Search Results (5,038)

Electric vehicles (EVs) are rapidly gaining popularity due to their environmental benefits, such as reducing greenhouse gas emissions. Considering the sociodemographic factors that influence the adoption of EVs is essential when developing equitable and efficient transportation policies. This article leverages the National Household Travel Survey (NHTS) 2022 data to analyze the sociodemographic factors influencing the adoption of EVs in the U.S. A binary logistic regression model and three machine learning models were employed to predict EV ownership in the U.S. The results of the regression model suggested that the Pacific division leads in EV adoption, most likely due to legislation and improved infrastructure, while regions such as East South Central suffer from lower EV adoption. The findings indicate that higher household income and home ownership significantly correlate with increased EV adoption. In contrast, renters and rural households exhibit lower adoption rates suggesting an increase in charging facilities in these regions can promote EV adoption. The Random Forest model outperforms others with an accuracy of 82.72%, suggesting its robustness in handling complex relationships between variables. Policy implications include the need for financial incentives for low-income households and increased charging infrastructure in rural and underserved urban areas to promote equitable EV adoption. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects over 1% of population over age 60. It is defined by motor and nonmotor symptoms including a spectrum of cognitive impairments known as Parkinson’s disease dementia (PDD). Currently, the only US Food and Drug Administration-approved treatment for PDD is rivastigmine, which inhibits acetylcholinesterase and butyrylcholinesterase increasing the level of acetylcholine in the brain. Due to its limited efficacy and side effect profile, rivastigmine is often not prescribed, leaving patients with no treatment options. PD has several derangements in neurotransmitter pathways (dopaminergic neurons in the nigrostriatal pathway, kynurenine pathway (KP), acetylcholine, α7 nicotinic receptor, and N-methyl-D-aspartate (NMDA) receptors) and rivastigmine is only partially effective as it only targets one pathway. Kynurenic acid (KYNA), a metabolite of tryptophan metabolism, affects the pathophysiology of PDD in multiple ways. Both galantamine (α7 nicotinic receptor) and memantine (antagonist of the NMDA subtype of the glutamate receptor) are KYNA modulators. When used in combination, they target multiple pathways. While randomized controlled trials (RCTs) with each drug alone for PD have failed, the combination of galantamine and memantine has demonstrated a synergistic effect on cognitive enhancement in animal models. It has therapeutic potential that has not been adequately assessed, warranting future randomized controlled trials. In this review, we summarize the KYNA-centric model for PD pathophysiology and discuss how this treatment combination is promising in improving cognitive function in patients with PDD through its action on KYNA. Full article

Large language models (LLMs) have shown their capabilities in numerical and logical reasoning, yet their capabilities in higher-order cognitive tasks, particularly causal reasoning, remain less explored. Current research on LLMs in causal reasoning has focused primarily on tasks such as identifying simple cause-effect relationships, answering basic “what-if” questions, and generating plausible causal explanations. However, these models often struggle with complex causal structures, confounding variables, and distinguishing correlation from causation. This work addresses these limitations by systematically evaluating LLMs’ causal reasoning abilities across three representative scenarios, namely analyzing causation from effects, tracing effects back to causes, and assessing the impact of interventions on causal relationships. These scenarios are designed to challenge LLMs beyond simple associative reasoning and test their ability to handle more nuanced causal problems. For each scenario, we construct four paradigms and employ three types of prompt scheme, namely zero-shot prompting, few-shot prompting, and Chain-of-Thought (CoT) prompting in a set of 36 test cases. Our findings reveal that most LLMs encounter challenges in causal cognition across all prompt schemes, which underscore the need to enhance the cognitive reasoning capabilities of LLMs to better support complex causal reasoning tasks. By identifying these limitations, our study contributes to guiding future research and development efforts in improving LLMs’ higher-order reasoning abilities. Full article

