bluuebunny/crossref_metadata_2025_split huggingface dataset:
A family-oriented psychosocial intervention reduces inflammation in low-SES African American youth
Authors: Miller Gregory E. , Brody Gene H. , Yu Tianyi , Chen Edith 
Published: July 2014

Significance
Children from families of low socioeconomic status (SES) are vulnerable to a variety of health problems. These risks begin in early childhood and persist across the lifecourse. Studies hint that nurturant parenting may offset these health risks, but it remains unclear whether these findings reflect a causal process and have clinical utility. Here we describe a randomized controlled trial, which sought to improve parenting and build youth competencies in low-SES African American families. The endpoint was low-grade inflammation, a process that underlies many health problems to which low-SES youth are vulnerable. Eight years after the intervention, youth who participated had significantly less inflammation than controls. If substantiated, these findings may provide a strategy for narrowing some of America’s social and racial disparities in health.
Method for identifying phosphorylated substrates of specific cyclin/cyclin-dependent kinase complexes
Authors: Li Yinyin , Cross Frederick R. , Chait Brian T. 
Published: July 2014

SignificanceDuring proliferation, eukaryotic cells go through a defined series of phases. The primary regulators of this process are kinases paired with protein partners called cyclins. Exactly how these specific cyclin–kinase pairs orchestrate the myriad cellular events during each cell phase has been difficult to define largely because it has proven challenging to identify their substrates. Here, we describe a method to identify cyclin- and phase-specific substrates with high confidence and also to pinpoint their sites of modification. The method enabled us to identify the phosphatase Cdc14 as a substrate of a cyclin–kinase pair that acts during DNA synthesis in budding yeast and to uncover a new means by which this major antagonist of the cyclin–kinase pair is itself controlled.
Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G
Authors: Papadopoulos Evangelos , Jenni Simon , Kabha Eihab , Takrouri Khuloud J. , Yi Tingfang , Salvi Nicola , Luna Rafael E. , Gavathiotis Evripidis , Mahalingam Poornachandran , Arthanari Haribabu , Rodriguez-Mias Ricard , Yefidoff-Freedman Revital , Aktas Bertal H. , Chorev Michael , Halperin Jose A. , Wagner Gerhard 
Published: July 2014

Significance
eIF4E is critical for protein synthesis and becomes hyperactive in cancer cells. Small-molecule inhibitors of the eIF4E/eIF4G initiation factor complex have recently been found to exhibit antitumor activity in vitro and in vivo. However, their mode of action at the atomic level has remained elusive. Here, we report high-resolution crystal structures of complexes of 4EGI-1 analogue inhibitors with eIF4E. We find that inhibition of eIF4G binding must be allosteric, because the 4EGI-1 and eIF4G bind at distant epitopes on eIF4E. Compound binding induces extension of an α-helix that stretches between the two binding sites. Indeed, mutations increasing helix propensity in this region reduce eIF4G affinity in the absence of the inhibitor, which is consistent with the proposed allosteric model.
Population of sensory neurons essential for asthmatic hyperreactivity of inflamed airways
Authors: Tränkner Dimitri , Hahne Nadeau , Sugino Ken , Hoon Mark A. , Zuker Charles 
Published: July 2014

Significance
Asthma is an inflammatory airway disease characterized by acute attacks in which airway constriction impedes breathing. The variable success of anti-inflammatory treatments in managing asthma attacks suggests that additional mechanisms contribute to this symptom. Here, we used a mouse model of acute asthma to show that a subset of sensory neurons mediates the hyperreactive airway responses. These findings define a cellular substrate outside the immune system that may serve as an important target in the management of asthmatic airway hyperreactivity.
Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription factor
Authors: Long Chengzu , Grueter Chad E. , Song Kunhua , Qin Song , Qi Xiaoxia , Kong Y. Megan , Shelton John M. , Richardson James A. , Zhang Chun-Li , Bassel-Duby Rhonda , Olson Eric N. 
Published: July 2014

