Search Results (1,701)

Background: Broad-spectrum antibiotics are often used for suspected infections in patients with hematologic malignancies due to the risk of severe infections. Although antibiotic use can lead to antimicrobial resistance and microbiome dysbiosis, the effects of antibiotics on the microbiome and resistome in patients with acute myeloid leukemia (AML) undergoing remission induction chemotherapy (RIC) are not well understood. Methods: Various statistical models were utilized to examine the effects of antibiotic administration on the microbiome and resistome over time, as well as differences in AR-infection (ARI) and colonization (ARC) by important CDC-threats in 119 AML patients. Results: A greater number of unique antibiotic classes administered correlated with a loss of unique antibiotic resistance genes (ARGs) (R = −0.39, p = 0.008). Specifically, although a greater number of oxazolidinone administrations was correlated with a greater loss of diversity (R = −0.58, p < 0.001), each additional day of linezolid reduced the risk of ARC by ~30% (HR: 0.663, p = 0.047) and decreased the odds of acquiring genes predicted to confer macrolide (HR: 0.50, p = 0.026) resistance. Conclusions: The number of antibiotic administrations and the types of antibiotics used can influence the risk of antibiotic resistance gene (ARG) expansion and ARC events in AML patients undergoing RIC. While certain antibiotics may reduce microbial diversity, they are not always linked to an increase in ARGs or ARC events. Full article

Background/Objectives: High-risk neuroblastoma patients are treated with approved anti-ganglioside GD2 antibodies of moderate (dinutuximab beta; DB) and higher binding affinity (naxitamab; NAXI). We evaluated the functional potency of DB compared to NAXI and investigated the target-mediated drug disposition (TMDD). Methods: Tumor spheroids were generated from neuroblastoma cells with varying GD2 expression, stably expressing iRFP680 as a viability marker. Antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) were assessed in a long-term life-cell viability assay using serial dilutions of the GD2 antibodies. Binding activity was determined by flow cytometry. Processes involved in TMDD were analyzed, including antibody binding to dead tumor cells and to soluble GD2 (sGD2), antibody internalization into tumor and immune cells and the impact of sGD2 on DB and NAXI-mediated ADCC. Results: DB and NAXI mediated a concentration-dependent ADCC response against GD2-positive spheroids and no response against GD2-negative spheroids. DB showed a significantly higher ADCC potency than NAXI in all GD2-positive spheroid models. Binding activity of DB and NAXI was not significantly different. However, the decrease of anti-GD2 antibody binding to viable GD2-positive tumor cells following co-incubation with dead GD2-positive tumor cells or sGD2 was significantly higher for NAXI than DB. Additionally, we found an increased internalization of NAXI compared to DB by tumor cells and particularly CD64+ monocytes. Finally, sGD2 impaired NAXI-mediated ADCC to a significantly greater extent than DB-mediated ADCC. Conclusions: DB has a higher ADCC potency over NAXI at clinically relevant concentrations, attributed to stronger TMDD effects of NAXI compared to DB. Full article

When the economy grows, people become wealthier and more autonomous from their intimate partners. This autonomy potentially has a negative impact on relationship stability: As per capita income increases, so does the divorce rate. Nevertheless, there is evidence that, after a certain income level, the divorce rate starts to decline, suggesting that the relationship between the two factors is not linear. The purpose of the current research is to examine the relationship between per capita income and divorce rate by analyzing historical data from the UK (obtained from the UK Office of National Statistics) and USA (obtained from the CDC and the Federal Reserve), as well as contemporary data encompassing a sample of 107 societies (obtained from the World Population Review and the World Bank). Our analysis finds a concave relationship between the two variables: an increase in per capita income corresponds to a rise in the divorce rate. However, beyond a certain threshold, the increase in per capita income is associated with a decrease in the divorce rate. Full article

