Search Results (6,459)

Background/Objectives: Cord blood mitochondrial DNA copy number (mtDNAcn) has been proposed as a biomarker reflecting environmental influences during fetal life, with reported associations with perinatal outcomes such as birth weight and length. Within the framework of the Developmental Origins of Health and Disease (DOHaD) theory, this study aimed to investigate whether cord blood mtDNAcn is related to postnatal physical growth in early childhood. Methods: We analyzed data from 150 newborns (68 females and 82 males) enrolled in the Tohoku Medical Megabank Birth and Three-Generation Cohort Study in Japan. Cord blood mtDNAcn was quantified using real-time PCR, and standard deviation scores for weight and height were assessed at 1, 2–3, 4–6, 18–24, and 36–48 months of age. Correlation analyses were conducted separately by sex. Results: Cord blood mtDNAcn showed no significant associations with body weight or height at any of the postnatal time points up to 48 months of age. Growth trajectories of infants with higher or lower mtDNAcn values at birth tended to converge toward the population mean during infancy and toddlerhood. Conclusions: Although no significant relationships were observed, this exploratory, hypothesis-generating study provides a foundation for future investigations. Larger cohorts with extended follow-up are needed to clarify the potential significance of cord blood mtDNAcn in early-life research on child growth and health. Full article

Background: Multidrug resistance (MDR), primarily driven by P-glycoprotein (P-gp)-mediated drug efflux, presents a significant challenge in cancer therapy, contributing to chemotherapy failure and poor patient outcomes. Objectives: In this study, we explored the potential of manidipine (MA), a clinically approved calcium channel blocker, to reverse P-gp-mediated MDR through modulation of calcium signaling via nuclear factor of activated T cells 2 (NFAT2). Methods: Paclitaxel (PTX) resistance ABCB1-overexpressing cancer in vitro and in vivo were used for evualting the anti-MDR effects of MA, as well as the underlying mechanism with siRNA of NFAT2. Results: We found that MA at non-toxic concentrations (0.6–5.4 μM) significantly sensitize drug-resistant colorectal (HCT-8/T) and non-small cell lung (A549/T) cells to PTX, reducing its IC₅₀ by up to 1328-fold in vitro models. Mechanistically, MA inhibited P-gp efflux activity without altering its expression, as shown by an increased intracellular accumulation of doxorubicin and Flutax-2 (2.3- and 3.1-fold, respectively) and dose-dependent modulation of ATPase activity (EC₅₀ = 4.16 μM). Notably, MA reduced intracellular calcium levels (52% reduction, p < 0.001) and downregulated NFAT2, an oncogene overexpressed in resistant cells. In vivo, MA (3.5 mg/kg) synergizes with PTX to inhibit tumor growth by 68% (p < 0.001) in A549/T xenograft model, without an observable decrease in weight. Conclusions: In sum, all these results position MA as a novel NFAT2 inhibitor to overcome P-gp-mediated MDR via modulating calcium signaling, which points to further investigation for its clinical applications. Full article

Digital financial services have transformed consumer financial behavior, yet their effects on sustainable development outcomes remain poorly understood. This study examines how mobile financial services (MFS) usage influences financial behaviors across temporal dimensions and investigates the moderating role of financial literacy from a systemic sustainability perspective. Drawing on Construal Level Theory, Dual Process Theory, and Social Cognitive Theory, we analyze data from 21,757 U.S. adults from the 2021 National Financial Capability Study to explore relationships between MFS usage, financial literacy dimensions—objective knowledge (OK), subjective knowledge (SK), and perceived ability (PA)—and both short-term and long-term financial behaviors. The results reveal a dual temporal pattern: MFS usage negatively affects short-term behaviors, including spending control and emergency preparedness, while positively influencing long-term behaviors such as retirement planning and investment participation. Financial literacy dimensions demonstrate differential moderating effects, with OK providing protective benefits against short-term risks, while PA can paradoxically exacerbate these adverse short-term effects. These findings highlight complex implications for sustainable development, demonstrating how individual behaviors aggregate to influence systemic financial resilience and progress toward Sustainable Development Goals related to poverty reduction, economic growth, and inequality reduction. Policymakers should adopt behaviorally informed regulatory approaches that address temporal trade-offs. Educators should design digital-specific literacy programs emphasizing realistic risk assessment alongside confidence-building, thereby promoting sustainable financial behaviors in increasingly digital environments. Full article