Significance
Neurodegenerative diseases are debilitating conditions that result from degeneration of the nervous system causing symptoms including ataxia and/or dementia. Calmodulin-binding transcription activator 1 (CAMTA1) is a transcription factor enriched in the brain with the highest levels of expression in the cerebellar granular layer and Purkinje cells, midbrain, pons, and hippocampus. When CAMTA1 is deleted from the nervous system of mutant mice, we observe a clear loss of Purkinje cells and reduced cerebellar size. Thus, we conclude that CAMTA1 plays a predominant role in the maturation and survival of cerebellar neurons rather than in the initial development of these cells. The neurological abnormalities associated with CAMTA1-mutant mice allow mechanistic analysis of these abnormalities and disease modeling.
Peptic Ulcer Disease in Helicobacter pylori–Infected Children
Authors: Hernández Caroll , Serrano Carolina , Einisman Helly , Villagrán Andrea , Peña Alfredo , Duarte Ignacio , Torres Javiera , Riera Francisca , Harris Paul R. 
Published: July 2014

ABSTRACTObjectives:Peptic ulcer disease (PUD) is highly prevalent among adults but less common in children. Helicobacter pylori infection, the main cause of PUD, is, however, acquired extremely early in life. The aim of the study was to analyze clinical characteristics of children with PUD in a country with a high prevalence of the disease and to evaluate which host factors could determine this clinical outcome.Methods:Children referred for upper gastrointestinal (GI) endoscopy with suspicion of peptic diseases were included prospectively during an 8‐year period. Antral biopsies were performed to determine H pylori presence and mucosal cytokines profile.Results:A total of 307 children between 3 and 18 years old were enrolled. Of the total, 237 children (46% boys) with complete data were included. H pylori infection was confirmed in 133 (56.1%) participants. Duodenal ulcer (DU) was diagnosed in 32 patients (13.5%); among them 29 were infected with H pylori (90.6%). Infected children had a nodular appearance of the gastric mucosa more often than noninfected children. Noninfected children had fewer lymphoid follicles and less inflammatory infiltrate than infected children. Only mucosal polymorphonuclear cell infiltration was more intense in DU‐infected children as compared with non–DU‐infected children. DU‐infected children had higher levels of mucosal interferon‐γ than noninfected and non–DU‐infected patients. Non–DU‐infected children had also higher levels of mucosal interleukin‐10 than noninfected patients (P < 0.05).Conclusions:PUD in children, especially DU, is strongly associated with H pylori infection in developing countries. There is no distinctive clinical presentation of children with PUD. T‐helper cytokine balance may influence clinical outcomes in children.
The Apical Actin Fringe Contributes to Localized Cell Wall Deposition and Polarized Growth in the Lily Pollen Tube
Authors: Rounds Caleb M. , Hepler Peter K. , Winship Lawrence J. 
Published: July 2014

AbstractIn lily (Lilium formosanum) pollen tubes, pectin, a major component of the cell wall, is delivered through regulated exocytosis. The targeted transport and secretion of the pectin-containing vesicles may be controlled by the cortical actin fringe at the pollen tube apex. Here, we address the role of the actin fringe using three different inhibitors of growth: brefeldin A, latrunculin B, and potassium cyanide. Brefeldin A blocks membrane trafficking and inhibits exocytosis in pollen tubes; it also leads to the degradation of the actin fringe and the formation of an aggregate of filamentous actin at the base of the clear zone. Latrunculin B, which depolymerizes filamentous actin, markedly slows growth but allows focused pectin deposition to continue. Of note, the locus of deposition shifts frequently and correlates with changes in the direction of growth. Finally, potassium cyanide, an electron transport chain inhibitor, briefly stops growth while causing the actin fringe to completely disappear. Pectin deposition continues but lacks focus, instead being delivered in a wide arc across the pollen tube tip. These data support a model in which the actin fringe contributes to the focused secretion of pectin to the apical cell wall and, thus, to the polarized growth of the pollen tube.
Chinese expert consensus workshop report: Guidelines for thermal ablation of primary and metastatic lung tumors
Authors: Ye Xin , Fan Weijun , Chen Jun‐hui , Feng Wei‐jian , Gu Shan‐zhi , Han Yue , Huang Guang‐hui , Lei Guang‐yan , Li Xiao‐guang , Li Yu‐liang , Li Zhen‐jia , Lin Zheng‐yu , Liu Bao‐dong , Liu Ying , Peng Zhong‐min , Wang Hui , Yang Wu‐wei , Yang Xia , Zhai Bo , Zhang Jun 
Published: July 2014

