bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the Affordable Care Act Medicaid expansion in the USA associated with reductions in intimate partner violence victimisation?
Authors: Bevilacqua Kristin G , Assini-Meytin Luciana C , Nair Reshmi , Decker Michele R , McGinty Emma E , Stuart Elizabeth A , Letourneau Elizabeth J
Published: December 2024

Objective

Intimate partner violence (IPV) affects an estimated 47% of women living in the USA in their lifetime and is associated with increased risk of physical and mental health concerns. Current prevention efforts focus on individual and family-level interventions rather than macrosystem-level policies. Thus, we sought to test the effects of Medicaid expansion on the rates of IPV and violence more broadly.

Methods

Present analyses use retrospective longitudinal data from the National Crime Victimization Survey (NCVS). State level rates of total violence and IPV were measured per 1000 population from the NCVS for years 2008–2018 as 3-year averages for each state. A two-way fixed-effects difference-in-differences model was fit to evaluate differences in the change in violence outcomes pre-2014/post-2014 in Medicaid expansion states versus non-expansion states.

Results

Comparison states had a significantly higher proportion of residents who were black, living below the federal poverty level and with lower educational attainment. Before Medicaid expansion, comparison states had a significantly lower mean rate of total violence and IPV per 1000 population. In two-way fixed effects difference-in-differences models, there was no statistically significant association between Medicaid expansion and IPV or total violence.

Discussion

Despite null findings, our study adds to the evidence base evaluating the impacts of macro-level policies on different forms of violence. The pathways by which Medicaid expansion could contribute to violence reduction are multifaceted with numerous mediators and those pathways may not be sufficiently strong to generate impacts. Additional work is warranted to further probe Medicaid expansion’s impact on violence prevention.
‘Finally making sense’: graphic medicine and ADHD diagnosis in adulthood
Authors: Venkatesan Sathyaraj , Tolani Prerna
Published: December 2024

This article aims to examine the lived experiences of attention-deficit/hyperactivity disorder (ADHD) diagnosis in adulthood, emphasising its revelatory nature and diverse emotional responses it provokes. The diagnosis serves as a pivotal moment of self-discovery, often evoking feelings of validation and identity affirmation. However, it also triggers a complex array of emotions, including grieving for the childhood self, frustration with society’s failure to recognise the legitimate challenges and evolving self-concept post diagnosis. Through a close reading of digitally published comics by Laura Balcerek, Amber Lewis and Juliette Yu-Ming Lizeray, this article studies how the graphic medium conveys these nuanced experiences. By dissecting narrative and visual elements inherent in the comics, the article studies the affordances of the comic medium to capture the lived experiences of ADHD diagnosis in adulthood. Ultimately, this article intends to deepen understanding of the diverse lived realities and underscores the expressive potential of graphic narratives of neurodivergence.
Give us a hand, mate! A holistic review of research on human-machine teaming
Authors: Patel Jitu , Boardman M , Files B , Gregory F , Lamb S , Sarkadi S , Tešić M , Yeung N
Published: December 2024

Defence has a significant interest in the use of artificial intelligence (AI)-based technologies to address some of the challenges it faces. At the core of future military advantage will be the effective integration of humans and AI into human-machine teams (HMT) that leverages the capabilities of people and technologies to outperform adversaries. Realising the full potential of these technologies will depend on understanding the relative strengths of humans and machines, and how we design effective integration to optimise performance and resilience across all use cases and environments.

Since the first robot appeared on the assembly line, machines have effectively augmented human capability and performance; however, they fall short of being a team member—someone you can ask to give you a hand! Working in teams involves collaboration, adaptive and dynamic interactions between team members to achieve a common goal. Currently, human-machine partnership is typically one of humans and machines working alongside each other, with each conducting discrete functions within predicable process and environments. However, with recent advances in neuroscience and AI, we can now envisage the possibility of HMT, not just in physical applications, but also complex cognitive tasks.

This paper provides a holistic review of the research conducted in the field of HMT from experts working in this area. It summarises completed and ongoing studies and research in the UK and USA by a broad group of researchers. This work was presented in the HMT thematic session at the Sixth International Congress on Soldiers’ Physical Performance (ICSPP23 London).
Thermal Inactivation of Clostridium sporogenes PA 3679 in Low Acid Foods: Case Study of Maple Sap Concentrates
Authors: Zareifard M. R. , Ali F. , Plamondon J. , Lapointe C. , Savard T. , Hubbard K. , Houde J. , Lagacé L.
Published: December 2024

