Pulmonary Circulation最新文献_第7页

Editorial on "Elective Thoracic Surgical Resections for Pulmonary Arteriovenous Malformations-A 16 Year Single-Center Experience". “选择性胸外科手术切除肺动静脉畸形-单中心16年经验”社论。

IF 2.2 4区医学

Pulmonary Circulation Pub Date : 2025-04-02 eCollection Date: 2025-04-01 DOI: 10.1002/pul2.70073

Raghav Murthy

引用次数: 0

Pediatric Pulmonary Hypertension is Associated With Increased Circulating Levels of BMP 7 and CHIP. 小儿肺动脉高压与循环中BMP - 7和CHIP水平升高有关

IF 2.2 4区医学

Pulmonary Circulation Pub Date : 2025-04-02 eCollection Date: 2025-04-01 DOI: 10.1002/pul2.70068

Edward C Kirkpatrick, Stephanie Handler, Melodee Liegl, Amy Y Pan, G Ganesh Konduri, Todd M Gudausky, Adeleye J Afolayan

{"title":"Pediatric Pulmonary Hypertension is Associated With Increased Circulating Levels of BMP 7 and CHIP.","authors":"Edward C Kirkpatrick, Stephanie Handler, Melodee Liegl, Amy Y Pan, G Ganesh Konduri, Todd M Gudausky, Adeleye J Afolayan","doi":"10.1002/pul2.70068","DOIUrl":"10.1002/pul2.70068","url":null,"abstract":"Pulmonary arterial endothelial and smooth muscle cell homeostasis is regulated through the bone morphogenetic protein (BMP) and transforming growth factor beta (TGF-β) receptor pathways. Pathway imbalance results in pulmonary hypertension (PH). Each pathway has ligands and modulators influencing this balance. How these pathways differ in pediatric PH patients is unknown. Ten PH and 20 control subjects (ages 2-17 years) were prospectively enrolled. Pulmonary artery serum BMP 2, 4, 6, 7, 9, 10, activin A, TGF-β1, carboxyl terminus of Hsc70-interating protein (CHIP), NT Pro BNP, and CRP were measured by ELISA. Analyses were made using the Fisher's exact test, the Mann-Whitney test, ROC analysis, and Pearson and Spearman correlations as appropriate. PH subjects were group 1 (four with simple shunts) or group 3 PH. Control subjects had shunts scheduled for catheter closure but no PH. Only BMP 7 and CHIP levels were statistically elevated in PH patients versus controls; (BMP 7 0.081(0.076-0.084) vs. 0.074(0.069-0.08) OD, p = 0.044), (CHIP 0.17(0.14-0.24) vs. 0.13(0.12-0.15) OD, p = 0.007) respectively. BMP 7 levels correlated with RV systolic pressure (0.431, p = 0.02) and pulmonary resistance (0.446, p = 0.013). CHIP correlated with mean pulmonary artery pressure (0.449, p = 0.013) and resistance ratios (Rp/Rs) (0.419, p = 0.02). BMP 7 OD of 0.077 had sensitivity/specificity of 80% and 70% for PH. CHIP OD of 0.136 had sensitivity/specificity of 90% and 65% for PH. BMP 7 and CHIP levels are heightened in pediatric PH patients which correlate with catheterization values. BMP 7 and CHIP could provide sensitive markers for PH to aid in diagnosis and disease monitoring.","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 2","pages":"e70068"},"PeriodicalIF":2.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hank the Heart and Animation-Based Education for Pulmonary Hypertension. 心脏和基于动画的肺动脉高压教育。

IF 2.2 4区医学

Pulmonary Circulation Pub Date : 2025-04-02 eCollection Date: 2025-04-01 DOI: 10.1002/pul2.70072

Michelle Cash, Barbara Giambra, Lara Stone, Melissa Magness, Kimberly Luebbe, Samantha Moore, Ryan Moore, Russel Hirsch, Kimberley Miles, Michael Kim, Paul J Critser

