bluuebunny/crossref_metadata_2025 huggingface dataset:
Collaborative global learning within an integrated STEM professional development using children's literature
Authors: Asim Sumreen , Haines Sarah , Wieselmann Jeanna , Menon Deepika
Published: January 2025

Elementary‐level teachers often express the need for assistance and support in teaching integrated science, technology, engineering, and mathematics (STEM) lessons. Many lack content knowledge in these disciplines, and many also report a lack of adequate opportunities to teach these subjects during their preservice programs or their in‐service careers. We addressed this need by offering online professional development (PD) opportunities in integrated STEM, using model lessons that are anchored in the BSCS 5E instructional model, also known as the learning cycle. Our broader goal is to establish a professional learning community for both preservice and in‐service elementary teachers focused on integrated STEM education. We based our design and implementation of an engineering‐focused PD sequence on research literature, integrating STEM content areas and emphasizing key factors for maximizing impact, such as active learning, content focus, coherence, duration, and participant engagement. In this article, we outline the structure and describe the activities we conducted over the summer, which included elements of collaboration, interaction, and reflection. Our team also chose to incorporate picture books featuring international STEM role models, like Zaha Hadid, in the book titled The World is not a Rectangle: A Portrait of Architect Zaha Hadid by Jeannette Winter. The insights gained from this iteration of the PD will inform the planning of future online PD offerings for elementary teachers.
Mean relative error and standard relative deviation
Authors: Chatfield Mark D. , Marquart‐Wilson Louise , Dobson Annette J. , Farewell Daniel M.
Published: January 2025

Statistics on the natural log scale, such as differences, regression coefficients, and standard deviations, frequently arise when analyzing log‐transformed data or modeling binary, count, or time‐to‐event data. The statistical properties of log‐transformed estimators (for example, log odds ratio estimators) frequently appear in statistical articles. Understanding the magnitude of these quantities can be useful. Remarkably, many can be readily interpreted, without exponentiation. In this note, we introduce four new interpretations. While a log‐scale standard deviation can be interpreted as an approximate coefficient of variation describing variation about an arithmetic mean, we argue it can be more useful to interpret it exactly as a “standard relative deviation” describing variation about a geometric mean. For positive‐valued estimators, we show how the standard error of a log‐transformed estimator can be interpreted as the “standard relative error” describing the precision of the untransformed estimator. We also show how the bias and root mean squared error of a the log‐transformed estimator can be interpreted as the “mean relative error” and “root mean squared relative error” of the untransformed estimator. We illustrate the usefulness of our interpretations for (i) the usual scale parameter of a lognormal distribution, (ii) statistical properties of a log odds ratio estimator, and (iii) a single measure of the precision of an odds ratio estimator which agrees with its usual, asymmetric 95% confidence interval.
Physiological rhythms and metabolic regulation: Shining light on skeletal muscle
Authors: Betts James A. , Bowden Davies Kelly A. , Smith Harry A. , Hawley John A.
Published: January 2025

Metabolic regulation is essential for maintaining homeostasis in response to fluctuating dietary nutrient availability. In this review, we explore how metabolic health can be affected by the temporal alignment between daily behavioural patterns (e.g., eating, physical activity and sleep) and recurring cycles in underlying physiology (e.g., ‘circadian’ rhythms). Misalignment within and/or between these patterns and cycles can lead to metabolic dysregulation, increasing the risk of chronic disease states such as obesity, type 2 diabetes and cardiovascular disease. Conversely, metabolic health can be improved by strategically aligning certain behavioural patterns with endogenous rhythms in physiology. Dietary interventions based upon this reasoning are referred to as chrono‐nutrition strategies. Skeletal muscle is an important tissue in relation to both whole‐body metabolism and behaviour and plays a central role in how physiological rhythms respond to the timing of nutrient delivery/availability. Few studies have examined rhythms in metabolism within human skeletal muscle, providing opportunities to advance current understanding of how nutrient timing affects muscle metabolism.
Cardiac muscle contracts more efficiently at lower contraction frequencies
Authors: Pham Toan , Taberner Andrew J. , Han June‐Chiew
Published: January 2025

This study investigated how contraction frequency impacts the mechano‐energetics of cardiac muscle performing mechanical work. Left‐ventricular trabeculae were isolated from rat hearts and mounted in our work‐loop calorimeter to assess their function at physiological temperature (37°C) across three stimulation frequencies, 2 Hz, 3.5 Hz and 5 Hz, in a randomised sequence. Each trabecula was subjected to two experimental protocols: work‐loop contractions under a range of afterloads and isometric contractions under a range of muscle lengths. Two contraction protocols allowed the partition of the various components of energy expenditure during cardiac contraction. By simultaneously measuring force–length work and heat output, mechanical efficiency was calculated over a range of afterloads to determine the peak value. Our findings revealed that force production, activation heat (energy associated with Ca2+ cycling) and cross‐bridge heat were unaffected by stimulation frequency. Trabeculae produced greater work output per twitch at 2 Hz and 3.5 Hz than at 5 Hz. Positive correlations among work output, shortening extent and mechanical efficiency were detected. From these findings it was concluded that the higher work output at lower frequencies is associated with greater extent of shortening, which correlates to greater mechanical efficiency. This study highlights the mechano‐energetic advantage of ventricular trabeculae in terms of increased work output and energy efficiency gained from operating at lower contraction frequencies, supporting the notion that heart rate reduction produces direct benefits on cardiac energetics.
‘Muscular wisdom’ revisited: Decaying rates of stimulation mitigate torque loss
Authors: Dudani Raaj A. , Zero Alexander M. , Rice Charles L.
Published: January 2025