AbstractAlthough surgical resection is the primary means of curing both primary and metastatic lung cancers, about 80% of lung cancers cannot be removed by surgery. As most patients with unresectable lung cancer receive only limited benefits from traditional radiotherapy and chemotherapy, many new local treatment methods have emerged, including local ablation therapy. The Minimally Invasive and Comprehensive Treatment of Lung Cancer Branch, Professional Committee of Minimally Invasive Treatment of Cancer of the Chinese Anti‐Cancer Association has organized multidisciplinary experts to develop guidelines for this treatment modality. These guidelines aim at standardizing thermal ablation procedures and criteria for selecting treatment candidates and assessing outcomes; and for preventing and managing post‐ablation complications.
Quality Indicators as a Tool in Improving the Introduction of New Medicines
Authors: Campbell Stephen M. , Godman Brian , Diogene Eduardo , Fürst Jurij , Gustafsson Lars L. , MacBride‐Stewart Sean , Malmström Rickard E. , Pedersen Hanne , Selke Gisbert , Vlahović‐Palčevski Vera , van Woerkom Menno , Wong‐Rieger Durhane , Wettermark Björn 
Published: July 2014

AbstractQuality indicators are increasingly used as a tool to achieve safe and quality clinical care, cost‐effective therapy, for professional learning, remuneration, accreditation and financial incentives. A substantial number focus on drug therapy but few address the introduction of new medicines even though this is a burning issue. The objective was to describe the issues and challenges in designing and implementing a transparent indicator framework and evaluation protocol for the introduction of new medicines and to provide guidance on how to apply quality indicators in the managed entry of new medicines. Quality indicators need to be developed early to assess whether new medicines are introduced appropriately. A number of key factors need to be addressed when developing, applying and evaluating indicators including dimensions of quality, suggested testing protocols, potential data sources, key implementation factors such as intended and unintended consequences, budget impact and cost‐effectiveness, assuring the involvement of the medical professions, patients and the public, and reliable and easy‐to‐use computerized tools for data collection and management. Transparent approaches include the need for any quality indicators developed to handle conflict of interests to enhance their validity and acceptance. The suggested framework and indicator testing protocol may be useful in assessing the applicability of indicators for new medicines and may be adapted to healthcare settings worldwide. The suggestions build on existing literature to create a field testing methodology that can be used to produce country‐specific quality indicators for new medicines as well as a cross international approach to facilitate access to new medicines.
Neuropsychological performance of patients with soft bipolar spectrum disorders
Authors: Lin Kangguang , Xu Guiyun , Lu Weicong , Ouyang Huiyi , Dang Yamei , Guo Yangbo , So Kwok‐Fai , Lee Tatia MC 
Published: July 2014

ObjectivesThere is much evidence that shows that a substantial number of individuals with DSM‐IV‐defined unipolar depression (UP) manifest hypomanic sub‐syndrome and bipolar diathesis. Other definitions have conceptualized the term soft bipolar spectrum (SBP) for these individuals. Little is known about the cognitive profiles of individuals with SBP. We hypothesized that they are representative of individuals with bipolar II disorder and are different from that of ‘strict’ UP.MethodsConsecutive referrals suffering major depressive episodes were categorically assigned to groups of either bipolar I disorder (n = 98), bipolar II disorder (n = 138), or UP (n = 300). Based on the SBP criteria by Akiskal and Pinto (17), patients with UP were subdivided into 81 SBP and 219 strict UP. We administered self‐ and clinician‐administered scales to evaluate affective temperaments, and neuropsychological tests to assess seven cognitive domains.ResultsPatients with SBP performed significantly better than strict UP patients in the domains of processing speed (p = 0.002), visual‐spatial memory (p = 0.017), and verbal working memory (p = 0.017). Compared to patients with bipolar I disorder, patients with SBP were significantly better in set shifting (p < 0.001) and visual‐spatial memory (p = 0.042). Patients with SBP performed similarly to patients with bipolar II disorder in all of the cognitive domains tested (p > 0.05). There was a group × cognitive domain interaction effect between bipolar I disorder, bipolar II disorder, SBP, and strict UP groups [Pillai's F = 2.231, df = (18,1437), p = 0.002].ConclusionsOur data suggest that patients with SBP differ from patients with UP not only in external validators (e.g., family history of bipolar disorder) and hypomanic symptoms, but also in neuropsychological performance and that the profiles of cognitive functioning were different across bipolar I disorder and ‘bipolar II spectrum’ that subsumes bipolar II disorder and SBP.
Mechanisms underlying the cytotoxicity of a novel quinazolinedione‐based redox modulator, QD232, in pancreatic cancer cells
Authors: Pathania Divya , Kuang Yuting , Sechi Mario , Neamati Nouri 
Published: July 2014

