
Authors: Bleackley Mark R. , Payne Jennifer A. E. , Hayes Brigitte M. E. , Durek Thomas , Craik David J. , Shafee Thomas M. A. , Poon Ivan K. H. , Hulett Mark D. , van der Weerden Nicole L. , Anderson Marilyn A. 
Published: August 2016

ABSTRACT

The plant defensin NaD1 is a potent antifungal molecule that also targets tumor cells with a high efficiency. We examined the features of NaD1 that contribute to these two activities by producing a series of chimeras with NaD2, a defensin that has relatively poor activity against fungi and no activity against tumor cells. All plant defensins have a common tertiary structure known as a cysteine-stabilized α-β motif which consists of an α helix and a triple-stranded β-sheet stabilized by four disulfide bonds. The chimeras were produced by replacing loops 1 to 7, the sequences between each of the conserved cysteine residues on NaD1, with the corresponding loops from NaD2. The loop 5 swap replaced the sequence motif (SKILRR) that mediates tight binding with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P
2
] and is essential for the potent cytotoxic effect of NaD1 on tumor cells. Consistent with previous reports, there was a strong correlation between PI(4,5)P
2
binding and the tumor cell killing activity of all of the chimeras. However, this correlation did not extend to antifungal activity. Some of the loop swap chimeras were efficient antifungal molecules, even though they bound poorly to PI(4,5)P
2
, suggesting that additional mechanisms operate against fungal cells. Unexpectedly, the loop 1B swap chimera was 10 times more active than NaD1 against filamentous fungi. This led to the conclusion that defensin loops have evolved as modular components that combine to make antifungal molecules with variable mechanisms of action and that artificial combinations of loops can increase antifungal activity compared to that of the natural variants.
IMP-27, a Unique Metallo-β-Lactamase Identified in Geographically Distinct Isolates of Proteus mirabilis
Authors: Dixon Nyssa , Fowler Randal C. , Yoshizumi A. , Horiyama Tsukasa , Ishii Y. , Harrison Lucas , Geyer Chelsie N. , Moland Ellen Smith , Thomson Kenneth , Hanson Nancy D. 
Published: August 2016

ABSTRACT

A novel metallo-β-lactamase gene,
bla
IMP-27
, was identified in unrelated
Proteus mirabilis
isolates from two geographically distinct locations in the United States. Both isolates harbor
bla
IMP-27
as part of the first gene cassette in a class 2 integron. Antimicrobial susceptibility testing indicated susceptibility to aztreonam, piperacillin-tazobactam, and ceftazidime but resistance to ertapenem. However, hydrolysis assays indicated that ceftazidime was a substrate for IMP-27.
Lipogenesis and Redox Balance in Nitrogen-Fixing Pea Bacteroids
Authors: Terpolilli Jason J. , Masakapalli Shyam K. , Karunakaran Ramakrishnan , Webb Isabel U. C. , Green Rob , Watmough Nicholas J. , Kruger Nicholas J. , Ratcliffe R. George , Poole Philip S. 
Published: August 2016

ABSTRACT

Within legume root nodules, rhizobia differentiate into bacteroids that oxidize host-derived dicarboxylic acids, which is assumed to occur via the tricarboxylic acid (TCA) cycle to generate NAD(P)H for reduction of N
2
. Metabolic flux analysis of laboratory-grown
Rhizobium leguminosarum
showed that the flux from [
13
C]succinate was consistent with respiration of an obligate aerobe growing on a TCA cycle intermediate as the sole carbon source. However, the instability of fragile pea bacteroids prevented their steady-state labeling under N
2
-fixing conditions. Therefore, comparative metabolomic profiling was used to compare free-living
R. leguminosarum
with pea bacteroids. While the TCA cycle was shown to be essential for maximal rates of N
2
fixation, levels of pyruvate (5.5-fold reduced), acetyl coenzyme A (acetyl-CoA; 50-fold reduced), free coenzyme A (33-fold reduced), and citrate (4.5-fold reduced) were much lower in bacteroids. Instead of completely oxidizing acetyl-CoA, pea bacteroids channel it into both lipid and the lipid-like polymer poly-β-hydroxybutyrate (PHB), the latter via a type III PHB synthase that is active only in bacteroids. Lipogenesis may be a fundamental requirement of the redox poise of electron donation to N
2
in all legume nodules. Direct reduction by NAD(P)H of the likely electron donors for nitrogenase, such as ferredoxin, is inconsistent with their redox potentials. Instead, bacteroids must balance the production of NAD(P)H from oxidation of acetyl-CoA in the TCA cycle with its storage in PHB and lipids.