During a sustained high‐intensity isometric maximal voluntary contraction (MVC), declining motor unit firing rates (MUFRs) accompany torque loss. This decline (∼50% over 60 s) helps to maintain torque by preserving peripheral electrical propagation and matching the slowing contractile properties with torque loss (i.e., ‘muscular wisdom’). However, it has been suggested that reduced MUFRs contribute to torque loss. Here, we compared torque loss between constant and decaying rates of electrical stimulation to mimic MUFRs reported during MVCs. The dorsiflexors of 8 males and 5 females (21–30 years) underwent three 60 s muscle fatiguing conditions: (1) sustained MVC; (2) constant high‐frequency electrical stimulation (40 Hz); and (3) exponentially decaying stimulation rate (from 40 to 20 Hz). The decaying rate demonstrated less torque loss compared with the sustained high‐frequency stimulation and the MVC conditions (P < 0.01). Furthermore, torque increased (by ∼17%, P < 0.005) when the constant high‐frequency condition was switched to 20 Hz for 2 s at task termination. Conversely, torque loss was accelerated when the decaying stimulation rate was switched from 20 to 40 Hz for 2 s at task termination (by ∼16%, P < 0.001). Following all conditions, evoked twitch responses slowed (by 29%–77%, P < 0.01) but M‐wave amplitude was reduced only for the constant high‐frequency condition (by ∼23%, P < 0.01). Thus, the reduction in stimulation rates maintained optimal activation by matching the fatigue‐induced contractile slowing in combination with preserved peripheral electrical conductance. Therefore, reducing the activation rate preserves torque, rather than contributing to torque loss during high‐intensity contractions, thereby supporting the muscle wisdom hypothesis.
Exergetic Efficiency of Reverse Osmosis Desalination Systems: Definitions and Discussions
Authors: Wang Yongqing , Morosuk Tatiana , Cao Wensheng
Published: January 2025

Reverse osmosis (RO) desalination is the dominant desalination technology worldwide. The exergetic efficiency—which is recognized as a true measure from a thermodynamic viewpoint—of RO systems has been addressed by many researchers, but the inconsistencies in existing definitions prevent not only objective evaluation of the exergetic performance of an individual RO system, but also a logical comparison of the results among different systems and studies. Strictly following the thermodynamic and exergoeconomic principles, this study presents general and consistent definitions of exergetic efficiency for RO systems, aiming to promote uniformity in this important criterion. Considering the purpose and parametric features of RO systems, total exergy is decomposed into chemical and physical (mechanical plus thermal) exergies. The exergetic efficiencies of over 50 cases are calculated, and the results from different relationships and studies are compared and discussed. For the first time, the exergetic efficiency of thermally-enhanced RO systems is discussed, and the influence of thermal exergy consumption and the thermal exergy increments of permeate and brine is analyzed. Furthermore, the reasons behind the significant deviations in the results of some studies are revealed, and the defects or even mistakes in some of the existing definitions are pointed out. This work clarifies the definition and improves the understanding of the exergetic efficiency of RO desalination systems.
Physical Activity Habits and Incident First-Ever Stroke in Middle-Aged Adults—A Prospective Cohort Study
Authors: Vahlberg Birgit , Ribom Eva , Wennberg Patrik , Söderberg Stefan
Published: January 2025

Background: Lifestyle affects the risk of cardiovascular events such as myocardial infarction and stroke. Several lifestyle factors, such as physical activity (PA), are modifiable, and in this study, we examined the association between leisure-time PA habits and the risk of a first-ever stroke. Methods: This prospective study included residents in Västerbotten, Sweden, who participated in the Västerbotten Intervention Programme at 40, 50, and 60 years of age. Altogether, 31,855 individuals (50.5% women, mean age: 42.6 [6.9] y at baseline) participated between 1989 and 2016. Leisure-time PA was categorized as irregular (never/now and then) or regular (once a week/2 or 3 times a week/more than 3 times a week). Changes in PA were compared between examinations (10 y apart). Cases of stroke were validated according to World Health Organization MONICA (Monitoring Trends and Determinants of Cardiovascular Disease) criteria. The risk related to changes in leisure-time PA was estimated using a multivariable Cox regression model. Results: During an average follow-up of 9.8 years (4.4), 609 incident first-ever stroke cases occurred (1.9%). A multivariable model showed that, compared with individuals with irregular PA at both examinations, those reporting regular PA over time had a lower risk of stroke (hazard ratio: 0.78, 95% CI, 0.61–0.99). Conclusion: Middle-aged adults who maintained regular PA during their leisure time over 10 years had a lower risk of a first-ever stroke. This association is probably partly mediated by lower body mass index and a reduced risk of hypertension and diabetes.
The time course and organization of hippocampal replay
Authors: Mallory Caitlin S. , Widloski John , Foster David J.
Published: January 2025

The mechanisms by which the brain replays neural activity sequences remain unknown. Recording from large ensembles of hippocampal place cells in freely behaving rats, we observed that replay content is strictly organized over multiple timescales and governed by self-avoidance. After movement cessation, replays avoided the animal’s previous path for 3 seconds. Chains of replays avoided self-repetition over a shorter timescale. We used a continuous attractor model of neural activity to demonstrate that neuronal fatigue both generates replay sequences and produces self-avoidance over the observed timescales. In addition, replay of past experience became predominant later into the stopping period, in a manner requiring cortical input. These results indicate a mechanism for replay generation that unexpectedly constrains which sequences can be produced across time.
A yeast-based reverse genetics system to generate HCoV-OC43 reporter viruses encoding an eighth subgenomic RNA
Authors: Duguay Brett A. , Tooley Trinity H. , Pringle Eric S. , Rohde John R. , McCormick Craig
Published: January 2025

