bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gaps in the Care of Pulmonary Hypertension: A Cross‐Sectional Patient Simulation Study Among Practicing Cardiologists and Pulmonologists
Authors: de Belen Enrico , McConnell John W. , Elwing Jean M. , Paculdo David , Cabaluna Ian , Linder Jörg , Peabody John W. 
Published: January 2023

Background
Diagnosis of pulmonary hypertension (PH) is often delayed or missed, leading to disease progression and missed treatment opportunities. In this study, we measured variation in care provided by board‐certified cardiologists and pulmonologists in simulated patients with potentially undiagnosed PH.

Methods and Results

In a cross‐sectional study (
https://www.clinicaltrials.gov
, NCT04693793), 219 US practicing cardiologists and pulmonologists cared for simulated patients presenting with symptoms of chronic dyspnea and associated signs of potential PH. We scored the clinical quality‐of‐care decisions made in a clinical encounter against predetermined evidence‐based criteria. Overall, quality‐of‐care scores ranged from 18% to 74%, averaging 43.2%±11.5%. PH, when present, was correctly suspected 49.1% of the time. Conversely, physicians incorrectly identified PH in 53.7% of non‐PH cases. Physicians ordered 2‐dimensional echocardiography in just 64.3% of cases overall. Physicians who ordered 2‐dimensional echocardiography in the PH cases were significantly more likely to get the presumptive diagnosis (61.9% versus 30.7%;
P
<0.001). Ordering other diagnostic work‐up items showed similar results for ventilation/perfusion scan (81.5% versus 51.4%;
P
=0.005) and high‐resolution computed tomography (60.4% versus 43.2%;
P
=0.001). Physicians who correctly identified PH were significantly more likely to order confirmatory right heart catheterization or refer to PH center (67.3% versus 15.8%;
P
<0.001).

Conclusions
A wide range of care in the clinical practice among simulated patients presenting with possible PH was found, specifically in the evaluation and plan for definitive diagnosis of patients with PH. The delay or misdiagnosis of PH is likely attributed to a low clinical suspicion, nonspecific symptoms, and underuse of key diagnostic tests.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04693793.
Age‐Dependent Association Between Modifiable Risk Factors and Incident Cardiovascular Disease
Authors: Kaneko Hidehiro , Yano Yuichiro , Okada Akira , Itoh Hidetaka , Suzuki Yuta , Yokota Isao , Morita Kojiro , Fujiu Katsuhito , Michihata Nobuaki , Jo Taisuke , Yamaguchi Satoko , Takeda Norifumi , Morita Hiroyuki , Node Koichi , Yamauchi Toshimasa , Nangaku Masaomi , Kadowaki Takashi , McEvoy John W. , Lam Carolyn S. P. , Yasunaga Hideo , Komuro Issei 
Published: January 2023

Background
There have been limited data examining the age‐dependent relationship of wide‐range risk factors with the incidence of each subtype of cardiovascular disease (CVD) event. We assessed age‐related associations between modifiable risk factors and the incidence of CVD.

Methods and Results
We analyzed 3 027 839 participants without a CVD history enrolled in the JMDC Claims Database (mean age, 44.8±11.0 years; 57.6% men). Each participant was categorized as aged 20 to 49 years (n=2 008 559), 50 to 59 years (n=712 273), and 60 to 75 years (n=307 007). Using Cox proportional hazards models and the relative risk reduction, we identified associations between risk factors and incident CVD, consisting of myocardial infarction, angina pectoris, stroke, and heart failure (HF). We assessed whether the association of risk factors for developing CVD would be modified by age category. Over a mean follow‐up of 1133 days, 6315 myocardial infarction, 56 447 angina pectoris, 28 079 stroke, and 56 369 HF events were recorded. The incidence of myocardial infarction, angina pectoris, stroke, and HF increased with age category. Hazard ratios of obesity, hypertension, and diabetes in the multivariable Cox regression analyses for myocardial infarction, angina pectoris, stroke, and HF decreased with age category. The relative risk reduction of obesity, hypertension, and diabetes for CVD events decreased with age category. For example, the relative risk reduction of hypertension for HF decreased from 59.2% in participants aged 20 to 49 years to 38.1% in those aged 60 to 75 years.

