bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein Kinase N Promotes Stress-Induced Cardiac Dysfunction Through Phosphorylation of Myocardin-Related Transcription Factor A and Disruption of Its Interaction With Actin
Authors: Sakaguchi Teruhiro , Takefuji Mikito , Wettschureck Nina , Hamaguchi Tomonari , Amano Mutsuki , Kato Katsuhiro , Tsuda Takuma , Eguchi Shunsuke , Ishihama Sohta , Mori Yu , Yura Yoshimitsu , Yoshida Tatsuya , Unno Kazumasa , Okumura Takahiro , Ishii Hideki , Shimizu Yuuki , Bando Yasuko K. , Ohashi Koji , Ouchi Noriyuki , Enomoto Atsushi , Offermanns Stefan , Kaibuchi Kozo , Murohara Toyoaki 
Published: September 2019

Background:
Heart failure is a complex syndrome that results from structural or functional impairment of ventricular filling or blood ejection. Protein phosphorylation is a major and essential intracellular mechanism that mediates various cellular processes in cardiomyocytes in response to extracellular and intracellular signals. The RHOA-associated protein kinase (ROCK/Rho-kinase), an effector regulated by the small GTPase RHOA, causes pathological phosphorylation of proteins, resulting in cardiovascular diseases. RHOA also activates protein kinase N (PKN); however, the role of PKN in cardiovascular diseases remains unclear.

Methods:

To explore the role of PKNs in heart failure, we generated tamoxifen-inducible, cardiomyocyte-specific PKN1- and PKN2-knockout mice by intercrossing the αMHC-CreERT2 line with
Pkn1
flox/flox
and
Pkn2
flox/flox
mice and applied a mouse model of transverse aortic constriction– and angiotensin II–induced heart failure. To identify a novel substrate of PKNs, we incubated GST-tagged myocardin-related transcription factor A (MRTFA) with recombinant GST-PKN-catalytic domain or GST-ROCK-catalytic domain in the presence of radiolabeled ATP and detected radioactive GST-MRTFA as phosphorylated MRTFA.

Results:

We demonstrated that RHOA activates 2 members of the PKN family of proteins, PKN1 and PKN2, in cardiomyocytes of mice with cardiac dysfunction. Cardiomyocyte-specific deletion of the genes encoding
Pkn1
and
Pkn2
(cmc-PKN1/2 DKO) did not affect basal heart function but protected mice from pressure overload– and angiotensin II–induced cardiac dysfunction. Furthermore, we identified MRTFA as a novel substrate of PKN1 and PKN2 and found that MRTFA phosphorylation by PKN was considerably more effective than that by ROCK in vitro. We confirmed that endogenous MRTFA phosphorylation in the heart was induced by pressure overload– and angiotensin II–induced cardiac dysfunction in wild-type mice, whereas cmc-PKN1/2 DKO mice suppressed transverse aortic constriction– and angiotensin II–induced phosphorylation of MRTFA. Although RHOA-mediated actin polymerization accelerated MRTFA-induced gene transcription, PKN1 and PKN2 inhibited the interaction of MRTFA with globular actin by phosphorylating MRTFA, causing increased serum response factor–mediated expression of cardiac hypertrophy– and fibrosis-associated genes.

Conclusions:
Our results indicate that PKN1 and PKN2 activation causes cardiac dysfunction and is involved in the transition to heart failure, thus providing unique targets for therapeutic intervention for heart failure.
Stratospheric Influences on the MJO-Induced Rossby Wave Train: Effects on Intraseasonal Climate
Authors: Hood Lon L. , Redman Malori A. , Johnson Wes L. , Galarneau Thomas J. 
Published: September 2019