Nutritional factors play a crucial role in many gynecological disorders, particularly those influenced by estrogen. Uterine fibroids are benign tumors that affect a large proportion of women of reproductive age, especially between 30 and 40 years. These lesions may cause significant symptoms, including pelvic pain, heavy menstrual bleeding, and infertility. In younger women, the onset of fibroids is often associated with familial and genetic predisposition, whereas in adulthood, hormonal influences linked to environmental factors and states of exogenous or endogenous hyperestrogenism are more frequently observed. In both contexts, supportive management through an appropriate diet may provide clinical benefit. Although the precise pathogenesis remains incompletely understood, hormonal, genetic, and environmental components—particularly hyperestrogenism—are considered key contributors to fibroid development. Current evidence suggests that consumption of saturated fats, particularly from red meat and full-fat dairy, may raise circulating estrogen concentrations and contribute to the development of fibroids. In contrast, diets abundant in fiber, fruits, and vegetables appear to exert a protective effect, potentially lowering fibroid risk. Obesity, through increased aromatization and consequent estrogen production, also represents an established risk factor. This narrative review aims to explore the role of nutritional determinants in the onset and progression of uterine fibroids, with a specific focus on the impact of individual nutrients, foods, and dietary patterns on clinical outcomes. Particular emphasis is placed on obesity and macronutrient composition (e.g., high-fat versus high-fiber dietary regimens) as potential modulators of circulating estrogen levels and, consequently, fibroid growth dynamics. Furthermore, the potential of nutritional strategies as complementary therapeutic approaches, capable of integrating established clinical practices, is examined. Full article

Background and Objectives: To evaluate the prognostic value of the Clinical–Pathologic Stage–Estrogen receptor status and Grade (CPS+EG) staging system, which combines clinical staging, pathological staging, oestrogen receptor (ER) status, and tumour grade in predicting survival outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant therapy (NACT). Materials and Methods: A retrospective review was performed on 245 female breast cancer patients who received anti-HER2 therapy alongside NACT at the Medical Oncology Department of Kartal Dr Lütfi Kırdar City Hospital, University of Health Sciences, from April 2012 to June 2024. The CPS+EG score was calculated using the MD Anderson Cancer Centre neoadjuvant treatment response calculator. Patients were categorised into two groups based on their CPS+EG score < 3 and ≥3. The primary outcomes assessed were disease-free survival (DFS) and overall survival (OS). Kaplan–Meier and log-rank tests were utilised for time-to-event analysis; Cox regression was used for multivariate analysis. A significance level of ≤0.05 was considered. Results: The median age of the patient cohort was 51 years (range: 27–82 years). Among these patients, 183 (74.6%) had a CPS+EG score less than 3, while 62 (25.3%) exhibited a score of 3 or higher. The median follow-up duration was 37.6 months. The pathological complete response (pCR) rate across the entire cohort was 51.8%. Specifically, the pCR rate was 56.3% in the group with CPS+EG scores below 3, and 38.7% in those with scores of 3 or higher (p = 0.017). Patients with CPS+EG scores less than 3 demonstrated superior overall survival (OS), which reached statistical significance in univariate analysis. Multivariate analysis identified the CPS+EG score as an independent prognostic factor for both overall survival and disease-free survival (DFS), with hazard ratios of 0.048 (95% CI: 0.004–0.577, p = 0.017) and 0.35 (95% CI: 0.14–0.86, p = 0.023), respectively. Conclusions: The CPS+EG score is an independent and practical prognostic marker, particularly for overall survival, in patients with HER2-positive breast cancer who have received neoadjuvant therapy. Patients with a CPS+EG score < 3 have higher pCR rates and survival rates. When used in conjunction with pCR, it can improve risk categorisation and contribute to the individualisation of adjuvant strategies in the post-neoadjuvant period. Due to its ease of calculation and lack of additional costs, this score can be instrumental in clinical practice for identifying high-risk patients. Our findings support the integration of the CPS+EG score into routine clinical decision-making processes, although prospective validation studies are necessary. Full article