Conclusions
The contribution of modifiable risk factor to the development of CVD is greater in younger compared with older individuals. Preventive efforts for risk factor modification may be more effective in younger people.
Rectified Ocean Heat Uptake from Oscillatory Surface Forcing
Authors: Pudig M. P. , Yung C. K. , Zika J. D. , Holmes R. M. 
Published: January 2023

Abstract
Ocean heat uptake is asymmetric with respect to the sign of radiative forcing. It is already known that surface cooling anomalies penetrate into the ocean faster than surface warming anomalies. Because of this asymmetry, the time-variable component of radiative forcing can induce a long-term, rectified cooling trend in ocean heat content, which is this work’s primary focus. Here, we explore this asymmetry and rectification on global and interannual scales, its implications, and its possible dependence on model parameters. We do so using a full-complexity global ocean–sea ice general circulation model and an idealized one-dimensional vertical mixing model, both forced with idealized abrupt and oscillatory surface forcing anomalies. In both models, the ocean heat uptake response to an abrupt cooling perturbation is larger than an equal-magnitude warming perturbation. This asymmetry is shown to be larger when the background vertical diffusivity is smaller, and is therefore likely model dependent. Sinusoidal oscillatory forcing with zero time mean induces a rectified cooling trend in both models, whose magnitude depends on both the diffusivity and the frequency of the interannual oscillatory forcing. The net rectified cooling can reach a rate of approximately −0.11 W m−2, which is substantial relative to the estimated anthropogenic warming rate of 0.47 W m−2 (von Schuckmann et al.). We discuss this rectification effect in the context of volcanic forcing in climate models, whose time-variable component may cause model-dependent ocean cooling in CMIP6 historical simulations, reaching 5%–30% the size of the total impact of volcanic forcing in our one-dimensional model. Correcting for this cooling may help reduce uncertainties in modeled ocean heat content evolution.
Predictors of suicidal ideation severity among treatment-seeking young people with major depressive disorder: The role of state and trait anxiety
Authors: Moller Carl I , Badcock Paul B , Hetrick Sarah E , Rice Simon , Berk Michael , Witt Katrina , Chanen Andrew M , Dean Olivia M , Gao Caroline , Cotton Sue M , Davey Christopher G 
Published: January 2023

Objective:Depression and suicidal ideation are closely intertwined. Yet, among young people with depression, the specific factors that contribute to changes in suicidal ideation over time are uncertain. Factors other than depressive symptom severity, such as comorbid psychopathology and personality traits, might be important contributors. Our aim was to identify contributors to fluctuations in suicidal ideation severity over a 12-week period in young people with major depressive disorder receiving cognitive behavioural therapy.Methods:Data were drawn from two 12-week randomised, placebo-controlled treatment trials. Participants ( N = 283) were 15–25 years old, with moderate to severe major depressive disorder. The primary outcome measure was the Suicidal Ideation Questionnaire, administered at baseline and weeks 4, 8 and 12. A series of linear mixed models was conducted to examine the relationship between Suicidal Ideation Questionnaire score and demographic characteristics, comorbid psychopathology, personality traits and alcohol use.Results:Depression and anxiety symptom severity, and trait anxiety, independently predicted higher suicidal ideation, after adjusting for the effects of time, demographics, affective instability, non-suicidal self-injury and alcohol use.Conclusions:Both state and trait anxiety are important longitudinal correlates of suicidal ideation in depressed young people receiving cognitive behavioural therapy, independent of depression severity. Reducing acute psychological distress, through reducing depression and anxiety symptom severity, is important, but interventions aimed at treating trait anxiety could also potentially be an effective intervention approach for suicidal ideation in young people with depression.
Self-Esteem, Perceived Social Support, and Suicidal Ideation and Behavior Among Adults Attracted to Children
Authors: Ingram Maggie , Thorne Evelyn , Letourneau Elizabeth J. , Nestadt Paul S. 
Published: January 2023