AbstractThe tropical Madden–Julian oscillation (MJO) excites a northward propagating Rossby wave train that largely determines the extratropical surface weather consequences of the MJO. Previous work has demonstrated a significant influence of the tropospheric El Niño–Southern Oscillation (ENSO) on the characteristics of this wave train. Here, composite analyses of ERA-Interim sea level pressure (SLP) and surface air temperature (SAT) data during the extended northern winter season are performed to investigate the additional role of stratospheric forcings [the quasi-biennial oscillation (QBO) and the 11-yr solar cycle] in modifying the wave train and its consequences. MJO phase composites of 20–100-day filtered data for the two QBO phases show that, similar to the cool phase of ENSO, the easterly phase of the QBO (QBOE) produces a stronger wave train and associated modulation of SLP and SAT anomalies. In particular, during MJO phases 5–7, positive SLP and negative SAT anomalies in the North Atlantic/Eurasian sector are enhanced during QBOE relative to the westerly phase of the QBO (QBOW). The opposite occurs during the earliest MJO phases. SAT anomalies over eastern North America are also more strongly modulated during QBOE. Although less certain because of the short data record, there is some evidence that the minimum phase of the solar cycle (SMIN) produces a similar increased modulation of SLP and SAT anomalies. The strongest modulations of SLP and SAT anomalies are produced when two or more of the forcings are superposed (e.g., QBOE/cool ENSO, SMIN/QBOE, etc.).
On the Structure of the Regional-Scale Circulation over Central Africa: Seasonal Evolution, Variability, and Mechanisms
Authors: Longandjo Georges-Noel T. , Rouault Mathieu 
Published: September 2019

AbstractAtmospheric circulation over central Africa is dominated by the tropical easterly jet, the African easterly jet, and the low-level westerly jet. In the lower troposphere, a zonal overturning cell occurs over central Africa, but the mechanisms driving its formation, seasonal evolution, and variability are still unclear. Here, using reanalyses (ERA-Interim, NCEP-2, and JRA-55) and the ECHAM5.3 atmospheric model forced by observed sea surface temperature, we highlight the existence, in the lower troposphere, of a separated single, closed, counterclockwise, and shallow zonal overturning cell, namely, the Congo basin cell. This Congo basin cell persists year round, with maximum intensity and width in August/September and minimum intensity and width in May. This shallow cell extracts heat from the warm central Africa landmass through latent and internal energies and transports it to the cold eastern equatorial Atlantic Ocean, reminiscent of the mixed Carnot–steam cycle. Indeed, the monsoon-like circulation triggered by the zonal surface pressure gradient between the warm central Africa landmass and surrounding cold oceans produces mass convergence at the Congo Air Boundary, providing necessary upward motion to air parcels to destabilize the atmosphere over central Africa. As result, convective updrafts depend on underlying moist static energy and the induced low-level westerly jet, controlled by the near-surface land–ocean thermal contrast through the zonal surface pressure gradient between the warm central African landmass and cold eastern equatorial Atlantic Ocean, rather than the midlevel easterly jet. This midlevel easterly jet is formed by the mechanical work that balances the convection associated with the saturation and rainfall. Furthermore, the efficiency of the Congo basin cell determines seasonality over central Africa.
Effects of a Self-Compassion Break Induction on Self-Reported Stress, Self-Compassion, and Depressed Mood
Authors: Williamson Jessica 
Published: September 2019

Introduction The objective of the study was to determine whether practicing a self-compassion induction would reduce self-reported stress, depressed mood, and increase self-compassion in a randomized controlled study measuring variables of interest at two time points spanning three weeks. Method Participants were 129 students (91 females and 38 males, Mage = 19.47, SD = 3.20) divided into three groups: Self-compassion Break, Time Management Control Group, and a No-Induction Control Group. Participants were part of the general student body and were not diagnosed or screened for clinical depression. Self-compassion, stress, and depressed mood were assessed at baseline and follow-up. Participants practiced their respective inductions over three weeks after being guided through their respective inductions at Time 1. Results There were no significant differences between groups in outcome variables. Results of this study may indicate the importance of weekly group check-in meetings to facilitate positive change as findings in this study did not mirror those of similar studies using frequent meetings.
Enhancement of flow measurement for graft verification
Authors: Vechersky Yury Y , Zatolokin Vasily V , Kozlov Boris N , Nenakhova Aleksandra A , Shipulin Vladimir M 
Published: September 2019

