Actus Santé

Background: Long-COVID is a complicated condition with prolonged SARS-CoV-2 symptoms. Several variables have been studied in this illness. Among the less studied variables are galanin and its receptor (GalR1). The Galanin system is involved in the pathophysiology of several age-related chronic disorders, including alcoholism, chronic pain, and bowel and skin inflammation. The aim of the study is to correlate the galanin system parameters with clinical and biochemical variables in Long-COVID. Methods: Serum levels of albumin, electrolytes, GAL, GALR1, and C-reactive protein (CRP) are measured by ELISA technique in 90 Long-COVID patients and 60 recovered subjects who are free from any symptoms of Long-COVID. Results: The study showed a significantly increased Galanin, GALR1, and the Gal/GALR1 ratio. On the contrary, serum albumin, total calcium, ionized calcium, total magnesium, and the ionized calcium/magnesium ratio were significantly decreased. Galanin and Galanin/GALR1 showed significant age-related associations ({rho}=0.353, p<0.01) and ({rho}=0.218, p<0.05), respectively. The lowest SpO2 was associated with Galanin ({rho}=-0.295, p<0.01) and GALR1 ({rho}=-0.232, p<0.05), respectively. According to ROC analysis results, the highest sensitivities for differentiating between patients and non-patient subjects were Galanin (71.7%) and GALR1 (60.0%). Conclusions: Galanin, GALR1, and Long-COVID disease are directly correlated. However, more research is needed to find out exactly what roles plasma Galanin and its receptor play in Long-COVID disease.

Introduction: This study examines the effectiveness of an e-voucher campaign to promote the use of a toll-free family planning call center (Honey&Banana), which is measured by the number of calls received by the call center. Methods: A comparative interrupted time series design is used to measure the effect of the e-voucher campaign on the call volume. The study design presumes that without the e-voucher campaign, the intervention and control groups would have parallel trends in terms of the number of calls received. The difference between the actual and anticipated number of calls received is used to estimate the effect of the campaign. Results: Before the e-voucher campaign, the monthly trend in the number of calls for family planning information in the intervention and control groups followed a similar pattern. As soon as the campaign was launched, the call center experienced a seven-fold increase in the number of family planning requests that were received from callers in the intervention zone, from under 400 calls per month to about 3,000 calls per month. No comparable increase occurred for the control zone. We estimate that the e-voucher campaign resulted in a net gain of over 12,000 requests for family planning information. When the campaign ended, the number of calls from the intervention zone decreases, but at least temporarily remained above the pre-intervention levels. Discussion: Earlier studies demonstrated that e-voucher campaigns can be effective for increasing use of smoking cessation hotlines. This study expands the evidence base by demonstrating the effectiveness of e-vouchers for increasing demand for family planning information hotlines. Additional research is needed to assess the long-term effects of such e-voucher campaigns, and to determine the extent to which increased use of family planning hotlines translates into improved family planning outcomes.

Background: Housing insecurity is an escalating problem in the UK. Limited empirical evidence exists from which to draw reliable causal inferences about the impact of insecure housing on health. Using nationally representative panel data and causally focussed methods, we examined the effect of insecure housing on mental health, sleep disturbance and cardiovascular health, during a period of government austerity. Methods: We used longitudinal survey data (2009-2019) from the UK Household Longitudinal Study. Health outcomes included probable common mental disorder; sleep disturbance due to worry; and new diagnoses of hypertension. The primary exposure was housing payment problems in the past 12 months. Using doubly robust marginal structural models) with inverse probability of treatment weights, we estimated absolute and relative health effects of housing payment problems, and population attributable fractions. We performed stratified analyses to assess potentially heterogeneous impacts across the population, and the potential modifying effects of austerity measures in the UK. Findings: The average absolute effect of housing payment problems was a 2.5 percentage point increased risk of experiencing a common mental disorder (95% CI 1.1%, 3.8%) and 2.0% increased risk of sleep disturbance (95% CI 0.7%, 3.3%). Effects were larger among renters, younger people, less educated, and households with children. Effects were also larger among people living in areas most affected by austerity-related cuts to housing support services. Evidence for a cardiovascular health impact was weak (95% CI -0.1%, 1.2%). Interpretation: Housing payment problems were associated with worse mental health and sleep disturbance in a large UK sample. Households at risk of falling into rent or mortgage arrears need more support, especially in areas where housing services have been diminished. Rapid and substantial investment is needed to improve supply of social and affordable housing.

