bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of ARRY-371797 in
LMNA
-Related Dilated Cardiomyopathy: A Phase 2 Study
Authors: MacRae Calum A. , Taylor Matthew R.G. , Mestroni Luisa , Moses John , Ashley Euan A. , Wheeler Matthew T. , Lakdawala Neal K. , Hershberger Ray E. , Sandor Victor , Saunders Michael E. , Oliver Colleen , Lee Patrice A. , Judge Daniel P. 
Published: December 2022

Background:

Lamin A/C gene (
LMNA
)-related dilated cardiomyopathy is a serious and life-threatening condition with a high unmet medical need. This phase 2 study assessed the effects of the oral selective p38 mitogen-activated protein kinase inhibitor ARRY-371797 on functional capacity and cardiac function in patients with
LMNA
-related dilated cardiomyopathy.

Methods:

Patients with
LMNA
-related dilated cardiomyopathy in New York Heart Association class II–IIIA, on background heart failure treatment, received ARRY-371797 100 or 400 mg twice daily for 48 weeks. The primary end point was change from baseline in the 6-minute walk test distance at 12 weeks. Secondary end points included changes over time in 6-minute walk test distance, NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration, left ventricular ejection fraction, and quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire. Data from the 2 dose groups were combined.

Results:
Twelve patients were enrolled; median (minimum, maximum) 6-minute walk test distance at baseline was 314 (246, 412) m. At week 12, the mean (80% CI) increase from baseline in 6-minute walk test distance was 69 (39, 100) m (median, 47 m). Median NT-proBNP concentration declined from 1409 pg/mL at baseline to 848 pg/mL at week 12. Mean left ventricular ejection fraction was stable at week 12. There was a trend toward improvement in Kansas City Cardiomyopathy Questionnaire Overall and Clinical Summary scores at week 12. No clinically significant drug-related safety concerns were identified.

Conclusions:

ARRY-371797 was well tolerated and resulted in potential increases in functional capacity and lower concentrations of cardiac biomarker NT-proBNP in patients with
LMNA
-related dilated cardiomyopathy.

Registration:

URL:
https://clinicaltrials.gov
; Unique identifier: NCT02057341.
Stroke Outcome Related to Initial Volume Status and Diuretic Use
Authors: Renner Christopher J. , Kasner Scott E. , Bath Philip M. , Bahouth Mona N. , Lees Kennedy R. , Alexandrov Andrei , Bath Philip M. , Bluhmki Erich , Bornstein Natan , Chen Christopher , Davis Stephen M. , Diener Hans‐Christoph , Donnan Geoffrey , Fisher Marc , Ginsberg Myron , Gregson Barbara , Grotta James , Hacke Werner , Hennerici Michael G. , Hommel Marc , Kaste Markku , Lyden Patrick , Marler John , Muir Keith , Roffe Christine , Sacco Ralph , Shuaib Ashfaq , Teal Philip , Venketasubramanian Narayanaswamy , Wahlgren Nils G. , Warach Steven , Weimar Christian 
Published: December 2022

Background
We hypothesized that stroke outcome is related to multiple baseline hydration‐related factors including volume contracted state (VCS) and diuretic use.

Methods and Results
We analyzed a prospective cohort of subjects with ischemic stroke <24 hours of onset enrolled in acute treatment trials within VISTA (Virtual International Stroke Trials Archive). A VCS was defined based on blood urea nitrogen‐to‐creatinine ratio. The primary end point was modified Rankin Scale score at 90 days. Primary analysis used generalized ordinal logistic regression over the mRS range, adjusted for Totaled Health Risks in Vascular Events score, onset‐to‐enrollment time, and thrombolytic use. Of 5971 eligible patients with stroke, 42% were taking diuretics at the time of hospitalization, and 44% were in a VCS. Patients in a VCS were older, had more vascular risk factors, were more likely taking diuretics, and had more severe strokes. Diuretic use was associated with both reduced chance of achieving a good functional outcome (odds ratio [OR], 0.57 [95% CI, 0.52–0.63]) and increased mortality at 90 days (OR, 2.30 [95% CI, 2.04–2.61]). VCS was associated with greater mortality 90 days after stroke (OR, 1.53 [95% CI, 1.33–1.76]). There was no evidence of effect modification among the 3 exposures of VCS, diuretic use, or hypokalemia in relation to outcome.

