Search Results (551)

Atypical teratoid rhabdoid tumor (AT/RT) is a rare, highly aggressive embryonal central nervous system malignancy occurring predominately in infants and toddlers. Spinal AT/RT (spAT/RT) cases are even more limited, and as a result, little is known regarding prognostic factors and optimal treatment regimens. Molecularly, AT/RT is divided into three groups: AT/RT-SHH, AT/RT-TYR and AT/RT-MYC. spAT/RT is predominantly of the MYC subtype. Additionally, a third of patients with AT/RT have a germline Rhabdoid Tumor Predisposition Syndrome (RTPS) that increases the likelihood of developing additional rhabdoid tumors, including renal rhabdoid tumors. Due to the rarity of these tumors, there is a lack of consensus on treatment strategies to be employed. This review paper details the published literature on spAT/RT, with particular emphasis on the recent advances in understanding the biology of these aggressive tumors and currently available therapeutic options, and highlights the challenges associated with the management of this extremely rare condition. Full article

Background: Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne viral disease with a high fatality rate, and no licensed vaccines are currently available. The nucleoprotein (NP) of the Crimean-Congo hemorrhagic fever virus (CCHFV) plays a critical role in viral replication and immune recognition, making it a promising target for vaccine development. This study aimed to design and evaluate a multiepitope recombinant DNA vaccine targeting the NP of CCHFV. Methods: Cytotoxic T lymphocyte (CTL) epitopes from the NP were predicted via immunoinformatics approaches and systematically assessed for antigenicity, allergenicity, toxicity, hydrophobicity, and global population coverage. The selected epitopes were incorporated into four DNA vaccine constructs driven by a cytomegalovirus promoter, adjuvanted with human β-defensin 3 (hBD3), and fused to the reporter protein mRuby3. The constructs were evaluated in vitro using a fluorescent reporter system designed to provide a readout of TCR signaling upon the co-culture of T lymphocytes with differentiated monocytic cells expressing antigens. In vivo immunogenicity and protective efficacy were assessed in BALB/c (exploratory pilot) and IFNAR^−/− mice, a highly susceptible model for viral infection. Cytokine responses were measured to assess immunogenicity. Results: In vitro assays showed predominantly antigen-independent T-cell activation, suggesting that nonspecific stimulation inherent to the reporter co-culture system likely obscured the detection of antigen-specific TCR signaling. In vivo analyses in BALB/c mice revealed that the constructs elicited only modest systemic cytokine profiles while CCHFV-specific IgG and IFN-γ secretion remained undetectable, indicating that antigen-specific T-cell and antibody responses were limited. In the IFNAR^−/− challenge model, several peptide groups achieved significant 2–3 log reductions in tissue viral RNA and infectious titers (p < 0.05 vs. sham). However, the observed viral modulations were insufficient to reach the protective threshold and did not translate to a survival benefit (0%). Conclusion: Despite a rational in silico foundation, the multiepitope DNA vaccine constructs demonstrated limitations in inducing potent, antigen-specific immunity across both mouse models. The lack of antigen-specific responses indicates limitations in epitope selection, construct design, and delivery strategies, requiring optimization of next-generation epitope-based vaccines. These findings highlight the complexity of translating computational epitope predictions into functional vaccines, and provide benchmark data as a framework to guide future optimizations. Full article

