bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardioprotective Effects of Metformin
Authors: Driver Christine , Bamitale Kayode D. S. , Kazi Aniessa , Olla Mehnaaz , Nyane Ntsoaki A. , Owira Peter M. O. 
Published: May 2018

Abstract:
Metformin, routinely used as first-line drug in the treatment of type 2 diabetes, has been shown to have cardioprotective effects beyond its glycemic control. These have been attributed to increases in Akt concentrations and activation of protein kinases in the RISK pathways, which prevent the mPTP from opening and rupturing it and therefore, protects myocyte viability. In myocardial infarction and subsequent reperfusion, metformin activation of AMPK promotes glycolysis and keeps the mPTP closed. Given as a preconditioning and/or postconditioning agent, metformin has been shown to decrease infarct size and improve survival rates after myocardial infarction. Metformin has further been reported to restore depleted PGC-1α levels and improve mitochondrial biogenesis by increasing phosphorylation of eNOSser1177, which produces NO and leads to reduced vascular inflammation and myocardial injury after ischemia. There is strong evidence suggesting that metformin improves cardiovascular outcomes by influencing metabolic signal transduction pathways. There are growing calls for metformin use to be expanded off-label beyond the traditional glycemic control. We review experimental evidence for metformin's impact on cardiovascular disease and its underlying molecular mechanisms of action and also discuss why significant gains made in experimental conditions have not translated into significant therapeutic applications.
Promotion of Home-Based Exercise Training as Secondary Prevention of Coronary Heart Disease
Authors: Torri Anna , Panzarino Claudia , Scaglione Anna , Modica Maddalena , Bordoni Bruno , Redaelli Raffaella , De Maria Renata , Ferratini Maurizio 
Published: May 2018

Background:
Although cardiac rehabilitation (CR) is cost- effective in improving the health of patients with coronary heart disease (CHD), less than half of eligible CHD patients attend a CR program. Innovative web-based technologies might improve CR delivery and utilization. We assessed the feasibility and impact on functional capacity and secondary prevention targets of a long-term web-monitored exercise-based CR maintenance program.

Methods:
Low- to moderate-risk CHD patients were recruited at discharge from inpatient CR after a coronary event or revascularization. We developed an interactive web-based platform for secure home individual access control, monitoring, and validation of exercise training. Of 86 eligible patients, 26 consented to participate in the study intervention (IG). Using a quasi-experimental design, we recruited in parallel 27 eligible patients, unavailable for regular web monitoring, who consented to a follow-up visit as usual care (UC).

Results:
Among IG, active daily data transmission was 100% during month 1, 88% at month 3, and 81% at 6 months, with sustained improvement in self-reported physical activity beginning with the first week after discharge from inpatient CR (2467 [1854-3554] MET-min/wk) to month 3 (3411 [1981-5347] MET-min/wk, P = .019). Both groups showed favorable changes over time in lipid profile, ventricular function, distance walked in 6 min, and quality of life. At 6 mo, IG achieved a significantly higher proportion of cardiovascular risk factor targets than UC (75 ± 20% vs 59 ± 30%, P = .029).

Conclusions:
Our web-based home CR maintenance program was feasible, well-accepted, and effective in improving physical activity during 6 mo and achieved higher overall adherence to cardiovascular risk targets than UC.
Severity Adjusted Risk of Long-term Adverse Sequelae Among Children With Osteomyelitis
Authors: Vorhies John S. , Lindsay Eduardo A. , Tareen Naureen G. , Kellum Rodney J. , Jo Chan Hee , Copley Lawson A. 
Published: May 2018

Background:
The purpose of this investigation was to evaluate the risk for long-term, adverse outcomes among children with osteomyelitis.

Methods:
Children with osteomyelitis were prospectively enrolled from 2012 to 2014. Care was accomplished by a multidisciplinary team according to an institutional algorithm. Data were collected to define the severity of illness during the initial hospitalization and assess short, intermediate and long-term outcomes. Clinical examination, radiographic assessment and functional outcome survey administration were performed at a minimum of 2 year follow-up. A comparison cohort analysis was performed according to initial severity of illness score of mild (0–2), moderate (3–6) and severe (7–10).