IMPORTANCE
Biological nitrogen fixation by symbiotic bacteria (rhizobia) in legume root nodules is an energy-expensive process. Within legume root nodules, rhizobia differentiate into bacteroids that oxidize host-derived dicarboxylic acids, which is assumed to occur via the TCA cycle to generate NAD(P)H for reduction of N
2
. However, direct reduction of the likely electron donors for nitrogenase, such as ferredoxin, is inconsistent with their redox potentials. Instead, bacteroids must balance oxidation of plant-derived dicarboxylates in the TCA cycle with lipid synthesis. Pea bacteroids channel acetyl-CoA into both lipid and the lipid-like polymer poly-β-hydroxybutyrate, the latter via a type II PHB synthase. Lipogenesis is likely to be a fundamental requirement of the redox poise of electron donation to N
2
in all legume nodules.
Role of theganSPQABOperon in Degradation of Galactan by Bacillus subtilis
Authors: Watzlawick Hildegard , Morabbi Heravi Kambiz , Altenbuchner Josef 
Published: August 2016

ABSTRACTBacillus subtilispossesses different enzymes for the utilization of plant cell wall polysaccharides. This includes a gene cluster containing galactan degradation genes (ganAandganB), two transporter component genes (ganQandganP), and the sugar-binding lipoprotein-encoding geneganS(previously known ascycB). These genes form an operon that is regulated by GanR. The degradation of galactan byB. subtilisbegins with the activity of extracellular GanB. GanB is an endo-β-1,4-galactanase and is a member of glycoside hydrolase (GH) family 53. This enzyme was active on high-molecular-weight arabinose-free galactan and mainly produced galactotetraose as well as galactotriose and galactobiose. These galacto-oligosaccharides may enter the cell via the GanQP transmembrane proteins of the galactan ABC transporter. The specificity of the galactan ABC transporter depends on the sugar-binding lipoprotein, GanS. Purified GanS was shown to bind galactotetraose and galactotriose using thermal shift assay. The energy for this transport is provided by MsmX, an ATP-binding protein. The transported galacto-oligosaccharides are further degraded by GanA. GanA is a β-galactosidase that belongs to GH family 42. The GanA enzyme was able to hydrolyze short-chain β-1,4-galacto-oligosaccharides as well as synthetic β-galactopyranosides into galactose. Thermal shift assay as well as electrophoretic mobility shift assay demonstrated that galactobiose is the inducer of the galactan operon regulated by GanR. DNase I footprinting revealed that the GanR protein binds to an operator overlapping the −35 box of the σA-type promoter of Pgan, which is located upstream ofganS.IMPORTANCEBacillus subtilisis a Gram-positive soil bacterium that utilizes different types of carbohydrates, such as pectin, as carbon sources. So far, most of the pectin degradation systems and enzymes have been thoroughly studied inB. subtilis. Nevertheless, theB. subtilisutilization system of galactan, which is found as the side chain of the rhamnogalacturonan type I complex in pectin, has remained partially studied. Here, we investigated the galactan utilization system consisting of theganSPQABoperon and its regulatorganR. This study improves our knowledge of the carbohydrate degradation systems ofB. subtilis, especially the pectin degradation systems. Moreover, the galactan-degrading enzymes may be exploited for the production of galacto-oligosaccharides, which are used as prebiotic substances in the food industry.
What Predicts a Positive Response to Acupuncture? A Secondary Analysis of Three Randomised Controlled Trials of Insomnia
Authors: Yeung Wing-Fai , Chung Ka-Fai , Yu Yee-Man Branda , Lao Lixing 
Published: August 2016