Coronaviruses have large, positive-sense single-stranded RNA genomes that challenge conventional strategies for mutagenesis. Yeast genetics has been used to manipulate large viral genomes, including those of herpesviruses and coronaviruses. This method, known as transformation-associated recombination (TAR), involves assembling complete viral genomes from dsDNA copies of viral genome fragments via homologous recombination in
Saccharomyces cerevisiae
. Here, we report our development of a TAR assembly and mutagenesis system for the endemic, seasonal human coronavirus (HCoV) strain OC43. HCoV-OC43 generally causes mild respiratory symptoms and is classified as a biosafety level 2 agent, making it useful for studying fundamental aspects of coronavirus biology and for comparative studies of more highly pathogenic betacoronaviruses. Following cDNA synthesis from HCoV-OC43 viral RNA, we generated five plasmids encompassing ~7.2 kb portions of the
ORF1ab
gene, the
NS2
to
M
segment, or the
N
gene and structured to facilitate reporter gene insertions in the
M
-to-
N
intergenic region. Using these plasmids, we completed independent assemblies of yeast centromeric plasmids encoding
ORF1ab
,
NS2a
to
N
, as well as full-length HCoV-OC43 plasmids. A wild-type virus (OC43
YA
), as well as mClover3-H2B (OC43-mClo
YA
), mRuby3-H2B (OC43-mRuby
YA
), and mCardinal (OC43-mCard
YA
) reporter viruses, were rescued. The OC43-mClo
YA
reporter virus replicated comparably to an OC43 reference strain and produced the mClover3-H2B protein from a novel subgenomic RNA through insertion of an eighth body transcription regulatory sequence, preventing the need to delete or mutate viral genes. This updated HCoV-OC43 reverse genetics system will contribute to a better understanding of betacoronavirus host-pathogen interactions and can accelerate studies of novel antivirals.

IMPORTANCE

Coronaviruses are ubiquitous pathogens that infect humans resulting in both mild and severe respiratory infections. Human coronavirus strain OC43 (HCoV-OC43) is one of many viruses responsible for common colds and is a useful model of more severe coronavirus infections. In this study, we describe an updated HCoV-OC43 mutagenesis system that uses yeast to capture six DNA fragments of the viral RNA genome and assemble them into full-length genomes in yeast/bacterial plasmids. The design of this system allowed for the rapid assembly and rescue of functional HCoV-OC43 viruses, including fluorescent reporter viruses with expanded genetic capacity. This updated reverse genetics system will enhance our ability to monitor viral replication, through building new reporter viruses, while also enhancing the study of betacoronavirus biology through the generation of mutant HCoV-OC43 viruses.
Severe pulmonary arterial hypertension and cardiogenic shock in acute systemic lupus erythematosus
Authors: Chi Elina , Chandrasekara Sahan , Keating Dominic T
Published: January 2025

We describe a woman in her late 20s with newly diagnosed systemic lupus erythematosus (SLE), who presented with fulminant pulmonary arterial hypertension (PAH) requiring inotropic and extracorporeal support. She was established on triple pulmonary vasodilator therapy with concurrent aggressive immunosuppression; however, treatment was complicated by infection and diffuse alveolar haemorrhage, necessitating delays in immunosuppression and withdrawal of epoprostenol. Despite this, with ongoing suppression of her SLE, her pulmonary haemodynamics improved, with normal pressures on right heart catheterisation several months later allowing stepdown to sildenafil monotherapy. Though long-term outcomes in patients with SLE-related PAH (SLE-PAH) remain unclear, this case highlights the importance of immunosuppression in the treatment of this cohort, with the potential for weaning pulmonary vasodilator therapy, provided that adequate control of the underlying autoimmune process is maintained.
Measurements of turbulence characteristics in a warped transition
Authors: Alkayed M. , Li S. Samuel , Lak B.
Published: January 2025

Transitions are needed to connect open-channel sections of different shapes and sizes that commonly exist in water supply channels, hydropower channels, irrigation canals and so on. A warped transition (WT) smoothly connects a rectangular channel-section with a trapezoidal one and is considered the most efficient transition type with the least flow separation. This paper aims to experimentally investigate the turbulence characteristics in the WT. It reports acoustic Doppler velocimetry measurements of fluctuations in turbulence intensity, kinetic energy and shear stress, as well as of the stationary flow field. The fluctuations are significant and entirely result from the influence of the transition. In the transition, the turbulence features a small jet-like core and reversed flows along one sidewall outside this core; even laterally averaged velocities have complicated vertical structures. This paper contributes to new benchmark turbulence conditions, useful for assessing the effectiveness of turbulence control devices and validating numerical models of turbulent flow.
Role of Traditional Chinese Medicine in Lung Cancer Management: A Review
Authors: Rao Zhijing , Wang Zhongqi , Deng Haibin , Su Wan , Huang Xiaowei , Xu Zhenye
Published: January 2025