Background We aimed to evaluate multiple transit-time flow measurements during coronary artery bypass grafting. Methods Transit-time flow measurements were performed first on the arrested heart both with and without a proximal snare on the target coronary artery, second, after weaning from cardiopulmonary bypass, and third, before chest closure. Results Among the 214 grafts considered, 9 (4.2%) were patent and 6 (2.8%) were failing. In the failed grafts, an abnormal transit-time flow was found during the first measurement, in 5 (2.3%) cases with a proximal snare and in one (0.47%) without a snare. In these cases, technical errors with the distal anastomoses were found and immediately corrected. A problem with the proximal anastomosis was found in one graft during the second measurement and corrected right away. Bending due to excessive length was found in 2 (0.93%) grafts during the third measurement, and graft repositioning was performed. The first transit-time flow measurement showed that mean graft flow was significantly decreased with a proximal snare compared to without a proximal snare, throughout the entire coronary territory. Pulsatility index during the first transit-time flow measurement was higher with a proximal snare than without one. Conclusions The 3-time transit-time flow measurement strategy makes it possible to verify and immediately correct technical problems with coronary bypass grafts.
Voriconazole prophylaxis in leukemic patients: A retrospective single-center study
Authors: Bui Vivian , Walker Sandra AN , Elligsen Marion , Vyas Anju , Kiss Alex , Palmay Lesley 
Published: September 2019

Background Invasive fungal infections commonly occur in acute myeloid and lymphoblastic leukemia patients receiving chemotherapy. In these patients with acute leukemia, posaconazole prophylaxis is recommended; however, voriconazole may be a less costly alternative. Objectives The objective of this study was to evaluate the efficacy and safety of voriconazole prophylaxis in acute leukemia patients. Methods A retrospective chart review of inpatients at Sunnybrook Health Sciences Centre between 2005 and 2017 was completed. Hospitalized adult acute leukemia patients who received voriconazole prophylaxis (cases) were compared to patients who received fluconazole or no prophylaxis during chemotherapy (controls). Statistical analyses comparing baseline characteristics, safety, and efficacy outcomes between the study cohorts were completed. A posaconazole literature-based weighted mean risk was compared to the voriconazole risk of invasive fungal infection identified in this study. Results Of 490 acute myeloid leukemia or acute lymphoblastic leukemia patients, 83 controls and 92 cases were eligible. Case patients received an average of 24.4 ± 10.8 days of voriconazole prophylaxis. The incidence of proven or probable invasive fungal infections with voriconazole was 3.3% (3/92) versus 7.2% (6/83) in the control cohort (p > 0.05) and was comparable to the literature reported weighted incidence of invasive fungal infection with posaconazole (2.4 ± 2.1%; 95% CI 1.3%–3.4%; p > 0.05). Voriconazole was well tolerated by patients (91%; 84/91; seven discontinued due to asymptomatic elevated liver function tests). Conclusions Voriconazole prophylaxis was found to be safe, effective, and comparable to literature-based efficacy data for risk of invasive fungal infection with posaconazole antifungal prophylaxis in patients with acute leukemia undergoing chemotherapy and could represent a significant cost advantage.
A Study on Nonthermal Irreversible Electroporation of the Thyroid
Authors: Lv Yanpeng , Zhang Yanfang , Huang Jianwei , Wang Yunlong , Rubinsky Boris 
Published: September 2019

Background: Nonthermal irreversible electroporation is a minimally invasive surgery technology that employs high and brief electric fields to ablate undesirable tissues. Nonthermal irreversible electroporation can ablate only cells while preserving intact functional properties of the extracellular structures. Therefore, nonthermal irreversible electroporation can be used to ablate tissues safely near large blood vessels, the esophagus, or nerves. This suggests that it could be used for thyroid ablation abutting the esophagus. This study examines the feasibility of using nonthermal irreversible electroporation for thyroid ablation. Methods: Rats were used to evaluate the effects of nonthermal irreversible electroporation on the thyroid. The procedure entails the delivery of high electric field pulses (1-3 kV/cm, 100 microseconds) between 2 surface electrodes bracing the thyroid. The right lobe was treated with various nonthermal irreversible electroporation pulse sequences, and the left was the control. After 24 hours of the nonthermal irreversible electroporation treatment, the thyroid was examined with hemotoxylin and eosin histological analysis. Mathematical models of electric fields and the Joule heating-induced temperature raise in the thyroid were developed to examine the experimental results. Results: Treatment with nonthermal irreversible electroporation leads to follicular cells damage, associated with cell swelling, inflammatory cell infiltration, and cell ablation. Nonthermal irreversible electroporation spares the trachea structure. Unusually high electric fields, for these types of tissue, 3000 V/cm, are needed for thyroid ablation. The mathematical model suggests that this may be related to the heterogeneous structure of the thyroid-induced distortion of local electric fields. Moreover, most of the tissue does not experience thermal damage inducing temperature elevation. However, the heterogeneous structure of the thyroid may cause local hot spots with the potential for local thermal damage. Conclusion: Nonthermal irreversible electroporation with 3000 V/cm can be used for thyroid ablation. Possible applications are treatment of hyperthyroidism and thyroid cancer. The highly heterogeneous structure of the thyroid distorts the electric fields and temperature distribution in the thyroid must be considered when designing treatment protocols for this tissue type.
Sequentially Determined Measures of Interobserver Agreement (Kappa) in Clinical Trials May Vary Independent of Changes in Observer Performance
Authors: Reeve Russell , Gottlieb Klaus 
Published: September 2019

