bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rate‐Control Drugs Affect Variability and Irregularity Measures of RR Intervals in Patients with Permanent Atrial Fibrillation
Authors: CORINO VALENTINA D.A. , ULIMOEN SARA R. , ENGER STEVE , MAINARDI LUCA T. , TVEIT ARNLJOT , PLATONOV PYOTR G. 
Published: November 2014

Heart Rate Variability and Irregularity During AFIntroductionIrregularity measures have been suggested as risk indicators in patients with atrial fibrillation (AF); however, it is not known to what extent they are affected by commonly used rate‐control drugs. We aimed at evaluating the effect of metoprolol, carvedilol, diltiazem, and verapamil on the variability and irregularity of the ventricular response in patients with permanent AF.Methods and ResultsSixty patients with permanent AF were part of an investigator‐blind cross‐over study, comparing 4 rate‐control drugs (diltiazem, verapamil, metoprolol, and carvedilol). We analyzed five 20‐minute segments per patient: baseline and the 4 drug regimens. On every segment, heart rate (HR) variability and irregularity of RR series were computed. The variability was assessed as standard deviation, pNN20, pNN50, pNN80, and rMSSD. The irregularity was assessed by regularity index, approximate (ApEn), and sample entropy. A significantly lower HR was obtained with all drugs, the HR was lowest using the calcium channel blockers. All drugs increased the variability of ventricular response in respect to baseline (as an example, rMSSD: baseline 171 ± 47 milliseconds, carvedilol 229 ± 58 milliseconds; P < 0.05 vs. baseline, metoprolol 226 ± 66 milliseconds; P < 0.05 vs. baseline, verapamil 228 ± 84; P < 0.05 vs. baseline, diltiazem 256 ± 87 milliseconds; P < 0.05 vs. baseline and all other drugs). Only β‐blockers significantly increased the irregularity of the RR series (as an example, ApEn: baseline 1.86 ± 0.13, carvedilol 1.92 ± 0.09; P < 0.05 vs. baseline, metoprolol 1.93 ± 0.08; P < 0.05 vs. baseline, verapamil 1.86 ± 0.22 ns, diltiazem 1.88 ± 0.16 ns).ConclusionModification of AV node conduction by rate‐control drugs increase RR variability, while only β‐blockers affect irregularity.
Representation of women as editors in the Cochrane collaboration
Authors: Bhaumik Soumyadeep , Mathew Rebecca Joyce 
Published: November 2014

AbstractObjectivesThere is considerable gender disparity in editorial boards of medical journals. Being an editor in a Cochrane review group (CRG), like being an editor in a medical journal, is an indirect representation of one's reputation and leadership abilities in a particular specialty. The aim of the study was to analyze the representation of women editors on the editorial teams of CRG's and the Central Editorial Unit (CEU) of the Cochrane Collaboration.MethodsInformation about editorial team members of CRGs and the CEU was extracted from respective websites. Gender of the individual was determined by inspection of names, individual profile description or photographs in the CRG or institutional webpage, social networking sites and internet search. Data was validated by two authors independently and differences sorted by consensus.ResultsA total of 788 editors across all CRGs and the CEU with an overall 371 females (47.1%) and 417 (52.9%) males were identified. of the CEU editors, 62.5% were females. There were 68 coordinating editors (35.3% females), and 62 managing editors (56% females), who provided leadership to the CRGs. Eighty‐four percent of trial search coordinators were found to be females. Ten CRGs had 75% or more of its editors as females while 7 CRGs had less than or equal to 25% female editors.ConclusionsThe representation of women editors in the Cochrane Collaboration was found to be better than in editorial boards of medical journals. There is still scope for improvement to ensure better gender diversity across all roles and in all CRG's.
The Affordable Care Act: a case study for understanding and applying complexity concepts to health care reform
Authors: Larkin D. Justin , Swanson R. Chad , Fuller Spencer , Cortese Denis A. 
Published: November 2014