With the continuous advancements in modern medicine, significant progress has been made in the treatment of lung cancer. Current standard treatments, such as surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, have notably improved patient survival. However, the adverse effects associated with these therapies limit their use and impact the overall treatment process. Traditional Chinese medicine (TCM) has shown holistic, multi-target, and multi-level therapeutic effects. Numerous studies have highlighted the importance of TCM’s role in the comprehensive management of lung cancer, demonstrating its benefits in inhibiting tumor growth, reducing complications, mitigating side effects, and enhancing the efficacy of conventional treatments. Here, we review the main mechanisms of TCM in combating lung cancer, inducing cancer cell cycle arrest and apoptosis. These include inhibiting lung cancer cell growth and proliferation, inhibiting cancer cell invasion and metastasis, suppressing angiogenesis and epithelial–mesenchymal transition (EMT), and modulating antitumor inflammatory responses and immune evasion. This paper aims to summarize recent advancements in the application of TCM for lung cancer, emphasizing its unique advantages and distinctive features. In promoting the benefits of TCM, we seek to provide valuable insights for the integrated treatment of lung cancer.
The Pharmacology and Toxicology of Ginkgolic Acids: Secondary Metabolites from Ginkgo biloba
Authors: Shao Yuting , Chen Yun , Zhu Qingyu , Yi Lingyan , Ma Yifan , Zang Xiangxu , Yao Wenjuan
Published: January 2025

Ginkgolic acids (GAs) are distinctive secondary metabolites of Ginkgo biloba (G. biloba) primarily found in its leaves and seeds, with the highest concentration located in the exotesta. GAs are classified as long-chain phenolic compounds, and exhibit structural similarities to lignoceric acid. Their structural diversity arises from variations in the length of side chains and their number of double bonds, resulting in six distinct forms within G. biloba extracts (GBE). Of these, GA (C15:1) is the most prevalent. As inhibitors of SUMOylation, GAs demonstrate significant antitumor activity, and can exert antineoplastic effects through multiple pathways, which positions them as potentially promising therapeutic agents for cancer treatment. Additionally, GAs exhibit notable anti-inflammatory, antibacterial, and antiviral properties, highlighting their multifaceted medicinal potential. Although the pharmacological properties of GAs have been extensively investigated, the associated risks of liver and kidney damage must not be overlooked. GAs can induce significant hepatic damage by promoting cellular apoptosis, oxidative stress, and the disruption of various metabolic processes. Furthermore, a limited number of studies have indicated that GAs may exhibit nephrotoxicity, as well as adverse effects on the skin and nervous system. Due to their recognized toxicity, the concentration of GAs is typically regulated to within 5[Formula: see text]ppm in the standardized G. biloba leaf extract EGb 761. Currently, there is no definitive evidence supporting the mutagenic toxicity of GAs. This review primarily synthesizes recent advancements in understanding the pharmacological and toxicological effects of GAs, along with their underlying mechanisms. It is anticipated that this review will stimulate scholarly discourse and elicit valuable insights.
Advances in Pharmacological Research on Icaritin: A Comprehensive Review
Authors: Guo Ran , Yan Zhiping , Wang Rui , Guo Tongxuan , Li Hao , Kong Minyu , Guo Wenzhi
Published: January 2025

Epimedium has been widely used in traditional Chinese medicine for several thousands of years. This plant is known for tonifying kidney Yang, strengthening muscles and bones, and dispelling wind and dampness. It is worth noting that icaritin, a prenylated flavonoid isolated from Epimedium, has received increasing attention in recent years due to its wide range of pharmacological activities. Icaritin exhibits significant therapeutic potential against various diseases, such as osteoporosis, tumors (hepatocellular carcinoma, stomach cancer, breast cancer, and glioblastoma), cerebral ischemia skin injury, thrombocytopenia, and systemic lupus erythematosus. We review the pharmacological activities of icaritin and its potential molecular mechanisms for the treatment of related diseases. The data suggest that icaritin can have the pharmacological effects of mediating Wnt/[Formula: see text]-catenin, IL-6/JAK2/STAT3, AMPK/mTOR, PTEN/AKT, MAPK, NF-[Formula: see text]B, and other signaling pathways. This paper also discusses the progress of clinical trials of icaritin. Icaritin was approved by the State Food and Drug Administration in January 2022 for the treatment of advanced HCC, and has various clinical drug prospects. Although it has some disadvantages, including poor solubility, and low bioavailability, icaritin is still a prospective candidate for the development of naturally derived drugs, especially in the treatment of tumors and inflammatory diseases. This review aims to update and deepen the understanding of icaritin, and provide a theoretical basis for its further study.
Dynamical Analysis and Chaos Control of Yaw Motion for Very Large Ships in Regular Longitudinal Waves
Authors: Su Zuojing , Zhang Xianku , Guan Wei
Published: January 2025

For the purpose of interpreting and controlling the irregular yaw motion of very large ships in waves, both analytical and numerical methods are employed in this study. A nonlinear dynamic model considering the behaviors of the human navigator for the yawing system of the ships in regular longitudinal waves is constructed and analyzed based on the bifurcation and chaos theory. The results of analysis indicate the existence of chaotic regions for the system, interpreting the irregular yaw motion of very large ships. Furthermore, to mitigate the chaotic yaw phenomenon of the subject ship, a concise robust integrator backstepping algorithm, incorporating the close-loop gain shaping algorithm is proposed based on the nonlinear dynamic model. It possesses a concise form and is easily implementable in marine practice. Comparative numerical experiments are conducted to validate the effectiveness and superiority of the proposed algorithm.
Kinetic Analysis of the YbCl3 Reduction Processes on Zn Cathode in Molten Salt Electrolysis
Authors: Wang Tao , He Peidong , Wang Ji , Li Wenlong , Jiang Tianjiao , Ning Shunyan , Wei Yuezhou , Hamza Mohammed F. , Yin Xiangbiao , Han Wei , Ji Nan
Published: January 2025