Background/Objectives: Syphilis, a re-emerging global public health issue, has shown increasing incidence over the past decade, particularly among key populations such as men who have sex with men (MSM), people living with HIV, and pregnant women. This narrative review aimed to synthesize global epidemiological trends of syphilis from 2015 to 2025, with a focus on surveillance gaps, regional disparities, and structural determinants. Methods: A broad narrative approach was used to collect and analyze epidemiological data from 2015 to 2025. The literature was retrieved from databases (PubMed, Scopus) and official reports from the WHO, CDC, and ECDC. Included materials span observational studies, surveillance reports, and modeling data relevant to global trends and public health responses. Results: Globally, syphilis incidence has increased, with notable surges in North America, Europe, and Asia. MSM remain disproportionately affected, while congenital syphilis is resurging even in high-income countries. Low- and middle-income countries report persistent burdens, especially among women of reproductive age, often exacerbated by limited screening and surveillance infrastructure. The COVID-19 pandemic disrupted syphilis-related services and further exacerbated underreporting, hindering timely detection and response efforts. Surveillance systems vary widely in their completeness and quality, which significantly hinders global data comparability and coordinated public health responses. Conclusions: Despite its curability, syphilis continues to spread due to fragmented prevention strategies, inequities in access to care, and insufficient surveillance. Strengthening diagnostic access, integrating prevention efforts into broader health systems, and addressing social determinants are essential. Improved surveillance, equitable access, and innovation—including diagnostics and potential vaccine research—are critical to controlling the global syphilis epidemic. Full article

Hypertension (HTN) is a major contributor to global morbidity and manifests in several variants, including salt-sensitive hypertension (SSHTN). SSHTN is defined by an increase in blood pressure (BP) in response to high dietary salt, and is associated with heightened cardiovascular risk, renal damage, and immune system activation. However, the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) has not yet been explored in the context of SSHTN. Previously, we reported that GM-CSF is critical in priming bone marrow-derived (BMD)-macrophages (BMD-Macs) and BMD-dendritic cells (BMD-DCs) to become activated (CD38+) in response to salt. Further exploration revealed these cells differentiated into BMD-M1 Macs, CD38+ BMD-M1 Macs, BMD-type-2 conventional DCs (cDC2s), and CD38+ BMD-cDC2s. Additionally, BMD-monocytes (BMDMs) grown with GM-CSF and injected into SSHTN mice traffic to the kidneys and differentiate into Macs, CD38+ Macs, DCs, and CD38+ DCs. In the current study, we treated SSHTN mice with an anti-GM-CSF antibody (aGM) and found that preventive aGM treatment mitigated BP, prevented renal inflammation, and altered renal immune cells. In mice with established SSHTN, aGM treatment attenuated BP, reduced renal inflammation, and differentially affected renal immune cells. Adoptive transfer of aGM-treated BMDMs into SSHTN mice resulted in decreased renal trafficking. Additionally, aGM treatment of BMD-Macs, CD38+ BMD-M1 Macs, BMD-DCs, and CD38+ BMD-cDC2s led to decreased pro-inflammatory gene expression. These findings suggest that GM-CSF plays a role in SSHTN and may serve as a potential therapeutic target. Full article

Background and Objective: Large language model (LLM)–based chatbots are increasingly utilized by postpartum individuals seeking guidance on breastfeeding. However, the chatbots’ content quality, readability, and alignment with clinical guidelines remain uncertain. This study was conducted to evaluate and compare the quality, readability, and factual accuracy of responses generated by three publicly accessible AI chatbots—ChatGPT-4o Pro, Gemini 2.5 Pro, and Copilot Pro—when prompted with common maternal questions related to breast-milk supply. Methods: Twenty frequently asked breastfeeding-related questions were submitted to each chatbot in separate sessions. The responses were paraphrased to enable standardized scoring and were then evaluated using three validated tools: ensuring quality information for patients (EQIP), the simple measure of gobbledygook (SMOG), and the global quality scale (GQS). Factual accuracy was benchmarked against WHO, ACOG, CDC, and NICE guidelines using a three-point rubric. Additional user experience metrics included response time, character count, content density, and structural formatting. Statistical comparisons were performed using the Kruskal–Wallis and Wilcoxon rank-sum tests with Bonferroni correction. Results: ChatGPT-4o Pro achieved the highest overall performance across all primary outcomes: EQIP score (85.7 ± 2.4%), SMOG score (9.78 ± 0.22), and GQS rating (4.55 ± 0.50), followed by Gemini 2.5 Pro and Copilot Pro (p < 0.001 for all comparisons). ChatGPT-4o Pro also demonstrated the highest factual alignment with clinical guidelines (95%), while Copilot showed more frequent omissions or simplifications. Differences in response time and formatting quality were statistically significant, although not always clinically meaningful. Conclusions: ChatGPT-4o Pro outperforms other chatbots in delivering structured, readable, and guideline-concordant breastfeeding information. However, substantial variability persists across the platforms, and none should be considered a substitute for professional guidance. Importantly, the phenomenon of AI hallucinations—where chatbots may generate factually incorrect or fabricated information—remains a critical risk that must be addressed to ensure safe integration into maternal health communication. Future efforts should focus on improving the transparency, accuracy, and multilingual reliability of AI chatbots to ensure their safe integration into maternal health communications. Full article