Maple sap is a sterile liquid extracted from maple trees in early spring. However, it is rapidly contaminated during handling and processing. Typically, raw sap undergoes a reverse osmosis process for concentration; meanwhile, this operation also concentrates the microorganisms present in the sap. The enrichment of microorganisms affects the quality of the sap and its derived products remarkably. Consumption of concentrated maple sap as a novel natural soft drink has increased considerably in recent years, mainly in North America but also worldwide. Adequate processing is required in order to eliminate the microorganisms and stabilize the quality of the concentrated maple sap for further consumption. Thermal processing is a safe preservation technique; however, severe thermal processing may affect negatively the quality of the product for consumer acceptance. Therefore, it is important to evaluate the right thermal processing parameters such as D‐ and Z‐values for a given product. Spores of Clostridium sporogenes PA 3679 strain were used as a surrogate to evaluate the thermal destruction kinetic parameters of spores in concentrated maple sap (10°Brix–30°Brix) over a range of temperatures (90°C–105°C). Obtained D‐values varied from 6.57 to 0.35 min depending on the sap concentration and temperature with an average Z‐value of 7.84 ± 0.42°C. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses indicate that the spore cortex and core break down first during conventional thermal treatment as a result of heat transfer from the external media to the spore interior. The results of this study can be used by maple sap industries to design and perform a safe thermal process for pasteurization and/or sterilization of concentrated sap. It could also serve as a benchmark in the development of advanced green technologies such as ohmic heating.
English Proficiency Test and Academic Performance in Purposive Communication: A Correlation Study
Authors: Galang Ruby T. , Arrozal Jocelyn Y. , Lumanlan Arnold D. , Cortez Leila
Published: December 2024

English is a critical subject in the Philippines; teachers themselves are also required to pass the English Proficiency Test before practic-ing in public schools. However, there has been a gradual decline in English language proficiency among Filipinos, as evidenced by vari-ous assessments. The study aims to explore the English proficiency of college students at the university in relation to the course Purpos-ive Communication which sought to answer the following ques-tions:1) What is the academic performance in Purposive Communi-cation course of the respondents?; 2) What are the English profi-ciency level test results of the respondents? 3) Is there a significant relationship between the general weighted average in the Purposive Communication course of the respondents and the English profi-ciency level test results of the respondents? The researchers utilized a correlational research design for the study to measure the rela-tionship between independent and dependent variables; it deter-mined that a correlational design was appropriate and beneficial. This phase statistical insights into the relationship between aca-demic performance and English proficiency. The findings contribut-ed to theory generation by shedding light on the role of specific col-lege courses in shaping English proficiency and informing educa-tional policies aimed at enhancing language proficiency among fu-ture teachers.
21st-Century Teaching Competencies, Learning Skills and Science Content Knowledge of STEM Students Among the DepEd Schools in the Province of Capiz: A Basis for Enhancement Program
Authors: Dacles Ginalyn G.
Published: December 2024

The mixed-method research design was used to determine the level of 21st-century teaching competencies, learning skills, and science content knowledge of STEM 12 students in the province of Capiz for the school year 2023-2024. The participants of this study were the 306 STEM 12 students from a total population of 1, 446 in the province of Capiz selected through stratified random sampling using the Raosoft sample size calculator. The research instruments used in this study were the 21st-century teaching competencies questionnaire, 21st-century learning skills questionnaire, and a science content knowledge test with the demographic profile of the respondents. The questionnaires were composed of: A 70-item researcher-made 21st-century teaching competencies questionnaire; 120-item 21st-century learning skills and an 80-item science content knowledge test adopted from Competency Based Assessment – DepEd (School Division of Capiz, 2021). Another instrument used in this study was the Focus Group Discussion (FGD) Guide. It was conducted to gather qualitative data for triangulation with the quantitative data gathered. Mean, frequency, percentage, and standard deviation were used for descriptive data analysis, while analysis of variance and Pearson r were used for inferential data analysis at 0.05 level of significance. The results show that STEM 12 teachers exhibited a high level of 21st-century teaching competencies across various aspects, such as magnifying meaning, elevating experience, amplifying agency, curating curriculum, busting barriers, teaching technology, and revamping roles. Similarly, STEM 12 students demonstrate a very high level of 21st-century learning skills, with critical thinking rated as high and other skills like creativity, collaboration, communication, information literacy, media literacy, technology literacy, flexibility, leadership, initiative, productivity, and social skills rated as very high. Regarding science content knowledge, STEM 12 students were found to have a high level of understanding, with General Biology I rated as high and General Physics I rated as moderately high. Notably, the study identified significant relationships between 21st-century learning skills and teaching competencies, as well as between 21st-century learning skills and science content knowledge. However, no significant relationship was observed between 21st-century teaching competencies and science content knowledge.
Based on the results, an enhancement program will be implemented to sustain and enhance the 21st-century teaching competencies of teachers, learning skills, and science content knowledge of students.
Resumption of In-Person Classes in Public Secondary Schools Division of Zambales: Priorities and Challenges for Shared Responsibility
Authors: Antigo Cristina L. , De Guzman Marie Fe D
Published: December 2024

This study sought to determine the priorities for shared responsibility in Public Secondary Schools Division of Zambales for the current resumption of facetoface in-person classes for the school year 2022-2023 conducted during the third quarter among school heads of the 13 Districts of Department of Education Schools Division of Zambales, Philippines. The research design was descriptive quantitative and utilized survey questionnaire as main research instrument. This study determined that the school heads are male middle aged adults, Master's degree holders, and served in the profession for two and a half decades as Principal I and IV while the teachers are female young adults, Baccalaureate degree holders with Master’s units; served in the teaching profession for a decade as Teacher I. The school heads and teachers’ perception towards the priorities for shared responsibility was very evident in terms of Provision of Support to Teachers. Both the school heads and teachers strongly agreed that there are challenges for shared responsibility during the resumption of in-person classes in public secondary schools. The ANOVA results revealed that there was significant difference in the perception on the priorities for shared responsibility during the resumption of in-person classes in terms of school heads’ highest educational attainment and designation. There was significant difference in terms of Provision of Support to Teachers, Students’ Study Habits and Parents’ Role in Learning when attributed to teachers’ length of service. The t-Test result showed that there was significant difference between the perceptions of the school heads and the teachers on the different priorities and challenges for shared responsibility during the resumption of in-person classes in public secondary schools. The findings resulted in the development of an Action Plan to address the priorities and challenges for shared responsibility during the resumption of in-person classes; and will become a basis for DepEd Division of Zambales policy, projects and plans consideration and future implementation.
Faculty Workload and Well-being at President Ramon Magsaysay State University: Impacts of Allied Tasks on Stress and Health
Authors: Vizcarra Myra Liza O. , Aragon Almay Elena A. , Tiangco Peter-Vir V. , Basarte Charie A.
Published: December 2024