Background and PurposePancreatic cancer is characterized by alterations in several key signalling proteins, including increased expression and activity of the Src tyrosine kinase and focal adhesion kinase (FAK), which have been linked to its chemoresistance. Sustained Src inhibition reactivates survival pathways regulated by the transcription factor STAT3, also leading to resistance. Therefore, simultaneously targeting Src/FAK and STAT3 signalling could provide an important strategy for treating pancreatic cancer. Recently, we described novel quinazolinediones that increased generation of reactive oxygen species (ROS) and were cytotoxic in pancreatic cancer cells. Here, we have investigated effects of our lead compound, QD232, on Src/FAK and STAT3 signalling.Experimental ApproachThe major signalling pathways affected by QD232 in pancreatic cancer cell lines were identified by Kinexus proteomic analysis. Changes in key signalling proteins were confirmed by Western blotting. Cell migration was assessed by Boyden chamber and wound healing assays. Direct inhibition of kinase activity in vitro was assayed with a panel of 92 oncogenic kinases. Safety and efficacy of QD232 were determined in a xenograft mouse model of pancreatic cancer.Key ResultsQD232 potently inhibited Src/FAK and STAT3 phosphorylation, decreasing pancreatic cancer cell viability and migration. Furthermore, QD232 arrested cell cycle progression and induced apoptosis in these cells at low micromolar concentrations. Effects of QD232 on Src/FAK and STAT3 phosphorylation were blocked by N‐acetylcysteine or glutathione.Conclusions and ImplicationsQD232 is a novel compound with a unique, ROS‐dependent mechanism, effective in drug‐resistant cancer cell lines. This compound shows potential as therapy for pancreatic cancer.
Fluoride effectiveness in high caries risk and medically complex Veterans
Authors: Jurasic M. Marianne , Gibson Gretchen , Wehler Carolyn J. , Nunn Martha , Orner Michelle B. , Nunez Elizabeth , O'Toole Terry G. , Jones Judith A. 
Published: July 2014

AbstractBackgroundThe Global Burden of Disease Study showed there was a 34.5% increase in years lived with disability due to dental caries from 1990 to 2010. With the aging of 76 million baby boomers, dental caries will continue to pose a significant challenge for older adults.ObjectiveTest the effectiveness of prescription or professionally applied fluoride in the prevention of new dental restorations in a clinical setting where patients are medically compromised and more dentally impaired than the general population.MethodsA retrospective cohort study, using multiple electronic databases within the Department of Veterans Affairs. Propensity scores were used to adjust for confounding by indication and logistic regression modeled the outcome and included all expected covariates.ResultsThe study sample included 140 114 high caries risk Veterans with a mean of 3.4 physical comorbidities, 1.2 mental comorbidities, and 11 medication groups per patient. Patients who received clinical fluoride treatments had 17–20% decreased odds of requiring a restoration during the follow‐up period.ConclusionsPrescription self‐applied or professionally applied fluoride provided either before or during an episode of care significantly reduced the likelihood of new restorations in high caries risk and medically compromised Veterans.
Childhood exposure to ambient polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells
Authors: Hew K. M. , Walker A. I. , Kohli A. , Garcia M. , Syed A. , McDonald‐Hyman C. , Noth E. M. , Mann J. K. , Pratt B. , Balmes J. , Hammond S. Katharine , Eisen E. A. , Nadeau K. C. 
Published: July 2014