{"title":"Hank the Heart and Animation-Based Education for Pulmonary Hypertension.","authors":"Michelle Cash, Barbara Giambra, Lara Stone, Melissa Magness, Kimberly Luebbe, Samantha Moore, Ryan Moore, Russel Hirsch, Kimberley Miles, Michael Kim, Paul J Critser","doi":"10.1002/pul2.70072","DOIUrl":"10.1002/pul2.70072","url":null,"abstract":"Pulmonary hypertension (PH) is a rare, complex disease affecting both children and adults. Efforts to provide health education are imperative as health literacy impacts patient and caregiver capacity to acquire, process, and understand health information and make informed health decisions. The current study sought to understand patient and family perception of \"Hank the Heart\", an animation used for enhancing health literacy, and preferred learning methods for future educational preferences. A qualitative study was conducted to assess the \"Hank the Heart\" animation using focus groups of family caregivers and patients. Focus group and interview transcripts underwent inductive thematic analysis. Patients and families have complicated health and educational needs that require a personalized approach, and they identified with the animated character as a representation of their reality. We identified three primary themes: (1) An animated video was found to be helpful but not sufficient to address all caregiver and patient educational needs, (2) Parents and children resonated strongly with elements of the video that represent their own experiences, and (3) Patient and family centered ongoing and tailored education is needed. The use of animation videos as a form of education was well received. Patient and family insights and suggestions were offered for improving future animation development.","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 2","pages":"e70072"},"PeriodicalIF":2.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cellular Communication Network Protein 2 in the Right Ventricle of Pulmonary Arterial Hypertension. 肺动脉高压右心室细胞通讯网络蛋白2的研究。

IF 2.2 4区医学

Pulmonary Circulation Pub Date : 2025-04-01 DOI: 10.1002/pul2.70067

Carly E Byrd, Jennifer E Schramm, Jun Yang, Allan E Barnes, Megan Griffiths, Anjira S Ambade, Darin T Rosen, Ilton M Cubero Salazar, Catherine E Simpson, Ryan J Tedford, Steven Hsu, Dhananjay Vaidya, Todd M Kolb, Michael W Pauciulo, William C Nichols, David D Ivy, Eric D Austin, Paul M Hassoun, Rachel L Damico, Allen D Everett

{"title":"Cellular Communication Network Protein 2 in the Right Ventricle of Pulmonary Arterial Hypertension.","authors":"Carly E Byrd, Jennifer E Schramm, Jun Yang, Allan E Barnes, Megan Griffiths, Anjira S Ambade, Darin T Rosen, Ilton M Cubero Salazar, Catherine E Simpson, Ryan J Tedford, Steven Hsu, Dhananjay Vaidya, Todd M Kolb, Michael W Pauciulo, William C Nichols, David D Ivy, Eric D Austin, Paul M Hassoun, Rachel L Damico, Allen D Everett","doi":"10.1002/pul2.70067","DOIUrl":"10.1002/pul2.70067","url":null,"abstract":"Cellular communication network 2 (CCN2) is a secreted matricellular protein associated with pulmonary arterial hypertension (PAH) but has not been studied relative to PAH severity, outcomes, or right ventricle (RV) structure and function in a large human cohort and preclinical animal model. This study assessed the associations between CCN2 and PAH severity, survival, hemodynamic measurements, and cardiovascular dysfunction. Serum CCN2 levels were compared in 2548 adults with PAH and 216 controls. CCN2 levels in PAH patients were compared to functional and hemodynamic measurements, and survival outcomes. RV-pulmonary artery coupling and RV morphology were also assessed in a small subset of patients via pressure-volume loops and cardiac magnetic resonance imaging. In a preclinical PAH model, plasma CCN2 levels were compared between ventricles with PAH progression. CCN2 mRNA levels in both ventricles in the preclinical model were measured to compare with morphologic histologic variables. CCN2 serum levels were significantly higher in PAH compared to controls (p < 0.0001). Higher CCN2 levels were associated with reduced RV contractility (p = 0.003). Higher CCN2 levels were associated with worse 6MWD (p = 0.035), and higher risk of mortality or transplant (p = 0.025). In the preclinical model, prepulmonary CCN2 plasma levels increased with the progression of disease. CCN2 mRNA levels in the RV were associated with decreased RV capillary density (p = 0.015) and increased RV fibrosis (p = 0.045). Though more investigation is needed, it appears that CCN2 plays a role in the development of PAH and potentially in RV maladaptation in PAH.","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 2","pages":"e70067"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heart Rate Variability as a Marker of Disease Severity in Pulmonary Arterial Hypertension: A Prospective Cohort Study. 心率变异性作为肺动脉高压疾病严重程度的标志：一项前瞻性队列研究。