Faculty members in higher education institutions are increasingly burdened by a growing workload, particularly non-teaching assignments or allied tasks. The time spent on workloads were observed to have increased in the past years. Hence, the researchers decided to undertake this study entitled,”Faculty Workload and Well-being at President Ramon Magsaysay State University: Impacts of Allied Tasks on Stress and Health,” during the academic year 2021-2022. A quantitative descriptive design was employed to evaluate the variables of the study. A researcher-made survey questionnaire was administered to forty-three faculty members using population sampling. Data were collected through online platform due to limited face to face interactions. A letter of consent was emailed to the three(3) Campus Directors of north campuses prior the online survey. Descriptive statistics such as percentage, weighted means, and Pearson Correlation was used in the treatment of data.  The findings revealed that on average, faculty members spent approximately 29.54 hours on teaching tasks and 34.73 hours on allied tasks per week. This study revealed significant differences in the time spent on allied tasks across various demographic groups, such as age, gender, civil status, highest educational attainment, and length of service. Additionally, a significant relationship was found between the time spent on teaching and allied tasks and the extent of experienced stress, but not on personal life, mental health, or physical health. Based on these findings, it is recommended that the university administration implement strategies such as offering mental health support services and creating a more supportive work environment. Reallocating administrative responsibilities or hiring support staff is highly encouraged.  Providing health breaks may also be implemented which could help address stress.
Thromboembolic Events in the Hemodialysis Setting: Understanding Risk Profiles and Cumulative Incidences to Inform Clinical Trial Design
Authors: Karaboyas Angelo , Zhao Junhui , Tanko Laszlo B. , Joergensen Kristian Tore , Pap Akos F. , Dasgupta Indranil , Nangaku Masaomi , Jadoul Michel , Pecoits‐Filho Roberto
Published: December 2024

Background

People with kidney failure have a high risk of cardiovascular morbidity/death, including thromboembolic events. Factor XIa inhibitors are a new class of anticoagulants in development that may offer antithrombotic benefits with a lower risk of incremental bleeding events than traditional therapies. We investigated major adverse vascular events (MAVEs), a relevant composite outcome for testing novel antithrombotic agents, in a large cohort of patients on hemodialysis, to better understand the key requirements to adequately design a phase 3 trial.

Methods and Results

We included 25 211 patients on hemodialysis for >90 days in phases 4 to 7 (2009–2021) of the DOPPS (Dialysis Outcomes and Practice Patterns Study). Atherosclerotic cardiovascular disease (ASCVD) was defined as history/presence of coronary, peripheral, or cerebrovascular disease. We estimated MAVE rates and cumulative incidence, overall and by ASCVD. Over half (52%) of the cohort met the ASCVD criteria. The MAVE hospitalization/death composite rate (per 100 patient‐years) was 6.0 in the overall cohort and 8.7 in the ASCVD subset. Three‐year cumulative incidence of MAVE was 13% in the overall cohort and 18% in the ASCVD subset. The estimated sample size to be randomized in a hypothetical trial in the ASCVD population was ≈7000 patients.

Conclusions

Even in the enriched ASCVD group, the observed MAVE incidence combined with a high competing risk, regulatory requirements (α=0.01), and limited recruitment pool makes feasibility of a potential randomized trial targeting MAVE reduction challenging. These results highlight key considerations and challenges for developers of novel therapies targeting systemic thromboembolic events in patients on hemodialysis.
Cardiovascular Health Status in US Adults With Chronic Diseases: National Health and Nutrition Examination Survey (NHANES), 2013–2018
Authors: Guo James W. , Ning Hongyan , Lloyd‐Jones Donald M.
Published: December 2024

Background

Cardiovascular health (CVH) assessment may have important benefits for adults with chronic diseases to prevent incident cardiovascular disease and additional chronic conditions. Few studies have compared CVH in adults with chronic diseases and healthy adults without chronic disease using the American Heart Association's (AHA's) Life's Essential 8 (LE8) metrics.

Methods and Results

We used National Health and Nutrition Examination Survey data from 2013 to 2018 to identify the presence of 16 chronic diseases by participant self‐report of diagnosis. We included adults aged 20 to 79 years. CVH was defined by AHA's LE8 metrics. Overall mean LE8 (range 0–100, higher = better CVH) and individual LE8 metric scores were calculated according to disease status for all participants and stratified by self‐identified sex, race, and ethnicity. There were 12 296 adults (51% women; mean age, 46 years) representing >186 million noninstitutionalized US adults. Significantly, and often substantially, lower CVH scores were noted for adults with chronic disease (14 of 16 diseases studied) versus unaffected adults, including all subtypes of cardiovascular disease, lung diseases, chronic kidney disease, liver conditions, cancer, arthritis, cognitive decline, and depression. For example, mean overall LE8 score was 14.0 points lower in those with versus without chronic obstructive pulmonary disease (51.0 versus 65.0,
P
<0.0001). Men and Black adults consistently had lower LE8 scores.