Background: Individualizing transcranial direct current stimulation (tDCS) parameters can improve precision in neuropsychiatric disorders. One important decision for the clinician is the selection of an appropriate montage—conventional or high-definition (HD)—to implement dose-controlled tDCS while maintaining the patient’s safety. Method: The present study simulated tDCS administration using T1-weighted brain images of 50 dementia, 25 depression patients, and 25 healthy individuals for two conventional and HD montages, targeting the regions of interest (ROIs) in the dorsal and ventral pathways that support language processing. For each tDCS configuration, the electric fields at the ROIs and the individualized dose required to achieve the desired current intensity at the target ROI across the subjects were estimated. Linear regression was performed on these parameters. Result: A significant relationship between atrophy and current dose that varies according to the disease was found. The dementia patients with significant brain atrophy required a higher personalized dosage for HD montage, as the current intensity at the target ROIs was lower and more variable than that of conventional montage. For dementia, tDCS individualization is pathway-dependent, wherein HD configuration of the dorsal route requires current dosages above the safety limit (>4 mA) for 46% of individuals. However, there was no significant difference in electrode configurations between the HD and traditional setups for depression and healthy volunteers without significant brain atrophy. Conclusions: HD-tDCS with fixed locations is limited, making conventional tDCS more effective for dose-controlled applications. In patients with atrophy, individualized adjustments based on simulations are needed due to the variable stimulation strength in the ROI. Full article

The gut microbiome plays a critical role in maintaining gut and metabolic health, and its composition is often altered by aging and obesity. This study aimed to investigate the protective effects of curcumin on gut dysbiosis, gut barrier integrity, and bile acid homeostasis in aged mice fed a high-fat, high-sugar diet (HFHSD). Eighteen- to twenty-one-month-old male C57BL/6 mice were divided into groups fed a normal chow diet or HFHSD, with or without curcumin supplementation (0.4% w/w) for 8 and 15 weeks. We assessed body weight, food intake, insulin sensitivity, gut microbiota composition, and gene expression in the gut and liver and performed histological analysis of gut tissues. Curcumin supplementation prevented HFHSD-induced weight gain and metabolic disturbances. In the gut, curcumin-treated mice showed a higher abundance of beneficial bacterial genera, such as Lachnospiraceae, Akkermansia, Mucispirillum, and Verrucomicrobiota, alongside a lower abundance of harmful bacterial genera like Desulfobacteria, Alistipes, and Muribaculaceae compared to control. This shift in gut microbiota was associated with improved gut integrity, as demonstrated by increased expression of the tight junction protein occludin and reduced levels of the pro-inflammatory marker interleukin-1β in the ileum. Additionally, curcumin modulated hepatic gene expression involved in bile acid homeostasis, suggesting a positive effect on liver health. Curcumin supplementation can alleviate the negative effects of aging and an HFHSD on the gut microbiome, improve gut barrier integrity, and maintain bile acid homeostasis. These findings highlight curcumin’s potential as a dietary intervention for managing obesity- and age-associated gut health issues. Full article

Latinx populations in the USA have grown steadily in recent decades, with significant increases taking place in “new destination communities” of the U.S. South. The focus of our paper is to highlight opportunities for working with these populations, including traditional sociolinguistic ethnographies and community-engaged research. We highlight an initiative named “The SEC Spanish Consortium” which is an interinstitutional collaboration centered on scholarship and service involving Latinx populations in new destination communities of the U.S. South. We show that ongoing and future scholarly work in the U.S. South can act as a mechanism for documenting these emerging Latinx communities while simultaneously serving the underrepresented and minority speakers of these linguistic varieties. Full article