This study analyzes the impact of research and development (R&D) investment on economic growth in Panama, an emerging economy with structural challenges in its innovation system. Using a multivariate econometric approach that included elastic net regularization and fixed-effect panel data estimation, the analysis incorporated key explanatory variables such as public education expenditure, inflation, infrastructure investment, population growth, and exports. The results indicated that both R&D and education spending have a positive and statistically significant effect on GDP growth, while inflation has a negative impact and exports show no significant effect. To ensure robustness, the study applied the augmented Dickey–Fuller test for stationarity, nonparametric bootstrapping (1000 replications), and multiple diagnostic tests, including RMSE, adjusted R², Durbin–Watson statistic, and White’s test. Scenario-based projections suggest that gradual and sustained increases in R&D investment, supported by stronger institutional coordination and absorptive capacity, could enhance Panama’s long-term productivity and innovation outcomes. The findings underscore that improving R&D funding alone is not sufficient; effective governance and coherent science, technology, and innovation (STI) policies are essential. This research contributes empirical evidence to a relatively underexplored area in the development literature and offers strategic insights for policymakers seeking to build more integrated and sustainable STI ecosystems in emerging economies. Full article

Bioactive agents can stimulate osteogenesis, angiogenesis, and cell proliferation; therefore, their application in bone regeneration offers significant therapeutic potential. The aim of this systematic review was to evaluate strategies for applying chitosan-based scaffolds with growth factors in bone regeneration. A structured literature search was conducted in July 2025 across the PubMed, Scopus, and Web of Science databases. Search terms included combinations of (chitosan scaffold) AND (growth factor OR BMP-2 OR VEGF OR FGF OR TGF-beta OR periostin OR PDGF OR IGF-1 OR EGF OR ANG-1 OR ANG-2 OR GDF-5 OR SDF-1 OR osteopontin). The study selection process followed PRISMA 2020 guidelines and the PICO framework. Out of 367 records, 226 were screened, and 17 studies met the eligibility criteria for qualitative analysis. BMP-2 was the most frequently investigated growth factor, studied in both in vitro and in vivo models, with rats and rabbits as the most common animal models. Scaffold compositions varied, incorporating hydroxyapatite, heparin, polyethylene glycol diacrylate, octacalcium phosphate-mineralized graphene, silk fibroin, and aloe vera. Growth factors were introduced using diverse methods, including microspheres, chemical grafting, covalent coupling, protein carriers, and nanohydroxyapatite mesopores. Most studies reported enhanced bone regeneration, although differences in models, scaffold composition, and delivery methods preclude definitive conclusions. The addition of growth factors generally improved osteoblast proliferation, angiogenesis, bone density, and expression of osteogenic markers (RunX2, COL1, OPN, OCN). Combining two bioactive agents further amplified osteoinduction and vascularization. Sustained-release systems, particularly those using heparin or hydroxyapatite, prolonged biological activity and improved regenerative outcomes. In conclusion, functionalization of chitosan-based scaffolds with growth factors shows promising potential for bone regeneration. Controlled-release systems and combinations of different bioactive molecules may offer synergistic effects on osteogenesis and angiogenesis. Further research should focus on optimizing scaffold compositions and delivery methods to tailor bioactive agent release for specific clinical applications. Full article