Objective. To identify risk factors for first episodes of suicidal ideation and suicide attempt in people with functional/dissociative seizures (FDS) or epilepsy. Methods. Retrospective cohort study from the UK s largest tertiary mental health care provider, with linked national admission data from the Hospital Episode Statistics (HES). Participants were 2383 people with a primary or secondary diagnosis of FDS or epilepsy attending between 01/01/2007 and 18/06/2021. Outcomes were a first report of suicidal ideation and a first hospital admission for suicide attempt (ICD-10 X60-X84). Demographic and clinical risk factors were assessed using multivariable bias-reduced binomial-response generalised linear models. Results. In both groups, ethnic minorities had significantly reduced odds of hospitalisations following a suicide attempt (OR: 0.45 - 0.49). Disorder-specific risk factors were gender, age, and comorbidity profile. In FDS, both genders had similar risk of suicidality; younger age was a risk factor for both outcomes (OR: 0.16 - 1.91) and a diagnosis of Depression or Personality Disorders was associated with higher odds of reporting suicidal ideation (OR: 1.91 and 3.01 respectively). In epilepsy, females had higher odds of being hospitalised following suicide attempt (OR: 1.64). Age had a quadratic association with both outcomes (OR: 0.88 - 1.06). A Substance Abuse Disorder was associated to higher suicidal ideation (OR: 2.67) whilst Developmental Disorders lowered the risk (OR: 0.16 - 0.24). Conclusions. This is the first study systematically reporting risk factors for suicidality in people with FDS. Results for the large epilepsy cohort complement previous studies and will be useful in future meta-analyses.

Partners resemble each other on many traits, such as health and education. The traits are usually studied one by one in data from established couples and with potential participation bias. We studied all Norwegian parents who had their first child between 2016 and 2020 (N=187,926) and the siblings of these parents. We analysed grade point averages (GPA), educational attainment (EA), and medical records with prospective diagnostic data on 10 mental and 10 somatic health conditions measured 10 to 5 years before childbirth. We found stronger partner similarity in mental (median r=0.14) than in somatic health conditions (median r=0.04), with ubiquitous cross-trait correlations for mental health conditions (median r=0.13). GPA correlated 0.43 and EA 0.47 between partners. High GPA or EA was associated with better mental (median r=-0.16) and somatic (median r=-0.08) health in partners. Elevated correlations for mental health (median r=0.25) in established couples indicated convergence. Analyses of data on siblings and in-laws revealed deviations from direct assortment, suggesting instead indirect assortment based on related traits. GPA and EA accounted for 30-40% of the partner correlations in health. This has implications for the distribution of risk factors among children and for studies of intergenerational transmission.

Problem: Maternal B vitamin deficiency increases the risk of fetal spina bifida (SB) and placental maldevelopment. It is unclear whether placental processes involving folate are altered in fetuses with SB in a contemporary cohort. We hypothesised that fetal SB would associate with reduced expression of key folate transporters (folate receptor- [FR], proton coupled folate receptor [PCFT], and reduced folate carrier [RFC]), and an increase in Hofbauer cell (HBC) abundance and folate receptor-{beta} (FR{beta}) expression by HBCs. Method of Study: FR, PCFT, and RFC protein localisation and expression (immunohistochemistry) and HBC phenotypes (RNA in situ hybridization) were assessed in placentae from fetuses with SB (cases; n=12) and with no congenital anomalies (controls; n=22). Results: Cases (vs. gestational age [GA]-matched controls) had a higher proportion of placental villous cells that were HBCs (6.9% vs. 2.4%, p=0.0001) and higher average FR{beta} expression by HBCs (3.2 mRNA molecules per HBC vs. 2.3, p=0.03). HBCs in cases were largely polarised to a regulatory (M2) phenotype (median 92.1% of HBCs). In sex-stratified analyses, male, but not female, cases had higher HBC levels and FR{beta} expression by HBCs than GA-matched controls. There were no differences between groups in the total percent of syncytium and stromal cells that were positive for FR, PCFT, or RFC protein immunolabelling. Conclusions: HBC abundance and FR{beta} expression by HBCs are increased in placentae of fetuses with isolated SB, suggesting immune-mediated dysregulation in placental development and function, and could contribute to SB-associated comorbidities, such as poor fetal growth.