Background: Cohen's kappa is a statistic that estimates interobserver agreement. It was originally introduced to help develop diagnostic tests. Interpretative readings of 2 observers, for example, of a mammogram or other imaging, were compared at a single point in time. It is known that kappa depends on the prevalence of disease and that, therefore, kappas across different settings are hard to compare. Methods: Using simulation, we examine an analogous situation, not previously described, that occurs in clinical trials where sequential measurements are obtained to evaluate disease progression or clinical improvement over time. Results: We show that weighted kappa, used for multilevel outcomes, changes during the trial even if we keep the performance of the observer constant. Conclusions: Kappa and closely related measures can therefore only be used with great difficulty, if at all, in quality assurance in clinical trials.
Existence and iteration of positive solution for fractional integral boundary value problems with p-Laplacian operator
Authors: He Ying , Bi Bo 
Published: September 2019

Abstract
This paper is concerned with an integral boundary value problem of fractional differential equations with p-Laplacian operator. Sufficient conditions ensuring the existence of extremal solutions for the given problem are obtained. Our results are based on the method of upper and lower solutions and monotone iterative technique.
Home management of lower limb lymphoedema with an intermittent pneumatic compression device: a feasibility study
Authors: Dunn Nyree , Williams E. Mark , Fishbourne Michelle , Dolan Gina , Davies Jane H. 
Published: September 2019

AbstractBackgroundLymphoedema is a chronic condition that causes swelling in the body tissues. Presently, there is no cure for lymphoedema; instead, current treatment is aimed at lifelong management to help control symptoms. Intermittent pneumatic compression (IPC) therapy can be considered as an adjunct to standard lymphoedema care; however, research regarding the efficacy of this treatment modality is limited.MethodsTwenty participants were recruited from an outpatient lymphoedema clinic (South Wales, UK) to a feasibility randomised control trial designed to evaluate the efficacy of an IPC device (LymphAssist, Huntleigh Healthcare) in reducing lower limb volume. The primary objective was to assess feasibility in terms of (1) study feasibility, including recruitment, retention and assessment of outcome measures, and (2) intervention feasibility, including intervention fidelity and acceptability to participants. Participants were randomly assigned to a control group (n = 10) or intervention group (n = 10). The control group received their standard lymphoedema care only for a 6-month period, whereas the intervention group received their standard lymphoedema care plus an IPC device to use for 6 months. A bilateral lower limb assessment and quality of life survey were undertaken at baseline and 3- and 6-month time points.ResultsThe study recruited to target within the planned time frame with a retention rate of 80%. Issues relating to potential recruitment bias and study attrition were identified and possible solutions explored. In addition, supplementary primary outcome measures that are important to the study population were identified and will be incorporated into the design of future studies.ConclusionThis feasibility study identified that a larger randomised controlled trial investigating the efficacy of home use IPC devices is feasible with modifications to the study protocol.Trial registrationThis trial is registered with clinicaltrials.gov (NCT03825263).
Complications Associated With the Anesthesia Transport of Pediatric Patients: An Analysis of the Wake Up Safe Database
Authors: Haydar Bishr , Baetzel Anne , Stewart Margaret , Voepel-Lewis Terri , Malviya Shobha , Christensen Robert 
Published: September 2019

BACKGROUND:
Transporting patients under anesthesia care incurs numerous potential risks, especially for those with critical illness. The purpose of this study is to identify and report all pediatric anesthesia transport-associated adverse events from a preexisting database of perioperative adverse events.