The present study examined the impact of adding methionine (Met) and its conjugated form (Met-Met) on Cornu aspersum snails. The primary focus was on the animals’ growth performance, the chemical composition of their carcass (whole body without the shell), the mineral profile, and the mechanical properties of their shells. In two experiments conducted under controlled laboratory conditions, diets supplemented with varying levels of Met addition (0.3, 0.6, 1.4 g/kg feed) were used, and the effects of free methionine, Met-Met and their mixture (1.4 g/kg feed) were compared. The study incorporated measurements of body weight, shell width, and mortality of snails. Analyses encompassing protein, fat, sulphur amino acids, glutathione levels, oxidative stress indices (DPPH, TAC, TBARS), and macro- and micronutrient content of carcass and shells were conducted. The findings demonstrated that adding 1.4 g Met/kg feed significantly enhanced the shells’ weight gain (+56% vs. Control), shell weight (+56%) and crushing force (+135%). Furthermore, an increase in the Met content of the carcass was observed (+18%), along with elevated carcass Ca (+28%) and P (+30%) and higher shell Ca (+12%) and Zn (+87%), alongside reduced carcass Fe (−38%) and Cu (−19%). In Experiment II, the Met-Met group exhibited the highest carcass weight (+16% vs. Control), the greatest carcass-to-body weight ratio, and the highest proportion of mature individuals (+27%). Moreover, Met-Met supplementation improved Cu absorption and retention in the carcass (+19%). Also, the results suggest that the conjugated form of methionine may improve Cu absorption and storage in the carcass (+19%). The study’s findings indicate that methionine addition, especially in Met-Met form, can substantially impact the efficiency of C. aspersum farming, enhancing both the productivity outcomes and the quality of the product. That is particularly important in increasing the shell’s mechanical resistance and the carcass’s nutritional value. Full article

Background/Objectives: Gingival tissue deficiencies present significant treatment challenges. We investigated three xenogeneic collagen scaffolds—Fibro-Gide, FibroMATRIX, and Mucoderm—with and without human gingival MSCs for soft tissue augmentation. Methods: The study assessed scaffold properties (mechanical properties and micro-CT structure), cytocompatibility, ex vivo vascular growth stimulation (CAM-test), and in vivo effects in rabbit model. Results: All scaffolds were cytocompatible and maintained MSC viability via extract and contact cytotoxicity tests. Fibro-Gide showed the highest porosity at 78.5%, followed by FibroMATRIX at 64.3%, while Mucoderm had the lowest porosity at 33.2%. Mucoderm exhibited the greatest stiffness due to its dense structure, contrasting with the more similar mechanical properties of Fibro-Gide and FibroMATRIX. In an ex vivo HET-Cam model of the angiogenic response, Fibro-Gide exhibited reduced blood vessel length and blood flow rate compared to FibroMATRIX and Mucoderm. In vivo, Mucoderm resorbed completely, FibroMATRIX demonstrated optimal partial degradation, and Fibro-Gide retained most of its collagen structure. Conclusions: The FibroMATRIX with MSCs combination showed particularly promising results for enhancing tissue thickness and vascularization, suggesting this approach could significantly improve gingival regeneration outcomes. Full article

Background/Objectives: Human epidermal growth factor receptor 2 (HER2) inhibitors have markedly improved outcomes in patients with HER2-positive breast cancer. Clinical treatment often involves the sequential or combined use of multiple HER2 inhibitors, making it essential to clarify their distinct adverse event (AE) profiles. However, AE trends remain insufficiently understood. This study aimed to comprehensively analyze characteristic AEs associated with HER2 inhibitors. Methods: Using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS, January 2004–September 2024), we conducted disproportionality analyses of AEs associated with HER2 inhibitors approved for breast cancer. Based on the natural logarithm of the reporting odds ratio (lnROR), hierarchical cluster analysis and principal component analysis (PCA) were performed. Results: Disproportionality analysis treating HER2 inhibitors as a single group identified several signals, with hair disorder (ROR 39.93 [95% CI: 37.68–42.32]) as a representative example. Hierarchical clustering showed that monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) diverged early in the dendrogram, and clusters broadly corresponded to pharmacological classes. The cluster of hair-related AEs closely corresponded to mAbs. PCA indicated that the first component reflected AE occurrence risk (R² = 0.655, p < 0.0001), the second component distinguished mAbs from TKIs (tucatinib: r = 0.667; trastuzumab: r = −0.567), and the third component separated molecular targeted agents from antibody–drug conjugates (neratinib: r = 0.521; T-DXd: r = −0.440). Conclusions: FAERS-based analyses enabled visualization of the distinct AE profiles of HER2 inhibitors. These findings may support safe drug selection, risk stratification, and improved AE management strategies. Full article