Conclusions
A VCS at the time of hospitalization was associated with more severe stroke and odds of death but not associated with worse functional outcome when accounting for relevant characteristics. Diuretic use and low serum potassium at the time of stroke onset were associated with worse outcome and may be worthy of further investigation.
Impact of Socioeconomic Status on Emergency Department Visits in Patients With Atrial Fibrillation: A Nationwide Population‐Based Cohort Study
Authors: Lee Seo‐Young , Lee So‐Ryoung , Choi Eue‐Keun , Han Kyung‐Do , Oh Seil , Lip Gregory Y. H. 
Published: December 2022

Background
Socioeconomic status (SES) differences could influence management and clinical outcomes in patients with atrial fibrillation (AF), reflecting health inequalities. The authors aimed to investigate emergency department (ED) visits in patients with AF according to SES level.

Methods and Results
The authors performed a cross‐sectional analysis of ED visits in patients with nonvalvular AF using the Korean National Health Insurance Service database in 2016. The patients were divided into health premium quartiles and medical aid groups, with quartile 4 the highest SES and medical aid the lowest SES. Among patients with AF, patients who had ≥1 ED visits in 2016 were identified. The prevalence and cause of ED visits, 30‐ and 90‐day mortality, and rehospitalization risk after ED visits were evaluated. Among the total 371 017 AF patients, 99 306 patients visited the ED in 2016. The medical aid group showed the highest ED visit rate (n=11 833, 38.0%), and patients with the highest quartile of SES (quartile 4 group) showed the lowest ED visit rate (n=38 037, 30.0%). The most common cause of ED visits was cerebral infarction in all groups. The 30‐ and 90‐day mortality rates and rehospitalization risk after ED visits was higher in groups with lower SES.

Conclusions
Patients with AF and with lower SES had a higher risk of ED visit rate, higher 30‐ and 90‐day mortality rates, and rehospitalization risk after ED visit. Tailored AF management according to different SES levels in patients with AF is needed to improve clinical outcomes.
A Unique High‐Output Cardiac Hypertrophy Phenotype Arising From Low Systemic Vascular Resistance in Cantu Syndrome
Authors: Singh Gautam K. , McClenaghan Conor , Aggarwal Manish , Gu Hongjie , Remedi Maria S. , Grange Dorothy K. , Nichols Colin G. 
Published: December 2022

Background
Cardiomegaly caused by left ventricular hypertrophy is a risk factor for development of congestive heart failure, classically associated with decreased systolic and/or diastolic ventricular function. Less attention has been given to the phenotype of left ventricular hypertrophy with enhanced ventricular function and increased cardiac output, which is potentially associated with high‐output heart failure. Lack of recognition may pose diagnostic ambiguity and management complexities.

Methods and Results

We sought to systematically characterize high‐output cardiac hypertrophy in subjects with Cantu syndrome (CS), caused by gain‐of‐function variants in
ABCC9
, which encodes cardiovascular K
ATP
(ATP‐sensitive potassium) channel subunits. We studied the cardiovascular phenotype longitudinally in 31 subjects with CS with confirmed
ABCC9
variants (median [interquartile range] age 8 years [3–32 years], body mass index 19.9 [16.5–22.9], 16 male subjects). Subjects with CS presented with significant left ventricular hypertrophy (left ventricular mass index 86.7 [57.7–103.0] g/m
2
in CS, n=30; 26.6 [24.1–32.8] g/m
2
in controls, n=17;
P
<0.0001) and low blood pressure (systolic 94.5 [90–103] mm Hg in CS, n=17; 109 [98–115] mm Hg in controls, n=17;
P
=0.0301; diastolic 60 [56–66] mm Hg in CS, n=17; 69 [65–72] mm Hg in control, n=17;
P
=0.0063). Most (21/31) subjects with CS exhibited eccentric hypertrophy with normal left ventricular wall thickness. Congestive heart failure symptoms were evident in 4 of the 5 subjects with CS aged >40 years on long‐term follow‐up.