METHODS:
An extract of the Wake Up Safe database was obtained on December 14, 2017, and screened for anesthesia transport-associated complications. This was defined as events occurring during or immediately after transport or movement of a pediatric patient during or in proximity to their care by anesthesiologists, including repositioning and transfer to recovery or an inpatient unit, if the cause was noted to be associated with anesthesia or handover. Events were excluded if the narrative clearly states that an event was ongoing and not impacted by anesthesia transport, such as a patient who develops cardiac arrest that then requires emergent transfer to the operating room. The search methodology included specific existing data elements that indicate transport of the patient, handover or intensive care status preoperatively as well as a free-text search of the narrative for fragments of words indicating movement. Screened events were reviewed by 3 anesthesiologists for inclusion, and all data elements were extracted for analysis.

RESULTS:
Of 2971 events in the database extract, 63.8% met screening criteria and 5.0% (148 events) were related to transport. Events were primarily respiratory in nature. Nearly 40% of all reported events occurred in infants age ≤6 months. A total of 59.7% of events were at least somewhat preventable and 36.4% were associated with patient harm, usually temporary. Of the 86 reported cardiac arrests, 50 (58.1%) had respiratory causes, of which 74% related to anesthesia or perioperative team factors. Respiratory events occurred at all stages of care, with 21.4% during preoperative transport and 75.5% postoperatively. Ninety-three percent of unplanned extubations occurred in patients 6 months and younger. Ten medication events were noted, 2 of which resulted in cardiac arrest. Root causes in all events related primarily to provider and patient factors, with occasional references to verbal miscommunication.

CONCLUSIONS:
Five percent of reported pediatric anesthesia adverse events are associated with transport. Learning points highlight the risk of emergence from anesthesia during transport to recovery or intensive care unit (ICU). ICU patients undergoing anesthesia transport face risks relating to transitions in providers, equipment, sedation, and physical positioning. Sedation and neuromuscular blockade may be necessary for transport in some patients but has been associated with adverse events in others.
Association Between Race and Ethnicity in the Delivery of Regional Anesthesia for Pediatric Patients: A Single-Center Study of 3189 Regional Anesthetics in 25,664 Surgeries
Authors: King Michael R. , De Souza Elizabeth , Rosenbloom Julia M. , Wang Ellen , Anderson T. Anthony 
Published: September 2019

BACKGROUND:
Racial and ethnic disparities in health care are well documented in the United States, although evidence of disparities in pediatric anesthesia is limited. We sought to determine whether there is an association between race and ethnicity and the use of intraoperative regional anesthesia at a single academic children’s hospital.

METHODS:
We performed a retrospective review of all anesthetics at an academic tertiary children’s hospital between May 4, 2014, and May 31, 2018. The primary outcome was delivery of regional anesthesia, defined as a neuraxial or peripheral nerve block. The association between patient race and ethnicity (white non-Hispanic or minority) and receipt of regional anesthesia was assessed using multivariable logistic regression. Sensitivity analyses were performed comparing white non-Hispanic to an expansion of the single minority group to individual racial and ethnic groups and on patients undergoing surgeries most likely to receive regional anesthesia (orthopedic and urology patients).

RESULTS:
Of 33,713 patient cases eligible for inclusion, 25,664 met criteria for analysis. Three-thousand one-hundred eighty-nine patients (12.4%) received regional anesthesia. One thousand eighty-six of 8884 (13.3%) white non-Hispanic patients and 2003 of 16,780 (11.9%) minority patients received regional anesthesia. After multivariable adjustment for confounding, race and ethnicity were not found to be significantly associated with receiving intraoperative regional anesthesia (adjusted odds ratios [ORs] = 0.95; 95% confidence interval [CI], 0.86–1.06; P = .36). Sensitivity analyses did not find significant differences between the white non-Hispanic group and individual races and ethnicities, nor did they find significant differences when analyzing only orthopedic and urology patients, despite observing some meaningful clinical differences.

CONCLUSIONS:
In an analysis of patients undergoing surgical anesthesia at a single academic children’s hospital, race and ethnicity were not significantly associated with the adjusted ORs of receiving intraoperative regional anesthesia. This finding contrasts with much of the existing health care disparities literature and warrants further study with additional datasets to understand the mechanisms involved.