Background: Soy intake has been proposed as a protective factor for breast cancer, especially when exposure occurs early in life. Mammographic density (MD) is a strong predictor of breast cancer risk, but evidence linking soy intake at specific life stages to adult mammographic density remains limited. Objective: The objective of this study was to evaluate the associations between dietary soy intake at different life stages and MD in premenopausal Chinese women. Methods: Dietary soy intake was assessed using a validated soy food frequency questionnaire for the past 12 months and retrospectively for earlier life stages (childhood: 6–12 years; adolescence: 13–18 years; young adulthood: 20–34 years), with recall aided by a life history calendar. MD was measured from bilateral cranio-caudal mammograms using a standardized computer-assisted method. Multivariable regression models were used to evaluate associations between soy protein and isoflavone intake at different life stages and MD, adjusting for relevant confounders. Results: Among 815 premenopausal women (mean age 40.9 y), mean current soy protein and isoflavone intakes were 10.3 g/day and 22.0 mg/day, respectively. Soy intakes across life stages were moderately correlated (r = 0.33–0.81). After multivariable adjustment, soy protein intake during adolescence (β = −0.067, SE = 0.029, p = 0.023) and childhood (β = −0.071, SE = 0.032, p = 0.028) was significantly and inversely associated with adult MD. Young adult intake showed a non-significant inverse trend (β = −0.052, p = 0.075), and current intake showed no association (p = 0.93). Higher mean early-life (ages 6–18) and life course soy intakes were also inversely associated with MD (β range: −0.077 to −0.082; all p < 0.05). Women with consistently high early-life soy intake had 5.8–6.6% lower adjusted MD than those with consistently low intake. Conclusions: Early-life soy exposure may influence adult breast tissue composition and represents a potentially modifiable protective factor in breast cancer prevention. These findings carry important public health implications, particularly for populations experiencing dietary westernization. Full article

Background/Objectives: Early intervention is associated with improved outcomes for young children with developmental delays, yet many with mild delays are ineligible for services under the Individuals with Disabilities Education Act (IDEA). The Early Discovery (ED) Program addressed this gap by providing short-term, targeted intervention for children ages 0–5 who did not qualify for publicly funded services. This study evaluated program outcomes across intervention types. Methods: During 2024–2025, 342 families completed the ED Program, receiving one of the following: speech-language (68%), general developmental (12%), occupational (14%), or behavioral (6%) intervention across 8–20 sessions. Eligibility required Miami-Dade residency and ineligibility for IDEA-funded services. Standardized pre- and post-intervention assessments were analyzed using descriptive statistics, correlations, and group comparisons. Results: Most households reported incomes <$70,000 (71%), with many experiencing additional risk factors including prematurity (15%), public or no insurance (47%), limited English proficiency (21%), and single-caregiver households (30%). Overall, 85% of children met criteria for improvement. Improvement rates varied by child ethnicity. No statistically significant differences were observed by child age, race, gender, prematurity, insurance status, caregiver demographics, household characteristics, or intervention type. Sensitivity analyses largely confirmed the primary findings, with ethnicity no longer significant and younger age emerging as a significant predictor of improvement. Conclusions: Findings suggest short-term, targeted intervention may support developmental progress among young children with mild delays who would otherwise remain unserved. Community-based programs such as ED may play a critical role in advancing developmental equity by reaching children with developmental and socioeconomic risk factors prior to school entry. Full article

Background: Endometrial cancer (EC) is the most common gynecological malignancy in Western countries. Although international guidelines recommend that patients with EC be treated at specialized oncology centers, many are still managed by general gynecologists. This study aimed to evaluate the influence of facility volume on treatment strategies and survival outcomes among EC patients. Methods: This is a retrospective multicenter study comparing 971 patients with EC treated at medium-volume centers (CVMs) (11–29 cases/year) with 1431 patients treated at high-volume centers (CVAs) (≥30 cases/year). Patient characteristics were recorded, including age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, comorbidities, surgical approach, lymphadenectomy, total number of lymph nodes removed, number of positive lymph nodes, length of hospital stay, histological characteristics, ESMO-ESGO (European Society for Medical Oncology–European Society of Gynaecological Oncology) classification system, adjuvant treatment, recurrence, progression-free survival (PFS), and overall survival (OS). Postoperative fever, hemoglobin changes, and blood transfusions were also reported. Results: Compared with patients treated at the MVCs, patients treated at the HVCs were younger (mean age, 65 vs. 66.4 years, p = 0.03) and had a lower rate of comorbidities (41% vs. 55%, p < 0.001). Patients treated at HVCs were mostly in higher ESMO-ESGO recurrence risk classes (p < 0.001), were treated mostly laparoscopically (58% vs. 47%, p < 0.001) and had better staging (higher number of lymph nodes harvested (mean 19 vs. 11, p < 0.001) and more peritoneal biopsies performed (27% vs. 14%, p < 0.001). HVC patients had fewer complications and received less adjuvant therapy (40% vs. 50%, p < 0.001) but, when treated, received chemotherapy more frequently, showed mostly loco-regional recurrences (34% vs. 14%) and fewer extra-abdominal recurrences (34% vs. 54%). HVC patients had better PFS and OS. Center volume was found to be an independent factor influencing PFS in multivariate analysis. Conclusions: All EC patients should be centrally managed to receive superior treatment to improve postoperative recovery and oncological outcomes, particularly for patients with more-aggressive tumors. Full article