Conclusions
The data define the natural history of high‐output cardiac hypertrophy resulting from decreased systemic vascular resistance in subjects with CS, a defining population for long‐term consequences of high‐output hypertrophy caused by low systemic vascular resistance, and the potential for progression to high‐output heart failure.
The Political Economy of Protected Area Designations: Commercial Interests in Conservation Policy
Authors: Alger Justin 
Published: December 2022

Abstract
States have increased the pace and scale of conservation efforts in recent years as they strive to meet ambitious terrestrial and marine protected area targets. The ecological gains made in this push for protections, however, seem to be no better than if governments designated protected areas at random. Many critics point to states prioritizing quantity over quality of protections—rightly so—but this point does not fully explain the shortcomings of the global biodiversity network. The problem is more deeply rooted in the processes through which governments designate protected areas. Governments prioritize minimizing short-term commercial losses over maximizing long-term ecological gains in conservation policy processes, leading to two predominant types of protected area: residual and paper park. The causal mechanism driving these processes is how salient industry interests are in an area targeted for protections, which predicts government policy response, demonstrated here through case studies in Australia and the United States.
Tracking Urban Footprint on Extreme Precipitation in an African Megacity
Authors: Doan Quang-Van , Kobayashi Shun , Kusaka Hiroyuki , Chen Fei , He Cenlin , Niyogi Dev 
Published: December 2022

Abstract
This study contributes to the body of current knowledge about the urban effect on extreme precipitation (EP) by investigating the city–EP interaction over Lagos, Nigeria. This is a unique, first-time study that adds a “missing piece” of this information about the African continent to the comprehensive global urban precipitation “puzzle.” The convection-permitting Weather Research and Forecasting (WRF) Model is employed within an ensemble simulation framework using combinations of different physical schemes and boundary/initial conditions to detect the urban signal on an extreme rainfall event that occurred on 30 May 2006. WRF simulations are verified against satellite-estimated and in situ observations, and the results from the best-performing ensemble members are used for analysis. The results show that the control simulation with urban representation generated 20%–30% more rainfall over the urban area than the nonurban sensitivity simulation, in which the city is replaced by forest. Physical mechanisms behind the differences were revealed. We found that the urbanization in Lagos reduced evapotranspiration, resulting in the increase of sensible heating (by 75 W m−2). This further enhances the urban heat-island effect (+1.5 K of air surface temperature), facilitating horizontal convergence and boosting daytime sea breeze. As a result, more moisture is transported from the southern sea area to inland areas; the moisture then converges over Lagos city, creating favorable conditions for enhancing convection and extreme-rainfall-generating processes.
Evaluation of Three Genesis Potential Indices for Tropical Cyclogenesis in the Arabian Sea: Two Case Studies Using WRF and ERA5
Authors: Ikram Farah , Ullah Kalim , Chen Deliang 
Published: December 2022

Abstract
Tropical cyclones (TCs) generated over the Arabian Sea can cause significant damage to infrastructure, human lives, landfall, and property near inshore and maritime trade route areas. A key to successful prediction of TCs is a skillful prediction of potential cyclogenesis locations. This study focuses on evaluating three genesis potential indices (GPIs) derived from a global reanalysis (ERA5) and dynamically downscaling using a regional model (WRF) for two TC cases: Gonu in 2007 and Kyarr in 2019, selected by analyzing the accumulated cyclone energy trend from the International Best Track Archive for Climate Stewardship (IBTrACS) dataset over the period of 1981–2019. The two TCs belong to category 4 and above on the Saffir–Simpson scale. To test the sensitivity of downscaling to cumulus parameterizations, two WRF experiments were conducted using the Kain–Fritsch and New Tiedke cumulus schemes, respectively. The calculated genesis locations with help of the three GPIs were compared with IBTrACS. The results show that 1) all indices have reasonable skills in reproducing genesis locations, although their performances differ somewhat; 2) the dynamic downscaling with two WRF experiments added value to the study by comparing two numerical schemes for estimating genesis locations; and 3) WRF with the New Tiedke and Kain–Fritsch schemes showed good skill in reproducing the spatial distribution of the most relevant dynamical parameters. The pattern correlations are well correlated with environmental parameters of untransformed GPI and higher correlations with binary logarithmic transformed GPI. The applicability to other cyclones is also tested (e.g., TC Nilofar in 2014) with encouraging results. This study demonstrates the usefulness of GPIs for forecasting TC genesis in the region.