Background Historically, soil-transmitted helminth (STH) control and prevention strategies have relied on mass drug administration efforts targeting preschool and school-aged children. While these efforts have succeeded in reducing morbidity associated with STH infection, recent modeling efforts have suggested that expanding intervention to treatment of the entire community could achieve transmission interruption in some settings. Testing the feasibility of such an approach requires large-scale clinical trials, such as the DeWorm3 cluster randomized trial. In addition, accurate interpretation of trial outcomes will require diagnostic platforms capable of accurately determining infection prevalence, particularly as infection intensity is reduced, at large population scale and with significant throughput. Here, we describe the development and validation of a multi-site, high-throughput molecular testing platform. Methodology/Principal Findings Through the development, selection, and validation of appropriate controls, we have successfully created and evaluated the performance of a testing platform capable of the semi-automated, high-throughput detection of four species of STH in human stool samples. Comparison of this platform with singleplex reference assays for the detection of these same pathogens has demonstrated comparable performance metrics across multiple testing locations, with index assay accuracy measuring at or above 99.5% and 98.1% for each target species at the level of the technical replicate and individual extraction respectively. Through the implementation of a rigorous validation program, we have developed a diagnostic platform capable of providing the necessary throughput and performance needed to meet the needs of the DeWorm3 cluster randomized trial and other large-scale operational research efforts for STH.

Background: The role of children and staff in SARS-CoV-2 transmission outside and within households is still not fully understood when large numbers are in regular, frequent contact in schools. Methods: We used the self-controlled case-series method during the alpha- and delta-dominant periods to explore the incidence of infection in periods around a household member infection, relative to periods without household infection, in a cohort of primary and secondary English school children and staff from November 2020 to July 2021. Results: We found the relative incidence of infection in students and staff was highest in the 1-7 days following household infection, remaining high up to 14 days after, with risk also elevated in the 6-12 days before household infection. Younger students had a higher relative incidence following household infection, suggesting household transmission may play a more prominent role compared with older students. The relative incidence was also higher amongst students in the alpha variant dominant period. Conclusions: This analysis suggests SARS-CoV2 infection in children, young people and staff at English schools were more likely to be associated with within-household transmission than from outside the household, but that a small increased risk of seeding from outside is observed.

Aim/hypothesis Growth/differentiation factor 15 (GDF15) is a therapeutic target for a variety of metabolic diseases, including type 1 diabetes (T1D). However, the nausea caused by GDF15 is a challenging point for therapeutic development. In addition, it is unknown why the endogenous GDF15 fails to protect from T1D development. Here, we investigate the GDF15 signaling in pancreatic islets towards opening possibilities for therapeutic targeting in beta cells and to understand why this protection fails to occur naturally. Methods GDF15 signaling in islets was determined by proximity-ligation assay, untargeted proteomics, pathway analysis, and treatment of cells with specific inhibitors. To determine if GDF15 levels would increase prior to disease onset, plasma levels of GDF15 were measured in a longitudinal prospective study of children during T1D development (n=132 cases vs. n=40 controls) and in children with islet autoimmunity but normoglycemia (n=47 cases vs. n=40 controls) using targeted mass spectrometry. We also investigated the regulation of GDF15 production in islets by fluorescence microscopy and western blot analysis. Results The proximity-ligation assay identified ERBB2 as the GDF15 receptor in islets, which was confirmed using its specific antagonist, tucatinib. The untargeted proteomics analysis and caspase assay showed that ERBB2 activation by GDF15 reduces beta cell apoptosis by downregulating caspase 8. In plasma, GDF15 levels were higher (p=0.0024) during T1D development compared to controls, but not in islet autoimmunity with normoglycemia. However, in the pancreatic islets GDF15 was depleted via sequestration of its mRNA into stress granules, resulting in translation halting. Conclusions/interpretation GDF15 protects against T1D via ERBB2-mediated decrease of caspase 8 expression in pancreatic islets. Circulating levels of GDF15 increases pre-T1D onset, which is insufficient to promote protection due to its localized depletion in the islets. These findings open opportunities for targeting GDF15 downstream signaling for pancreatic beta-cell protection in T1D and help to explain the lack of natural protection by the endogenous protein.