Challenging behaviors, including noncompliance, aggression, hyperactivity, and impulsivity, are common among individuals with Fragile X Syndrome (FXS) and Down Syndrome (DS). To identify treatment needs specific to these populations, we conducted focus groups with caregivers and educators and used their input to adapt an evidence-based caregiver training program originally designed for caregivers of autistic children (i.e., The Research Units in Behavioral Intervention; RUBI). We then completed a feasibility trial in which five families of children with FXS and four families of children with DS completed a nine-session caregiver training program targeting behavioral principles, syndrome-specific information, and visual supports tailored to the unique needs of FXS or DS (adapted version of RUBI for non-autism developmental disabilities; RUBI-DD). The program demonstrated strong acceptability, with high caregiver satisfaction, 100% retention, and 100% session attendance. Across the combined sample, caregiver reports indicated significant improvements in irritability/aggression (F_(2,15.14) = 4.42, p = 0.03), lethargy/social withdrawal (F_(2,14.47) = 3.97, p = 0.04), stereotypies (F_(2,15.29) = 4.45, p = 0.03), hyperactivity (F_(2,15.14) = 6.51, p = 0.009), social inflexibility (F_(2,15.43) = 6.33, p = 0.01), demand-based noncompliance (F_(2,15.41) = 4.95, p = 0.02), and the impact of behavior on the family (F_(2,15.07) = 4.23, p = 0.04) following participation in RUBI-DD. Caregivers of children with FXS reported significant reductions in lethargy/social withdrawal (F_(2,8.000) = 6.256, p = 0.023) and hyperactivity (F_(2,8.000) = 12.497, p = 0.003) immediately post-treatment and upon 12-week follow-up (g = 1.153, p = 0.044, and g = 1.178, p = 0.003, respectively). Among families of children with DS, caregivers reported reductions in irritability and aggression (F_(2,5.047) = 14.073, p = 0.009) and improvements in the impact on the family (F_(2,6.000) = 5.489, p = 0.044) immediately post-treatment and at follow-up (g = 1.643, p = 0.016, and g = 0.448, p = 0.045, respectively). These findings support the feasibility, acceptability, and preliminary efficacy of RUBI-DD for children with FXS or DS. Full article