Introduction: People who are attracted to children may be at elevated risk for suicidal ideation and behavior compared to the general population. However, factors associated with suicidal ideation and behavior in this population represent a gap in the literature. Methods: The current study used multilinear regression to explore the impact of self-esteem and perceived social support on suicidal ideation and behavior in a sample of 154 adults attracted to children. Mediation analysis was conducted to investigate the role of lifetime major depressive disorder and hopelessness in these relationships. Results: Results showed high prevalence of past-year and lifetime suicidal ideation and behavior in the sample. Both self-esteem and perceived social support demonstrated significant, inverse relationships with suicidal ideation and behavior after adjustment for covariates. Mediation analyses provided support for the role of hopelessness, but not depression, in these relationships. Conclusion: Results demonstrate high rates of suicidal ideation and behavior among adults attracted to children and highlight important opportunities for prevention and intervention. Improving self-esteem, bolstering perceived social support, reducing hopelessness, and removing barriers to help-seeking may be targets for improving mental health and preventing suicidal ideation and behavior in this population.
Early results of cyanoacrylate adhesive ablation versus laser ablation for the treatment of great saphenous vein insufficiency in the Chinese mainland population
Authors: Qi Xiaotong , Zhang Mingyi , Yu Wu , Ran Kun , Chen Yikuan 
Published: January 2023

Objective In this study, we present our early outcomes of cyanoacrylate ablation (CA) versus endovenous laser ablation (EVLA) for the treatment of great saphenous vein (GSV) insufficiency in the Chinese mainland population. Methods We retrospectively analyzed 108 patients (53 patients in the CA group and 55 patients in the EVLA group) with GSV insufficiency who were treated with CA and EVLA between May 2020 and May 2021. The Venous Clinical Severity Score and Aberdeen Varicose Vein Questionnaire were used to assess clinical symptoms and quality of life, respectively. Total closure rates and procedure-related adverse events were also recorded in both groups. Results There was no significant difference between patients treated with CA or EVLA in terms of demographic and clinical characteristics. The average procedure time was 17 min in the CA group and 35 min in the EVLA group ( p < 0.001). The CA group had lower pain scores during the procedure and 3 days afterward than the EVLA group ( p < 0.001). At month 12, the CA group had a 90.4% closure rate, while the EVLA group had an 83.0% closure rate, with no significant difference between the two groups ( p > 0.05). There was no significant difference in the Venous Clinical Severity Score or Aberdeen Varicose Vein Questionnaire score between the groups ( p > 0.05). During follow-up, neither group experienced any significant adverse events, such as pulmonary embolism or deep venous thrombosis. The incidence of ecchymosis and paresthesia was significantly lower in the CA group than in the EVLA group ( p < 0.05). Conclusions Cyanoacrylate ablation has a high feasibility profile and is an effective approach to accomplish complete GSV target vein closure at early follow-up in the Chinese patients. Compared to EVLA, the improvement in quality-of-life outcomes is also sustained and similar, with less pain and fewer complications due to the absence of tumescence anesthesia and postprocedural compression stockings.
Preventive interventions for lateral ankle sprains: A systematic review and meta-analysis
Authors: Wang Fanjia , Guan Yonghao , Bamber Zoe , Cao Xianxin , Qi Qi , Niu Wenxin , Chen Bin 
Published: January 2023