Results:
Of 195 children enrolled, 139 (71.3%) returned for follow-up at an average of 2.4 years (range, 2.0–5.0 years). Children with severe illness were less likely to have normal radiographs (severe, 4.0%; moderate, 38.2%; mild, 53.2%, P < 0.0001), and more likely to have osteonecrosis, chondrolysis, or deformity (severe, 32.0%; moderate, 5.9%; mild, 1.3%, P < 0.0001). Functional outcome measures did not significantly differ between severity categories. By regression analysis severity of illness score, plus age less than 3 years and Methicillin-resistant Staphylococcus aureus predicted severe sequelae with an area under the curve of 0.8617 and an increasing odds ratio of 1.34 per point of increase in severity score.

Conclusion:
Long-term severe adverse outcomes among children with osteomyelitis occurred in 11 of 139 (7.9%) children and were predicted by initial severity of illness. Other risks that diminished the likelihood of complete resolution or increased the risk of severe sequelae included Methicillin-resistant Staphylcoccus aureus etiology and young age. The majority of children with osteomyelitis do not require long-term follow-up beyond the initial treatment period.
Clinical Reasoning: Survey of Teaching Methods and Assessment in Entry-Level Physical Therapist Clinical Education
Authors: Huhn Karen , Black Lisa , Christensen Nicole , Furze Jennifer , Vendrely Ann , Wainwright Susan 
Published: May 2018

Background.
Clinical reasoning skills have been identified as an integral part of physical therapist education developed in both the academic and clinical settings. There is limited understanding of clinical instructors (CIs) expectations related to the anticipated level of clinical reasoning (CR) skills achieved by students and how CR is taught and assessed in the clinic.

Objective.
The purpose of this research was to explore how CIs teach and assess student physical therapists' CR skills and garner an understanding of CIs' expectations related to CR skills attained at various levels of clinical experience.

Design.
A descriptive, cross-sectional survey was used to gather data from CIs.

Methods.
Participants identified from an American Physical Therapy Association database of credentialed CIs were asked to complete an 18-question electronically delivered survey.

Results.
A nationwide sample of 749 CIs completed the survey. The data clearly demonstrated that CIs value and recognize the importance of clinical education in the development of CR. They also value the use of engaged discussion and reflection to foster the development of reasoning skills. Most CIs did not expect students to achieve entry-level CR skills during the third year.

Conclusions.
Clinical instructors see the importance of clinical experiences and engaged discussion to foster the development of CR. Further research is needed to understand why most clinical educators did not expect students to achieve “entry-level” CR skills as defined by the Clinical Performance Instrument by the final year of the program.
Prevalence of Extracochlear Electrodes: Computerized Tomography Scans, Cochlear Implant Maps, and Operative Reports
Authors: Holder Jourdan T. , Kessler David M. , Noble Jack H. , Gifford René H. , Labadie Robert F. 
Published: May 2018

Objective:
To quantify and compare the number of cochlear implant (CI) electrodes found to be extracochlear on postoperative computerized tomography (CT) scans, the number of basal electrodes deactivated during standard CI mapping (without knowledge of the postoperative CT scan), and the extent of electrode insertion noted by the surgeon.

Study Design:
Retrospective.

Setting:
Academic Medical Center.

Methods:
Two hundred sixty-two patients underwent standard cochlear implantation and postoperative temporal bone CT scanning. Scans were analyzed to determine the number of extracochlear electrodes. Standard CI programming had been completed without knowledge of the extracochlear electrodes identified on the CT. These standard CI maps were reviewed to record the number of deactivated basal electrodes. Lastly, each operative report was reviewed to record the extent of reported electrode insertion.

Results:
13.4% (n = 35) of CIs were found to have at least one electrode outside of the cochlea on the CT scan. Review of CI mapping indicated that audiologists had deactivated extracochlear electrodes in 60% (21) of these cases. Review of operative reports revealed that surgeons correctly indicated the number of extracochlear electrodes in 6% (2) of these cases.