The Atomic Clock Ensemble in Space (ACES) mission, currently operating aboard the International Space Station (ISS), is designed to provide high-precision time and frequency measurements and to test fundamental aspects of relativistic physics. Gravitational redshift (GRS), a fundamental prediction of General Relativity (GR), implies that clocks positioned at different gravitational potentials experience relative time dilation. Previous GRS experiments have focused primarily on microwave technologies, with negligible experimental coverage in the optical domain, particularly for ground-to-space links. Motivated by the European Laser Timing (ELT) experiment and the high-precision laser-cooled cesium clock aboard ACES, we introduce and evaluate an optical time-transfer method designed to achieve high-accuracy measurements of GRS. In the absence of actual ELT/ACES optical data, a high-fidelity numerical simulation framework was developed to assess the performance of this method. The framework incorporates representative ELT/ACES mission parameters, including the space-based cesium clock and the H-MASER clock located at the reference ground station, both providing frequency stability at the level of ${10}^{-15}$ for 1000 s averaging time. Applying a $\pm 1\sigma$ filtering criterion, we obtain a simulated dataset comprising 33 ELT/ACES passes, representing a total observation time of 4.38 h over a single week. Analysis of this high-fidelity dataset reveals a GRS deviation from GR of $(-7.19\pm 0.63)\times {10}^{-5}$, achieving a 3.4 orders of magnitude improvement over the best previous laser-ranging experiment conducted at the University of Maryland (UMD), USA, 51 years ago. These simulation results demonstrate that the optical time-transfer link constitutes a powerful tool for testing fundamental physics and, when combined with next-generation optical atomic clocks, enables unprecedented capabilities in space-based timekeeping and geoscience applications. Full article

Visual transgenic marker systems enabling rapid and non-destructive transformant detection are crucial for efficient plant genetic transformation and selection. RUBY is a highly effective reporter system based on betalain biosynthesis; however, its application to species outside of the order Caryophyllales (i.e., species lacking betalains) has not been established. In this study, we performed the first systematic evaluation of the RUBY system using Petunia × hybrida lines obtained via Agrobacterium-mediated gene transformation. Stable RUBY transgenic plants were obtained from an optimized transformation and organogenesis system. The transgenic lines displayed a gradient of betalain accumulation, with pigment intensity positively correlated with RUBY expression levels and metabolite contents. In a morphological analysis, there was a negative correlation between RUBY expression and corolla opening, suggesting that RUBY pigment overaccumulation is associated with altered floral development and morphology. RUBY overexpression significantly reduced expression levels of gibberellin biosynthetic genes (PhGA20ox1 and PhGA3ox1) and flowering- and senescence-related regulators (PhNF-YC2 and PhOBF1). These findings indicate that high-level betalain accumulation is associated with changes in floral development and gene expression, highlighting both the utility of the RUBY system as a visual reporter and the importance of carefully evaluating potential developmental effects under strong expression conditions. Full article

In the post-pandemic era, monitoring adaptive immunity of the population to emerging SARS-CoV-2 variants remains an important public health priority. To address this need, we developed a test that can simultaneously assess the neutralization ability of three SARS-CoV-2 variants. A panel of lentiviral pseudoviruses, each bearing the S-protein of different SARS-CoV-2 variants (Wuhan-Hu-1, BA.1, and XBB.1.5) and expressing a unique fluorescent protein (Clover, mRhubarb713, or mRuby3) was generated and used to transduce hACE2-overexpressing cells. The percentage of infected target cells for each variant was quantified via flow cytometry. Co-infection led to a minor reduction in the percentage of infected cells compared to mono-infection controls, confirming the robustness of the assay. We then applied the test to the analysis of human sera samples, which were collected in the Sirius Federal Territory (Russian Federation) and revealed the following: (1) sera collected in 2021 neutralized the Wuhan-Hu-1 variant and demonstrated cross-specificity to the BA.1 variant, but not to the XBB.1.5 variant; (2) sera collected after the Omicron emergence point neutralized Wuhan-Hu-1 and BA.1, and possessed a weak ability to neutralize the XBB.1.5. This assay provides a valuable tool for efficient profiling of humoral immunity and monitoring its development in response to ongoing viral diversity. Full article