Significance Statement
The trend analysis of accumulated cyclone energy (ACE) over the Arabian Sea (AS) shows an increase over the period of 1981–2019 with the highest ACE values for 2019. The genesis potential indices (GPI) show strong ability for use as a forecasting tool for tropical cyclone genesis, and hence, are helpful for providing a reference for future studies. WRF experiments were able to reproduce the GPI with slight differences from the observations and ERA5. WRF schemes show good performance in reproducing key meteorological fields. The analysis of the GPI and WRF schemes shows the potential to be implemented for maritime forecasts of the tropical cyclones in the region. This study will be helpful scientifically and strategically with a significant impact on socioeconomic activities in the region.
Trends and Demographic Differences in the Incidence and Mean Age of Starting to Smoke Cigarettes Regularly, National Health Interview Survey, 1997-2018
Authors: Cheng Yiling J. , Cornelius Monica E. , Wang Teresa W. , Homa David M. 
Published: December 2022

Objectives: Surveillance of cigarette smoking behavior provides evidence for evaluating the impact of current tobacco control measures. We examined temporal changes and demographic differences in the incidence and mean age of starting to smoke cigarettes regularly in the United States. Methods: We conducted retrospective birth-cohort and cross-sectional analyses using self-reported data from the 1997-2018 National Health Interview Survey to evaluate trends and demographic differences in the incidence and mean age of starting to smoke cigarettes regularly among participants aged 18-84 years. We estimated the incidence and mean age of starting to smoke cigarettes regularly by using Poisson and linear regression. Results: Among adults born during 1950-1999, the incidence of starting to smoke cigarettes regularly before age 35 years decreased by 18.8% (95% CI, 17.0%-20.7%) per 10 years, with a peak incidence at age about age 18 years. Male, non-Hispanic White, and US-born people had a higher incidence of starting to smoke cigarettes regularly than female, other racial and ethnic, and non–US-born people, respectively ( P < .001 for all). From 1997 to 2018, the mean age of starting to smoke cigarettes regularly decreased by 0.4% (95% CI, 0.2%-0.6%) per 10 years among adults who ever smoked. Conclusion: The incidence of starting to smoke cigarettes regularly decreased dramatically at all ages during the study period, which suggests a positive impact of current tobacco control measures. For evaluating trends in starting to smoke cigarettes regularly, incidence can be a more sensitive indicator of temporal change than mean age. Differences in smoking incidence by demographic subgroup suggest that additional opportunities exist to further reduce the incidence of starting to smoke cigarettes regularly.
Developmental characteristics of a 0- to 3-year-old gifted child based on video analysis
Authors: Bildiren Ahmet , Firat Tahsin , Kavruk Sevinç Z. 
Published: December 2022

The purpose of the present case study was to conduct a detailed analysis of the developmental characteristics of a gifted child. WISC-R intelligence test was administered to a 7-year-old participant. The test result was 140 IQ. The early developmental characteristics of the participant were evaluated using parent-recorded videos over a 3-year period, from birth to 3 years of age. First, all video recordings were transcribed by the research team, then the accuracy and completeness of the transcriptions were verified. The results showed that the participant displayed early gifted developmental characteristics in fine motor skills, cognitive, language, social, and personal developmental domains.
Effect of the posterior sagging control device to the posterior tibial translation during posterior-stabilized total knee arthroplasty with modified gap technique
Authors: Maeyama Akira , Asayama Isao , Ishimatsu Tetsuro , Yamamoto Takuaki 
Published: December 2022