Molten salt electrolysis represents an economical technique for the extraction and purification of metals while also enabling the reprocessing of spent fuel. The kinetic parameters of the electrolytic refining process are intricate and significant influence the separation of lanthanides and actinides. Here we report an investigation of the kinetics of the reduction process of Yb(III) on a cathodic Zn electrode and the influencing factors that impact the efficiency of electrolytic extraction in LiCl-KCl molten salt. The exchange current densities of Yb(II)/Ybin Zn couple on the liquid Zn electrode was measured by polarization curves, and the activation energy was calculated 18.02 kJ mol−1. Moreover, Yb was extracted on the Zn electrode from molten salt by potentiostatic electrolysis and galvanostatic electrolysis. The concentration of Yb(III) in the molten salt was measured using ICP-OES every 2 h, and the extraction efficiency and average extraction rate were calculated. The electrolysis condition with the highest extraction efficiency (98.39%) was by GE at 47.24 mA cm−2 when the electrolysis time was 10 h. The products of extraction were characterized by X-ray diffraction and scanning electron microscopy energy-dispersive spectroscopy to analyze the phase composition and microstructure of the alloy.
Noncoding RNAs in Atopic Dermatitis: Insight Into Inflammation and Immune Regulation
Authors: Zhu Lemei , Liu Yuqing , Gong Zhuo , Zhu Bohua , Zhang Chenghao , Zhang Haoqi , Liu Wei , Hui Shan , Duan Shuangni , Bing Pingping
Published: January 2025

Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting approximately 20% of children and 10% of adults. While previous studies have linked AD to allergen exposure, disruption of the skin barrier, and Type 2 immune responses, the precise pathophysiology of AD remains elusive, significantly limiting the effectiveness of current treatments. Noncoding RNAs (ncRNAs), a diverse group of transcripts that do not encode proteins and account for at least 98% of the human genome, are implicated in numerous physiological and pathological processes. A growing body of evidence underscores the pivotal role of ncRNAs in the pathogenesis and progression of AD. This review offers a detailed synthesis of the latest insights into the involvement of ncRNAs in AD, as well as their potential as diagnostic biomarkers and therapeutic targets.
Robotic Congenital Cardiac Surgery Practice Worldwide: A Systematic Review
Authors: Lee Madonna E. , Amabile Andrea , Hameed Irbaz , Antonios James , Awad Ahmed K. , Brackett Alexandria , Krane Markus , Gruber Peter J. , Geirsson Arnar
Published: January 2025

Background: With the increasing adoption of robotic technology in adult cardiac surgery patients, improved surgeon experience and wider utilization have been reported. However, interpreting trends in robotic congenital surgery is more challenging. By performing a systematic review, the authors aim to evaluate the current literature on robotic congenital operations.

Methods: The protocol was registered with PROSPERO. The inclusion and exclusion criteria were established based on the population, intervention, comparison, and outcome (PICO) framework. A comprehensive literature search was conducted from January 1998 to December 2021. Studies involving patients undergoing congenital cardiac surgery operations performed with robotic assistance were included. Two independent reviewers screened titles/abstracts and then full text of eligible studies. A third reviewer resolved any discrepancies. The Newcastle–Ottawa Scale was applied to quantify quality assessment for nonrandomized observational studies.

Results: A total of one‐hundred twenty‐eight publications underwent full‐text review, and 66 studies were included. Overwhelmingly, the majority are from single institutions and observational and retrospective studies. The population was mostly adults with only 10.6% (7/66) studies solely reporting pediatric patients. About 50% of the studies were case reports (28/66). Selective reporting of outcomes varied widely across studies. Cumulative mortality rates were 0.3%. The highest incidence of morbidities included pleural effusion (12.3%), reoperation for bleeding (10.7%), atrial fibrillation (10.7%), heart block (9.5%), and peripheral cannulation–related complications (8.6%). The overall quality of the studies was unsatisfactory, with the majority of studies receiving a score of 3 out of 9.

Conclusions: Most publications were case reports or small case series performed in adults and restricted to a few international institutions. To address these clinical challenges, technological improvements and advanced training will be mandatory before wider application to children and complex congenital diagnoses. Unfortunately, the overall quality of studies is poor, with inconsistent outcomes reporting. Improved and standardized reporting will be necessary before an appropriate evaluation of robotics in the treatment of congenital heart disease is feasible.
Successful Response to First-Line Carboplatin, Pemetrexed, and Bevacizumab for Peritoneal Mesothelioma: Two Case Reports
Authors: Koizumi Tomonobu , Kanda Shintaro , Sekiguchi Nodoka , Noguchi Takuro , Eda Sei-ichiro , Kitahara Hiroto
Published: January 2025