Objective To evaluate the effect of preventive interventions for lateral ankle sprain in the general population. Data sources A search of PubMed, EMBASE, Cochrane CENTRAL, Medline, CINAHL, and ClinicalTrials.gov was conducted up to August 2022. Review methods Randomized controlled trials and prospective cohort studies that evaluated any interventions for preventing lateral ankle sprain were included. Two reviewers independently conducted the search, screening, and data extraction. The methodological quality of each study was assessed using the revised Cochrane risk-of-bias tool for randomized trials or using the Cochrane Risk Of Bias In Non-Randomized Studies tool for prospective cohort studies. Results Seventeen studies met the inclusion criteria. Proprioceptive training exhibited better effects on preventing future lateral ankle sprain compared with the control group (risk ratio = 0.59, p < 0.001), and a stronger preventive effect was observed in participants with a history of lateral ankle sprain in the subgroup analysis (risk ratio = 0.49, p = 0.02). Compared with no bracing, ankle bracing had no significant better effect in preventing lateral ankle sprain (risk ratio = 0.43, p = 0.05). Proprioceptive training and ankle bracing had similar preventive effects (risk ratio = 0.98, p = 0.97). Limited evidence hindered the synthesis of data on pain, swelling, costs, and time loss. Conclusion Proprioceptive training is recommended for preventing lateral ankle sprain, especially for people with a history of lateral ankle sprain. Bracing seems to have an ambiguous preventive effect and requires more further investigation.
The Role of Parental Socio-Economic Status and Perceived Career-Related Behaviors in Developmental Trajectories of Educational Identity in Adolescence: A Four-Wave Study
Authors: Timar-Anton Casandra , Negru-Subtirica Oana , Damian Lavinia E. 
Published: January 2023

Personal identity formation is a key developmental task of adolescence, with the educational domain being a core life domain. Parents are gatekeepers of adolescent career development but their role in facilitating educational identity formation still needs to be uncovered. The present study investigated developmental trajectories of educational identity processes (commitment, in-depth exploration, and reconsideration of commitment) across two academic years. Educational identity processes, parental socio-economic status, and parental career-related behaviors (support, interference, lack of engagement) were appraised through a four-wave longitudinal study with 5- to 6-month intervals ( N = 744; M age = 15.2 years, 55% girls). Results of the latent class growth analysis revealed five educational identity trajectories (i.e., Undifferentiated, Searching moratorium, Foreclosed, Diffusion, and Achievement). Commitment and in-depth exploration processes were stable for all five trajectories. The undifferentiated trajectory (medium stable levels for all identity processes) was the most prevalent. Parental socio-economic status and perceived parental support correlated positively with achievement and searching moratorium trajectories and negatively with diffused and undifferentiated trajectories. Foreclosed adolescents perceived their parents as the most engaged. Trajectories characterized by high reconsideration of commitment also correlated the most with perceived parental interference. The results bring forward valuable insights into the role parents play in their adolescents’ educational identity development.
Non-Clinical Cell Therapy Development Using the NCG Mouse Model as a Test System
Authors: Smutova Viktorija , Pará Camila , Foret Morgan K. , Bennamoune Nehla , Hung Selly , Spickler Catherine , Riffon Renee , Rowe Jenny , Festin Stephen , Authier Simon 
Published: January 2023

The NCG triple immunodeficient mice on a NOD/Nju background lack functional/mature T, B, and NK cells, and have reduced macrophage and dendritic cell function. This study characterized the NCG mouse model for toxicity, engraftment and tumorigenicity assessments of cell therapies, using CD34+ hHSPC adult mobilized cells with two myeloablation regimens. Mice received sub-lethal irradiation or busulfan and were then injected intravenously with CD34+ hHSPCs (1.0 x 106 cells/mouse) or PBS (control), while positive control animals received 2 x 106 HL-60 cells/mouse. hCD34+ cell donors were treated with the mobilizing agent G-CSF prior to leukapheresis. Following injections, mouse blood samples were collected to assess engraftment rates by flow cytometry with body weights recorded periodically up to 20 weeks post-cell injection. No significant clinical signs or body weight changes were observed. At week 10 post-cell injection, the peripheral blood chimerism of hCD45+ cells was above 20%. While mCD45+ concentration was constant between week 10 and 17 in whole blood samples, hCD45+ concentration and chimerism slightly decreased at week 17. However, chimerism remained above 10%, with busulfan-treated mice presenting higher values. Chimerism was further assessed by quantifying human Alu sequences in blood and multiple organs using qPCR. Alu sequences were most abundant in the spleen and bone marrow, while lowest in the testes. In the positive control group, expected mortalities due to tumorigenesis were observed between days 27 and 40 post-cell injection. Overall, study results may be used to inform study design and potential toxicological endpoints relevant to non-clinical cell therapy development.
Clinical Benefit of Vagus Nerve Stimulation for Epilepsy: Assessment of Randomized Controlled Trials and Prospective Non-Randomized Studies
Authors: Cramer Samuel W , McGovern Robert A , Chen Clark C , Park Michael C 
Published: January 2023

