bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble IL-1 decoy receptor is associated with gastric adenocarcinoma
Authors: Cakir Isil , Kilic Eser , Ozel Coskun Banu Demet , Cakir Nuri 
Published: January 2017

Abstract

Background
In recent years, studies on gastric cancer include changes in cancer associated immune system activation and the levels of immune system markers. It has been demonstrated that TNF-α (tumor necrosis factor-alpha) and IL-6 (interleukin-6) play a role in inflammatory associated carcinogenesis.

Objective
Our aim was to investigate serum soluble IL-1 decoy receptor (sIL- 1RII), TNF-α and IL-6 levels in gastric adenocarcinoma patients.

Materials and methods
Male gastric adenocarcinoma patients and dyspeptic participants, in total 55 cases were included. Serum sIL-1RII, TNF-α and IL-6 concentrations were measured.

Results
The median sIL-1RII levels of the patients were statistically significantly lower than the median of the control group (3111 ng/mL; 3601 ng/mL, respectively) (p=0.003). But the median TNF-α and IL-6 levels (58.17 ng/mL; 10.22 ng/mL, respectively) were both numerically higher than those of control group levels (16.62 ng/mL; 5.74 ng/mL, respectively). Also, patients’ median TNF-α levels were found statistically significantly higher (p=0.034).

Conclusion
This study showed the increase of TNF-α, IL-6 levels and for the first time the decrease of sIL-1RII in gastric cancer patients. We propose that negative regulation of gastric cancer using sIL-1RII could be a new anti-cancer strategy.

General significance
Our study provides target pathways for further studies in the pathophysiology of gastric cancer.
Alkylation of tetrathiotungstate anions: crystal structures of the alkylthiolatotrithiotungstate complexes [PPh4]2[WS3(S
n
Pr)][WS3(S
n
Bu)]·½C6H6 and [PPh4][WS3(SCH2C6H4CH2Cl-4)]
Authors: Qian Ting-Ting , Hu Meng-Jie , Xin Zhifeng , Jia Ai-Quan , Zhang Qian-Feng 
Published: January 2017

Abstract
The reaction of [PPh4]2[WS4] in CH3CN with excess n-propylbromide or n-butylbromide gave alkylthiolatotrithiotungstate complexes, [PPh4][WS3(SR)] (1: R=n-propyl; 2: R=n-butyl). The analogous reaction with 1-bromomethyl-4-chloromethyl-benzene afforded a benzylthiolatotrithiotungstate complex, [PPh4][WS3(SCH2C6 H4CH2Cl-4)] (3), whereas the reaction with 1,4-bis-bromomethyl-benzene led to isolation of a dinuclear complex [PPh4]2[WS3(μ-SCH2C6H4CH2S)WS3] (4). Complexes 1–4 were characterized spectroscopically and the crystal structures of 1/2·½C6H6 and 3 have been determined by X-ray diffraction.
Amygdala Contributions to Stimulus–Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning
Authors: Rudebeck Peter H. , Ripple Joshua A. , Mitz Andrew R. , Averbeck Bruno B. , Murray Elisabeth A. 
Published: January 2017

Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus–reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus–reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus–reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus–reward associations rapidly by shaping encoding within OFC and MFC.SIGNIFICANCE STATEMENTAltered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus–reward associations. MFC also showed increased encoding of the instrumental responses that monkeys made on each trial. Behaviorally, changes in neural activity were accompanied by slower stimulus–reward learning. The findings suggest that interactions among amygdala, OFC, and MFC contribute to learning about stimuli that predict rewards.
Histone Deacetylase Inhibitors Protect Against Pyruvate Dehydrogenase Dysfunction in Huntington's Disease
Authors: Naia Luana , Cunha-Oliveira Teresa , Rodrigues Joana , Rosenstock Tatiana R. , Oliveira Ana , Ribeiro Márcio , Carmo Catarina , Oliveira-Sousa Sofia I. , Duarte Ana I. , Hayden Michael R. , Rego A. Cristina 
Published: January 2017