Introduction: Peritoneal mesothelioma is an extremely rare malignancy of the peritoneum. It has a poor prognosis, and the optimal systemic chemotherapy remains controversial. Here, we report two cases of peritoneal mesothelioma with long-term survival and complete response to carboplatin, pemetrexed, and bevacizumab chemotherapy. Case Presentation: Both patients were treated with six cycles of carboplatin (AUC 5), pemetrexed (750 mg/m2), and bevacizumab (15 mg/kg) followed by pemetrexed and bevacizumab as maintenance therapy. Partial response continued for over 6 years in case 1, and complete response was obtained in case 2. The patient in case 1 died after 7 years due to accidental pneumonia, and the patient in case 2 remained disease-free for over 2 years after initiation of chemotherapy. Conclusion: Little information is available regarding angiogenesis in malignant peritoneal mesothelioma, and carboplatin/pemetrexed/bevacizumab are off-labeled chemotherapy by Japanese healthcare system as yet. However, our experience suggested that combined chemotherapy with bevacizumab is a feasible option for systemic chemotherapy in cases of peritoneal mesothelioma.
Burden of leptospirosis in Brazil in the last decade
Authors: Linhares Gisele de Paula , Zequinao Tiago , Buso Gustavo Martini , Cruz June Alisson Westarb , Tuon Felipe Francisco
Published: January 2025

OBJECTIVES: To correlate the incidence of leptospirosis with sociodemographic data in the Brazilian Unified Health System from 2011 to 2022.METHODS: This ecological study used national health and economic secondary data sources. Secondary analyses summarized the scenario of disease-related hospitalizations among federative units. In total, two analyses were conducted: variable description for relationship analysis and a secondary analysis with population health and sanitation indicators and economic indicators from the Instituto Brasileiro de Geografia e Estatística (IBGE - Brazilian Institute of Geography and Statistics). The statistical analysis following this framework summarized raw data by year-monthfederative unit. A time series regression was conducted, comparing the time variable with other national-level variables. Then, several simple linear regressions were performed.RESULTS: Linear regressions show the relationship between the reduction in cases and improved access to treated water and sewage collection, whereas an increase in per capita income seems to be inversely related to leptospirosis incidence. Geospatial distribution shows higher incidence in the Brazilian South and Southeast. Disease lethality varied over time but without significant change during the period. The average treatment cost remained constant over the years, despite its complexity. CONCLUSION: Leptospirosis incidence in Brazil from 2011 to 2021 decreased and wasassociated with improvements in socioeconomic conditions despite no changes in lethality.
Infection‐Related Hospitalization and Incident Heart Failure: The Atherosclerosis Risk in Communities Study
Authors: Molinsky Rebecca L. , Shah Amil , Yuzefpolskaya Melana , Yu Bing , Misialek Jeffrey R. , Bohn Bruno , Vock David , MacLehose Richard , Borlaug Barry A. , Colombo Paolo C. , Ndumele Chiadi E. , Ishigami Junichi , Matsushita Kunihiro , Lutsey Pamela L. , Demmer Ryan T.
Published: January 2025

Background

The immune response to infections may become dysregulated and promote myocardial damage contributing to heart failure (HF). We examined the relationship between infection‐related hospitalization (IRH) and HF, HF with preserved ejection fraction, and HF with reduced ejection fraction.

Methods and Results

We studied 14 468 adults aged 45 to 64 years in the ARIC (Atherosclerosis Risk in Communities) Study who were HF free at visit 1 (1987–1989). IRH was identified using select
International Classification of Diseases
(
ICD
) codes in hospital discharge records and was treated as a time‐varying exposure. HF incidence was defined as the first occurrence of either a hospitalization that included an
ICD, Ninth Revision
(
ICD‐9
) discharge code of 428 (428.0–428.9) among the primary or secondary diagnoses or a death certificate with an
ICD‐9
code of 428 or an
ICD, Tenth Revision
(
ICD‐10
) code of I50 among any of the listed diagnoses or underlying causes of death. We used multivariable‐adjusted Cox proportional hazards models to assess the association between IRH and incident HF, HF with reduced ejection fraction, and HF with preserved ejection fraction. Median follow‐up time was 27 years, 55% were women, 26% were Black, mean age at baseline was 54±6 years, 46% had an IRH, and 3565 had incident HF. Hazard ratio (HR) for incident HF events among participants who had an IRH compared with those who did not was 2.35 (95% CI, 2.19–2.52). This relationship was consistent across different types of infections. Additionally, IRH was associated with both HF with reduced ejection fraction and HF with preserved ejection fraction: 1.77 (95% CI, 1.35–2.32) and 2.97 (95% CI, 2.36–3.75), respectively.

Conclusions

IRH was associated with incident HF, HF with reduced ejection fraction, and HF with preserved ejection fraction. IRH might represent a modifiable risk factor for HF pathophysiology.
Abstract 18: Relation of Migraine to Stroke Risk in Postmenopausal Women: Findings from the Women’s Health Initiative
Authors: Madsen Tracy , Raker Christina , Pavlovic Jelena , Allison Matthew , Harrington Laura , Haring Bernard , Ikramuddin Farha , Liu Longjian , Liu Simin , Manson JoAnn , Penzien Don , Saquib Nazmus , SCHNATZ PETER , Shadyab Aladdin , Stefanick Marcia , Wactawski-Wende Jean , Wild Robert , Silver Brian
Published: January 2025

Introduction:
Migraines are a known risk factor for stroke among reproductive-aged women, though the relation of migraines to stroke risk among postmenopausal women remains unclear. We assessed the association between a history of diagnosed migraine and incident stroke among postmenopausal women and investigated age differences in the association.

Methods:
We included women enrolled in the Women’s Health Initiative (WHI), a large longitudinal cohort study of postmenopausal women in the U.S. We excluded women with a history of stroke or TIA at baseline or with missing data on history of migraine or key covariates. The primary exposure was a history at baseline of self-reported migraine diagnosed by a physician. The primary outcome was incident stroke (total, ischemic [IS], or hemorrhagic [ICH]). Multivariable Cox proportional hazards models were used to test the cause-specific hazard ratios (HRs) between migraine history and total stroke, IS (overall and by subtype), and ICH, sequentially adjusted for age and traditional and female-specific risk factors. Using multivariable Cox proportional hazard models, we then quantified the association between migraine history and total stroke by age in 5-year groups at baseline.