We examined the efficacy of vagal nerve stimulation (VNS) for patients suffering from medically intractable epilepsy. Four randomized controlled trials (RCTs - 3 adult RCTs and 1 pediatric RCT) were identified in our comprehensive literature search. Across the 4 studies, high frequency VNS stimulation (frequency >20 Hz) consistently achieved a greater seizure frequency reduction (23.4-33.1%) relative to low frequency VNS stimulation (1 Hz, .6-15.2%). We identified 2 RCTs examining whether the parameters of stimulation influenced seizure control. These studies reported that VNS achieved seizure control comparable to those reported by the first 4 RCTs (22-43% seizure frequency reduction), irrespective of the parameters utilized for VNS stimulation. In terms of VNS associated morbidity, these morbidities were consistently higher in adults who underwent high frequency VNS stimulation (eg dysphonia 37-66%, dyspnea 6-25.3%). However, no such differences were observed in the pediatric population. Moreover, <2% of patients withdrew from the RCTs/prospective studies due to intolerable symptoms. To provide an assessment of how the risks and benefits of VNS impact the patient experience, 1 study assessed the well-being of enrolled patients (as a secondary end point) and found VNS was associated with an overall improvement in well-being. Consistent with this observation, we identified a prospective, non-randomized study that demonstrated improved quality of life for epilepsy patients managed with VNS and best medical practice relative to best medical practice alone. In aggregate, these RCT studies support the efficacy and benefit of VNS as a neuro-modulatory platform in the management of a subset of medically refractory epilepsy patients.
Comparison of design methods for a safety run-in phase of a phase II clinical trial
Authors: Ji Lingyun , Alonzo Todd A 
Published: January 2023

Background/Aims: In pediatric oncology, a Phase II trial often utilizes a safety run-in phase followed by an efficacy phase that enrolls at the dose level selected based on the safety run-in. Different from a Phase I trial, a Phase II safety run-in often assesses a very small number of dose levels. In the context of a safety run-in that assesses two or three dose levels, this article aims to compare three design methods, including the algorithm-based designs 3 + 3 and Rolling 6, and the model-assisted designs such as the Bayesian optimal interval design. Methods: Extensive simulations were conducted to evaluate and compare operating characteristics of the three design methods for a safety run-in with two or three dose levels, varying the starting dose level. Results: The performance of algorithm-based and model-assisted designs can be influenced by selection of the starting dose level, with trials starting at a lower dose level having a higher probability of selecting a low dose or considering all doses as toxic. The impact is larger for 3 + 3 and Rolling 6 but to a lesser extent for Bayesian optimal interval design. For a safety run-in with two dose levels, using 3 + 3 or Rolling 6 and starting at the higher dose often lead to similar performance to Bayesian optimal interval design. For safety run-in with three dose levels, starting at the middle dose with 3 + 3, Rolling 6 or Bayesian optimal interval design is a good compromise between improving correct dose selection and imposing a toxic dose to less patients. Conclusions: Despite being sensitive to the starting dose level, the 3 + 3, Rolling 6 and Bayesian optimal interval designs overall demonstrate reasonable performance, which can be further improved with wise selection of the starting dose level. The Rolling 6 design remains the recommended design method especially if pharmacokinetics is important or required with this design having the feature of treating six patients per dose level. When designing a safety run-in, selection of a design method or selection of a starting dose should consider both the performance of the design approaches with different choices of a starting dose level and the magnitude of safety concerns with the dose levels under investigation.