IF 2.2 4区医学

Pulmonary Circulation Pub Date : 2025-03-31 eCollection Date: 2025-04-01 DOI: 10.1002/pul2.70064

Arun Jose, Alex D Moseley, Manisha Das, Robert E O'Donnell, Jean M Elwing

{"title":"Heart Rate Variability as a Marker of Disease Severity in Pulmonary Arterial Hypertension: A Prospective Cohort Study.","authors":"Arun Jose, Alex D Moseley, Manisha Das, Robert E O'Donnell, Jean M Elwing","doi":"10.1002/pul2.70064","DOIUrl":"10.1002/pul2.70064","url":null,"abstract":"Pulmonary arterial hypertension (PAH) is a disease that can eventually progress to right ventricular failure. Heart rate variability (HRV), including standard deviation of R-to-R intervals (SDNN), has been associated with increased mortality across different populations. The purpose of this study was to examine the association between HRV and disease severity in PAH. This was a prospective cohort study of adult incident PAH patients who underwent cardiac magnetic resonance imaging (CMR) at baseline and following 6 months. Study subjects recorded HRV using wearable chest actigraphy devices for at least 1 h every 2 weeks. The primary end point was correlation between HRV and right ventricular ejection fraction (RVEF) on CMR. Multivariable mixed effects regression models were used. A total of 20 subjects completed the study, predominantly female and White race, with severe PAH at the time of enrollment that improved significantly following 6 months of treatment. Linear relationships were observed between HRV (SDNN) and measures of PAH severity on CMR, including RVEF (SDNN coefficient 0.18, p = 0.006) and right ventricular-pulmonary arterial coupling ratio (SDNN coefficient 0.008, p = 0.003). Comparable relationships were observed between heart rate captured using HRV device and these CMR measures (RVEF coefficient -0.37, p = 0.007; coupling ratio coefficient -0.013, p = 0.016). We conclude that noninvasively captured HRV (SDNN) and heart rate strongly correlate with PAH disease severity (right ventricular structure and function) on CMR, and may complement existing methods of risk assessment in PAH, particularly in high-risk incident PAH.","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 2","pages":"e70064"},"PeriodicalIF":2.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High Altitude May Protect Against the Early Development of Irreversible Pulmonary Hypertension in Patients With Congenital Heart Disease. 高海拔可预防先天性心脏病患者不可逆肺动脉高压的早期发展。

IF 2.2 4区医学

Pulmonary Circulation Pub Date : 2025-03-26 eCollection Date: 2025-01-01 DOI: 10.1002/pul2.70049

Inge von Alvensleben, Brian B Graham, Gustavo A Balanza, Carlos Brockmann, Ericka C Pérez, Ximena Y Vicente, Carla Arteaga, Claudia Scherer, Franz P Freudenthal, Rubin M Tuder, Alexandra Heath