The discovery of bioactive natural compounds from microbes holds promise for regenerative medicine. In this study, we identified and characterized a steroid-like compound, 3,12-dioxochola-4,6-dien-24-oic acid (DOCDA), from a crude extract of Rhodococcus sp. DOCDA significantly promoted wound healing by enhancing HaCaT cell invasion and migration. It upregulated key growth factors (EGF, VEGF-A, IGF, TGF-β, and HGF), indicating the activation of regenerative signaling. Additionally, DOCDA increased the expression of genes related to focal adhesion and cytoskeletal regulation (ITGB1, ITGA4, FAK, SRC, RHOA, CDC42, RAC1, and paxillin), supporting enhanced cellular motility and remodeling. Notably, DOCDA promoted stem-like properties in HaCaT cells, as shown by increased spheroid formation and elevated levels of the stemness markers ALDH1 and CD44. Target prediction and molecular docking identified the glucocorticoid receptor (GR) as the primary target of DOCDA, with a docking score of −7.7 kcal/mol. Network and pathway enrichment analysis revealed that GR-linked pathways were significantly associated with wound healing, including steroid hormone signaling, inflammation, immune responses, and cell migration. In vivo, the topical application of DOCDA led to over 70% wound closure in mice by day 5. These findings suggest that DOCDA is a steroid-like compound that accelerates wound healing and may serve as a potential agent in regenerative therapy. Full article

The Centers for Diseases Control (CDC) light trap is widely used for malaria vector surveillance, but its acquisition logistics pose challenges in Africa. Evaluating new traps can improve surveillance tools. This study compared the efficiency of the BG-Pro UV and Silver Bullet 2.1 UV (SB 2.1 UV) against the UV LED CDC trap in western Kenya’s rice irrigation area. The traps were tested indoors in eight houses over 64 nights. Light properties and fan speed were analyzed using spectrometry and an anemometer. The BG-Pro UV trap performed better than the UV LED CDC trap for An. gambiae s.l. (RR 2.0, 95% CI 0.9–3.9) and An. funestus s.l. (RR 3.5, 95% CI 1.9–6.4). The SB 2.1 UV trap was more effective in capturing An. gambiae s.l. (RR 4.3, 95% CI 2.5–7.3) and An. funestus s.l. (RR 7.1, 95% CI 3.9–13.1), and also caught three times more Culex spp. (RR 2.7, 95% CI 1.2–6.0). SB 2.1 UV had the highest downstream force, and all traps emitting UV-A light had consistent wavelengths. Overall, the BG-Pro and SB 2.1 traps’ trapping efficiency was three to six times more than the CDC trap, making them promising surveillance tools, particularly in low-density malaria settings. Full article

This study examines how memorable tourism experiences (MTEs) influence tourists’ intention to recommend coastal tourism destinations. Using a quantitative approach of PLS-SEM analysis and a disjoint two-stage approach, this study examines MTE as a higher-order construct (HOC) with its seven dimensions and the moderating role of coastal destination competitiveness (CDC) in structural relationships. Data were collected through purposive sampling from 339 tourists who had visited Likupang, one of the priority tourism destinations in Indonesia. The results show that MTE plays a crucial role in increasing perceived economic value (PEV) and place attachment (PLA), and it is directly related to the intention to recommend the destination (ITRD). In addition to the prominent mediation role of PEV, these findings reveal that the CDC can strengthen or weaken the influence of these factors on tourists’ intention to provide recommendations. Specifically, the CDC can strengthen PLA influence towards intention to recommend, whereas, in contrast, it weakens the PEV in driving these intentions. The findings of this study expand the horizon of managing coastal tourism with an understanding of tourist behavior, particularly through a focus on improving MTE from the dynamics of its seven dimensions in encouraging promotion through tourist recommendations while optimizing the natural competitiveness elements of Likupang. Full article