Conclusions

CVH is significantly poorer in adults with many chronic diseases compared with unaffected adults. These data suggest the utility of the LE8 score to identify groups for targeted optimization of CVH to enhance primary and secondary prevention efforts for cardiovascular disease and potentially for concomitant chronic diseases of aging.
Fatigue After Stroke Educational Recovery Program: A Prospective, Phase III, Randomized Controlled Trial
Authors: Jones Kelly , Krishnamurthi Rita , Barker‐Collo Suzanne , De Silva Sulekha , Henry Nathan , Zeng Irene , Vorster Anja , Te Ao Braden , Green Geoff , Ratnasabapathy Yogini , Feigin Valery
Published: December 2024

Background

Poststroke fatigue affects ≈50% of patients with stroke, causing significant personal, societal, and economic burden. In the FASTER (Fatigue After Stroke Educational Recovery) study, we assessed a group‐based educational intervention for poststroke fatigue.

Methods and Results

Two hundred patients with clinically significant fatigue were included and randomized to either a general stroke education control or fatigue management group (FMG) intervention and assessed at baseline, 6 weeks, and 3 months. The FMG involved weekly psychoeducation sessions over 6 weeks. Coprimary outcomes were the Fatigue Severity Scale and Multidimensional Fatigue Inventory‐20 total scores. Adjusted mean total Fatigue Severity Scale scores at 6 weeks (primary end point) were nearly identical for the education control and FMG groups. The adjusted mean difference between treatment groups was −0.13 (SE, 1.4;
P
=0.92) at 6 weeks and 1.67 (SE, 1.4;
P
=0.26) at 3 months. Although there were no significant effects, Fatigue Severity Scale outcomes were in the direction of a treatment effect based on the estimated change. Adjusted mean total Multidimensional Fatigue Inventory‐20 scores at 6 weeks (primary end point) were similar for the education control and FMG groups. The adjusted mean difference between treatment groups was −0.91 (SE, 1.54;
P
=0.55) at 6 weeks and −1.26 (SE, 1.8;
P
=0.49) at 3 months. Both groups had similar secondary outcomes (eg, Multidimensional Fatigue Inventory‐20 subscales, sleep, pain, mood, quality of life) at 6 weeks and 3 months.

Conclusions

We found no evidence of significant group‐level benefits of FMG over and above general stroke education. Educational group‐based interventions for poststroke fatigue should continue to be refined and examined, including consideration of potential impacts at an individual level.

Registration

URL:
https://www.anzctr.org.au/
; UnIque identifier: ACTRN12619000626167.
Association Between Sleep Duration and Cardiovascular Disease Among Asian Americans
Authors: Nadarajah Santhosh , Akiba Risa , Maricar Isabelle , Vohra Sanah , Jamal Armaan , Yano Yuichiro , Srinivasan Malathi , Kim Gloria , Huang Robert J. , Palaniappan Latha , Kim Karina , Elfassy Tali , Yang Eugene
Published: December 2024

Background

Cardiovascular disease (CVD) prevalence varies widely among Asian American adults. The American Heart Association added healthy sleep to its metrics to define ideal cardiovascular health. Little is known about the association between sleep and CVD prevalence among Asian subgroups. We aim to examine the association between suboptimal sleep duration and CVD risk prevalence among Asian American subgroups.

Methods and Results

We used 2012 to 2018 National Health Interview Survey data to examine the association between suboptimal sleep duration and CVD prevalence. We included 6868 self‐identifying Asian adults age >40 years (Asian Indian [n=1053], Chinese [n=1415], Filipino [n=1734], and Other Asian [n=2666] adults). Suboptimal sleep was defined as <7 or >9 hours per night. CVD was defined as self‐reported stroke, heart attack, coronary artery disease, or angina. Logistic regression was used to calculate odds ratios and 95% CI to estimate the association between suboptimal sleep duration and CVD prevalence. Filipino and Other Asian participants with suboptimal sleep had the highest prevalence of CVD. Aggregated Asian American participants with suboptimal sleep duration had a higher prevalence of CVD (odds ratio [95% CI, 1.35 [1.09–1.68]) compared with those with optimal sleep duration. After stratification by race or ethnicity or both, a significant association persisted for Other Asian participants (1.77 [95% CI, 1.27–2.46]) but not among all other Asian American subgroups.

