bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep phenotyping of unaffected carriers of pathogenicBMPR2variants screened for pulmonary arterial hypertension
Authors: Tóth Eszter N. , Celant Lucas R. , Niglas Marili , Jansen Samara , Tramper Jelco , Baxan Nicoleta , Ashek Ali , Wessels Jeroen N. , Marcus J. Tim , Meijboom Lilian J. , Houweling Arjan C. , Nossent Esther J. , Aman Jurjan , Grynblat Julien , Perros Frédéric , Montani David , Vonk Noordegraaf Anton , Zhao Lan , de Man Frances S. , Bogaard Harm Jan 
Published: July 2024

IntroductionPathogenic variants in the gene encoding forBMPR2are a major genetic risk factor for heritable pulmonary arterial hypertension. Owing to incomplete penetrance, deep phenotyping of unaffected carriers of a pathogenicBMPR2variant through multimodality screening may aid in early diagnosis and identify susceptibility traits for future development of pulmonary arterial hypertension.Methods28 unaffected carriers (44±16 years, 57% female) and 21 healthy controls (44±18 years, 48% female) underwent annual screening, including cardiac magnetic resonance imaging, transthoracic echocardiography, cardiopulmonary exercise testing and right heart catheterisation. Right ventricular pressure–volume loops were constructed to assess load-independent contractility and compared with a healthy control group. A transgenicBmpr2Δ71Ex1/+rat model was employed to validate findings from humans.ResultsUnaffected carriers had lower indexed right ventricular end-diastolic (79.5±17.6 mL·m−2versus62.7±15.3 mL·m−2; p=0.001), end-systolic (34.2±10.5 mL·m−2versus27.1±8.3 mL·m−2; p=0.014) and left ventricular end-diastolic (68.9±14.1 mL·m−2versus58.5±10.7 mL·m−2; p=0.007) volumes than control subjects.Bmpr2Δ71Ex1/+rats were also observed to have smaller cardiac volumes than wild-type rats. Pressure–volume loop analysis showed that unaffected carriers had significantly higher afterload (arterial elastance 0.15±0.06 versus0.27±0.08 mmHg·mL−1; p<0.001) and end-systolic elastance (0.28±0.07 versus0.35±0.10 mmHg·mL−1; p=0.047) in addition to lower right ventricular pulmonary artery coupling (end-systolic elastance/arterial elastance 2.24±1.03versus1.36±0.37; p=0.006). During the 4-year follow-up period, two unaffected carriers developed pulmonary arterial hypertension, with normal N-terminal pro-brain natriuretic peptide and transthoracic echocardiography indices at diagnosis.ConclusionUnaffectedBMPR2mutation carriers have an altered cardiac phenotype mimicked inBmpr2Δ71Ex1/+transgenic rats. Future efforts to establish an effective screening protocol for individuals at risk for developing pulmonary arterial hypertension warrant longer follow-up periods.
Medical hypnosis mitigates laboratory dyspnoea in healthy humans: a randomised, controlled experimental trial
Authors: Morélot-Panzini Capucine , Arveiller-Carvallo Cécile , Rivals Isabelle , Wattiez Nicolas , Lavault Sophie , Brion Agnès , Serresse Laure , Straus Christian , Niérat Marie-Cécile , Similowski Thomas 
Published: July 2024

QuestionDyspnoea persisting despite treatments of underlying causes requires symptomatic approaches. Medical hypnosis could provide relief without the untoward effects of pharmacological approaches. We addressed this question through experimentally induced dyspnoea in healthy humans (inspiratory threshold loading (excessive inspiratory effort) and carbon dioxide stimulation (air hunger)).Material and methods20 volunteers (10 women, aged 21–40 years) were studied on four separate days. The order of the visits was randomised in two steps: firstly, the “inspiratory threshold loading first”versus“carbon dioxide first” group (n=10 in each group); secondly, the “medical hypnosis first”versus“visual distraction first” subgroup (n=5 in each subgroup). Each visit comprised three 5-min periods (reference, intervention, washout) during which participants used visual analogue scales (VAS) to rate the sensory and affective dimensions of dyspnoea, and after which they completed the Multidimensional Dyspnea Profile.ResultsMedical hypnosis reduced both dimensions of dyspnoea significantly more than visual distraction (inspiratory threshold loading: sensory reduction after 5 min 34% of full VASversus8% (p=0.0042), affective reduction 17.6%versus2.4% (p=0.044); carbon dioxide: sensory reduction after 5 min 36.9%versus3% (p=0.0015), affective reduction 29.1%versus8.7% (p=0.0023)). The Multidimensional Dyspnea Profile showed more marked sensory effects during inspiratory threshold loading and more marked affective effects during carbon dioxide stimulation.Answer to the questionMedical hypnosis was more effective than visual distraction at attenuating the sensory and affective dimensions of experimentally induced dyspnoea. This provides a strong rationale for clinical studies of hypnosis in persistent dyspnoea patients.
Barriers to and enablers of physical activity and its association with daily steps after hospitalisation for a COPD exacerbation: what patients say matters
Authors: Valeiro Beatriz , Rodríguez Esther , Ferrer Jaume , Pasarín Alejandro , Ibañez Jordi , Ramon María Antonia 
Published: July 2024