Introduction: Design thinking (DT), a methodology for solving complex problems, has the potential to create powerful, human-centred healthcare improvement. We applied DT methodology to the context of peripheral arterial disease (PAD). PAD is increasingly prevalent globally and associated with significant morbidity and mortality. We fall short of achieving effective secondary prevention due to persistent underdiagnosis and undertreatment of this disease. In this study, we sought to identify novel and creative solutions to improve diagnosis and secondary prevention of PAD. Methods: We describe the initial 'Empathize', 'Define', and 'Ideate' stages of the five-stage DT model proposed by the Hasso Plattner Institute of Design at Stanford University. We engaged patients with PAD, caregivers, clinicians, and other stakeholders in a co-design process using semi-structured interviews, a DT workshop, and post-workshop survey. Data from the interviews and workshop were analyzed using inductive thematic analysis, and data from the survey were analyzed using an idea prioritization matrix. Results: Exploring the lived experience of those with PAD and those delivering PAD care emphasized the influence of system-level barriers. Many of the solutions proposed by workshop participants target evidence-based, system-level interventions through improved funding support, institutional support, outreach efforts and technological applications. The connections between insights derived in the 'Empathize' stage and solutions proposed during the 'Ideate' stage showed the success of the co-design process in inspiring empathy-driven solutions. Discussion: This study demonstrates how DT methodology can be applied to complex healthcare problems such as PAD care, to systematically develop human-centred solutions. In the next stages of this study, we will use the results of this co-design process to iteratively implement, evaluate, and optimize the proposed solutions which were prioritized as being most feasible and high impact.

Background: Despite routine infant vaccination and blood donor screening, the Democratic Republic of Congo (DRC) has high hepatitis B virus (HBV) prevalence compared to the United States and Europe. Through the cross-sectional Horizontal and Vertical Transmission of Hepatitis B (HOVER-HBV) study, we characterized household prevalence in DRC's capital, Kinshasa, to inform additional prevention efforts. Methods: We introduced HBV surface antigen (HBsAg) screening alongside existing HIV screening as part of routine antenatal care (ANC) in high-volume maternity clinics in Kinshasa. We recruited households of pregnant women who were HBsAg-positive and HBsAg-negative, defining households as "exposed" and "unexposed," respectively. Household members underwent HBsAg testing and an epidemiological survey. We evaluated HBsAg prevalence and potential transmission correlates. Results: We enrolled 1,006 participants from 200 households (100 exposed, 100 unexposed) across Kinshasa. HBsAg prevalence was more than twice as high in exposed households (5.0%; 95% CI: 2.8%-7.1%) as in unexposed households (1.9%; 0.6%-3.2%). Exposed direct offspring had 3.3 (0.9, 11.8) times the prevalence of unexposed direct offspring. Factors associated with HBsAg-positivity included older age, marriage, and having multiple recent partners or any new sexual partners among index mothers; and older age, lower household wealth, sharing nail clippers, and using street salons among exposed offspring. Conclusions: Vertical and horizontal HBV transmission within households is ongoing in Kinshasa. Factors associated with infection reveal opportunities for HBV prevention efforts, including perinatal prevention, protection during sexual contact, and sanitation of shared personal items.