Background: COVID-19 can have adverse effects on individuals’ lung functions for up to 6 months or more after the episode. As a result, people may be reluctant to exercise, and this can have further adverse effects on their lung capacity and fitness. This study aimed to examine the effectiveness of a telemedicine program designed to increase the exercise participation of young adults after COVID-19 and evaluate the changes in lung function after exercise training. Methods: The quasi-experimental pre–post study recruited sixty university students who had suffered from COVID-19 within the past 12 months. Four pulmonary outcomes were compared: forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), and the ratio of FEV1 to FVC. The telemedicine exercise (TE) group (n = 36) received an intervention to carry out regular stepping exercise (up to 10,000 steps) via online video instruction and frequent WhatsApp reminder messages. The control group (n = 24) only received an initial WhatsApp message to carry out regular stepping exercise, with no further follow-up. Results: The FVC, FEV1, and FEV1/FVC ratio revealed significant overall improvement both within groups and between groups (p < 0.001), with moderate effect sizes. PEFR showed a significant improvement within groups (p = 0.007) but not between groups (p = 0.533). The TE group recorded a significant increase in daily step count (from 7165 to 9733, p < 0.001) after 4 weeks of training. The control group showed a significant reduction in step count (from 6975 to 6442, p = 0.049). Conclusions: The results confirmed the beneficial effects of the telemedicine exercise program in contributing to increased exercise participation and improved lung functions. Full article

Deteriorated seeds of okra varieties ‘Smooth Green’ and ‘Red Ruby’ were reinvigorated by soaking in plasma-activated water (PAW). After PAW treatment, germination and seedling characteristics were determined and compared with hydroprimed deteriorated seeds, unprimed deteriorated seeds, and healthy untreated seeds. Differences among treatments were analyzed using ANOVA and Tukey’s HSD test at α = 0.05. PAW-treated deteriorated seeds exhibited higher vigor and faster germination in both varieties compared with untreated seeds. Furthermore, PAW-treated seedlings developed longer and heavier shoots and roots. It is concluded that soaking deteriorated seeds in PAW enhanced germination by 12–16%. These findings demonstrate that PAW treatment can improve the germination and seedling characteristics of deteriorated okra seeds. Full article

Background/Objectives: National data show that about 250 preschoolers are suspended or expelled daily in the United States. Jump Start is a multi-tiered infant and early childhood mental health consultation program that strengthens early care and education centers’ capacity to support children’s social–emotional development and prevent school suspension and expulsion. This retrospective study examined center-level exclusionary discipline practices, Jump Start participation, and related changes in discipline and expulsion policies. Methods: Data from 270 early care and education centers across Miami-Dade County that received Jump Start services during one of three academic years (2022–2023, 2023–2024, or 2024–2025) were included. Analyses examined associations between baseline exclusionary discipline practices, program duration, discipline and expulsion policy changes, and post-Jump Start exclusionary discipline practices. Results: Statistically significant reductions were observed in the frequency of traditional suspensions/expulsions and soft expulsions following Jump Start participation. The association between the Jump Start duration and post-Jump Start soft expulsions was significantly moderated by changes in center discipline policies, such that Jump Start was effective at reducing soft expulsions only when discipline policies showed meaningful improvement. Conclusions: Infant and early childhood consultation models, such as Jump Start, show promise in reducing exclusionary discipline practices, especially when implementation improves discipline policies. Full article

Background/Objectives: Inappropriate use of antibiotics contributes to the rise in antibiotic-resistant bacteria and can result in adverse drug effects for individuals. Informed discussions between patients and general practitioners (GPs) can help ensure that treatment decisions about antibiotic use align with the best health outcomes for individuals. Methods: We implemented a set of information resources designed to support clinical discussions and decision-making for patients with common infections in primary care. A suite of patient information sheets, which had been co-designed with primary care providers and consumers, were implemented in eight general practices in metropolitan Melbourne and regional Victoria, from August to November 2020. Results: Post-implementation evaluation, conducted through interviews with 15 primary care providers and 13 patients, revealed that the information sheets were simple, easy to use and generated discussion within consultations. GPs reported using the sheets to reinforce their decision-making during consultations with patients, reduce potential conflict, provide alternatives to antibiotic prescriptions, and offer patients a written summary of management recommendations. Patients found the sheets informative and that they made it easier to understand their diagnosis and to manage their conditions. Both GPs and patients agreed that the content was relevant and effectively enhanced patients’ knowledge of disease conditions, treatment options, and when to seek medical advice and were facilitators of meaningful conversations during consultations. Conclusion: These resources are acceptable in Australian primary care and publicly available for use by GPs, pharmacists and patients in Australia. Full article