Purpose In modern total knee arthroplasty (TKA), flexion and extension gaps between the femur and tibia are equilibrated before implanting the final components. Uncontrolled intraoperative posterior tibial translation (PTT) could cause an artifactual widening of the flexion gap, which could lead surgeons to alter the femoral component size. We designed an intraoperative posterior sagging control device to prevent intraoperative PTT. In this study, we investigated whether the use of this device could prevent artifactual widening of the flexion gap. Methods Twenty-five patients, 21 women and four men, aged 74.2 years, were enrolled in this prospective study. All patients underwent postero-stabilized TKA using a navigation system. Intraoperative PTT, flexion and extension gaps with or without using the posterior sagging control device were measured with navigation system. These measurements were compared with or without the posterior sagging control device and after the final implantation also. Results There were significant differences between the measurements performed with or without the posterior sagging control device when compared to the post-implantation measurements. The use of the device reduced the number of patients with a >3 mm increase in flexion gap from 7 (28%) to 1 (4%). Conclusion This study suggests that the posterior sagging control device prevents PTT and artificial flexion gap widening. This could prevent an unnecessary increase in component size.
Ponesimod: An Oral Second-Generation Selective Sphingosine 1-Phosphate Receptor Modulator for the Treatment of Multiple Sclerosis
Authors: Alnaif Amal , Oiler Isabelle , D’Souza Manoranjan S. 
Published: December 2022

Objective: To describe the safety, efficacy, and potential role in therapy of ponesimod, which was recently approved by the Food and Drug Administration (FDA) as a therapeutic option for the treatment of multiple sclerosis (MS). Data Sources: A PubMed literature search using the following terms: ponesimod and MS (January 1, 2012-October 31, 2022). FDA product labeling was also reviewed for pertinent data sources. Study Selection and Data Extraction: All relevant English-language articles examining efficacy and/or safety of ponesimod were considered for inclusion. Data Synthesis: Ponesimod is an orally administered second-generation sphingosine 1-phospate (S1-P) receptor modulator classified as a disease modifying treatment (DMT) for MS. Clinical studies have shown that ponesimod prevents relapse in patients with relapsing-remitting MS (RRMS) and has superior efficacy compared with teriflunomide. Nasopharyngitis, upper respiratory tract infections, headache, high blood pressure, and liver dysfunction were some of the common adverse effects associated with ponesimod. Dyspnea, bradyarrhythmias, atrioventricular conduction delays, and macular edema were some of the rare but serious adverse effects associated with ponesimod. Relevance to Patient Care and Clinical Practice in Comparison With Existing Agents: Some advantages of ponesimod over other S1-P receptor modulators approved for RRMS include selectivity for the S1-P1 receptor and short half-life, which allows for quick reversal of immunosuppressive effects. However, data from long-term efficacy and safety studies and more direct comparison studies with other DMTs are required. Conclusion: Currently available data suggest that ponesimod is a useful addition to other high-efficacy DMTs available to treat patients with MS.
The Impact of Prior Antithrombotic use on Thromboembolic Events in Patients with Cardiovascular Disease and Severe COVID-19 Infection
Authors: Bouchlarhem Amine , Boulouiz Soumia , el Aidouni Ghizlane , Bkiyar Houssam , Bazid Zakaria , Ismaili Nabila , Housni Brahim , El Ouafi Noha 
Published: December 2022

Objective Our objective in this study was to determine the predictive factors of thromboembolic complications in patients with previous heart disease and severe covid-19 infection and the impact of previous use of antithrombotics on protection against these complications. Methods We conducted a single-center retrospective study of 158 patients with heart disease admitted to an intensive care unit for severe SARS-COV-2 infection. In order to determine the predictive factors, we used logistic regression analysis. Results Out of 158 patients, 22 were complicated by a thrombo-embolic event (13.9%), mean age of our population 64.03 (SD = 15.27), with a male predominance of 98 (62%). For the predictive factors of thromboembolic complications, and after multivariate analysis, we find the short duration of hospitalization (OR = 0.92; 95%CI (0.863–0.983), P = .014, previous use of antithrombotic drugs ((OR = 0.288, 95%CI (0.091–0.911), P = .034 for antiplatelet agents) and (OR = 0.322, 95% CI (0, 131–0.851), P = .021) for anticoagulants) as protective factors, and admission thrombocytosis as a risk factor (OR = 4.58, 95%CI (1.2–10.627), P = .021). D-dimer was not detected as a risk factor, and this can be explained by the characteristics of our population. Although prior use of antithrombotic drugs protects against thromboembolic complications during severe infection, there was no benefit in mortality. Conclusion Prior use of antithrombotic drugs is a protective factor against thromboembolic complications in patients with a history of heart disease but without effect on mortality.