SARS-CoV-2 was first detected in Sudan on 13th March 2020. Here, we describe the genomic epidemiology of SARS-CoV-2 in Sudan between May 2020 and April 2022 to understand the introduction and transmission of SARS-CoV-2 variants in the country. A total of 667 SARS-CoV-2 positive samples were successfully sequenced using the nCoV-19 Artic protocol on the Oxford Nanopore Technology ([≥]70% genome completeness). The genomes were compared with a select contemporaneous global dataset to determine genetic relatedness and estimate import/export events. The genomes were classified into 37 Pango lineages within the ancestral strain (107 isolates across 13 Pango lineages), Eta variant of interest (VOI) (78 isolates in 1 lineage), Alpha variant of concern (VOC) (10 isolates in 2 lineages), Beta VOC (26 isolates in 1 lineage), Delta VOC (171 isolates across 8 lineages) and Omicron VOC (242 isolates across 12 lineages). We estimated a total of 144 introductions of the observed variants from different countries across the globe. Multiple introductions of the Eta VOI, Beta VOC and Omicron VOC were observed in Sudan mainly from Europe and Africa. These findings suggest a need for continuous genomic surveillance of SARS-CoV-2 to monitor their introduction and spread consequently inform public health measures to combat SARS-CoV-2 transmission.

Introduction The presence of tumor-infiltrating lymphocytes (TILs) in melanoma has been linked to survival. Their predictive capability for immune checkpoint inhibition (ICI) response remains uncertain. Therefore, we investigated the association between treatment response and TILs in the largest cohort to date and analyzed if this association was independent of known clinical predictors of response. Methods In this multicenter cohort study, patients who received first-line anti-PD1 {+/-} anti-CTLA4 for advanced cutaneous melanoma were identified. TILs were scored as absent, non-brisk or brisk on hematoxylin and eosin (H&E) slides of primary melanoma and pre-treatment metastases. Scoring systems evaluating the infiltration and intensity patterns (MIA-score) and the percentage of stromal TILs were also evaluated. The primary outcome was objective response rate (ORR), with PFS and OS being secondary outcomes. Univariable and multivariable logistic regression and Cox proportional hazard regression analyses were performed, adjusting.for age, sex, disease stage, ICI type, BRAF mutation, lactate dehydrogenase (LDH) level and WHO performance score. Results Metastatic melanoma specimens were available for 650 patients and primary specimens from 565 patients.. No association was found between TILs in primary melanoma specimens and response. In metastatic specimens, patients with non-brisk TILs (aOR 1.56, 95% CI 1.06-2.29) and brisk TILs (aOR 3.28, 95% CI 1.72-6.56) had a higher probability of response, longer median PFS (9.2 and 19.4 vs. 6.5months [p=0.009]) and median OS (49.5 and 40.9 vs 21.3 months [p=0.007]) when compared to absent TILs. Similar results were noted using the MIA- and stromal TIL scores. Conclusion In advanced melanoma patients, TIL patterns on H&E slides of pre-treatment metastases are associated with ICI response. This is independent of known clinical predictors. TILs are easily scored on readily available H&Es, which facilitates the use of this biomarker for ICI outcomes in clinical practice.

We describe three cases of critical acute myositis with myocarditis occurring within 22 days of each other at a single institution, all within one month of receiving the initial cycle of the anti-PD-1 drug Pembrolizumab. Analysis of T cell receptor repertoires from peripheral blood and tissues revealed a high degree of clonal expansion and public clones between cases, with several T cell clones expanded within the skeletal muscle putatively recognizing viral epitopes. All patients had recently received a COVID-19 mRNA booster vaccine prior to treatment and were positive for SARS-CoV2 Spike antibody. In conclusion, we report a series of unusually severe myositis and myocarditis following PD-1 blockade and the COVID-19 mRNA vaccination.