Transcriptional deregulation and changes in mitochondrial bioenergetics, including pyruvate dehydrogenase (PDH) dysfunction, have been described in Huntington's disease (HD). We showed previously that the histone deacetylase inhibitors (HDACIs) trichostatin A and sodium butyrate (SB) ameliorate mitochondrial function in cells expressing mutant huntingtin. In this work, we investigated the effect of HDACIs on the regulation of PDH activity in striatal cells derived from HD knock-in mice and YAC128 mice. Mutant cells exhibited decreased PDH activity and increased PDH E1alpha phosphorylation/inactivation, accompanied by enhanced protein levels of PDH kinases 1 and 3 (PDK1 and PDK3). Exposure to dichloroacetate, an inhibitor of PDKs, increased mitochondrial respiration and decreased production of reactive oxygen species in mutant cells, emphasizing PDH as an interesting therapeutic target in HD. Treatment with SB and sodium phenylbutyrate, another HDACI, recovered cell viability and overall mitochondrial metabolism in mutant cells. Exposure to SB also suppressed hypoxia-inducible factor-1 (HIF-1α) stabilization and decreased the transcription of the two most abundant PDK isoforms, PDK2 and PDK3, culminating in increased PDH activation in mutant cells. Concordantly, PDK3 knockdown improved mitochondrial function, emphasizing the role of PDK3 inactivation on the positive effects achieved by SB treatment. YAC128 mouse brain presented higher mRNA levels of PDK1–3 and PDH phosphorylation and decreased energy levels that were significantly ameliorated after SB treatment. Furthermore, enhanced motor learning and coordination were observed in SB-treated YAC128 mice. These results suggest that HDACIs, particularly SB, promote the activity of PDH in the HD brain, helping to counteract HD-related deficits in mitochondrial bioenergetics and motor function.SIGNIFICANCE STATEMENTThe present work provides a better understanding of mitochondrial dysfunction in Huntington's disease (HD) by showing that the pyruvate dehydrogenase (PDH) complex is a promising therapeutic target. In particular, the histone deacetylase inhibitor sodium butyrate (SB) may indirectly (through reduced hypoxia-inducible factor 1 alpha stabilization) decrease the expression of the most abundant PDH kinase isoforms (e.g., PDK3), ameliorating PDH activity and mitochondrial metabolism and further affecting motor behavior in HD mice, thus constituting a promising agent for HD neuroprotective treatment.
Cortical Representation of Interaural Time Difference Is Impaired by Deafness in Development: Evidence from Children with Early Long-term Access to Sound through Bilateral Cochlear Implants Provided Simultaneously
Authors: Easwar Vijayalakshmi , Yamazaki Hiroshi , Deighton Michael , Papsin Blake , Gordon Karen 
Published: January 2017

Accurate use of interaural time differences (ITDs) for spatial hearing may require access to bilateral auditory input during sensitive periods in human development. Providing bilateral cochlear implants (CIs) simultaneously promotes symmetrical development of bilateral auditory pathways but does not support normal ITD sensitivity. Thus, although binaural interactions are established by bilateral CIs in the auditory brainstem, potential deficits in cortical processing of ITDs remain. Cortical ITD processing in children with simultaneous bilateral CIs and normal hearing with similar time-in-sound was explored in the present study. Cortical activity evoked by bilateral stimuli with varying ITDs (0, ±0.4, ±1 ms) was recorded using multichannel electroencephalography. Source analyses indicated dominant activity in the right auditory cortex in both groups but limited ITD processing in children with bilateral CIs. In normal-hearing children, adult-like processing patterns were found underlying the immature P1 (∼100 ms) response peak with reduced activity in the auditory cortex ipsilateral to the leading ITD. Further, the left cortex showed a stronger preference than the right cortex for stimuli leading from the contralateral hemifield. By contrast, children with CIs demonstrated reduced ITD-related changes in both auditory cortices. Decreased parieto-occipital activity, possibly involved in spatial processing, was also revealed in children with CIs. Thus, simultaneous bilateral implantation in young children maintains right cortical dominance during binaural processing but does not fully overcome effects of deafness using present CI devices. Protection of bilateral pathways through simultaneous implantation might be capitalized for ITD processing with signal processing advances, which more consistently represent binaural timing cues.SIGNIFICANCE STATEMENTMultichannel electroencephalography demonstrated impairment of binaural processing in children who are deaf despite early access to bilateral auditory input by first finding that foundations for binaural hearing are normally established during early stages of cortical development. Although 4- to 7-year-old children with normal hearing had immature cortical responses, adult patterns in cortical coding of binaural timing cues were measured. Second, children receiving two cochlear implants in the same surgery maintained normal-like input from both ears, but this did not support significant effects of binaural timing cues in either auditory cortex. Deficits in parieto-occiptal areas further suggested impairment in spatial processing. Results indicate that cochlear implants working independently in each ear do not fully overcome deafness-related binaural processing deficits, even after long-term experience.
Protein abundance of AKT and ERK pathway components governs cell type‐specific regulation of proliferation
Authors: Adlung Lorenz , Kar Sandip , Wagner Marie‐Christine , She Bin , Chakraborty Sajib , Bao Jie , Lattermann Susen , Boerries Melanie , Busch Hauke , Wuchter Patrick , Ho Anthony D , Timmer Jens , Schilling Marcel , Höfer Thomas , Klingmüller Ursula 
Published: January 2017