{"title":"High Altitude May Protect Against the Early Development of Irreversible Pulmonary Hypertension in Patients With Congenital Heart Disease.","authors":"Inge von Alvensleben, Brian B Graham, Gustavo A Balanza, Carlos Brockmann, Ericka C Pérez, Ximena Y Vicente, Carla Arteaga, Claudia Scherer, Franz P Freudenthal, Rubin M Tuder, Alexandra Heath","doi":"10.1002/pul2.70049","DOIUrl":"10.1002/pul2.70049","url":null,"abstract":"Congenital heart disease (CHD) occurs at increased prevalence at high altitude, but there may be a paradoxical later onset of the development of Eisenmenger syndrome. We hypothesized that congenital heart disease patients at high altitude are protected from an early onset of irreversible pulmonary hypertension. We present a ospective observational case series study, supported by a PVRI grant, of patients in La Paz, Bolivia, located at 3600 m, who underwent surgery for CHD. 10 consecutive patients aged 5 to 29 years (mean 12) with left-to-right shunts and pulmonary hypertension underwent diagnostic catheterization to assess pulmonary pressure pre-operatively and six to 9 months postoperatively, and had a lung biopsy performed at the time of the surgery. Control lung tissue was obtained from patients living at the same altitude who underwent pulmonary hydatid cyst resection. 10 CHD patients and 4 control patients were analyzed. Pre-operatively, the patients had a significant response to hyperoxia with a fall in mean pulmonary pressure (mPAP) from 59.6 mmHg (SD 7.74) to 46.3 mmHg (SD 11.1); (p < 0.05). Postoperatively, the patients had an excellent response to surgery, with a mPAP of 26.4 mmHg (SD 6.42) (p < 0.05 vs. preoperative pressures). Analysis of the lung histology did not show evidence of pulmonary vascular remodeling in the CHD patients compared to the control patients. During the follow-up in up to 11 years, pulmonary pressure assessed by echocardiography remained normal. In conclusion, chronic hypobaric hypoxemia at high altitude may delay the development of pulmonary vascular disease in CHD patients.","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 1","pages":"e70049"},"PeriodicalIF":2.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Flow Cytometric Determination of Circulating Progenitor Cells in Patients With Pulmonary Arterial Hypertension: A Systematic Review. 流式细胞术测定肺动脉高压患者循环祖细胞：一项系统综述。

IF 2.2 4区医学

Pulmonary Circulation Pub Date : 2025-03-20 eCollection Date: 2025-01-01 DOI: 10.1002/pul2.70065

Kimia Heydari, Carrie Johnson, I Diane Cooper, Kadija Hersi, Carl Tanba, Junfeng Sun, Michael A Solomon, Jason M Elinoff

{"title":"Flow Cytometric Determination of Circulating Progenitor Cells in Patients With Pulmonary Arterial Hypertension: A Systematic Review.","authors":"Kimia Heydari, Carrie Johnson, I Diane Cooper, Kadija Hersi, Carl Tanba, Junfeng Sun, Michael A Solomon, Jason M Elinoff","doi":"10.1002/pul2.70065","DOIUrl":"10.1002/pul2.70065","url":null,"abstract":"Pulmonary arterial hypertension (PAH) is characterized by progressive narrowing and obliteration of distal, pre-capillary pulmonary vessels. Yet, noninvasive biomarkers that reflect this disease-defining process are lacking. A systematic review of PAH studies that measured circulating progenitor cells (CPCs) or circulating endothelial cells (CECs) in PAH by flow cytometry was performed to understand how future studies, leveraging state-of-the-art single-cell analyses, can advance the field. The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews. Of the 2422 studies identified, 20 met inclusion criteria. Nineteen studies measured CPCs by flow cytometry, only one study examined CECs. A total of 647 PAH patients were included across all 19 CPC studies. Marker schemes chosen to define CPCs, and the methods of flow cytometry used, varied significantly across studies. Meta-analysis of a subgroup of CPC studies (n = 8) similarly identified a significant amount of heterogeneity even amongst studies using the same marker scheme. In conclusion, a systematic review of CPC studies in PAH patients reveals the limitations of the current literature. Future studies should include contemporary risk assessments, disease duration, reporting of comorbid conditions, and serial sampling over time. Furthermore, methods that incorporate best practices for detecting rare cell populations by flow cytometry are essential and should be reported in sufficient detail in future publications. With the emergence of single-cell technologies, future studies of circulating progenitor and endothelial cells in PAH remain relevant and may incorporate several insights from the current review to build upon the existing literature.","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 1","pages":"e70065"},"PeriodicalIF":2.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pulmonary Embolism as a Cause of Death in Lung Transplant Recipients: Data From a Nationwide Registry. 肺栓塞作为肺移植受者死亡的原因：来自全国登记的数据