Language models (LMs) such as BERT and GPT have revolutionized natural language processing (NLP). However, the medical field faces challenges in training LMs due to limited data access and privacy constraints imposed by regulations like the Health Insurance Portability and Accountability Act (HIPPA) and the General Data Protection Regulation (GDPR). Federated learning (FL) offers a decentralized solution that enables collaborative learning while ensuring data privacy. In this study, we evaluated FL on 2 biomedical NLP tasks encompassing 8 corpora using 6 LMs. Our results show that: 1) FL models consistently outperformed models trained on individual clients' data and sometimes performed comparably with models trained with polled data; 2) with the fixed number of total data, FL models training with more clients produced inferior performance but pre-trained transformer-based models exhibited great resilience. 3) FL models significantly outperformed large language models using zero-/one-shot learning and offered lightning inference speed.

A significant challenge of video-electroencephalography (vEEG) in epilepsy diagnosis is timing monitoring sessions to capture epileptiform activity. Given the significant consequences of misdiagnosis or delayed diagnosis, new techniques to improve diagnostic yield of vEEG are needed. In this study, we introduce and validate pro-ictal EEG scheduling, a method to schedule vEEG monitoring to coincide with periods of heightened seizure probability as a low-risk approach to enhance the diagnostic yield. A database of long-term ambulatory vEEG monitoring sessions (n=5038) of adults and children was examined. Data from linked electronic seizure diaries were extracted (minimum 10 self-reported events over 12-months) to generate cycle-based estimates of seizure risk. VEEG monitoring sessions coinciding with periods of estimated high-risk were allocated to the high-risk group (adults n=305, children n=82) and compared to remaining studies (baseline: adults n=3586, children n=1065). Test of Proportions and Risk-Ratios (RR) were used to index differences in proportions and likelihood of capturing outcome measures (abnormal report, confirmed seizure and diary event) during monitoring. The impact of clinical and demographic factors (sex, epilepsy-type, medication) was also explored. During vEEG monitoring, the high-risk group was 25% more likely to have an abnormal vEEG report (190/305:62.3% vs 1790/3586:49.9%, RR=1.25, 95% CI[1.137:1.370], p<0.001), 63% more likely to present with a confirmed seizure (56/305:18.4% vs 424/3586:11.3%, RR=1.63, 95% CI[1.265:2.101], p<0.001) and 42% more likely to report an event (153/305:50.2% vs 1267/3586:35.3%, RR=1.420, 95% CI[1.259:1.602], p<0.001). In children, the high-risk group was 93% more likely to have a confirmed seizure (21/82:25.6% vs 141/1065:13.2%, RR=1.93, 95% CI[1.297:2.885], p=0.002). Similar effects were observed across clinical and demographic features. This study provides the first large-scale validation of pro-ictal EEG scheduling in improving the yield of vEEG. This innovative approach offers a pragmatic and low-risk strategy to enhance the diagnostic capabilities of vEEG monitoring, significantly impacting epilepsy management.

Background: As sexual history encompasses sensitive information about private lives, patients as well as providers may find it difficult to discuss during patient-provider encounters. Objectives: To ascertain the incidence of absent documentation about sexual history among patients at seven adult hospitals of a multi-hospital medical center during the year 2022. Materials and Methods: The multi-hospital medical center information technology team ran a search query in electronic medical records to extract census of unique patient identifications quantifying absent documentation rates about social history categories of Tobacco, Alcohol, Substance Abuse, Home/Environment, Sexual, Nutrition/Health, Exercise, Employment/School, Other. Results: Among the patients managed in the year 2022 (n=25005), Other and Sexual social history categories were least frequently documented (1-2%). Contrarily, Home/Environment and Tobacco social history categories were most frequently documented (81-82%). Conclusion: Among the patients managed at the multi-hospital medical center, sexual history was one of the least frequently documented social history during the year 2022.