Background: Myocarditis is associated with increased mortality due to complications such as cardiogenic shock and arrhythmia. Trends of myocarditis-related mortality in the United States, along with demographic and regional disparities and changes during the COVID-19 pandemic, are unknown. Methods: We used the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database to extract data for myocarditis deaths from 1999 to 2023. The Joinpoint Regression Program was used to analyze long-term trends in mortality, and R Studio (version 4.4.1) was used to calculate expected and excess mortality for 2020 to 2023. Results: There were 33,016 myocarditis-related deaths from 1999 to 2023. The age-adjusted mortality rate (AAMR) of myocarditis deaths decreased by 46.08% from 7.40 (95% CI: 7.04–7.76) in 1999 to 3.99 (95% CI: 3.74–4.23) in 2019, with an APC of −2.59 (95% CI: −2.97 to −2.24). From 2019 to 2021, the AAMR increased by 46.62% to 5.85 (95% CI: 5.56–6.14) by 2021 (2019–2021 APC 22.3%*), reversing the gains of the previous two decades. By 2023, the AAMR recovered to 4.33 (95% CI: 4.09 to 4.58), though mortality was still higher than expected from pre-pandemic trends. From 2020 to 2023, there were 40.12% more deaths than expected, with 54.94% higher mortality in 2021. Briefly, 70.33% of excess myocarditis-related deaths also had COVID-19, with a peak of 76.15% of excess myocarditis deaths in 2021 being reported as involving COVID-19 infection. Significant disparities in mortality trends persisted, with males, NH Black or African Americans, and the elderly having higher mortality rates. Conclusions: Myocarditis mortality decreased in the United States from 1999 to 2019 but significantly increased during the COVID-19 pandemic years 2020 and 2021. At the height of the pandemic, COVID-19 infection contributed to almost three-quarters of excess myocarditis mortality. Significant disparities in myocarditis mortality persisted from 1999 to 2023. Full article

Background/Objectives: Radiotherapy (RT) is a mainstay of clinical cancer therapy that causes broad immune responses. The complement system is a pivotal effector mechanism in the innate immune response, but the impact of RT is less well understood. This study investigates the interaction between RT and the complement system as a possible approach to improve immune responses in cancer treatment. Methods: Human solid cancer (lung, prostate, liver, breast cancer), lymphoma, and leukemia cells were irradiated using X-rays and treated with polyclonal antibodies or anti-CD20 monoclonal antibodies, respectively. Chromium release assay was applied to measure cell lysis after radiation with or without complement-activating antibody treatment. The expression of membrane-bound complement regulatory proteins (mCRPs; CD46, CD55, CD59), which confer resistance against complement activation, CD20 expression, apoptosis, and radiation-induced DNA double-strand breaks (γH2AX), was measured by flow cytometry. The radiosensitivity of tumor cells was assessed by colony-forming assay. Results: We demonstrate that RT profoundly impacts complement function by upregulating the expression of membrane-bound complement regulatory proteins (mCRPs) on tumor cells in a dose- and time-dependent manner. Impaired complement-mediated tumor cell lysis could thus potentially contribute to radiotherapeutic resistance. We also observed RT-induced upregulation of CD20 expression on lymphoma and leukemic cells. Notably, complement activation prior to RT proved more effective in inducing RT-dependent early apoptosis compared to post-irradiation treatment. While complement modulation does not significantly alter RT-induced DNA-damage repair mechanisms or intrinsic radiosensitivity in cancer cells, our results suggest that combining RT with complement-based anti-cancer therapy may enhance complement-dependent cytotoxicity (CDC) and apoptosis in tumor cells. Conclusions: This study sheds light on the complex interplay between RT and the complement system, offering insights into potential novel combinatorial therapeutic strategies and a potential sequential structure for certain tumor types. Full article

Oocytes and cumulus cells undergo meiotic resumption and proliferation via gonadotropins and growth factors during maturation, and various small G proteins are activated when COCs undergo physiological changes. This study investigated the influence of gonadotropins and growth factors on Ras and its GTPases during porcine COC maturation. Unmatured COCs were treated with FSH, LH, or EGF for 44 h. The mRNA expression levels of the Ras subfamily (H-Ras, K-Ras, N-Ras, and R-Ras), its GTPases (RASA1 and SOS1), and proliferation factors (ERK, CCNB1, and Cdc2) were analyzed using RT-PCR. In contrast to other Ras subfamilies, R-Ras expression is upregulated during COC maturation. We evaluated the effects of FSH, LH, and EGF at various concentrations that most effectively regulated the expression of R-Ras and GTPases. The results demonstrated that 0.5 µg/mL FSH, 10 IU/mL human chorionic gonadotropin (hCG), and 10 ng/mL EGF effectively enhanced R-Ras expression and cell proliferation. FSH supplementation during porcine COC maturation significantly upregulated R-Ras and ERK expression, independent of LH and EGF, and downregulated Cdc2 expression. These results indicated that FSH regulates R-Ras expression, thereby promoting cell proliferation during COC maturation. These results provide fundamental knowledge for understanding the role of Ras and its family members in the development of follicular environments in pigs. Full article