First-trimester placental development comprises many critical yet understudied cellular events that determine pregnancy outcomes. Improper placentation leads to a host of health issues that not only impact the fetal period but also influence later-life offspring health. Thus, an experimental paradigm for studying early placental development is necessary and has spurred the development of new in vitro models. Organoid model systems are three-dimensional structures comprising multiple differentiated cell types that originate from a progenitor population. Trophoblasts are the progenitor cells that serve as the proliferative base for the differentiation and maintenance of the placenta. Due to research constraints, experimental studies on the causal mechanisms underlying pathological pregnancies cannot readily be performed in human subjects. The nonhuman primate (NHP) offers a solution to this problem as it circumvents the limitations of human pregnancy sampling. Importantly, NHPs share many developmental features of human pregnancy, including placenta type and a similar fetal growth trajectory, making longitudinal pregnancy studies feasible and relevant. Since perturbations made in vivo can be validated in vitro, an NHP model of early pregnancy would facilitate mechanistic studies of pregnancy disorders. Herein, we describe the methodology for the establishment of a first-trimester NHP placenta trophoblast organoid model system. Full article

Caffeine is one of the most widely consumed psychoactive substances globally and is a common component of daily diets, particularly among women of reproductive age. Numerous in vitro and in vivo studies have indicated potential adverse effects of prenatal caffeine exposure, including disturbances in fetal growth, metabolic dysregulation, organ malformations, and neurodevelopmental alterations. These findings suggest that caffeine may influence multiple physiological pathways during gestation, including epigenetic modifications and metabolic programming. However, evidence from human studies remains heterogeneous and often inconclusive. Recent cohort studies and meta-analyses have reported that moderate maternal caffeine intake is not significantly associated with increased risks of gestational diabetes mellitus, gestational hypertension, or preeclampsia, although higher intake levels have been linked to anemia, preterm birth, and low birth weight in some populations. Furthermore, emerging data suggest potential associations between prenatal caffeine exposure and early neurodevelopmental outcomes, including behavioral changes, subtle structural brain differences, and alterations in offspring metabolic health and obesity risk. Despite these findings, the magnitude and clinical relevance of these effects remain uncertain, partly due to variability in caffeine sources, dosages, study designs, and reliance on self-reported intake. This review aims to synthesize current evidence on maternal caffeine consumption, its impact on pregnancy complications, fetal development, and long-term child health outcomes. By integrating experimental and clinical data, the study provides a comprehensive overview that may assist clinicians and healthcare professionals in counseling pregnant women regarding caffeine intake and potential risks. Full article

Bone metastases continue to be a major cause of morbidity and mortality in patients with advanced cancers, driven by the dynamic remodeling of the bone marrow niche. Traditionally viewed as passive space-fillers, bone marrow adipocytes (BMAs) are now recognized as active regulators of tumor growth, therapeutic resistance, and skeletal pathology. BMAs comprise a significant portion of the adult marrow space, particularly in aging and obesity, and facilitate metastatic colonization through various mechanisms. These include metabolic coupling, where adipocyte-derived fatty acids fuel tumor oxidative phosphorylation; the secretion of adipokines such as leptin and IL-6, which promote epithelial-to-mesenchymal transition, invasion, and immune evasion; regulation of osteoclastogenesis via RANKL expression; and the release of extracellular vesicles that reprogram cancer cell metabolism. Clinical and experimental studies show that BMA expansion correlates with increased tumor burden and poorer outcomes in breast, prostate, lung cancers, and multiple myeloma. Additionally, BMAs actively promote therapeutic resistance through metabolic rewiring and drug sequestration. Experimental models, ranging from in vitro co-cultures to in vivo patient-derived xenografts, demonstrate the complex roles of BMAs and also reveal important translational gaps. Despite promising preclinical approaches such as metabolic inhibitors, PPARγ modulation, adipokine blockade, and lifestyle changes, no therapies directly targeting BMAs have yet reached clinical practice. This review compiles current evidence on the biology of BMAs, their tumor-promoting interactions, and potential therapeutic strategies, while also highlighting unresolved questions about BMA heterogeneity, lipid flux, and immunometabolic crosstalk. By revealing how bone marrow adipocytes actively shape the metastatic niche through metabolic, endocrine, and immunological pathways, this review highlights their potential as novel biomarkers and therapeutic targets for improving the management of bone metastases. Full article