Results:
130,277 participants were included. The median age at baseline was 61 years (IQR 56-67 years) for those with a migraine history compared to 63 years (IQR 57-69 years) for those without. Overall, 5,743 strokes occurred over a median follow-up period of 19.9 years (IQR 9.1-25). In multivariable-adjusted models (Table), there was a marginal association between migraine history and total stroke (HR=1.07; 95% CI, 0.99-1.17) and a significant association between migraine history and IS (HR=1.12; 95% CI, 1.02-1.23), most pronounced in the cardioembolic category. Migraine was not associated with risk of ICH (HR=0.85, 95%CI, 0.67-1.09). Risk appears to be of greatest magnitude in early (HR 1.26, 95% 0.93-1.72) and late (HR 1.16, 95%CI 0.89-1.50) postmenopausal years (Figure), though the differences by age group were not statistically significant.

Conclusions:
Over a 20-year follow-up period, postmenopausal women with self-reported histories of migraine had a higher risk of IS, but not total or ICH, suggesting that migraine history contributes to ischemic stroke risk during the postmenopausal years. Along with other known risk factors, migraine history should be considered in stroke risk factor screening and prevention efforts after menopause.
Abstract 28: Bihemispheric transcranial direct current stimulation did not add benefit to stance-phase gait training using virtual reality setting for chronic motor deficits after stroke
Authors: Pundik Svetlana , Skelly Margaret , Salameh Ahlam , Duncan Kelsey , Mosca Luke , Leonhardt Lisa , Hisel Terri , Hardin Elizabeth , Zink Elizabeth , McCabe Jessica
Published: January 2025

Introduction:
Chronic gait deficits after stroke are prevalent. Current therapy fails to restore normal gait for many stroke survivors. Transcranial Direct Current Stimulation (tDCS), a form of non-invasive brain stimulation, is a promising adjunct intervention that may enhance motor-learning induced neuroplasticity. tDCS is readily deployable into the clinic owing to its safety, ease of set-up, and feasibility to be paired with gait therapies. Our objective was to test whether bihemispheric tDCS would improve response to stance-phase focused gait therapy in a double-blind randomized control trial.

Methods:
44 subjects (65.2±9.8 y/o; 27.3% female; 4.5±4.2 years post-stroke) were randomized to active or sham tDCS+gait training. Ten treatment sessions consisted of 30 min of virtual-reality obstacle clearance training on a treadmill followed by 30 min of overground stance phase training. 2mA tDCS with anode over ipsilesional primary motor cortex (M1) and cathode over contralesional M1 was applied during the first 15 min of training. Individuals were assigned custom home exercises. Primary outcome was fastest gait speed with 10-meter walk test(10MWT) and secondary outcomes were preferred gait speed during 2-min walk test(2MWT), Fugl-Meyer(FM), Timed Up and Go(TUG), Functional Gait Assessment (FGA), and Gait Assessment and Intervention Tool(GAIT). Outcomes were collected at baseline, mid-treatment, post-treatment, and 6-week follow up. Statistical analyses included longitudinal linear mixed-effects models and analysis of treatment group by time interaction effects.

Results:
At baseline(mean(SD)): 10MWT=0.71(0.40) m/s, 2MWT=0.55(0.28) m/s, FM=25.0(3.7), TUG =33.2(30.6) s; FGA=12.7(4.1) points, GAIT=16.9(7.3) points. None of the longitudinal linear mixed-effects models detected a significant group by time interaction. However, there were significant improvements from baseline for all measures as follows (median(95%CI)): 10MWT(m/s) of 0.12(0.08, 0.16) post-treatment, and 0.11(0.07, 0.16) at follow-up; 2MWT(m/s) of 0.05(0.03, 0.07) and 0.05(0.02, 0.09); FM (points) of 2.5(2, 3) and 3(2.5,3.5); TUG(s) of 3.9(2.5, 5.6) and 3.3(2, 5.2); FGA(points) 3(2.5,3.5) and 3(2,3.5); GAIT(points) of 2.5(2, 3.5) and 3(2,4).

Conclusions:
Bihemispheric tDCS did not enhance improvements that were achieved by a 10-session gait training intervention targeting stance phase.
Abstract 82: Effect Of Chronic Nicotine Exposure On Long-term Outcomes Following Intracerebral Hemorrhage
Authors: Nooka Akash , Mallepalli Suresh , Nieto Juan , Tietsworth Julia , Cho Sunjoo , Rehni Ashish , Dave Kunjan
Published: January 2025

Background:
Spontaneous intracerebral hemorrhage (sICH) is a neurological condition characterized by the rupture of blood vessels within the brain, resulting in the formation of a hematoma and subsequent brain injury. Tobacco use is a major modifiable risk factor for sICH and is associated with worsened outcomes following the occurrence of sICH. Tobacco use is also correlated with worsened outcomes following sICH. Previously, we observed that prior chronic exposure to nicotine results in increased hematoma volume following collagenase-induced sICH when compared to saline-exposed animals. This study aims to evaluate the effect of prior chronic nicotine exposure on long-term outcomes post-sICH.

Hypothesis:
Prior chronic nicotine exposure will result in more significant brain damage following an autologous blood injection-induced sICH.