Objective Few studies have investigated the predictors of the specific and non-specific effects of acupuncture. The aim of this secondary analysis was to determine patient characteristics that may predict a better treatment response to acupuncture for insomnia. Methods We pooled the data of three randomised, double-blind, placebo-controlled trials of acupuncture for insomnia to examine sociodemographic variables, clinical characteristics, baseline sleep-wake variables, and treatment expectancy in relation to acupuncture response. Subjects with an improvement in insomnia severity index (ISI) scores of ≥8 points from baseline to 1 week post-treatment were classified as responders. Factors were compared between responders and non-responders, and also by univariate and multivariate logistic regression analysis. Results A total of 116 subjects who received traditional needle acupuncture were included, of which 37 (31.9%) were classified as responders. Acupuncture responders had a higher educational level (p<0.01) and higher baseline ISI score (p<0.05), compared to non-responders. In the multivariate logistic regression analysis, only the number of years spent in full-time education remained significant as a predictor of treatment response (OR 1.21, 95% CI 1.06 to 1.38, p<0.01). Conclusions Consistent with previous studies, our data suggest that the response to acupuncture is difficult to predict. Although the predictive power of educational level is weak overall, our findings provide potentially valuable information that could be built upon in further research (including a larger sample size), and may help to inform patient selection for the treatment of chronic insomnia with acupuncture in the future. Trial registration number ClinicalTrials.gov: #NCT00839592; Results, #NCT00838994; Results, and #NCT01707706; Results.
Association of volunteering with mental well-being: a lifecourse analysis of a national population-based longitudinal study in the UK
Authors: Tabassum Faiza , Mohan John , Smith Peter 
Published: August 2016

ObjectivesThe association of volunteering with well-being has been found in previous research, but mostly among older people. The aim of this study was to examine the association of volunteering with mental well-being among the British population across the life course.DesignBritish Household Panel Survey, a population-based longitudinal study.SettingUK.Participants66 343 observations (person-years).Main outcome measuresMental well-being was measured by using the General Health Questionnaire (GHQ-12 or GHQ); high values denote high mental disorder. Four groups of volunteering participation were created: frequent (once a week), infrequent (once a month/several times a year), rare (once or less a year) and never. Multilevel linear models were used to analyse variations in mental well-being over the life course by levels of volunteering.ResultsWhen not considering age, those who engaged in volunteering regularly appeared to experience higher levels of mental well-being than those who never volunteered. To explore the association of volunteering with the GHQ across the life course, interaction terms were fitted between age and volunteering. The interactions were significant, demonstrating that these associations vary by age. The association between volunteering and well-being did not emerge during early adulthood to mid-adulthood, instead becoming apparent above the age of 40 years and continuing up to old age. Moreover, in early adulthood, the absence of engagement in voluntary activity was not related to mental well-being, but GHQ scores for this group increased sharply with age, levelling off after the age of 40 and then increasing again above the age of 70 years. The study also indicates variation in GHQ scores (65%) within individuals across time, suggesting evidence of lifecourse effects.ConclusionsWe conclude that volunteering may be more meaningful for mental well-being at some points of time in the life course.
Endovascular treatment for AIS with underlying ICAD
Authors: Al Kasab Sami , Almadidy Zayed , Spiotta Alejandro M , Turk Aquilla S , Chaudry M Imran , Hungerford John P , Turner Raymond D 
Published: August 2016