Conclusions

Our study highlights the heterogeneity of CVD prevalence associated with suboptimal sleep duration among Asian American adults. Future studies should consider how different measures of sleep duration and quality affect CVD outcomes among disaggregated Asian American subgroups.
Diacylglycerol Kinase ζ Attenuates Doxorubicin‐Induced Cardiotoxicity Through p53 Degradation
Authors: Tachibana Shingo , Otaki Yoichiro , Watanabe Tetsu , Goto Jun , Ochi Haruki , Tanaka Toshiaki , Ono Hiroe , Yamaguchi Ryuhei , Sato Junya , Takahashi Hiroki , Arimoto Takanori , Goto Kaoru , Watanabe Masafumi
Published: December 2024

Background

Doxorubicin‐induced cardiotoxicity is still an important medical problem associated with a high mortality rate in cancer survivors. p53 plays a key role in doxorubicin‐induced cardiotoxicity. Diacylglycerol kinase ζ (Dgkζ), a 130‐kDa enzyme abundant in cardiomyocytes, regulates the p53 protein expression level in neurons. To elucidate the mechanism of doxorubicin‐induced cardiotoxicity, we focused on the functional role of Dgkζ and its interaction with heat shock protein 70 (Hsp70)–related ubiquitin E3 ligases such as E6‐associated protein (E6ap) and C‐terminus of Hsp70‐interacting protein.

Methods and Results

Protein interactions of Dgkζ with Hsp70 and E6ap were confirmed by immunoprecipitation, but not C‐terminus of Hsp70‐interacting protein. We administered doxorubicin in cardiac‐specific overexpression of Dgkζ transgenic (Dgkζ‐Tg) mice and wild‐type littermates. Dgkζ‐Tg mice showed lower p53 protein expression levels, preserved cardiac function, and improved survival rates compared with wild‐type littermates after doxorubicin administration. RNA sequence analysis of myocardial tissues from Dgkζ‐Tg after doxorubicin stimulation identified
Hspa1b
encoding Hsp70 as the differentially expressed gene. Dgkζ overexpression increased proteasomal p53 degradation and attenuated cardiomyocyte apoptosis after doxorubicin stimulation in cardiomyocytes, which was reversed by knockdown of E6ap. Dgkζ interacted with E6ap through ankyrin‐like repeats. The overexpression of mutant Dgkζ, lacking ankyrin‐like repeats, failed to inhibit p53 protein expression after doxorubicin stimulation. In Dgkζ‐overexpressing cardiomyocytes, expression levels of p53 and caspase‐3 were increased by knockdown of the C‐terminus of Hsp70‐interacting protein.

Conclusions

We demonstrated for the first time that Dgkζ augments p53 ubiquitin‐proteasome degradation and ameliorates doxorubicin‐induced cardiotoxicity by interacting with Hsp70 and E3 ligases such as E6ap and C‐terminus of Hsp70‐interacting protein.
Myocarditis in Patients Starting Combination Checkpoint Inhibitor Therapy: Analysis of a Commercial Claims Database
Authors: Lindsay Alistair C. , Walker Alexander M. , Schneeweiss Sebastian
Published: December 2024

Background

Immune checkpoint inhibitors have improved the clinical outcomes of several cancers but have also been associated with a greater risk of immune‐related adverse effects, especially when combined. The objective of this study was to investigate the incidence of myocarditis in relation to the use of dual concurrent versus single immune checkpoint inhibitors therapies.

Methods and Results

A cohort study was conducted using medical and pharmacy claims data (2011–2022) from a large US commercial insurer. Cox regression quantified the comparative risks of myocarditis or heart failure in patients with cancer receiving treatment with combination therapy (nivolumab and ipilimumab) in comparison to taking a single immune checkpoint inhibitor only. Mean follow‐up time in 53 018 patients was 226 days (interquartile range, 93–495 days). There were 148 cases of myocarditis (0.3%), 33 (0.7%) in patients on combination therapy, and 115 (0.2%) in patients on monotherapy. The risk of myocarditis per 1000 patients was 7.40 in the combination therapy group and 2.37 in the monotherapy group (risk ratio, 3.12 [95% CI, 2.12–4.60]). Using multivariable regression analysis, the hazard ratio for myocarditis in the combination therapy group was 2.38 (1.57–3.63). No difference in the risk of heart failure was found between combination and single therapy.

Conclusions

Therapy with 2 immune checkpoint inhibitors was associated with an increased risk of myocarditis compared with monotherapy, with most cases occurring in the first 6 months of therapy.
Single Cell Transcriptomic Profiling of
MYBPC3
‐Associated Hypertrophic Cardiomyopathy Across Species Reveals Conservation of Biological Process But Not Gene Expression
Authors: Ali Samia A. , Perera Gayani , Laird Jason , Batorsky Rebecca , Maron Martin S. , Rivas Victor N. , Stern Joshua A. , Harris Samantha , Chin Michael T.
Published: December 2024

Background

Hypertrophic cardiomyopathy (HCM) is a common heritable heart disease where the most frequently associated mutations occur in the myosin‐binding protein C (
MYBPC3
) sarcomere‐associated gene. HCM is also a common veterinary clinical problem in certain cat breeds such as Maine Coons and Ragdolls, also most associated with mutations in
MYBPC3
. Mouse models of HCM in which
Mybpc3
mutations are introduced recapitulate some, but not all, features of human HCM.

Methods and Results

To elucidate the common and distinctive pathological pathways across species and foster a greater understanding of the concordance of mouse HCM models to clinical
mybpc3
‐associated HCM, we generated single nuclei RNA‐sequencing data sets from feline, human, and murine heart tissue carrying
MYBPC3
variants. Numerous genes were differentially expressed between mutation positive and mutation negative cell types within each species, identified using the model‐based analysis of single‐cell transcriptomics algorithm. Gene Ontology enrichment analysis of differentially expressed genes in cardiomyocytes across species revealed alterations in genes involved in muscle development, muscle contraction, muscle hypertrophy, regulation of sarcoplasmic calcium release, ATP metabolic process, and oxidative phosphorylation.