Methods:
Young male and female (estrous matched) rats were randomly assigned to a saline (control) or nicotine-exposed group. Rats received nicotine or saline via. osmotic pumps for 2-3 weeks. The pump was removed before the induction of sICH by the stereotaxic injection of autologous blood into the striatum. The autologous blood injection-induced sICH model was used to obtain equal hematoma volume in all experimental groups. Rats then underwent perfusion fixation, and brains were harvested for histopathological analysis. Paraffin-embedded brain blocks were cut into 10 µm coronal sections between bregma -2.0 to +2.0, stained with hematoxylin and eosin, scanned with a high-resolution scanner, and analyzed using ImageJ to measure lesion area. Student’s t-test was used to determine significant differences in mean lesion volume between treatment groups. Two-way ANOVA was used to assess the interaction effect between sex and lesion volume.

Results:
For the male group, the brain lesion volume in nicotine-exposed rats was significantly (p<0.01) larger by 121% (6.11± 0.81 mm
3
) when compared to the lesion volume in saline-exposed rats (2.77± 0.26 mm
3
). For the female group, the brain lesion volume of the nicotine group was significantly (p<0.01) larger by 62% (4.98±0.39 mm
3
) when compared to the lesion volume of the saline group (3.07± 0.53 mm
3
). Sex had no significant effect on mean lesion volume.

Conclusion:
Chronic nicotine exposure worsens long-term outcomes post-sICH in young rats of both sexes.
Abstract 98:
RNF213
Mutation Associated with the Progression from Middle Cerebral Artery Steno-occlusive Disease to Moyamoya Disease
Authors: Sasagasako Tomoki , Mineharu Yohei , Funaki Takeshi , Fushimi Yasutaka , Chihara Hideo , Park Silsu , Nakajima Kota , Kikuchi Takayuki , Okawa Masakazu , Arakawa Yoshiki
Published: January 2025

Background:
Middle cerebral artery steno-occlusive disease (MCAD) has been recognized as a different clinical entity from moyamoya disease (MMD). Although MCAD can progress to MMD, the extent to which patients actually progress and the risk factors for this progression have not been fully elucidated.

Methods:
We retrospectively reviewed patients with MCAD who underwent
RNF213
genotyping. Demographic features,
RNF213
p.R4810K mutation, medical history, and longitudinal changes in angiography were analyzed.

Results:
Sixty patients with 81 affected hemispheres were enrolled. During the follow-up period 17 patients developed MMD, and the
RNF213
p.R4810K mutation was the only factor significantly associated with progression to MMD (odds ratio, 16.1; 95% CI, 2.13–731;
P
= 0.001). The log-rank test demonstrated that patients with the mutation had a higher risk of progression to MMD (
P =
0.007), stenosis progression (
P =
0.010), and symptomatic cerebral infarction or hemorrhage (
P =
0.026). In Cox regression analysis the p.R4810K mutation remained a significant factor after adjusting for age group (childhood or adult onset) at diagnosis (hazard ratio, 8.42; 95%CI, 1.10–64.4). Hemisphere-based analysis also showed that the mutation was associated with a higher risk of progression to the MMD hemisphere (
P =
0.002), stenosis progression (
P =
0.005), and cerebral infarction or hemorrhage (
P =
0.012).

Conclusions:
The
RNF213
p.R4810K mutation was identified as a risk factor for progression from MCAD to MMD.Genotyping for this mutation may contribute to risk stratification in MCAD.
Abstract HUP17: Insufficient Demographic and Data Collection Hinders Understanding the Health Outcomes in Patients with Limited English Proficiency
Authors: Pena Shaney , Jones Ann
Published: January 2025

Background:
Stroke patients with limited English proficiency (LEP) in the United States have limited stroke recovery and reduced post-stroke neurological care.

Objective:
Identify 90-day stroke outcomes using the modified Rankin Score (mRS) for patients discharged from Methodist Hospital with LEP. The secondary objective was to identify post-stroke neurological follow-up and rehab therapies utilized by patients with LEP.

Methods:
Retrospective data collection of 1,026 charts from 2019-2022 tracking demographic findings, treatments, post-stroke neurological follow-up care, and 90-day mRS scores. Patients included in this study received either thrombolysis, thrombectomy, or both and were cared for at Methodist Hospital in Indianapolis, Indiana.

Results:
Between the years of 2019-2022, there were 2,815 ischemic stroke patients at Methodist Hospital. Of those, 1,026 underwent an acute intervention either with thrombolysis, thrombectomy, or both. There were 55 identified as LEP. Of the 55 patients, 11 (1%) received an acute treatment. All LEP patients followed discharge recommendations: six to acute rehab, four discharged home, and one patient died. Two of the 11 (18%) patients had neurological follow-up care within a year. The majority of mRS scores for LEP patients at 90-day were not captured (36%). Further, 20% of LEP patients had language preference incorrectly labeled or uncategorized. Comparatively, to English proficient patients, 315 (39%) had follow-up neurological care and 16% had uncaptured mRS scores at 90-days.

Conclusion:
The study did not show a statistical difference in 90-day mRS scores between LEP and English-proficient patients. The study was underpowered because of the small sample size. Demographic factors like language preference were not accurately captured. This study revealed no formalized protocol to document patient demographics including language or other social determinants of health. This suggests the hospital system needs to implement a formalized process to improve documentation. Additionally, there is disparate outpatient care for LEP stroke patients. To begin diversity, equity, and inclusion research medical centers need to adopt a formalized process to capture patient demographics and actively track outcomes of all patients to ensure equitable stroke care.