AbstractSignaling through the AKT and ERK pathways controls cell proliferation. However, the integrated regulation of this multistep process, involving signal processing, cell growth and cell cycle progression, is poorly understood. Here, we study different hematopoietic cell types, in which AKT and ERK signaling is triggered by erythropoietin (Epo). Although these cell types share the molecular network topology for pro‐proliferative Epo signaling, they exhibit distinct proliferative responses. Iterating quantitative experiments and mathematical modeling, we identify two molecular sources for cell type‐specific proliferation. First, cell type‐specific protein abundance patterns cause differential signal flow along the AKT and ERK pathways. Second, downstream regulators of both pathways have differential effects on proliferation, suggesting that protein synthesis is rate‐limiting for faster cycling cells while slower cell cycles are controlled at the G1‐S progression. The integrated mathematical model of Epo‐driven proliferation explains cell type‐specific effects of targeted AKT and ERK inhibitors and faithfully predicts, based on the protein abundance, anti‐proliferative effects of inhibitors in primary human erythroid progenitor cells. Our findings suggest that the effectiveness of targeted cancer therapy might become predictable from protein abundance.
Identification of Unannotated Small Genes in Salmonella
Authors: Baek Jonghwan , Lee Jiyoung , Yoon Kihoon , Lee Hyunwoo 
Published: January 2017

Abstract
Increasing evidence indicates that many, if not all, small genes encoding proteins ≤100 aa are missing in annotations of bacterial genomes currently available. To uncover unannotated small genes in the model bacterium Salmonella enterica Typhimurium 14028s, we used the genomic technique ribosome profiling, which provides a snapshot of all mRNAs being translated (translatome) in a given growth condition. For comprehensive identification of unannotated small genes, we obtained Salmonella translatomes from four different growth conditions: LB, MOPS rich defined medium, and two infection-relevant conditions low Mg2+ (10 µM) and low pH (5.8). To facilitate the identification of small genes, ribosome profiling data were analyzed in combination with in silico predicted putative open reading frames and transcriptome profiles. As a result, we uncovered 130 unannotated ORFs. Of them, 98% were small ORFs putatively encoding peptides/proteins ≤100 aa, and some of them were only expressed in the infection-relevant low Mg2+ and/or low pH condition. We validated the expression of 25 of these ORFs by western blot, including the smallest, which encodes a peptide of 7 aa residues. Our results suggest that many sequenced bacterial genomes are underannotated with regard to small genes and their gene annotations need to be revised.
Endogenous RNAi Pathways Are Required in Neurons for Dauer Formation in Caenorhabditis elegans
Authors: Bharadwaj Pallavi S , Hall Sarah E 
Published: January 2017