Conclusions

These common biological processes across species are consistent with known phenotypic aspects of HCM such as hypertrophy, hypercontractility, diastolic dysfunction, and altered energy metabolism. Surprisingly, among conserved biological processes within cardiomyocytes across species, the individual genes driving the biological processes were distinct. This work to identify common and species‐specific disease‐promoting pathway differences will allow development of targeted therapies for both human and veterinary application and will facilitate an understanding of the idiosyncrasies of mouse models.
Mechanical Circulatory Support for Massive Pulmonary Embolism
Authors: Abdulaziz Salman , Kakar Vivek , Kumar Praveen G. , Hassan Ibrahim Fawzy , Combes Alain , Brodie Daniel , Barrett Nicholas A. , Tan Jack , Al Ali Saleh Fares
Published: December 2024

Up to 50% of patients with pulmonary embolism (PE) experience hemodynamic instability and approximately 70% of patients who die of PE experience an accelerated cascade of symptoms within the first hours of onset of symptoms, thus necessitating rapid evaluation and intervention. Venoarterial extracorporeal membrane oxygenation and other ventricular assist devices, depending on the hemodynamic derangements present, may be used to stabilize patients with massive PE refractory to initial therapies or with contraindications to other interventions. Given the abnormalities in both pulmonary circulation and gas exchange caused by massive PE, venoarterial extracorporeal membrane oxygenation may be considered the preferred form of mechanical circulatory support for most patients. Venoarterial extracorporeal membrane oxygenation unloads the right ventricle and improves oxygenation, which may not only help buy time until definitive treatment but may also reduce myocardial ischemia and myocardial dysfunction. This review summarizes the available clinical data on the use of mechanical circulatory support, especially venoarterial extracorporeal membrane oxygenation, in the treatment of patients with massive PE. Furthermore, this review also provides practical guidance on the implementation of this strategy in clinical practice.
Prognostic Implication of Computational Angiography–Derived Fractional Flow Reserve in Patients With Nonobstructive Coronary Artery Disease
Authors: Hung Yik‐Ming , Xuan Hao‐Chen , Ren Qing‐Wen , Huang Jia‐Yi , Yu Si‐Yeung , Tse Yi‐Kei , Zhang Jing‐Nan , Gu Wen‐Li , Guo Ran , Leung Calvin Ka‐Lam , Yiu Kai‐Hang
Published: December 2024

Background

Risk stratification of patients with symptomatic nonobstructive coronary artery disease remains uncertain. Our study assessed the clinical value of single‐vessel, multivessel, and 3‐vessel computational angiography–derived fractional flow reserve (caFFR) measurement in patients with nonobstructive coronary artery disease.

Methods and Results

We enrolled patients with ≤50% stenosis with a caFFR value ≥0.8 in all 3 coronary arteries on coronary angiography. The sum of caFFR values in the 3 vessels was computed for each patient. Patient stratification was based on the median value of the following criteria: single‐vessel analysis, multivessel analysis, and 3‐vessel analysis. The primary end point of this study was major adverse cardiac events at 5 years, defined as a composite of cardiac death, myocardial infarction, and ischemia‐driven revascularization. A total of 490 patients were included. The 5‐year major adverse cardiac event rates in single‐vessel analysis were statistically insignificant between low‐ and high‐caFFR groups (left anterior descending artery [
P
=0.163]; left circumflex artery [
P
=0.797]; right coronary artery [
P
=0.127]). In multivessel analysis, patients in the multiple‐vessel low‐caFFR group (with 2–3 vessels lower than median value of all coronary arteries) showed an increased risk of 5‐year major adverse cardiac events compared with patients in the single‐vessel low‐caFFR group (0–1 vessel) (hazard ratio [HR], 2.648 [95% CI, 1.141–6.145];
P
=0.023). In 3‐vessel analysis, patients in the low 3‐vessel caFFR group demonstrated a greater 5‐year major adverse cardiac event risk than the high 3‐vessel caFFR group (HR, 2.43 [95% CI, 1.087–5.433];
P
=0.031).

Conclusions

We demonstrated that both multiple‐vessel and 3‐vessel caFFR measurements serve as valuable prognostic indicators for risk assessment in patients with nonobstructive coronary artery disease.
Predictors of Early Death in Patients With Wild‐Type Transthyretin Cardiac Amyloidosis
Authors: Milani Paolo , Sanna Giuseppe Damiano , Mussinelli Roberta , Basset Marco , Guida Gianluigi , Attanasio Andrea , Nanci Martina , Fabris Francesca , Bellofiore Claudia , Fogliani Alessandro , Novello Elisa , Benigna Francesca , Obici Laura , Benvenuti Pietro , Ciardo Martina , Nuvolone Mario , Averaimo Manuela , Casu Gavino , Foli Andrea , Perlini Stefano , Merlini Giampaolo , Palladini Giovanni
Published: December 2024

Background

For the time being, tafamidis is the only approved treatment for wild‐type transthyretin cardiac amyloidosis. However, benefits on all‐cause death only emerge after ≈18 months. The current available staging systems are unable to specifically discriminate patients at high risk of death within 18 months from diagnosis, and the selection of patients who are expected to benefit from tafamidis is left to the clinical judgment of treating physicians, being often based primarily (and sometimes only) on age. We searched baseline variables able to discriminate patients at risk of death within 18 months.