IntroductionExacerbations of COPD decrease physical activity. Physical activity interventions after these events are desirable but have had mixed results. Understanding the barriers to and enablers of physical activity may help to improve the results of these interventions. We aimed to assess the barriers to and enablers of physical activity after COPD exacerbation and their association with daily steps.MethodsWe carried out a cross-sectional analysis of patients with COPD enrolled during a hospitalisation for an exacerbation. Physical activity was measured with an accelerometer for 7 days after discharge. Patients completed anad hoc6-point Likert scale questionnaire about 13 barriers to and nine enablers of physical activity. We analysed the association between each item and patients’ daily step counts.Results46 patients with a mean±sdforced expiratory volume in 1 s of 48.6±15.9% predicted completed the assessments. They were 65±10 years old, spent 8±2 days hospitalised and walked 5633±3314 steps·day−1after discharge. The patients who reported “breathlessness” as a barrier (≥2 out of 6 points on the Likert scale) took statistically fewer daily steps (median (25th–75th centile) 3813 steps·day−1(2664–5639 steps·day−1)versus5549 steps·day−1(3692–9984 steps·day−1), p=0.034). There was a similar finding for those who reported “low mood” as a barrier (≥2 out of 6 points) (3813 steps·day−1(2456–5471 steps·day−1)versus5426 steps·day−1(3612–8942 steps·day−1), p=0.047). If they considered “physical activity as healthy” as an enabler, they walked statistically more (5085 steps·day−1(3538–8703 steps·day−1)versus2760 steps·day−1(2271–5298 steps·day−1), p=0.031).ConclusionSome barriers to and enablers of physical activity reported by patients after a COPD exacerbation relate to daily steps. Assessing physical activity barriers and enablers could be useful to improve future physical activity interventions after these events.
Do-not-attempt-resuscitation decision making: physicians’ recommendations differ from the GO-FAR score predictions
Authors: Alao David Olukolade , Abraham Snaha , Dababneh Emad , Roby Roxanne , Farid Mohammed , Mohammed Nada , Rojas-Perilla Natalia , Cevik Arif Alper 
Published: July 2024

Abstract
Background and aim
In-hospital cardiac arrest (IHCA) is a major cause of mortality globally, and over 50% of the survivors will require institutional care as a result of poor neurological outcome. It is important that physicians discuss the likely outcome of resuscitation with patients and families during end-of-life discussions to help them with decisions about cardiopulmonary resuscitation. We aim to compare three consultants’ do-not-resuscitate (DNR) decisions with the GO-FAR score predictions of the probability of survival with good neurological outcomes following in-hospital cardiac arrest (IHCA).

Methods
This is a retrospective study of all patients 18 years or older placed on a DNR order by a consensus of three consultants in a tertiary institution in the United Arab Emirates over 12 months. Patients’ socio-demographics and the GO-FAR variables were abstracted from the electronic medical records. We applied the GO-FAR score and the probability of survival with good neurological outcomes for each patient.

Results
A total of 788 patients received a DNR order, with a median age of 71 years and a majority being males and expatriates. The GO-FAR model categorized 441 (56%) of the patients as having a low or very low probability of survival and 347 (44%) as average or above. There were 219 patients with a primary diagnosis of cancer, of whom 148 (67.6%) were in the average and above-average probability groups. There were more In-hospital deaths among patients in the average and above-average probability of survival group compared with those with very low and low probability (243 (70%) versus 249 (56.5%) (P < 0.0001)). The DNR patients with an average or above average chance of survival by GO-FAR score were more likely to be expatriates, oncology patients, and did not have sepsis.