BackgroundAcute large vessel occlusion (LVO) can result from thromboemboli or underlying intracranial atherosclerotic disease (ICAD). Although the technique for revascularization differs significantly for these two lesions (simple thrombectomy for thromboemboli and balloon angioplasty and stenting for ICAD), the underlying etiology is often unknown in acute ischemic stroke (AIS).ObjectiveTo evaluate whether procedural complications, revascularization rates, and functional outcomes differ among patients with LVO from ICAD or thromboembolism.MethodsA retrospective review of thrombectomy cases from 2008 to 2015 was carried out for cases of AIS due to underlying ICAD. Thirty-six patients were identified. A chart and imaging review was performed to determine revascularization rates, periprocedural complications, and functional outcomes. Patients with ICAD and acute LVO were compared with those with underlying thromboemboli.ResultsAmong patients with ICAD and LVO, mean National Institutes of Health Stroke Scale (NIHSS) score on admission was 12.9±8.5, revascularization (Thrombolysis In Cerebral Infarction, TICI ≥2b) was achieved in 22/34 (64.7%) patients, 11% had postprocedural intracerebral hemorrhage (PH2), and 14/33 (42.4%) had achieved a modified Rankin Scale (mRS) score of 0–2 at the 3-month follow-up. Compared with patients without underlying ICAD, there was no difference in NIHSS on presentation, or in the postprocedural complication rate. However, procedure times for ICAD were longer (98.5±59.8 vs 37.1±34.2 min), there was significant difference in successful revascularization rate between the groups (p=0.001), and a trend towards difference in functional outcome at 3 months (p=0.07).ConclusionsDespite AIS with underlying ICAD requiring a more complex, technically demanding recanalization strategy than traditional thromboembolic AIS, it appears safe, and good outcomes are obtainable.
RNA Sequencing Identifies Transcriptionally Viable Gene Fusions in Esophageal Adenocarcinomas
Authors: Blum Andrew E. , Venkitachalam Srividya , Guo Yan , Kieber-Emmons Ann Marie , Ravi Lakshmeswari , Chandar Apoorva K. , Iyer Prasad G. , Canto Marcia I. , Wang Jean S. , Shaheen Nicholas J. , Barnholtz-Sloan Jill S. , Markowitz Sanford D. , Willis Joseph E. , Shyr Yu , Chak Amitabh , Varadan Vinay , Guda Kishore 
Published: August 2016

Abstract
Esophageal adenocarcinoma is a deadly cancer with increasing incidence in the United States, but mechanisms underlying pathogenesis are still mostly elusive. In addressing this question, we assessed gene fusion landscapes by comprehensive RNA sequencing (RNAseq) of 55 pretreatment esophageal adenocarcinoma and 49 nonmalignant biopsy tissues from patients undergoing endoscopy for Barrett's esophagus. In this cohort, we identified 21 novel candidate esophageal adenocarcinoma–associated fusions occurring in 3.33% to 11.67% of esophageal adenocarcinomas. Two candidate fusions were selected for validation by PCR and Sanger sequencing in an independent set of pretreatment esophageal adenocarcinoma (N = 115) and nonmalignant (N = 183) biopsy tissues. In particular, we observed RPS6KB1–VMP1 gene fusion as a recurrent event occurring in approximately 10% of esophageal adenocarcinoma cases. Notably, esophageal adenocarcinoma cases harboring RPS6KB1–VMP1 fusions exhibited significantly poorer overall survival as compared with fusion-negative cases. Mechanistic investigations established that the RPS6KB1–VMP1 transcript coded for a fusion protein, which significantly enhanced the growth rate of nondysplastic Barrett's esophagus cells. Compared with the wild-type VMP1 protein, which mediates normal cellular autophagy, RPS6KB1–VMP1 fusion exhibited aberrant subcellular localization and was relatively ineffective in triggering autophagy. Overall, our findings identified RPS6KB1–VMP1 as a genetic fusion that promotes esophageal adenocarcinoma by modulating autophagy-related processes, offering new insights into the molecular pathogenesis of esophageal adenocarcinomas. Cancer Res; 76(19); 5628–33. ©2016 AACR.
Genetic and Methylation-Induced Loss of miR-181a2/181b2 within chr9q33.3 Facilitates Tumor Growth of Cervical Cancer through the PIK3R3/Akt/FoxO Signaling Pathway
Authors: Mei Qian , Li Xiang , Zhang Kang , Wu Zhiqiang , Li Xiaolei , Meng Yuanguang , Guo Mingzhou , Luo Guangbin , Fu Xiaobing , Han Weidong 
Published: August 2016