Conclusions:
Extracochlear electrodes were correctly identified audiologically in 60% of cases and in surgical reports in 6% of cases; however, it is possible that at least a portion of these cases involved postoperative electrode migration. Given these findings, postoperative CT scans can provide information regarding basal electrode location, which could help improve programming accuracy, associated frequency allocation, and audibility with appropriate deactivation of extracochlear electrodes.
SOX11, a key oncogenic factor in mantle cell lymphoma
Authors: Beekman Renée , Amador Virginia , Campo Elias 
Published: May 2018

Purpose of review
SOX11 has emerged as a key transcription factor in the pathogenesis of mantle cell lymphoma (MCL) whereas it is not expressed in normal B cells or virtually in any other mature B-cell neoplasm. This review will examine the role of SOX11 as a biomarker in MCL, the new information on its transcriptional targets, and the mechanisms regulating its expression in MCL.

Recent findings
SOX11 is highly expressed in conventional MCL, including cyclin D1-negative cases, but it is not expressed in the indolent leukemic nonnodal MCL subtype. These two MCL subtypes also differ in their cell-of-origin, IGHV mutational status and genomic instability. SOX11 promotes tumor growth of MCL cells in vivo and regulates a broad transcriptional program that includes B-cell differentiation pathways and tumor–microenvironment interactions, among others. The mechanisms upregulating SOX11 in MCL are not well understood but are mediated in part by the three-dimensional reconfiguration of the DNA, bringing together a distant enhancer region and the SOX11 promoter.

Summary
SOX11 is a relevant element in the pathogenesis of MCL and has been instrumental to identify two distinct clinicobiological subtypes of this tumor. Further studies should clarify the mechanisms mediating its oncogenic potential and leading to its intriguing expression in these tumors.
Precision medicine and lymphoma
Authors: Heward James A. , Kumar Emil A. , Korfi Koorosh , Okosun Jessica , Fitzgibbon Jude 
Published: May 2018

Purpose of review
The treatment of the germinal center lymphomas, diffuse large B cell (DLBCL) and follicular lymphoma, has changed little beyond the introduction of immunochemotherapies. However, there exists a substantial group of patients within both diseases for which improvements in care will involve appropriate tailoring of treatment.

Recent findings
DLBCL consists of two major subtypes with striking differences in their clinical outcomes paralleling their underlying genetic heterogeneity. Recent studies have seen advances in the stratification of germinal center lymphomas, through comprehensive profiling of 1001 DLBCLs alongside refinements in the identification of high-risk follicular lymphoma patients using m7-FLIPI and 23G models. A new wave of novel therapeutic agents is now undergoing clinical trials for germinal center lymphomas, with BCR and EZH2 inhibitors demonstrating preferential benefit in subgroups of patients. The emergence of cell-free DNA has raised the possibility of dynamic disease monitoring to potentially mitigate the complexity of spatial and temporal heterogeneity, whilst predicting tumor evolution in real time.

Summary
Altogether knowledge of the genomic landscape of germinal center lymphomas is offering welcome opportunities in patient risk stratification and therapeutics. The challenge ahead is to establish how best to combine upfront or dynamic prognostication with precision therapies, while retaining practicality in clinical trials and the real-world setting.
The Esophageal‐Atresia‐Quality‐of‐life Questionnaires
Authors: Dellenmark‐Blom Michaela , Dingemann Jens , Witt Stefanie , Quitmann Julia H. , Jönsson Linus , Gatzinsky Vladimir , Chaplin John E. , Bullinger Monika , Flieder Sofie , Ure Benno M. , Dingemann Carmen , Abrahamsson Kate 
Published: May 2018