Methods and Results

We randomly divided our prospectively maintained database in 2 cohorts, a testing (two thirds) and a validating (one third) set, respectively. We used the Eastern Cooperative Oncology Group–Performance Status as a simple scoring of frailty. We analyzed the clinical, laboratory and instrumental features of 691 consecutive wild‐type transthyretin cardiac amyloidosis patients diagnosed between 2006 and 2021. Median follow‐up was 43 months, and 367 patients (53%) died. Eighteen‐month death was predicted by NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; cutoff 4200 ng/L), cardiac troponin I (cutoff 92 ng/L), and age (cutoff 80 years). At multivariable analysis, Eastern Cooperative Oncology Group–Performance Status >1 along with the selected variables were independent prognostic determinants and outperformed New York Heart Association functional class. The combination of these variables identified standard‐ and high‐risk patients (all variables above the cutoffs) with a median survival of 57 and 17 months, respectively (
P
<0.001). This was confirmed in the validation set.

Conclusions

A simple scoring system including age, cardiac biomarkers, and Eastern Cooperative Oncology Group–Performance Status identifies subjects with cardiac wild‐type transthyretin cardiac amyloidosis at high risk of early death.
Multiparametric Assessment of Right Ventricular Dysfunction in Heart Failure: An Analysis From PARAGON‐HF
Authors: Lu Henri , Inciardi Riccardo M. , Abanda Martin , Shah Amil M. , Cikes Maja , Claggett Brian L. , Prasad Narayana , Lam Carolyn S. P. , Redfield Margaret , McMurray John J. V. , Pfeffer Marc A. , Solomon Scott D. , Hegde Sheila M. , Skali Hicham
Published: December 2024

Background

This study aims to characterize right ventricular dysfunction (RVD) in heart failure (HF) with preserved ejection fraction and understand the cumulative prognostic value of abnormal RV echocardiographic parameters in HF with preserved ejection fraction.

Methods and Results

Data from 809 patients in the PARAGON‐HF (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin‐Receptor Blocker Global Outcomes in HF With Preserved Ejection Fraction) echocardiographic substudy (55% women, mean age 74±8 years) were analyzed. Correlates of RVD (defined as tricuspid annular plane systolic excursion <1.7 cm, fractional area change <35% or absolute RV free wall longitudinal strain <20%) were identified using multivariable logistic regression models. We further assessed the prognostic value of the number of abnormal RV parameters (0, 1, ≥2) on total HF hospitalizations (HFH) and cardiovascular death, total HFH, first HFH or cardiovascular death, all‐cause death, and cardiovascular death. RVD was identified in 461 (57%) patients. Correlates of RVD included older age, higher heart rate, atrial fibrillation/flutter, greater left ventricle wall thickness, higher N‐terminal pro‐B‐type natriuretic peptide levels, lower systolic blood pressure, and lower left ventricle absolute global longitudinal strain. These results were consistent across sexes, except atrial fibrillation/flutter and LV wall thickness, which were associated with a higher risk of RVD in men but not in women. Participants with ≥2 abnormal RV parameters had a significantly higher adjusted risk of total HFH and cardiovascular death (rate ratio, 2.13 [95% CI, 1.13–4.01]), first HFH or cardiovascular death, all‐cause death, and cardiovascular death. Conversely, an isolated abnormal RV parameter was not associated with a worse outcome.

Conclusions

RV measures may underestimate the burden of RVD in HF with preserved ejection fraction when considered in isolation. Clinicians should consider multiple dimensions to comprehensively assess RV function in patients with HF with preserved ejection fraction.
Cardiovascular and Metabolic Effects of Modulating Circulating Ketone Bodies With 1,3‐Butanediol in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Guldbrandsen Halvor , Gopalasingam Nigopan , Christensen Kristian Hylleberg , Hørsdal Oskar Kjærgaard , Nielsen Roni , Wiggers Henrik , Berg‐Hansen Kristoffer
Published: December 2024

Background

Oral treatment with the exogenous ketone body 3‐hydroxybutyrate improves cardiac function in patients with heart failure with reduced ejection fraction, but ketosis is limited to 3 to 4 hours. Treatment with (R)‐1,3‐butanediol (BD) provides prolonged ketosis in healthy controls, but the hemodynamic and metabolic profile is unexplored in patients with heart failure with reduced ejection fraction.

Methods and Results

This was a randomized, single‐blind, placebo‐controlled, crossover study. Transthoracic echocardiography and venous blood samples were performed at baseline and hourly for 6 hours after an oral dose of BD (0.5 g/kg) or taste‐matched placebo. The primary end point was the average between‐treatment difference in cardiac output during the 6‐hour period after intake. Secondary end points were stroke volume, heart rate, left ventricular ejection fraction, circulating 3‐hydroxybutyrate, and free fatty acids. Twelve patients with heart failure with reduced ejection fraction were included. BD treatment provided significant increase in circulating 3‐hydroxybutyrate by 1400 μmol/L (95% CI, 1262–1538 μmol/L,
P
<0.001) and increased cardiac output by 0.9 L/min (95% CI, 0.7–1.1 L/min,
P
<0.001) compared with placebo. Stroke volume increased by 15 mL (95% CI, 11–19 mL,
P
<0.001), and heart rate remained similar between treatments (
P
=0.150). Left ventricular ejection fraction increased by 3 percentage points (95% CI, 1–4 percentage points,
P
<0.001). Global longitudinal strain improved (
P
<0.001). Left ventricular contractility estimates increased after BD intake, and parameters of afterload were reduced. Finally, free fatty acids and glucose levels decreased.