Abstract
Purpose: Loss of Chr9q31–33 is one of the most common chromosome imbalances of cervical cancer, but the underlying mechanism has not been well documented.
Experimental Design: The loss of heterozygosity (LOH) status of Chr9q31–33 was investigated utilizing 26 microsatellite markers. We detected the expression of miR-181a2/181b2 by qRT-PCR analysis of cervical cancer cell lines and 100 paired tumor samples and corresponding adjacent non-tumor tissues. Kaplan–Meier and Cox proportional hazard regression analyses were performed to identify the prognostic value of miR-181a2/181b2. Regulation of expression was analyzed by methylation-specific PCR. The tumor-suppressing effects of miR-181a2/181b2 were determined in vitro and in vivo. The target gene and signaling pathway that mediated the function of miR-181a2/181b2 were also identified.
Results: Chr9q33.3 was identified as one of the most deleted regions in cervical cancer. Underexpression of miR-181a2/181b2 was detected in 46% of cervical cancer and was induced by the LOH of chr9q33.3 and promoter hypermethylation. Attenuated miR-181a2/181b2 expression predicted a poor prognostic phenotype and advanced clinical stage of cervical cancer. miR-181a2/181b2 prominently dampened cell-cycle progression, suppressed cell growth, and promoted apoptosis of tumor cells in vitro. They also effectively impeded tumor formation and growth in vivo. miR-181a2/181b2 exert the tumor suppressor ability by depressing the direct target PIK3R3 (p55γ) and consequently modulating the PIK3R3/Akt/FoxO signaling pathway.
Conclusions: We demonstrated a cause-and-effect event beginning from loss of chr9q33.3, a frequent event in cervical cancer, to the underexpression of miR-181a2/181b2, leading to the elevated activation of the PI3K pathway. Clin Cancer Res; 23(2); 575–86. ©2016 AACR.
Safety profile of lamotrigine in overdose
Authors: Alabi Akintunde , Todd Adam , Husband Andrew , Reilly Joe 
Published: August 2016

Background: Lamotrigine is an anticonvulsant as well as a mood stabilizer. Apart from its established use in the treatment of epilepsy, there has been an expansion of its use in the treatment of mental disorders. Patients with epilepsy as well as those with mental disorders are at increased risk of deliberate drug overdoses. An evidence base for the safety profile of lamotrigine in overdose is an essential tool for prescribers. The objective of this study was to carry out a narrative synthesis of the existing evidence for the safety profile of lamotrigine in overdose. Methods: A systematic search was conducted of EMBASE (1974 to December 2015), MEDLINE (1946 to December 2015), PsycINFO (1806 to December 2015) and CINAHL (1981 to December 2015) databases. Studies were included in which there was a deliberate or accidental single drug overdose of lamotrigine, with its toxic effects described. Studies that did not involve an overdose were excluded. A narrative synthesis of the described toxic effects was carried out. Results: Out of 562 articles identified, 26 studies were included, mainly in the form of case reports and series. The most commonly described toxic effects of lamotrigine were on the central nervous system, specifically seizures, movement disorders and reduced consciousness. Other toxic effects included QTc interval and QRS complex prolongations, hypersensitivity reactions, serotonin syndrome as well as rhabdomyolysis possibly due to seizures and/or agitation. Deaths were recorded in two studies, with cardiovascular and neurological toxic effects described. Conclusions: Even though lamotrigine has been reported to be well tolerated, there is a risk of toxic effects which can be life threatening in overdose. This needs to be borne in mind when prescribing to patients at an increased risk of deliberate drug overdose.