Menstruation is a natural process for women that shows a healthy female reproductive system, yet women are stigmatized during this experience. A woman's physical, mental, and social well-being are significantly impacted by menstruation. Thus, menstrual disorders are widespread and are a major social problem. There have been variations in people's perceptions of menstruation and gaps in research comparing gender and beliefs about menstruation and its impact on academic performance. This study investigates gender and beliefs about menstruation and how it affects academic performance and social life using a self-administered online questionnaire that inquires about general knowledge of menstruation, participants' beliefs and experiences with menstruation, participants' academic performance and demographic questions. Participants responded using a 5-point Likert scale, showing that 40.44% of the respondents' knowledge and understanding of menstruation have positively influenced over the years.Furthermore, the results from the chi-square analysis revealed an association between men's and women's perceptions of menstruation. Interestingly, women stated that menstruation has no effect on their academic performances, but on the other hand, men were indecisive about its impact on women's intellectual tasks. Also, 28.72% of respondents reported that they find studying and excelling during menstruation uneasy. The result shows that women can excel at any task, even during menstruation. Knowledge of menstruation is essential in furthering a better understanding of women's health, demystifying menstruation myths, and advancing the social well-being of this gender.

Background Pulsta valve is increasingly used for percutaneous pulmonary valve implantation (PPVI) in patients with large native right ventricular outflow tract (RVOT). The aim of this study is to reveal Pulsta valve implantation outcomes within the native RVOT and to evaluate the adaptability of Pulsta valve to diverse native main pulmonary artery (PA). Methods A multicenter retrospective study encompassing 183 patients with moderate to severe pulmonary regurgitation (PR) in the native RVOT who underwent PPVI with Pulsta valves(R) between February 2016 and August 2023 at the five Korean and Taiwanese tertiary referral centers. Results Successful implantation of the Pulsta valves was achieved in 180 out of 183 patients (98.4 %) with an average age of 26.6 {+/-} 11.0 years. Mean follow-up duration was 29 months. Baseline assessments revealed enlarged right ventricle (RV) volume (mean indexed RV end-diastolic volume: 163.1(Interquartile range, IQR, 152.2-179.9) mL/m2), which significantly decreased to 123.0(IQR: 106.9-137.2) mL/m2 after one year. In this study, the main PA types were classified as follows: pyramidal (3.8%), straight (38.3%), reverse pyramidal (13.7%), convex (26.2%), and concave (18.0%) shapes. Pulsta valve placement was adapted, with distal main PA for pyramidal shapes and proximal or mid-PA for reverse pyramidal shapes. The remaining patients underwent Pulsta valve implantation in the proximal or mid part of the main PA, depending on the anatomical features and size of the main PA. Two patients experienced Pulsta valve embolization to RV, necessitating surgical removal, and one patient encountered valve migration to the distal main PA, necessitating surgical fixation. Conclusions Customized valve insertion sites are pivotal in self-expandable PPVI considering diverse native RVOT shape. Rather soft and compact structure of Pulsta valve has characteristics to be adaptable to diverse native RVOT geometries. Key words percutaneous pulmonary valve implantation; native right ventricular outflow tract type; congenital heart disease; pulmonary regurgitation

Background: Population-level prevention efforts in the US have yet to correct the upward trends in increasing US obesity prevalence. Italy, France, and Japan are high-income countries that have employed approaches aimed at obesity prevention that may have contributed to their favorable obesity trends. It is plausible that these efforts could be culturally adapted with similar effectiveness to the US population. This paper outlines the protocol of a scoping review that will identify and characterize the range of obesity prevention efforts implemented in Italy, France, and Japan to inform potential strategies for obesity prevention in the US. Methods and analysis: We will conduct a systematic search in PubMed, Embase, and Cochrane. We will assess articles that describe any national, regional, or local public health and/or clinical guideline, recommendation, intervention, campaign, policy or other population-level effort targeting obesity prevention in Italy, France, and Japan. Two independent reviewers will screen the articles, and a third independent reviewer will resolve conflicts that arise upon screening. Descriptive synthesis will be performed to describe the country-specific prevention strategies and summarize the available evidence for their effectiveness. Discussion: The purpose of this paper is to describe the study protocol for a scoping review that will provide a comprehensive summary of available evidence for obesity prevention strategies that have been implemented in Italy, France, and Japan. These strategies will inform potential prevention efforts for consideration in the US. Scoping review registration DOI: https://doi.org/10.17605/OSF.IO/M35YX