Epinephrine is the most common medication used in cardiac arrest. Although the medication has been a mainstay of treatment over the last century, the utility and efficacy of epinephrine has been re-evaluated in recent years. This study aims to evaluate the literature describing the efficacy, timing, and dosing of epinephrine use in cardiac arrest. We utilized an extensive PubMed and SCOPUS search that included randomized control trials, prospective observational studies, and secondary analysis of observational data. These articles evaluated the administration of epinephrine in cardiac arrest and reported patient outcomes, including survival rates, neurological function, and return of spontaneous circulation. Dosing of epinephrine has been standardized at 1 mg per administration in adults and studies show that higher doses may not have better outcomes and can potentially be harmful. Research on the optimal timing of epinephrine has shown that earlier administration of epinephrine in cardiac arrest is more likely to have improved outcomes compared to later administration and longer intervals, although there are still conflicting results on the improvement of neurological outcomes. Intravenous is the preferred route of administration for epinephrine, but new research suggests intramuscular administration may be beneficial. While epinephrine has been shown to improve the rates of return of spontaneous circulation and even survival to hospital discharge in several studies, epinephrine use may not provide patients who survive cardiac arrest with a meaningful neurological recovery. Full article

This study explores and compares the motivations behind badminton participation among older adult players from Taiwan and the United States (U.S.), with a specific focus on cultural and gender differences. A total of 139 participants aged 60 and above took part in the study, with 55 from the United States (24 females, 31 males) and 84 from Taiwan (39 females, 45 males). Utilizing the Exercise Motivations Inventory-2 (EMI-2), this research examines differences in motivations across cultural and gender lines, identifying key factors such as health-related motivations, personal achievement, social interactions, and competition. The results reveal that Taiwanese players are more motivated by health benefits and stress reduction, while U.S. players emphasize personal achievement and recognition. Additionally, gender-specific motivations emerged, with female players from both countries placing greater importance on social interactions compared to their male counterparts. These findings underscore the need for culturally and gender-sensitive approaches to promote sports participation among older adults in diverse settings. Full article

Background/Objectives: To overcome the side effects of conventional cancer treatment, multifunctional nanoparticles with image-guidance properties are increasingly desired to obtain enhanced therapeutic efficacy without any toxicity of the treatment. Herein, we introduce the potential of Polydopamine Radioimmunotherapy with Image-guided Monitoring and Enhanced (drug) Release System (PRIMERS) to meet the challenges of currently used cancer therapy. Methods: The PDA nanobowls were synthesized using an emulsion-induced interfacial anisotropic assembly method followed by surface modification with high-Z material to obtained the final product PRIMERS. Results: The engineered multifunctional nanosystem “PRIMERS” could serve as fiducial markers with the potential for use in combination cancer therapy. By leveraging the advantages of the excellent surface functionalization capability of PDA, the anisotropic nanostructure (PDA nanobowls) has been successfully functionalized with gadolinium, which shows strong MRI contrast signal both in vitro in phantom and in vivo in animals. The results of anti-cancer drug loading and releasing efficiency of these functionalized nanobowls are presented. Moreover, the gadolinium-coated PDA nanobowls demonstrate the capacity for loading immunotherapy drugs (Anti-CD40) with activated release in acidic pH levels characteristic of the tumor microenvironment, with enhanced release following administration of radiation therapy in vitro. Conclusions: Overall, the results highlight the potential of this new technology for combining radiotherapy with activated image-guided drug delivery, which offers broad opportunities to overcome current challenges in cancer treatment. Full article

Breast cancer is a heterogeneous disease comprising multiple molecularly distinct subtypes with varied prevalence, prognostics, and treatment strategies. Among them, triple-negative breast cancer, though the least prevalent, is the most aggressive subtype, with limited therapeutic options. Recent emergence of competing endogenous RNA (ceRNA) networks has highlighted how long noncoding RNAs (lncRNAs), microRNAs (miRs), and mRNA orchestrate a complex interplay meticulously modulating mRNA functionality. Focusing on TNBC, this study aimed to construct a ceRNA network using differentially expressed lncRNAs, miRs, and mRNAs. We queried the differentially expressed lncRNAs (DElncRNAs) between TNBC and luminal samples and found 389 upregulated and 386 downregulated lncRNAs, including novel transcripts in TNBC. DElncRNAs were further evaluated for their clinical, functional, and mechanistic relevance to TNBCs using the lnc2cancer 3.0 database, which presented LUCAT1 (lung cancer-associated transcript 1) as a putative node. Next, the ceRNA network (lncRNA–miRNA–mRNA) of LUCAT1 was established. Several miRNA–mRNA connections of LUCAT1 implicated in regulating stemness (LUCAT1-miR-375-Yap1, LUCAT1-miR181-5p-Wnt, LUCAT1-miR-199a-5p-ZEB1), apoptosis (LUCAT1-miR-181c-5p-Bcl2), drug efflux (LUCAT1-miR-200c-ABCB1, LRP1, MRP5, MDR1), and sheddase activities (LUCAT1-miR-493-5p-ADAM10) were identified, indicating an intricate regulatory mechanism of LUCAT1 in TNBC. Indeed, LUCAT1 silencing led to mitigated cell growth, migration, and stem-like features in TNBC. This work sheds light on the LUCAT1 ceRNA network in TNBC and implies its involvement in TNBC growth and progression. Full article