Conclusions
The GO-FAR score provides a guide for joint decision-making on the possible outcomes of CPR in the event of IHCA. The physicians’ recommendation and the ultimate patient’s resuscitation choice may differ due to more complex contextual medico-social factors.
Emotion-focused therapy for women with premenstrual dysphoric disorder: a randomized clinical controlled trial
Authors: Dehnavi Saeideh Izadi , Mortazavi Seyede Salehe , Ramezani Mohammad Arash , Gharraee Banafshe , Ashouri Ahmad 
Published: July 2024

Abstract
Background
Premenstrual dysphoric disorder (PMDD) is a debilitating condition, affecting women of reproductive age. It is characterized by severe periodic physical and psychological symptoms, which end after the onset of menstruation. This study aimed to evaluate the effectiveness of emotion-focused therapy (EFT) for PMDD patients.

Methods
A total of 48 PMDD women, in the age range of 18–44 years, were randomly assigned to two intervention and control groups. The intervention group participated in 16 weeks of EFT treatment, while the control group was selected based on the waiting list (waitlist control group) and followed-up after three months. Forty-four patients finally completed this study. The participants completed the Premenstrual Syndrome Screening Tool (PSST), Difficulties in Emotion Regulation Scale (DERS), and Depression Anxiety Stress Scale-21 (DASS-21) in the first premenstrual period before treatment, the first premenstrual period after treatment, and the premenstrual period three months after treatment.

Results
Based on the repeated measure analysis of variances, the total score of DERS and the total score of PSST decreased significantly (P < 0.05). Also, in DASS-21, the scores of depression and stress subscales reduced significantly (P < 0.05), while there was no significant decrease in the score of anxiety subscale (P > 0.05).

Conclusion
Based on the present results, EFT can be an effective treatment for alleviating the symptoms of PMDD. This treatment can reduce the emotion regulation difficulties of women with PMDD and alleviate the symptoms of depression and stress.

Trial registration
Iranian Registry of Clinical Trials, IRCT ID: IRCT20220920055998N1, Registered on: 12/2/2023.
Collaboration in providing intimate-partner violence services to women with disabilities
Authors: Namatovu Fredinah , Ineland Jens 
Published: July 2024

Abstract
Background
There is a consensus among scholars, policymakers, and implementers that addressing the complex nature of intimate partner violence (IPV) requires a collaborative response. However, there is limited literature on how various professionals work collaboratively to address the needs of women with disabilities who experience IPV. This study combines the perspectives of women with disabilities and those of professionals to understand collaboration in providing IPV services to women with disabilities.

Methods
Twenty-nine in-depth interviews were conducted with 18 IPV service providers and 11 women with disabilities. The data were analyzed using reflective thematic analysis.

Results
The findings are presented under three themes: the first shows a consensus among different IPV service providers and disabled women on the importance of collaboration when supporting victims of IPV with disabilities; the second depicts the common ways in which collaboration occurs when supporting women with disabilities; and the third illuminates the critical elements that boost effective collaboration.

Conclusion
Supporting IPV victims with disabilities requires active collaboration at both an internal and external level. Strengthening collaboration among different actors requires trust, specified roles, and the allocation of adequate resources.
Unravelling factors influencing demand for modern contraception and evaluating coverage progress since 2015 in Ethiopia, Kenya, and Nigeria: insights from multilevel and geostatistical modelling
Authors: Khundi McEwen , Mzembe Themba , Ngwira Tabitha , Mankhwala Chifuniro S , Chifungo Chimwemwe , Peterson Maame B , Vellemu Ruth , Madise Nyovani J , Chipeta Michael G 
Published: July 2024

Abstract
Introduction
The United Nations established the Sustainable Development Goals (SDGs) in 2015 to enhance global development. In this study, we examine an SDG indicator: the percentage of women aged 15–49 whose family planning needs are met by modern contraception (mDFPS). We evaluate both the factors influencing its coverage and its progress since 2015.

Methods
We used nationally representative surveys data (Demographic and Health Surveys (DHS) and Performance Monitoring for Action (PMA)) from Ethiopia, Kenya, and Nigeria. We assessed predictors of mDFPS. We also computed mDFPS coverage across countries and subnational areas, assessing coverage changes from the SDGs onset to the most recent period, using a Bayesian model-based geostatistical approach. We assessed whether the subnational areas exceeded the minimum recommended WHO mDFPS coverage of 75%.