Ascending placentitis is a significant cause of equine pregnancy loss, yet the upstream inflammatory triggers are poorly defined. Recently, we identified S100A8/S100A9 (S100A8/A9) alarmins as potential upstream regulators in a chronic equine placentitis model. The current study aimed to determine whether this upregulation is sustained in the acute model and in clinical cases, and to elucidate the expression of their downstream inflammatory mediators. Using an experimental model, we quantified S100A8/A9 mRNA expression in acute (n = 5) and chronic (n = 6) placentitis induced by Streptococcus equi ssp. zooepidemicus. We found mRNA expression of S100A8 and S100A9 was significantly upregulated in chorioallantois during both acute (p < 0.001) and chronic (p < 0.0001) disease compared to controls (n = 5), demonstrating their role is not limited to chronic pathology. A strong positive correlation (r = 0.945) underscored their coordinated expression. Immunohistochemistry revealed minimal staining in controls but dense infiltrations of S100A8/A9-positive neutrophils and macrophages in placentitis tissues. To define the clinical relevance of the downstream pathway, we analyzed RNA sequencing data from clinical placentitis cases (placentitis, n = 4) compared to normal postpartum placenta (control, n = 4). This confirmed upregulation of S100A8/A9 and revealed a concurrent increase in their receptors (TLR4, RAGE) and a spectrum of NF-κB-driven effectors, including pro-inflammatory cytokines (IL1β, IL6, TNF), chemokines (CXCL8, CCL2, CXCL10), and the apoptotic mediator CASP3. Our findings establish that S100A8/A9 upregulation is a sustained feature of equine placentitis and delineates a coherent S100A8/A9-TLR4/RAGE-NF-κB signaling axis that drives inflammation and tissue damage in clinical disease. These findings highlight the diagnostic potential of S100A8/A9 and position this alarmin system as a promising therapeutic target for mitigating infection-induced pregnancy loss. Full article

Several mammarenaviruses (MaAv), chiefly Lassa virus (LASV) in Western Africa and Junin virus (JUNV) in the Argentinean Pampas, cause severe disease in humans and pose important public health problems in their endemic regions. In addition, the globally distributed MaAv lymphocytic choriomeningitis virus (LCMV) is an underrecognized human pathogen of clinical significance, especially in congenital infections, and LCMV poses a serious risk for immunocompromised individuals. There are no FDA-approved MaAv vaccines or antivirals, and current anti-MaAv therapy is limited to an off-label use of ribavirin, whose efficacy remains controversial. This highlights an urgent unmet need for developing antivirals against human pathogenic MaAv. Halofuginone (HF), a derivative of the natural alkaloid febrifugine, has been shown to exhibit antiviral activity against several RNA viruses. Here, we present evidence that HF exhibits potent dose-dependent antiviral activity against LCMV, and against the hemorrhagic fever causing MaAv LASV and JUNV. HF binds to the bifunctional enzyme glutamyl-prolyl-tRNA synthetase 1 (EPRS1) and specifically inhibits its prolyl-tRNA synthetase (PRS) activity, resulting in translation inhibition via the amino acid starvation (AAS) response with preferential impact on proline-rich proteins. HF anti-LCMV activity was prevented by the addition of exogenous proline supporting that inhibition of PRS activity plays a critical role in the anti-MaAv activity of HF. We found that HF did not affect LCMV cell entry, modestly (twofold) reduced the activity of the virus ribonucleoprotein (vRNP), but strongly inhibited (>90%) Z budding activity, a process involving the Z proline-rich late domain motifs. Full article