AbstractRationale, aims and objectivesThe current health system in the United States is the result of a history of patchwork policy decisions and cultural assumptions that have led to persistent contradictions in practice, gaps in coverage, unsustainable costs, and inconsistent outcomes. In working toward a more efficient health system, understanding and applying complexity science concepts will allow for policy that better promotes desired outcomes and minimizes the effects of unintended consequences.MethodsThis paper will consider three applied complexity science concepts in the context of the Patient Protection and Affordable Care Act (PPACA): developing a shared vision around reimbursement for value, creating an environment for emergence through simple rules, and embracing transformational leadership at all levels.Results and conclusionsTransforming the US health system, or any other health system, will be neither easy nor quick. Applying complexity concepts to health reform efforts, however, will facilitate long‐term change in all levels, leading to health systems that are more effective, efficient, and equitable.
Systematic Review of Outcomes from Home‐Based Primary Care Programs for Homebound Older Adults
Authors: Stall Nathan , Nowaczynski Mark , Sinha Samir K. 
Published: November 2014

ObjectivesTo describe the effect of home‐based primary care for homebound older adults on individual, caregiver, and systems outcomes.DesignA systematic review of home‐based primary care interventions for community‐dwelling older adults (aged ≥65) using the Cochrane, PubMed, and MEDLINE databases from the earliest available date through March 15, 2014. Studies were included if the house calls visitor was the ongoing primary care provider and if the intervention measured emergency department visits, hospitalizations, hospital beds days of care, long‐term care admissions, or long‐term care bed days of care.SettingHome‐based primary care programs.ParticipantsHomebound community‐dwelling older adults (N = 46,154).MeasurementsEmergency department visits, hospitalizations, hospital bed days of care, long‐term care admissions, long‐term care bed days of care, costs, program design, and individual and caregiver quality of life and satisfaction with care.ResultsOf 357 abstracts identified, nine met criteria for review. The nine interventions were all based in North America, with five emerging from the Veterans Affairs system. Eight of nine programs demonstrated substantial effects on at least one inclusion outcome, with seven programs affecting two outcomes. Six interventions shared three core program components: interprofessional care teams, regular interprofessional care meetings, and after‐hours support.ConclusionSpecifically designed home‐based primary care programs may substantially affect individual, caregiver and systems outcomes. Adherence to the core program components identified in this review could guide the development and spread of these programs.
Cognitive Function in the Prefrailty and Frailty Syndrome
Authors: Robertson Deirdre A. , Savva George M. , Coen Robert F. , Kenny Rose‐Anne 
Published: November 2014

ObjectivesTo explore the relationship between cognitive function and frailty.DesignA cross‐sectional study using data from Wave 1 of The Irish Longitudinal Study on Ageing, a population representative study of adults aged 50 and older in the Republic of Ireland.SettingCommunity‐dwelling adults completed a home‐ or health center–based nurse‐led assessment.ParticipantsIndividuals aged 50 and older without a history of stroke, Parkinson's disease, or severe cognitive impairment (Mini‐Mental State Examination (MMSE) score <18) and not taking antidepressants (N = 4,649).MeasurementsA cognitive battery including MMSE, Montreal Cognitive Assessment, Color Trails Test, Cambridge Mental Disorders of the Elderly Examination memory and executive function subtests, 10‐word recall, Sustained Attention to Response Task, and choice reaction time was used to generate composite scores of cognitive domains. Frailty was assessed according to weakness, slowness, exhaustion, low physical activity, and weight loss.ResultsAfter full adjustment, cognitive function across all domains except self‐rated memory and processing speed was significantly worse in prefrail and frail participants (P < .05) than in those who were robust. Weakness and walking speed were most consistently linked to poorer cognition, whereas low activity and weight loss were not independently associated with any cognitive domain. Exhaustion was associated with global cognition (B = −0.18 ± 0.06), with some evidence of links to objectively measured and self‐rated memory.ConclusionCognitive function is worse across multiple cognitive domains in prefrail and frail individuals aged 50 and older than in those who are robust, although the absolute differences are small after adjusting for confounding factors.
Effect of elevated CO2 concentration on photosynthetic characteristics of hyperaccumulator Sedum alfredii under cadmium stress
Authors: Li Tingqiang , Tao Qi , Di Zhenzhen , Lu Fan , Yang Xiaoe 
Published: November 2014