Drought stress has a significant impact on cotton growth, development, and productivity. This study conducted drought stress treatment and normal water treatment (control group) on 502 cotton accessions and analyzed data on eight phenotypic traits closely related to drought stress tolerance. The results showed that all indicators changed significantly under drought stress conditions compared to the control group, with varying degrees of response among different indicators. To comprehensively evaluate the drought resistance of cotton during the germination period, the values of drought resistance comprehensive evaluation (D-value), weight drought resistance coefficient (WDC-value), and comprehensive drought resistance coefficient (CDC-value) were calculated based on membership function analysis and principal component analysis. Cluster analysis based on the D-value divided the germplasm into five drought-resistant grades, followed by the selection of one extreme material, each from the strongly drought-resistant and strongly drought-sensitive groups. An evaluation model was established using stepwise regression analysis, including the following effective indicators: Relative Fresh Weight (RFW), Relative Hypocotyl Length (RHL), Relative Seeds Water Absorption Rate (RAR), Relative Germination Rate (RGR), Relative Germination Potential (RGP), and Relative Drought Tolerance Index (RDT). The validation of the D-value prediction model based on the Best Linear Unbiased Prediction (BLUP) showed that the results obtained from two independent biological replicates were highly consistent. The comprehensive evaluation system and screening indicators established in this study provide a reliable method for identifying drought tolerance during the germination period. Full article

Introduction: Chronic pain affects approximately 20% of U.S. adults, imposing significant burdens on individuals and healthcare systems. Medical cannabis has emerged as a potential therapy, yet its impact on healthcare utilization remains unclear. Methods: This retrospective cohort study analyzed administrative data from a telehealth platform providing medical cannabis certifications across 36 U.S. states. Patients were classified as cannabis-exposed if they had used cannabis in the past year, while unexposed patients had no prior cannabis use. Outcomes included self-reported urgent care visits, emergency department (ED) visits, hospitalizations, and quality of life (QoL), measured using the CDC’s Healthy Days measure. Targeted Maximum Likelihood Estimation with SuperLearner estimated causal effects, adjusting for numerous covariates. Results: Medical cannabis users exhibited significantly lower healthcare utilization. Specifically, exposure was associated with a 2.0 percentage point reduction in urgent care visits (95% CI: −0.036, −0.004), a 3.2 percentage point reduction in ED visits (95% CI: −0.051, −0.012) and fewer unhealthy days per month (−3.52 days, 95% CI: −4.28, −2.76). Hospitalization rates trended lower but were not statistically significant. Covariate balance and propensity score overlap indicated well-fitting models. Conclusions: Medical cannabis use was associated with reduced healthcare utilization and improved self-reported QoL among chronic pain patients. Full article

Background: To improve the prognosis of patients with lung adenocarcinoma (LUAD), revolutionary treatments for metastatic lesions are essential. Methods: To identify genes closely involved in LUAD-cell-derived metastasis, we used RNA sequencing to generate microRNA (miRNA) expression signatures of brain metastatic lesions. Once tumor-suppressive miRNAs are identified, it will be possible to explore the numerous tumor-promoting genes that are regulated by miRNAs. Results: By comparison with a previously created LUAD signature, we identified several miRNAs whose expression was significantly suppressed in brain metastases. We focused on both strands of pre-miR-195 (miR-195-5p and miR-195-3p), which were significantly downregulated in brain metastatic tissues, and confirmed by ectopic expression assays that both strands of pre-miR-195 attenuated the aggressive phenotypes (cell proliferation, migration, and invasion) of LUAD cells. These data suggest that both strands of pre-miR-195 have tumor-suppressive functions in LUAD cells. Next, we explored the target molecules that each miRNA strand regulates in LUAD cells. We identified 159 target genes regulated by miR-195-5p and miR-195-3p, of which 12 genes (ANLN, CDC6, CDCA2, CDK1, CEP55, CHEK1, CLSPN, GINS1, KIF23, MAD2L1, OIP5, and TIMELESS) affect cell cycle/cell division and the prognosis of LUAD patients. Finally, we focused on two genes, ANLN (miR-195-5p target) and MAD2L1 (miR-195-3p target), and demonstrated their oncogenic functions and the molecular pathways they regulate in LUAD cells. Conclusions: The miRNA signature derived from lung cancer brain metastasis will be a landmark in the field, and analysis of this miRNA signature will accelerate the identification of genes involved in lung cancer brain metastasis. Full article