ABSTRACTObjectives:Esophageal atresia (EA) is a rare malformation characterized of discontinuity of the esophagus, concurrent with or without a tracheoesophageal fistula (TEF). We report the feasibility validity and reliability of a condition‐specific quality‐of‐life (QOL) tool for EA/TEF children, the age‐adapted EA‐QOL‐questionnaires, when used in Sweden and Germany.Methods:A total of 124 families of children with EA/TEF participated in the study; 53 parents completed the EA‐QOL‐questionnaire for children aged 2 to 7 years; 62 children/71 parents the EA‐QOL‐questionnaire for children 8 to 17 years. Feasibility was determined from the percentage of missing item responses. Based on clinical data and previously validated generic QOL‐instruments (PedsQL 4.0, DISABKIDS‐12), the final EA‐QOL scores were evaluated against hypotheses of validity (known‐groups/concurrent/convergent) and reliability (internal consistency/retest reliability of scores for 3 weeks). Significant level was P < 0.05.Results:In the questionnaire for EA/TEF children aged 2 to 7 years, 16/18 items were completed with missing values <6% (range 0%–7.5%), and in the questionnaire for 8 to 17‐year‐olds, 24/24 child‐reported items (range 0%–4.8%) and 21/24 parent‐reported items (range 0%–7.0%). In both age‐specific EA‐QOL‐questionnaires, desirable standards for known‐groups and concurrent validity were fulfilled; digestive symptoms and feeding difficulties negatively impacted EA‐QOL‐Total‐scores (P < 0.001), and as hypothesized, in 2 to 7‐year‐olds, respiratory symptoms decreased EA‐QOL‐Total‐scores (P = 0.002). Correlations between the EA‐QOL and generic QOL questionnaires supported convergent validity. Internal consistency reliability was satisfactory. The level of agreements of EA‐QOL‐scores between the field‐ and retest study were good to excellent.Conclusions:The overall psychometric performance of the EA‐QOL‐questionnaires for EA/TEF children is satisfactory and can enhance outcome evaluations in future research and clinical practice.
Bidirectional Prospective Associations Between Cardiac Autonomic Activity and Inflammatory Markers
Authors: Hu Mandy Xian , Lamers Femke , Neijts Melanie , Willemsen Gonneke , de Geus Eco J.C. , Penninx Brenda W.J.H. 
Published: May 2018

ABSTRACT

Objective
Autonomic nervous system (ANS) imbalance has been cross-sectionally associated with inflammatory processes. Longitudinal studies are needed to shed light on the nature of this relationship. We examined cross-sectional and bidirectional prospective associations between cardiac autonomic measures and inflammatory markers.

Methods
Analyses were conducted with baseline (n = 2823), 2-year (n = 2099), and 6-year (n = 1774) data from the Netherlands Study of Depression and Anxiety. To compare the pattern of results, prospective analyses with ANS (during sleep, leisure time, and work) and inflammation were conducted in two data sets from the Netherlands Twin Register measured for 4.9 years (n = 356) and 5.4 years (n = 472). Autonomic nervous system measures were heart rate (HR) and respiratory sinus arrhythmia (RSA). Inflammatory markers were C-reactive protein (CRP) and interleukin (IL)-6.

Results
The Netherlands Study of Depression and Anxiety results showed that higher HR and lower RSA were cross-sectionally significantly associated with higher inflammatory levels. Higher HR predicted higher levels of CRP (B = .065, p < .001) and IL-6 (B = .036, p = .014) at follow-up. Higher CRP levels predicted lower RSA (B = −.024, p = .048) at follow-up. The Netherlands Twin Register results confirmed that higher HR was associated with higher CRP and IL-6 levels 4.9 years later. Higher IL-6 levels predicted higher HR and lower RSA at follow-up.

Conclusions
Autonomic imbalance is associated with higher levels of inflammation. Independent data from two studies converge in evidence that higher HR predicts subsequent higher levels of CRP and IL-6. Inflammatory markers may also predict future ANS activity, but evidence for this was less consistent.
Cross-Sectional and Longitudinal Associations of Systolic Blood Pressure With Quality of Life and Depressive Mood in Older Adults With Cardiovascular Risk Factors: Results From the Observational DIAST-CHF Study
Authors: Herrmann-Lingen Christoph , Meyer Thomas , Bosbach Alexandra , Chavanon Mira-Lynn , Hassoun Lina , Edelmann Frank , Wachter Rolf 
Published: May 2018

ABSTRACT

Objective
Although diagnosed arterial hypertension and antihypertensive medication usually have an adverse impact on quality of life, recent studies suggest that actual blood pressure may be positively related to better well-being. However, data in older patients with cardiovascular risk factors are lacking, for whom such an association may be of particular relevance.

Methods
In 1300 adults aged 50 to 85 years with cardiovascular risk factors (51.5% men, mean age = 65.7 ± 8.2 years) participating in an observational study, we performed standardized measurements of blood pressure and assessed quality of life and depressive symptoms at baseline and 1-year follow-up using the Short Form-36 (SF-36) and the Hospital Anxiety and Depression Scale (HADS).