AbstractThe combined effects of elevated CO2 and cadmium (Cd) on photosynthetic rate, chlorophyll fluorescence and Cd accumulation in hyperaccumulator Sedum alfredii Hance were investigated to predict plant growth under Cd stress with rising atmospheric CO2 concentration. Both pot and hydroponic experiments were conducted and the plants were grown under ambient (350 µL L−1) or elevated (800 µL L−1) CO2. Elevated CO2 significantly (P < 0.05) increased Pn (105%–149%), Pnmax (38.8%–63.0%) and AQY (20.0%–34.8%) of S. alfredii in all the Cd treatments, but reduced chlorophyll concentration, dark respiration and photorespiration. After 10 days growth in medium with 50 µM Cd under elevated CO2, PSII activities were significantly enhanced (P < 0.05) with Pm, Fv/Fm, Φ(II) and qP increased by 66.1%, 7.5%, 19.5% and 16.4%, respectively, as compared with ambient‐grown plants. Total Cd uptake in shoot of S. alfredii grown under elevated CO2 was increased by 44.1%–48.5%, which was positively correlated with the increase in Pn. These results indicate that elevated CO2 promoted the growth of S. alfredii due to increased photosynthetic carbon uptake rate and photosynthetic light‐use efficiency, and showed great potential to improve the phytoextraction of Cd by S. alfredii.
Structural and functional analysis of an asymmetric bidirectional promoter in Arabidopsis thaliana
Authors: Liu Shi‐Juan , Yue Qiu‐Juan , Zhang Wei 
Published: November 2014

AbstractBidirectional promoters are relatively abundant in eukaryotic genomes, suggesting that they have an important biological significance. As yet, few of these promoters have been characterized in detail. Here, using a promoter::GUS transgene approach has revealed that the intergenic region of Arabidopsis thaliana divergent genes At1g71850 and At1g71860 is an asymmetric bidirectional promoter, which exhibits an orientation‐dependent expression profile. The strength of the forward promoter was greater than that of the reverse promoter, and their tissue specificities were not identical. Deletion analyses revealed that this bidirectional promoter could be divided into three functional regions. The basal level and tissue specificity of the promoter in the reverse orientation were regulated positively by region II and negatively by region III, whereas promoter activity in the forward orientation was regulated negatively by region II and positively by region I. Thus the 52‐bp stretch of region II had a dual function, enhancing expression in the reverse orientation and suppressing it in the forward orientation. These results demonstrated that the activity of the At1g71850‐At1g71860 bidirectional promoter was modulated by complex interactions between both positive and negative cis‐acting elements. These findings will enhance our understanding of the regulatory mechanisms of plant bidirectional promoters.
Hypoxic regulation of plasminogen activator inhibitor‐1 expression in human buccal mucosa fibroblasts stimulated with arecoline
Authors: Tsai Chung‐Hung , Lee Shiuan‐Shinn , Chang Yu‐Chao 
Published: November 2014

BackgroundOral submucous fibrosis (OSF) is regarded as a pre‐cancerous condition with fibrosis in oral subepithelial connective tissue. Hypoxia‐inducible factor (HIF)‐1α regulates a wide variety of profibrogenic genes, which are closely associated with tissue fibrosis. The aim of this study was to compare HIF‐1α expression in normal buccal mucosa tissues and OSF specimens and further explore the potential mechanisms that may lead to the induction of HIF‐1α expression.MethodTwenty‐five OSF specimens and six normal buccal mucosa were examined by immunohistochemistry. The expression of HIF‐1α from fibroblasts cultured from OSF and normal buccal mucosa was measured by Western blot. Arecoline, a major areca nut alkaloid, was challenged to normal buccal mucosa fibroblasts (BMFs) to elucidate whether HIF‐1α expression could affect by arecoline. In addition, the effects of arecoline on plasminogen activator inhibitor (PAI)‐1 expression were evaluated in environmental hypoxia.ResultsHIF‐1α expression was significantly higher in OSF specimens and expressed mainly by fibroblasts, epithelial cells, and inflammatory cells. Fibroblasts derived from OSF were found to exhibit higher HIF‐1α protein expression than BMFs (P < 0.05). Arecoline was found to upregulate HIF‐1α protein in a dose‐dependent manner (P < 0.05). Hypoxia increased arecoline‐induced PAI‐1 protein expression than normoxic conditions (P < 0.05).ConclusionThese results suggest that HIF‐1α expression is significantly upregulated in OSF tissues from areca quid chewers, implying a potential role as a biomarker for local tissue hypoxia. The activation of HIF‐1α may promote fibrogenesis by an increase of PAI‐1 expression and a subsequent elevation of extracellular matrix production in oral submucosa leading to fibrosis.
ZEB1 as an indicator of tumor recurrence for areca quid chewing‐associated oral squamous cell carcinomas
Authors: Ho Cho Ming , Hu Fang‐Wei , Lee Shiuan‐Shinn , Shieh Tzong‐Ming , Yu Chuan‐Hang , Lin Shih‐Shen , Yu Cheng‐Chia 
Published: November 2014