Results
Varied individual and community-level determinants emerged, highlighting the countries’ uniqueness. Factors such as being part of a female-headed household, and low household wealth, lowered the odds of mDFPS, while rural-residence had low odds only in Ethiopia and Nigeria. The results indicate mDFPS stagnation in most administrative areas across the three countries. Geographic disparities persisted over time, favouring affluent regions. The predicted posterior proportion of mDFPS and exceedance probability (EP) for WHO target for Ethiopia was 39.85% (95% CI: [4.51, 83.01], EP = 0.08) in 2016 and 46.28% (95% CI: [7.15, 85.99], EP = 0.13) in 2019. In Kenya, the adjusted predicted proportion for 2014 was 30.19% (95% CI: [2.59, 80.24], EP = 0.06) and 44.16% (95%CI: [9.35, 80.24], EP = 0.13) in 2022. In Nigeria, the predicted posterior proportion of mDFPS was 17.91% (95% CI: [1.24, 61.29], EP = 0.00) in 2013, and it was 23.08% (95% CI: [1.80, 56.24], EP = 0.00) in 2018. None of the sub-national areas in Ethiopia and Nigeria exceeded the WHO target. While 9 out of 47 counties in Kenya in 2022 exceeded the WHO mDFPS target.

Conclusion
The study unveils demographic, geographic, and socioeconomic mDFPS disparities, signalling progress and stagnation across administrative areas. The findings offer policymakers and governments insights into targeting interventions for enhanced mDFPS coverage. Context-specific strategies can address local needs, aiding SDG attainment.
The impact of sleep quality on emotion regulation difficulties in adolescents: a chained mediation model involving daytime dysfunction, social exclusion, and self-control
Authors: Wang Wenjuan , Zhu Yuqiong , Yu Hang , Wu Chengcong , Li Tiancheng , Ji Chenguang , Jiang Yulian , Ding Dongyan 
Published: July 2024

Abstract
Objective
Previous studies have revealed associations between sleep quality and mental health, yet the comprehensive role of sleep quality, daytime dysfunction, social exclusion, and self-control in difficulties with emotion regulation remains unclear. This study aimed to elucidate how sleep quality affects emotion regulation difficulties among middle school students through pathways involving daytime dysfunction, social exclusion, and self-control, thereby providing a more comprehensive theoretical basis for mental health interventions.

Methods
Utilizing the pittsburgh sleep quality index, the adolescent social exclusion scale, the brief self-control scale, and emotion regulation scale-short form, we assessed 1067 students randomly selected from four middle schools from October to November 2023. After the removal of extreme values (those exceeding 3 standard deviations), 806 students were retained for data analysis.

Results
Our findings indicate that poor sleep quality significantly contributes to increased daytime dysfunction(β = 0.86, SE = 0.07, p < .001), which in turn affects social exclusion(β = 0.60, SE = 0.16, p < 0 0.001), self-control abilities(β = 1.27, SE = 0.16, p < .001) and emotion regulation difficulties(β = 1.56, SE = 0.30, p < .001). Social exclusion mediates the relationship between sleep quality and emotion regulation difficulties(Estimate = 0.11, SE = 0.04, 95% CI [0.04, 0.20] ).

Conclusion
The aim of this study is to provide new insights into the development of effective intervention measures to improve sleep and mental health in adolescents.
Administration of the American Board of Anesthesiology’s virtual APPLIED Examination: successes, challenges, and lessons learned
Authors: Keegan Mark T. , Harman Ann E. , McLoughlin Thomas M. , Macario Alex , Deiner Stacie G. , Gaiser Robert R. , Warner David O. , Suresh Santhanam , Sun Huaping 
Published: July 2024