Epidemiological approaches for examining human health responses to environmental exposures in observational studies frequently address confounding by employing advanced matching techniques and statistical methods grounded in conditional likelihood. This study incorporates a recently developed Bayesian hierarchical spatiotemporal model within a conditional logistic regression framework to capture the heterogeneous effects of environmental exposures in a case-crossover (CCO) design. Spatial and temporal dependencies are modeled through random effects incorporating multivariate conditional autoregressive priors. Flexible frailty structures are introduced to explore strategies for managing temporal variables. Parameter estimation and inference are conducted using a Monte Carlo Markov chain method within a Bayesian framework. Model fit and optimal model selection are evaluated using the deviance information criterion. Simulations assess and compare model performance across various scenarios. Finally, the approach is illustrated with workers’ compensation claims data from New York and Florida to examine spatiotemporal heterogeneity in hospitalization rates related to heat prostration. Full article

Myeloproliferative neoplasms, polycythemia vera, essential thrombocytosis, and primary myelofibrosis are a unique group of clonal hematopoietic stem cell neoplasms that share somatic, gain-in-function driver mutations in JAK2, CALR, and MPL. As a consequence, these disorders exhibit similar phenotypic features, the most common of which are the ceaseless production of normal erythrocytes, myeloid cells, platelets alone or in combination, extramedullary hematopoiesis, myelofibrosis, and a potential for leukemic transformation. In the case of polycythemia vera and essential thrombocytosis, however, prolonged survival is possible. With an incidence value in the range of 0.5–2.0/100,000, myeloproliferative neoplasms are rare disorders, but they are not new disorders, and after a century of scrutiny, their clinical features and natural histories are well-defined, though their individual management continues to be controversial. With respect to polycythemia vera, there has been a long-standing dispute between those who believe that the suppression of red blood cell production by chemotherapy is superior to phlebotomy to prevent thrombosis, and those who do not. With respect to essential thrombocytosis, there is a similar dispute about the role of platelets in veinous thrombosis, and the role of chemotherapy in preventing thrombosis by suppressing platelet production. Linked to these disputes is another: whether therapy with hydroxyurea promotes acute leukemia in disorders with a substantial possibility of longevity. The 21st century revealed new insights into myeloproliferative neoplasms with the discovery of their three somatic, gain-of-function driver mutations. Almost immediately, this triggered changes in the diagnostic criteria for myeloproliferative neoplasms and their therapy. Most of these changes, however, conflicted with prior well-validated, phenotypically driven diagnostic criteria and the management of these disorders. The aim of this review is to examine these conflicts and demonstrate how genomic discoveries in myeloproliferative neoplasms can be used to effectively complement the known phenotypic features of these disorders for their diagnosis and management. Full article