BackgroundOral squamous cell carcinoma (OSCC) is the sixth most prevalent malignancy worldwide and the third most common cancer in developing nation. Most OSCC patients relapse within months after receiving treatment. Therefore, searching the biomarkers of recurrence is urgently required to improve OSCC patient survival.MethodsWe set out to explore whether expression of ZEB1 could be triggered in oral epithelial cells (SG and FaDu) by arecoline in vitro. Control and ZEB1‐knockdown arecoline‐stimulated SG and FaDu were subjected to migration/invasiveness/anchorage‐independent growth assay. Primary and recurrent OSCC tissues from areca quid chewers were analyzed using real‐time RT‐PCR analysis for ZEB1 expression.ResultsArecoline led to dose‐dependent elevation of ZEB1 expression in SG and FaDu cells. Downregulation of ZEB1 by lentiviral infection significantly reversed arecoline‐induced oncogenicity including migration ability, cell invasiveness, and anchorage‐independent growth in SG and FaDu cells. Clinically, the level of ZEB1 expression was higher in recurrent OSCC tumor samples but lower in primary lesions.ConclusionsTargeting ZEB1 might offer a new strategy for the treatment of OSCC patients. ZEB1 can serve as a progression and relapse marker in OSCC patients.
Melatonin feedback on clock genes: a theory involving the proteasome
Authors: Vriend Jerry , Reiter Russel J. 
Published: November 2014

AbstractThe expression of ‘clock’ genes occurs in all tissues, but especially in the suprachiasmatic nuclei (SCN) of the hypothalamus, groups of neurons in the brain that regulate circadian rhythms. Melatonin is secreted by the pineal gland in a circadian manner as influenced by theSCN. There is also considerable evidence that melatonin, in turn, acts on theSCNdirectly influencing the circadian ‘clock’ mechanisms. The most direct route by which melatonin could reach theSCNwould be via the cerebrospinal fluid of the third ventricle. Melatonin could also reach the pars tuberalis (PT) of the pituitary, another melatonin‐sensitive tissue, via this route. The major ‘clock’ genes include the period genes,Per1andPer2, the cryptochrome genes,Cry1andCry2, theclock(circadian locomotor output cycles kaput) gene, and theBmal1(aryl hydrocarbon receptor nuclear translocator‐like) gene. Clock and Bmal1 heterodimers act on E‐box components of the promoters of the Per and Cry genes to stimulate transcription. A negative feedback loop between the cryptochrome proteins and the nucleus allows the Cry and Per proteins to regulate their own transcription. A cycle of ubiquitination and deubiquitination controls the levels ofCRYprotein degraded by the proteasome and, hence, the amount of protein available for feedback. Thus, it provides a post‐translational component to the circadian clock mechanism.BMAL1 also stimulates transcription ofREV‐ERBαand, in turn, is also partially regulated by negative feedback byREV‐ERBα. In the ‘black widow’ model of transcription, proteasomes destroy transcription factors that are needed only for a particular period of time. In the model proposed herein, the interaction of melatonin and the proteasome is required to adjust theSCNclock to changes in the environmental photoperiod. In particular, we predict that melatonin inhibition of the proteasome interferes with negative feedback loops (CRY/PERandREV‐ERBα) on Bmal1 transcription genes in both theSCNandPT. Melatonin inhibition of the proteasome would also tend to stabilizeBMAL1 protein itself in theSCN, particularly at night when melatonin is naturally elevated. Melatonin inhibition of the proteasome could account for the effects of melatonin on circadian rhythms associated with molecular timing genes. The interaction of melatonin with the proteasome in the hypothalamus also provides a model for explaining the dramatic ‘time of day’ effect of melatonin injections on reproductive status of seasonal breeders. Finally, the model predicts that a proteasome inhibitor such as bortezomib would modify circadian rhythms in a manner similar to melatonin.
Cardioprotective effects of melatonin against myocardial injuries induced by chronic intermittent hypoxia in rats
Authors: Yeung Hang‐Mee , Hung Ming‐Wai , Lau Chi‐Fai , Fung Man‐Lung 
Published: November 2014