Abstract
Animals can adapt to unfavorable environments through changes in physiology or behavior. In the nematode, Caenorhabditis elegans, environmental conditions perceived early in development determine whether the animal enters either the reproductive cycle, or enters into an alternative diapause stage named dauer. Here, we show that endogenous RNAi pathways play a role in dauer formation in crowding (high pheromone), starvation, and high temperature conditions. Disruption of the Mutator proteins or the nuclear Argonaute CSR-1 result in differential dauer-deficient phenotypes that are dependent upon the experienced environmental stress. We provide evidence that the RNAi pathways function in chemosensory neurons for dauer formation, upstream of the TGF-β and insulin signaling pathways. In addition, we show that Mutator MUT-16 expression in a subset of individual pheromone-sensing neurons is sufficient for dauer formation in high pheromone conditions, but not in starvation or high temperature conditions. Furthermore, we also show that MUT-16 and CSR-1 are required for expression of a subset of G proteins with functions in the detection of pheromone components. Together, our data suggest a model where Mutator-amplified siRNAs that associate with the CSR-1 pathway promote expression of genes required for the detection and signaling of environmental conditions to regulate development and behavior in C. elegans. This study highlights a mechanism whereby RNAi pathways mediate the link between environmental stress and adaptive phenotypic plasticity in animals.
The Predicted Cross Value for Genetic Introgression of Multiple Alleles
Authors: Han Ye , Cameron John N , Wang Lizhi , Beavis William D 
Published: January 2017

AbstractHan et al. introduce a new metric, the Predicted Cross Value (PCV), for selecting breeding parents. Unlike estimated breeding values, which represent...We consider the plant genetic improvement challenge of introgressing multiple alleles from a homozygous donor to a recipient. First, we frame the project as an algorithmic process that can be mathematically formulated. We then introduce a novel metric for selecting breeding parents that we refer to as the predicted cross value (PCV). Unlike estimated breeding values, which represent predictions of general combining ability, the PCV predicts specific combining ability. The PCV takes estimates of recombination frequencies as an input vector and calculates the probability that a pair of parents will produce a gamete with desirable alleles at all specified loci. We compared the PCV approach with existing estimated-breeding-value approaches in two simulation experiments, in which 7 and 20 desirable alleles were to be introgressed from a donor line into a recipient line. Results suggest that the PCV is more efficient and effective for multi-allelic trait introgression. We also discuss how operations research can be used for other crop genetic improvement projects and suggest several future research directions.
Asthma-Related Health Care Resource Use Among Asthmatic Children With and Without Concomitant Allergic Rhinitis
Authors: Thomas Mike , Kocevar Vasilisa Sazonov , Zhang Qiaoyi , Yin Donald D. , Price David 
Published: January 2017

Objective. To determine the incremental effect of allergic rhinitis on health care resource use in children with asthma.Design. Population-based historical cohort study.Setting. Data in a general practice database in the United Kingdom during 1998 to 2001.Patients. Children 6 to 15 years old with asthma and with ≥1 asthma-related visits to a general practitioner (GP) during a 12-month follow-up period.Main Outcome Measures. Asthma-related hospitalizations, GP visits, and prescription drug costs during the 12-month follow-up period for patients with and without comorbid allergic rhinitis.Results. Of 9522 children with asthma, 1879 (19.7%) had allergic rhinitis recorded in the GP medical records. Compared with children with asthma alone, children with comorbid allergic rhinitis experienced more GP visits (4.4 vs 3.4) and more of them were hospitalized for asthma (1.4% vs 0.5%) during the 12-month follow-up period. In multivariable regression analyses, comorbid allergic rhinitis was an independent predictor of hospitalization for asthma (odds ratio: 2.34; 95% confidence interval [CI]: 1.41–3.91) and was associated with increases in the number of asthma-related GP visits (mean increase: 0.53; 95% CI: 0.52–0.54) and asthma drug costs (mean increase £: 6.7; 95% CI: 6.5–7.0). The association between allergic rhinitis and higher costs of prescriptions for asthma drugs was independent of asthma severity, measured indirectly by the intensity of use of asthma drugs.Conclusions. Children with comorbid allergic rhinitis incurred greater prescription drug costs and experienced more GP visits and hospitalizations for asthma than did children with asthma alone. A unified treatment strategy for asthma and allergic rhinitis, as recommended by the Allergic Rhinitis and Its Impact on Asthma initiative, might reduce the costs of treating these conditions.
Adverse Events and Preventable Adverse Events in Children
Authors: Woods Donna , Thomas Eric , Holl Jane , Altman Stuart , Brennan Troy 
Published: January 2017