Results
Bivariate analysis demonstrated that systolic blood pressure was associated with higher SF-36 mental component summary scores (r = 0.100, p < .001) and reduced HADS depression (r = −0.082, p = .003). Multivariate regression models adjusting for age, sex, and disease severity confirmed that higher systolic blood pressure significantly predicted both better mental quality of life (β = 0.070, p = .012) and less depressive mood (β = −0.083, p = .003) at baseline, independently of antihypertensive medication and diagnosed hypertension. Moreover, the beneficial effects of baseline systolic blood pressure remained stable for both summary components of the SF-36 as well as HADS depression at 1-year follow-up. All results remained unchanged, when limiting the analyses to the 1072 patients with diagnosed hypertension.

Conclusions
In older adults with cardiovascular risk factors, higher systolic blood pressure readings are independently related to better quality of life and fewer depressive symptoms in both cross-sectional and longitudinal settings, although the magnitude of the effect sizes is typically small.
Blood Pressure, Emotional Dampening, and Risk Behavior: Implications for Hypertension Development
Authors: McCubbin James A. , Nathan Aaron , Hibdon Melissa A. , Castillo Anastasia V. , Graham Jack G. , Switzer Fred S. 
Published: May 2018

ABSTRACT

Objective
Elevated resting blood pressure (BP) is associated with risk for hypertension and emotional dampening, including reduced responses to emotionally meaningful stimuli. Perception of threat is a critical motivator in avoidance of risky health-damaging behavior. We hypothesize that BP-associated dampening of threat appraisal may increase risk-taking behavior.

Methods
We measured resting BP, perception of affect, and risk behavior in 92 healthy women (n = 49) and men (n = 43) recruited from university students and staff as well as members of the surrounding community. Mean (SE) age for the sample was 21.5 (4.3) year. BP was measured using an automated BP monitor, and risk behavior was assessed with a modified National College Health Risk Behavior Survey. We also measured recognition of affect using the Perception of Affect Task (PAT).

Results
Risk-taking behavior was positively correlated with both systolic (r(89) = .278, p = .008) and diastolic BP (r(89) = .309, p < .003). Regression analyses indicated that the association between risk-taking behavior and BP was not mediated by PAT scores.

Conclusions
Results show that persons with higher resting BP levels report increased risk-taking behavior. PAT scores, while correlated with systolic BP, did not mediate the relationship between BP and risk. The relationship between BP and risk behavior reflects the potential involvement of central nervous system regulation of both BP and emotional responsivity, and its relationship to health-damaging behavior and risk for hypertension.
Comparative Evaluation of Cell Viability Immediately After Osteotomy for Implants With Drills and Piezosurgery: Immunohistochemistry Analysis
Authors: Pereira Cassiano Costa Silva , Batista Fábio Roberto de Souza , Jacob Ricardo Garcia Mureb , Nogueira Lamis Meorin , Carvalho Abrahão Cavalcante Gomes de Souza , Gealh Walter Cristiano , Garcia-Júnior Idelmo Rangel , Okamoto Roberta 
Published: May 2018

Objective:
To evaluate the effect of reusing drills and piezosurgery tips during implant osteotomy on immediate bone cell viability through immunohistochemical analysis.

Materials and Methods:
Six male rabbits were divided into 2 groups and then divided into 5 subgroups—correspond to drills and tips used 10, 20, 30, 40, and 50 times, respectively. All animals received 10 osteotomies in each tibia, by use of the classic drilling procedure in one group (G1) and the piezosurgery device in the other group (G2). For immunohistochemical technique were utilized the osteoprotegerin, RANKL, osteocalcin, and caspase 3. Control procedures were performed by omitting the primary antibodies (negative control).

Results:
Bone formation and resorption responses presented in more intense way during the piezosurgery. The expression of osteocalcin had become quite intense in piezosurgery groups, but with reduced immunostaining from the 30th osteotomy. The caspase 3 showed the viability of the osteoblast from the 20th osteotomy with piezosurgery and remained constant until the 50th.

Conclusion:
Piezosurgery provides greater osteoblastic cell viability than the system of conventional drilling.

Clinical Relevance:
This study will provide data so that the authors can recycle the drills and tips for implant placement, thus enabling a better cell viability for osseointegration.