AbstractObstructive sleep apnea (OSA) associated with chronic intermittent hypoxia (CIH) increases the morbidity and mortality of ischemic heart disease in patients. Yet, there is a paucity of preventive measures targeting the pathogenesis of CIH‐induced myocardial injury. We examined the cardioprotective effect of melatonin against the inflammation, fibrosis and the deteriorated sarcoplasmic reticulum (SR) Ca2+ homeostasis, and ischemia/reperfusion (I/R)‐induced injury exacerbated by CIH. Adult male Sprague Dawley rats that had received a daily injection of melatonin (10 mg/kg) or vehicle were exposed to CIH treatment mimicking a severe OSA condition for 4 wk. Systolic pressure, heart weights, and malondialdehyde were significantly increased in hypoxic rats but not in the melatonin‐treated group, when compared with the normoxic control. Levels of the expression of inflammatory cytokines (TNF‐α, IL‐6, and COX‐2) and fibrotic markers (PC1 and TGF‐β) were significantly elevated in the hypoxic group but were normalized by melatonin. Additionally, infarct size of isolated hearts with regional I/R was substantial in the hypoxic group treated with vehicle but not in the melatonin‐treated group. Moreover, melatonin treatment mitigated the SR‐Ca2+ homeostasis in the cardiomyocyte during I/R with (i) Ca2+ overloading, (ii) decreased SR‐Ca2+ content, (iii) lowered expression and activity of Ca2+‐handling proteins (SERCA2a and NCX1),and (iv) decreased expressions of CAMKII and phosphorylated eNOSser1177. Furthermore, melatonin ameliorated the level of expression of antioxidant enzymes (CAT and MnSOD) and NADPH oxidase (p22 and NOX2). Results support a prophylactic usage of melatonin in OSA patients, which protects against CIH‐induced myocardial inflammation and fibrosis with impaired SR‐Ca2+ handling and exacerbated I/R injury.
Receipt of Regular Primary Care and Early Cancer Detection in Appalachia
Authors: Camacho Fabian , Hwang Wenke , Kern Teresa , Anderson Roger T. 
Published: November 2014

AbstractPurposeThe objective was to examine the impact of regular primary care encounters (PCE) on early breast cancer detection in an Appalachian sample of Medicare beneficiaries diagnosed 2006‐2008. Determinants of PCE were investigated and a mediation analysis was conducted where PCE was a mediator to cancer stage.MethodsA total of 3,589 cases were identified from Appalachian areas in Pennsylvania, Kentucky, Ohio, and North Carolina, and health care services were examined 2 months to 2 years prior to diagnosis. A regular care PCE variable was constructed with 4 ordinal levels: none, any, “annual,” and “semi‐annual.” Association of PCE with stage, mortality and covariables was conducted using ordinal logistic regressions and Cox Proportional Hazards survival models.ResultsSixty‐eight percent of the cases had semi‐annual PCE. Regular PCE was strongly associated with late‐stage cancer rates (39%‐13% by increasing PCE level,P< .0001) and 5‐year all‐cause mortality (42%‐24%,P< .0001). Subgroup analysis revealed variations by hypertension and urban status, with nonhypertensives with no PCE being at particularly increased risk. Significant determinants of PCE included age, rural/urban status, comorbidity, dual Medicaid insurance, Appalachian region economic classification, state, select comorbidities, hypertension, and minimum distance to provider. Mediation analysis results were consistent with lower number of comorbidities leading to increased late cancer detection due to patients having a decreased PCE.ConclusionPCE is an important determinant of cancer detection, with a dose‐response relationship. Variations exist by geography and hypertension. Comorbidity may influence both PCE and late‐stage rates with partial mediation through PCE.