SummaryBackgroundEvidence suggests that exposure to polycyclic aromatic hydrocarbons (PAHs) increases atopy; it is unclear how PAH exposure is linked to increased severity of atopic diseases.ObjectiveWe hypothesized that ambient PAH exposure is linked to impairment of immunity in atopic children (defined as children with asthma and/or allergic rhinitis) from Fresno, California, an area with elevated ambient PAHs.MethodsWe recruited 256 subjects from Fresno, CA. Ambient PAH concentrations (ng/m3) were measured using a spatial‐temporal regression model over multiple time periods. Asthma diagnosis was determined by current NHLBI criteria. Phenotyping and functional immune measurements were performed from isolated cells. For epigenetic measurements, DNA was isolated and pyrosequenced.ResultsWe show that higher average PAH exposure was significantly associated with impaired Treg function and increased methylation in the forkhead box protein 3 (FOXP3) locus (P < 0.05), conditional on atopic status. These epigenetic modifications were significantly linked to differential protein expression of FOXP3 (P < 0.001). Methylation was associated with cellular functional changes, specifically Treg dysfunction, and an increase in total plasma IgE levels. Protein expression of IL‐10 decreased and IFN‐γ increased as the extent of PAH exposure increased. The strength of the associations generally increased as the time window for average PAH exposure increased from 24 hr to 1 year, suggesting more of a chronic response. Significant associations with chronic PAH exposure and immune outcomes were also observed in subjects with allergic rhinitis.Conclusions and Clinical RelevanceCollectively, these results demonstrate that increased ambient PAH exposure is associated with impaired systemic immunity and epigenetic modifications in a key locus involved in atopy: FOXP3, with a higher impact on atopic children. The results suggest that increased atopic clinical symptoms in children could be linked to increased PAH exposure in air pollution.
Predictors of quality of life in patients evaluated for liver transplantation
Authors: Jara Maximilian , Bednarsch Jan , Malinowski Maciej , Lüttgert Katja , Orr James , Puhl Gero , Seehofer Daniel , Neuhaus Peter , Stockmann Martin 
Published: July 2014

AbstractIntroductionHealth‐related quality of life (HRQOL) is severely impaired in advanced liver disease. The purpose of this study was to evaluate the impact of actual liver function and disease‐specific factors on HRQOL of patients evaluated for liver transplantation.Patients and MethodsDisease‐specific QOL was analyzed in 142 patients evaluated for liver transplantation using the German version of the Chronic Liver Disease Questionnaire (CLDQ‐D). We performed quantitative liver function tests and collected clinical and demographical data of patients after their referral to our transplant department. Values were correlated with CLDQ‐D scores.ResultsNeither model for end‐stage liver disease (MELD) nor dynamic liver function test results were related to quality of life. Serum albumin concentration was a strong but not independent factor correlated with global CLDQ‐D (r = 0.269, p < 0.001). Independent predictors of global CLDQ‐D were ascites and butyrylcholinesterase serum concentration (B = −0.486, p < 0.001 and B = 0.196, p = 0.002, respectively).ConclusionActual liver function is not related to decreased quality of life, whereas ascites and hypoproteinemia represent the major factors influencing physical and social aspects of daily life in potential liver transplant candidates.
Evaluation of the Effect of Cardiac Rehabilitation on Left Atrial and Left Ventricular Function and Its Relationship with Changes in Arterial Stiffness in Patients with Acute Myocardial Infarction
Authors: Acar Rezzan Deniz , Bulut Mustafa , Ergün Sunay , Yesin Mahmut , Akçakoyun Mustafa 
Published: July 2014

BackgroundThe main aim of this study was to detect the possible early effect of cardiac rehabilitation (CR) on left atrium (LA) and left ventricle (LV) function and relation to aortic stiffness in patients with acute myocardial infarction (AMI).MethodsFifty‐four patients with AMI were enrolled in this study. Left atrial strain analysis was performed by two‐dimensional speckle tracking echocardiography. The deceleration time (DT) was measured by pulsed‐wave Doppler. The ratio of E/e' to LA peak strain was used to estimate the LA stiffness (Stiffnessstrain) Aortic elasticity parameters were calculated using the formulas including aortic systolic and diastolic diameter with M‐Mode echocardiography and blood pressure. Anterior wall aortic expansion velocity was measured by tissue Doppler imaging.ResultsLeft ventricle ejection fraction (EF) and LA functional parameters were significantly better in trained subjects. Also in training group, the LV diastolic functional parameters were better in CR group than the control group. Aortic elasticity parameters were better with CR.ConclusionsIn patients with CR, an increase in LA strain was correlated with increase in aortic strain and improved aortic distensibility, likely indicating favorable LA and aortic interactions with exercise training.