We refine a bottom-up, quantity-clearing framework of Bitcoin price formation that couples its fixed 21-million-coin cap with plausible demand growth and execution behavior. This approach relies on first-principles economic supply-and-demand dynamics rather than assumptions about anticipated Bitcoin price appreciation, its price history, or its potential effectiveness in demonetizing other asset classes. We considered five key high-level factors that may affect price determination: level of market demand; intertemporal investment preferences; fiat-denominated withdrawal sensitivity; initial liquid supply; and daily withdrawal levels from liquid supply. With a goal of both increasing understanding of the impacts of price drivers and developing probabilistic forecasts, we show two models: (1) a baseline to assess the impacts of parameter changes, alone and in combination, on Bitcoin price trajectories and liquid supply over time and (2) a Monte Carlo simulation that incorporates uncertainty across a range of uncertain parameterizations and presents probabilistic price and liquid supply forecasts to 2036. Our baseline model highlighted the importance of liquid supply and withdrawal sensitivity in price impacts. The Monte Carlo simulation results suggest a 50% likelihood that Bitcoin price will exceed USD 5.17 M by April 2036. Generally, prices from the low single millions to the low tens of millions per Bitcoin by 2036 emerge under broad parameter sets; hyperbolic paths to higher price levels are relatively rare and concentrate when liquid supply falls near or below BTC 2 M and withdrawal sensitivity is low. Our results help locate where right-tail risk and disorderly market outcomes concentrate and suggest that policy tools are available to help guide trajectories. Full article

Background and Objectives: Iron deficiency anemia (IDA) is the most common cause of anemia in pregnant women and can adversely affect both maternal and fetal health. This study aimed to compare pregnancy outcomes between women with and without IDA in Northern Thailand, a region with a high prevalence of anemia. Methods: A retrospective cohort study was conducted on all singleton pregnancies attending antenatal care (ANC) and/or delivering at Maharaj Nakorn Chiang Mai Hospital between 2003 and 2024. The study group consisted of women diagnosed with IDA in the first half of pregnancy, while the control group comprised women with low-risk pregnancies during the same study period. Results: Of the 38,979 pregnancies, after applying exclusion criteria, 634 pregnancies (2.2%) with laboratory-confirmed IDA and 28,132 controls remained available for analysis. Women with IDA had significantly higher parity, lower socioeconomic status, and lower hemoglobin levels throughout pregnancy. Multivariate regression analysis revealed that IDA was significantly associated with increased risks of preterm birth (adjusted odds ratio; aOR 1.04; 95% CI: 1.01–1.07), fetal growth restriction (FGR) (aOR 1.02; 95% CI: 1.00–1.04), and low birth weight (aOR 1.05; 95% CI: 1.03–1.08). Conclusions: IDA, even with treatment, may still slightly increase the risk of adverse pregnancy outcomes, particularly preterm birth, fetal growth restriction, and low birth weight. The residual risk likely reflects incomplete correction of anemia. Optimizing management requires strict compliance, judicious use of parenteral iron, and attention to coexisting nutritional deficiencies, underscoring the need for closer monitoring and improved care strategies. Full article