Background: The relationship between consuming Thai desserts—predominantly composed of carbohydrates—and gut microbiome profiles remains unclear. This study aimed to evaluate the effects of consuming various Thai desserts with different GI values on the gut microbiomes of healthy volunteers. Methods: This open-label, parallel randomized clinical trial involved 30 healthy individuals aged 18 to 45 years. Participants were randomly assigned to one of three groups: Phetchaburi’s Custard Cake (192 g, low-GI group, n = 10), Saraburi’s Curry Puff (98 g, medium-GI group, n = 10), and Lampang’s Crispy Rice Cracker (68 g, high-GI group, n = 10), each consumed alongside their standard breakfast. Fecal samples were collected at baseline and 24 h post-intervention for metagenomic analysis of gut microbiome profiles using 16S rRNA gene sequencing. Results: After 24 h, distinct trends in the relative abundance of various gut microbiota were observed among the dessert groups. In the high-GI dessert group, the abundance of Collinsella and Bifidobacterium decreased compared to the low- and medium-GI groups, while Roseburia and Ruminococcus showed slight increases. Correlation analysis revealed a significant negative relationship between sugar intake and Lactobacillus abundance in the medium- and high-GI groups, but not in the low-GI group. Additionally, a moderately negative association was observed between Akkermansia abundance and sugar intake in the high-GI group. These bacteria are implicated in energy metabolism and insulin regulation. LEfSe analysis identified Porphyromonadaceae and Porphyromonas as core microbiota in the low-GI group, whereas Klebsiella was enriched in the high-GI group, with no predominant bacteria identified in the medium-GI group. Conclusions: The findings suggest that Thai desserts with varying GI levels can influence specific gut bacteria, though these effects may be temporary. Full article

Parkinson’s disease (PD) is a progressive neurological disease that causes both motor and nonmotor symptoms. While our understanding of putative mechanisms has advanced significantly, it remains challenging to verify biomarkers with sufficient evidence for regular clinical use. Clinical symptoms are the primary basis for diagnosing the disease, which can be mild in the early stages and overlap with other neurological disorders. As a result, clinical testing and medical records are mostly relied upon for diagnosis, posing substantial challenges during both the initial diagnosis and the continuous disease monitoring. Recent biochemical, neuroimaging, and genetic biomarkers have helped us understand the pathophysiology of Parkinson’s disease. This comprehensive study focuses on these biomarkers, which were chosen based on their relevance, methodological excellence, and contribution to the field. Biochemical biomarkers, including α-synuclein and glial fibrillary acidic protein (GFAP), can predict disease severity and progression. The dopaminergic system is widely used as a neuroimaging biomarker to diagnose PD. Numerous genes and genome wide association study (GWAS) sites have been related to the development of PD. Recent research on the SNCA gene and leucine-rich repeat protein kinase 2 (LRRK2) has shown promising results. By evaluating current studies, this review intends to uncover gaps in biomarker validation and use, while also highlighting promising improvements. It emphasizes the need for dependable and reproducible indicators in improving PD diagnosis and prognosis. These biomarkers may open up new avenues for early diagnosis, disease progression tracking, and the development of personalized treatment programs. Full article

Aflatoxins are mycotoxins produced by Aspergillus flavus and several other related organisms and are common contaminants of numerous grains and nuts, especially maize (corn) and peanuts. Although, undoubtedly, aflatoxins have been present in the food of humans for millennia, their toxic effects were not discovered until 1960, first becoming evident as a non-infectious outbreak of poisoning of turkeys (Turkey X disease) arising from contaminated groundnut meal. The elucidation of specific chemical structures in 1963 led to the rapid characterization of aflatoxins as among the most potent chemical carcinogens of natural origin ever discovered. As a frontispiece to the Special Issue “65 Years on from Aflatoxin Discovery—A Themed Issue in Honor of Professor John D. Groopman”, we highlight many of Professor Groopman’s important contributions utilizing urinary (aflatoxin–N⁷–guanine) and, especially, serum (aflatoxin–albumin adducts) biomarkers; this work focused on over 40+ years of the development of analytical methods to measure biomarkers of aflatoxin exposure and their application in experimental and clinical studies. Collectively, this work serves as a template for using chemical-specific biomarkers as key tools to probe ‘exposure–disease relationships’—in this instance, dietary aflatoxins and liver cancer. New approaches to measuring carcinogen biomarkers will build upon this ‘aflatoxin paradigm’ to inform the public health implications of diverse exposures around the world. Full article