Context. Patient safety has been recognized as an important problem in health care. However, knowledge about adverse events and preventable adverse events in children is relatively limited.
Objective. To describe the incidence and types of adverse events and preventable adverse events in children.
Design. Analysis of pediatric hospitalizations in the Colorado and Utah Medical Practice Study, which involved a retrospective, 2-level (nurse and physician) medical record review of a population-based, representative sample of all pediatric hospital discharges.
Main Measures. Adverse events were defined as an injury caused by medical management rather than disease processes that resulted in either prolonged hospitalization or disability at discharge. A preventable adverse event was defined as an avoidable adverse event based on currently available knowledge and accepted practices.
Patients. 3719 discharged hospital patients, 0–20 years old, and 7528 nonelderly (21–65 years old) discharged adult patients in Colorado and Utah.
Setting. All hospitals in Colorado and Utah.
Results. Adverse events occurred in 1% of pediatric hospitalizations in Colorado and Utah; 0.6% were preventable. Preventable adverse events rates were 0.53% in neonates and infants (0–0.99 years), 0.22% in children 1–12 years of age, and 0.95% in adolescents 13–20 years of age, compared with a rate of 1.50% in nonelderly adults. Of preventable adverse event types, birth related (32.2%) and diagnostic related (30.4%) events were the most common and were significantly more common than surgically related preventable adverse events (3.5%).
Conclusions. These data suggest that ∼70 000 children hospitalized in the United States experience an adverse event each year; 60% of these events may be preventable. The epidemiology of adverse events and preventable adverse events in children is different than in adults. To reduce the adverse events that occur in hospitalized children, research should focus on adolescent hospitalized patients, birth-related medical care, and diagnostics in pediatric medicine.
Trends in Prenatal Diagnosis, Pregnancy Termination, and Perinatal Mortality of Newborns With Congenital Heart Disease in France, 1983–2000: A Population-Based Evaluation
Authors: Khoshnood Babak , De Vigan Catherine , Vodovar Véronique , Goujard Janine , Lhomme Anne , Bonnet Damien , Goffinet François 
Published: January 2017

Objective. To examine population-based overall and malformation-specific trends in the prenatal diagnosis, pregnancy termination, and perinatal mortality for congenital heart disease (CHD) during a period of rapid progress in prenatal diagnosis and medical management of CHD and to explore the impact of prenatal diagnosis on early neonatal mortality for specific (isolated) cardiac malformations.
Methods. A total of 1982 cases of CHD, which were not associated with a known chromosomal anomaly, were obtained from the Paris Registry of Congenital Malformations. Main outcome measures were trends in the proportions diagnosed and terminated before birth, stillbirth, and early (&lt;1 day, 1-week) neonatal mortality for (1) all cases; (2) all cases excluding isolated ventricular septal defects; and (3) malformation-specific trends for transposition of great arteries, hypoplastic left heart syndrome, coarctation of aorta, and tetralogy of Fallot. Analyses included cusum and binomial regression models for analysis of the trends during 1983–2000.
Results. Prenatal diagnosis rates for CHD increased from 23.0% (95% confidence interval [CI]: 19.0–27.4) in 1983–1988 to 47.3% (95% CI: 43.8–50.8) in 1995–2000. Termination rates increased between 1983 and 1989 (9.9%; 95% CI: 7.2–13.2) and 1989 and 1994 (14.7%; 95% CI: 12.3–17.4) but seemed to remain stable thereafter. Other than for hypoplastic left heart syndrome, pregnancy termination was exceptional for the other 3 specific malformations examined. Early neonatal mortality decreased to less than one third in the period 1995–2000 as compared with 1983–1989 (risk ratio, first-week mortality: 0.31; 95% CI: 0.18–0.53). First-week mortality was significantly lower for cases of transposition of great arteries that were diagnosed before birth (risk difference: 15.4%; 95% CI: 4.0–26.7).
Conclusions. Progress in clinical management, together with policies for increased access to prenatal diagnosis, has resulted in both a substantial increase in the prenatal diagnosis and considerable reductions in early neonatal mortality of CHD in the Parisian population.