Conclusions

Oral dosing of BD led to prolonged ketosis and cardiovascular and metabolic benefits in patients with heart failure with reduced ejection fraction. Treatment with BD is an attractive option to achieve beneficial effects from sustained therapeutic ketosis.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT05768100.
Thrombosis, Translational Medicine, and Biomarker Research: Moving the Needle
Authors: Shaw Joseph R. , Nopp Stephan , Stavik Benedicte , Youkhana Kimberley , Michels Alison L. , Kennes Soetkin , Rak Janusz , ten Cate Hugo
Published: December 2024

Arterial and venous thromboembolism are leading causes of morbidity and death worldwide. Despite significant advances in the diagnosis, prognostication, and treatment of thrombotic diseases over the past 3 decades, the adoption of findings stemming from translational biomarker research in clinical practice remains limited. Biomarkers provide an opportunity to enhance our understanding of pathophysiological processes and optimize treatment strategies. They hold the promise of revolutionizing patient care. Still, this potential remains untapped, and several factors impede their use for near‐patient applications. We sought to provide an overview of biomarker research in arterial and venous thromboembolic disease. We then aimed to discuss key barriers to the broader clinical implementation of biomarker research and highlight promising strategies to overcome them. We emphasize the merits of translational and implementation science to bridge the gaps from bench to bedside. Innovative trial design, data sharing, and collaborative efforts between academia and industry will be essential. Purposeful regression methodology using rational conceptual framework design, causal mediation analysis, and artificial intelligence might better leverage the use of observational data. Dedicated translational science training programs geared toward educating physicians on the appropriate measurement, interpretation, and integration of biomarker data in clinical practice should foster endorsement by frontline physicians. Finally, we make the case in support of a paradigm shift in cardiovascular medicine. Improved recognition of biomarker research and a greater emphasis on mechanistic evidence can better equip clinicians to deal with the uncertainty that defines the practice of thrombosis medicine.
Immunometabolism in the Aging Heart
Authors: Mapuskar Kranti A. , London Barry , Zacharias Zeb R. , Houtman Jon C.D. , Allen Bryan G.
Published: December 2024

Structural, functional, and molecular‐level changes in the aging heart are influenced by a dynamic interplay between immune signaling and cellular metabolism that is referred to as immunometabolism. This review explores the crosstalk between cellular metabolic pathways including glycolysis, oxidative phosphorylation, fatty acid metabolism, and the immune processes that govern cardiac aging. With a rapidly aging population that coincides with increased cardiovascular risk and cancer incidence rates, understanding the immunometabolic underpinnings of cardiac aging provides a foundation for identifying therapeutic targets to mitigate cardiac dysfunction. Aging alters the immune environment of the heart by concomitantly driving the changes in immune cell metabolism, mitochondrial dysfunction, and redox signaling. Shifts in these metabolic pathways exacerbate inflammation and impair tissue repair, creating a vicious cycle that accelerates cardiac functional decline. Treatment with cancer therapy further complicates this landscape, as aging‐associated immunometabolic disruptions augment the susceptibility to cardiotoxicity. The current review highlights therapeutic strategies that target the immunometabolic axis to alleviate cardiac aging pathologies. Interventions include modulating metabolic intermediates, improving mitochondrial function, and leveraging immune signaling pathways to restore cardiac health. Advances in immunometabolism thus hold significant potential for translating preclinical findings into therapies that improve the quality of life for the aging population and underscore the need for approaches that address the immunometabolic mechanisms of cardiac aging, providing a framework for future research.
Mathematical Modelling of Multiphase Hybrid Gyro-tactic Nanofluid Flow Through Porous Convergent Pipe with Injection and Suction Using BVP4c
Authors: David Chepkonga , Kinyanjui Mathew , Kiogora Roy , Giterere Kang’ethe
Published: December 2024

This research focuses on enhancing fluid mobility by optimizing heat transfer, a crucial aspect in various industrial applications, including oil recovery. The study introduces an innovative framework that integrates microorganisms, hybrid nanoparticles, non-Newtonian fluid properties, a power law model, and inclined magnetic fields. The underlying dynamics are described by nonlinear partial differential equations, which are converted to ordinary differential equations using similarity transformation and subsequently solved through the BVP4c method. Key results demonstrate that fluid velocity increases with higher Reynolds, Hartman, Thermal Grashof, and Mass Grashof numbers due to factors such as reduced viscous drag, the Lorentz force’s acceleration effect, and enhanced buoyancy. On the other hand, a higher Prandtl number slightly reduces velocity, while an increased Schmidt number raises it by steepening the velocity gradient. Regarding temperature, higher Reynolds and Prandtl numbers, along with increased Eckert and Radiation parameters, result in elevated fluid temperatures due to enhanced convective heat transfer, decreased thermal diffusivity, viscous dissipation, and radiative heat effects. The insights gained from this study are valuable for improving oil extraction efficiency by identifying and manipulating key parameters that affect fluid behavior.