IF 2.2 4区医学

Pulmonary Circulation Pub Date : 2025-03-11 eCollection Date: 2025-01-01 DOI: 10.1002/pul2.70056

Hye Sung Kim, Rohit Gupta, Parth Rali

引用次数: 0

Contribution of QRS Prolongation to Transplant-Free Survival in Sarcoidosis-Related Pulmonary Hypertension. QRS延长对结节病相关性肺动脉高压患者无移植生存的贡献。

IF 2.2 4区医学

Pulmonary Circulation Pub Date : 2025-03-11 eCollection Date: 2025-01-01 DOI: 10.1002/pul2.70021

Juan V Rodriguez, Haihua Zhang, Nathan Mesfin, Elizabeth S Klings, Justin K Lui

引用次数: 0

Developing Benchmarks in the Diagnosis and Treatment of Pulmonary Arterial Hypertension in a Tertiary, Academic Medical Center. 在一家三级学术医疗中心制定肺动脉高压诊断和治疗基准。

IF 2.2 4区医学

Pulmonary Circulation Pub Date : 2025-03-03 eCollection Date: 2025-01-01 DOI: 10.1002/pul2.70063

Cyrus A Kholdani, Justin H Lee, Kai E Swenson, Juliana Liu, Andrew Hsi, Kristina T Kudelko, Andrew J Sweatt, Edda F Spiekerkoetter, Vinicio De Jesus Perez, Joseph Rigdon, Haley Hedlin, Adam M Andruska, Raquel L Lyn, Roham T Zamanian, Yon K Sung

{"title":"Developing Benchmarks in the Diagnosis and Treatment of Pulmonary Arterial Hypertension in a Tertiary, Academic Medical Center.","authors":"Cyrus A Kholdani, Justin H Lee, Kai E Swenson, Juliana Liu, Andrew Hsi, Kristina T Kudelko, Andrew J Sweatt, Edda F Spiekerkoetter, Vinicio De Jesus Perez, Joseph Rigdon, Haley Hedlin, Adam M Andruska, Raquel L Lyn, Roham T Zamanian, Yon K Sung","doi":"10.1002/pul2.70063","DOIUrl":"10.1002/pul2.70063","url":null,"abstract":"Benchmarks of clinical management are essential for improving the quality of care. However, the lack of established quality metrics for pulmonary arterial hypertension (PAH) contributes to practice heterogeneity. We assessed our center's diagnostic practices, therapeutic practices, and risk-adjusted survival patterns over time for the purpose of establishing quality benchmarks. We analyzed the demographics, clinical characteristics, and diagnostic evaluation of 702 PAH patients enrolled between 1999 and 2019. We examined outcomes in this cohort, including an analysis of risk stratification, therapeutic practice patterns, hospitalizations, organ transplant, and survival. Initial diagnostic workup of incident PAH cases demonstrated excellent completion of echocardiographic (99%) and pulmonary function testing (91%), with improved completion of VQ scanning over the study time period (90% between 2015 and 2019). Right heart catheterization (RHC) was performed in all patients; RHC performed at our center was more likely to include complete hemodynamic data than those performed at referring institutions (55.4% and 30.4% respectively). The average number of PAH-specific medications prescribed increased over time; however, there was no significant increase in the use of parenteral therapy over time, even when stratified by the REVEAL risk score. Survival rates in the cohort were 94% at 1 year, 75% at 5 years, and 60% at 10 years, comparable to those of other PAH cohorts. Analysis of our well-characterized cohort of PAH patients reveals the extent to which guideline-directed diagnostic and therapeutic care is delivered at our specialty center, and the associated outcomes; these data may serve as a benchmark for continued improvements in quality of PAH care.","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 1","pages":"e70063"},"PeriodicalIF":2.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0