AbstractIn response to the COVID-19 pandemic, the American Board of Anesthesiology transitioned from in-person to virtual administration of its APPLIED Examination, assessing more than 3000 candidates for certification purposes remotely in 2021. Four hundred examiners were involved in delivering and scoring Standardized Oral Examinations (SOEs) and Objective Structured Clinical Examinations (OSCEs). More than 80% of candidates started their exams on time and stayed connected throughout the exam without any problems. Only 74 (2.5%) SOE and 45 (1.5%) OSCE candidates required rescheduling due to technical difficulties. Of those who experienced “significant issues”, concerns with OSCE technical stations (interpretation of monitors and interpretation of echocardiograms) were reported most frequently (6% of candidates). In contrast, 23% of examiners “sometimes” lost connectivity during their multiple exam sessions, on a continuum from minor inconvenience to inability to continue. 84% of SOE candidates and 89% of OSCE candidates described “smooth” interactions with examiners and standardized patients/standardized clinicians, respectively. However, only 71% of SOE candidates and 75% of OSCE candidates considered themselves to be able to demonstrate their knowledge and skills without obstacles. When compared with their in-person experiences, approximately 40% of SOE examiners considered virtual evaluation to be more difficult than in-person evaluation and believed the remote format negatively affected their development as an examiner. The virtual format was considered to be less secure by 56% and 40% of SOE and OSCE examiners, respectively. The retirement of exam materials used virtually due to concern for compromise had implications for subsequent exam development. The return to in-person exams in 2022 was prompted by multiple factors, especially concerns regarding standardization and security. The technology is not yet perfect, especially for testing in-person communication skills and displaying dynamic exam materials. Nevertheless, the American Board of Anesthesiology’s experience demonstrated the feasibility of conducting large-scale, high-stakes oral and performance exams in a virtual format and highlighted the adaptability and dedication of candidates, examiners, and administering board staff.
Dual inhibition of SUMOylation and MEK conquers MYC-expressing KRAS-mutant cancers by accumulating DNA damage
Authors: Kotani Hiroshi , Oshima Hiroko , Boucher Justin C. , Yamano Tomoyoshi , Sakaguchi Hiroyuki , Sato Shigeki , Fukuda Koji , Nishiyama Akihiro , Yamashita Kaname , Ohtsubo Koushiro , Takeuchi Shinji , Nishiuchi Takumi , Oshima Masanobu , Davila Marco L. , Yano Seiji 
Published: July 2024

Abstract
Background
KRAS mutations frequently occur in cancers, particularly pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer. Although KRASG12C inhibitors have recently been approved, effective precision therapies have not yet been established for all KRAS-mutant cancers. Many treatments for KRAS-mutant cancers, including epigenome-targeted drugs, are currently under investigation. Small ubiquitin-like modifier (SUMO) proteins are a family of small proteins covalently attached to and detached from other proteins in cells via the processes called SUMOylation and de-SUMOylation. We assessed whether SUMOylation inhibition was effective in KRAS-mutant cancer cells.

Methods
The efficacy of the first-in-class SUMO-activating enzyme E inhibitor TAK-981 (subasumstat) was assessed in multiple human and mouse KRAS-mutated cancer cell lines. A gene expression assay using a TaqMan array was used to identify biomarkers of TAK-981 efficacy. The biological roles of SUMOylation inhibition and subsequent regulatory mechanisms were investigated using immunoblot analysis, immunofluorescence assays, and mouse models.

Results
We discovered that TAK-981 downregulated the expression of the currently undruggable MYC and effectively suppressed the growth of MYC-expressing KRAS-mutant cancers across different tissue types. Moreover, TAK-981-resistant cells were sensitized to SUMOylation inhibition via MYC-overexpression. TAK-981 induced proteasomal degradation of MYC by altering the balance between SUMOylation and ubiquitination and promoting the binding of MYC and Fbxw7, a key factor in the ubiquitin–proteasome system. The efficacy of TAK-981 monotherapy in immunocompetent and immunodeficient mouse models using a mouse-derived CMT167 cell line was significant but modest. Since MAPK inhibition of the KRAS downstream pathway is crucial in KRAS-mutant cancer, we expected that co-inhibition of SUMOylation and MEK might be a good option. Surprisingly, combination treatment with TAK-981 and trametinib dramatically induced apoptosis in multiple cell lines and gene-engineered mouse-derived organoids. Moreover, combination therapy resulted in long-term tumor regression in mouse models using cell lines of different tissue types. Finally, we revealed that combination therapy complementally inhibited Rad51 and BRCA1 and accumulated DNA damage.

Conclusions
We found that MYC downregulation occurred via SUMOylation inhibition in KRAS-mutant cancer cells. Our findings indicate that dual inhibition of SUMOylation and MEK may be a promising treatment for MYC-expressing KRAS-mutant cancers by enhancing DNA damage accumulation.