Search Results (7,148)

The therapeutic landscape of adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is undergoing a paradigm shift, driven by the development of immunotherapy-based “chemo-free” and “chemo-light’ regimens. These strategies aim to achieve high efficacy with reduced toxicity, particularly in older adults who may not tolerate intensive chemotherapy. In Philadelphia chromosome-positive (Ph+) BCP-ALL, the incorporation of ABL tyrosine kinase inhibitors (TKIs) with blinatumomab (CD3/CD19 bispecific T-cell engager) has shown remarkable efficacy, with some studies reporting molecular response rates in the range of 90–100% and long-term survival exceeding 80% without the need for intensive chemotherapy or allogeneic hematopoietic cell transplantation (allo-HCT). In Philadelphia-negative (Ph−) BCP- ALL, an immunotherapy-based combination of blinatumomab and inotuzumab ozogamicin (anti-CD22 antibody-drug conjugate) has demonstrated high rates of complete remission and measurable residual disease (MRD) negativity, with manageable toxicity. While chimeric antigen receptor (CAR) T-cell therapy remains a transformative option for relapsed/refractory B-ALL, its integration into frontline treatment is still under investigation. Ongoing trials are evaluating the optimal sequencing and combinations of these agents and their potential to obviate the need for chemotherapy and/or allo-HCT in selected patients. As evidence continues to accumulate, chemo-free and chemo-light regimens, incorporating minimal chemotherapy with targeted agents to balance efficacy and reduced toxicity, are poised to redefine the standard of care for adults BCP-ALL, offering the possibility of durable remissions with reduced treatment-related morbidity. Full article

Background/Objectives: Proteinuria, a marker of renal dysfunction, has been implicated in cancer risk, yet its role in gastric carcinogenesis remains underexplored in high-incidence populations. This study evaluated the association between urine dipstick proteinuria severity and gastric cancer incidence in a nationwide Korean cohort. Methods: We analyzed data from the Korean National Health Insurance Service–National Sample Cohort, including 220,941 adults aged > 40 years, without a diagnosis of cancer, who received health examinations in 2009. Proteinuria was classified by single dipstick testing as negative, 1+, or ≥2+. Participants were followed for a mean of 4.37 ± 0.49 years (965,601.2 person-years). Multivariable Cox proportional hazards models adjusted for age, sex, body mass index, systolic blood pressure, fasting glucose, LDL cholesterol, estimated glomerular filtration rate, smoking status, alcohol intake, and physical activity were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During follow-up, 1934 participants (0.88%) developed gastric cancer. A significant dose–response relationship emerged (p for trend = 0.037). In fully adjusted models, 1+ proteinuria conferred no significant risk increase (HR 1.10; 95% CI, 0.80–1.51), whereas ≥2+ proteinuria was associated with a 42% higher gastric cancer risk (HR 1.42; 95% CI, 1.00–2.02). Conclusions: Severe dipstick proteinuria independently predicts elevated gastric cancer risk in Korean adults. Integration of urine dipstick testing into gastric cancer screening protocols may offer a simple, cost-effective strategy for risk stratification, particularly in high-incidence settings. Full article

Background: Parenting styles are associated with various health outcomes among children, such as fruit and vegetable consumption, physical activity, and emotional well-being. Previous literature suggests that responsive parenting styles are associated with improved mental health outcomes. This study examines the association between an adult’s responsive parenting style and the psychosocial outcomes of emotion regulation and loneliness among children. Methods: Using data from the U.S. National Cancer Institute’s Family Life, Activity, Sun, Health, and Eating (FLASHE) cross-sectional survey, this secondary data analysis study seeks to understand how perceived parental responsiveness is associated with adolescents’ emotional health outcomes from the perspective of the adolescent. The sample consisted of 12- to 17-year-olds (n = ~1560), mostly female (50.2%) and non-Hispanic White (63.7%), with a mean age of 14.48 years (SD = 1.61). Results: Through multivariable regression, we found that perceived parental responsiveness negatively predicted adolescent emotion suppression (β = −0.29, p < 0.001), even after controlling for sex, age, race/ethnicity, parental marital status, parental education level, parent’s time spent at work, and the number of kids in the household (β = −0.29, p < 0.001). We also found that perceived parental responsiveness was the strongest predictor for adolescent loneliness (β = −0.27, p < 0.001), even when controlling for sex, age, race/ethnicity, parental marital status, parental education level, parent’s time spent at work, and the number of kids in the household (β = −0.28, p < 0.001). Conclusions: These results suggest that implementing interventions targeting parental responsiveness may be beneficial to improving adolescents’ emotional well-being. Full article

Objectives: Sex-based disparities in COVID-19 outcomes are well-documented, with men experiencing greater acute severity and women showing increased vulnerability to post-viral syndromes. However, longitudinal immunometabolic trajectories in vaccinated individuals remain underexplored. In this study, sex-based differences in long-term metabolic, endocrine, renal, cardiovascular, and inflammatory responses were investigated among vaccinated individuals recovering from SARS-CoV-2 infection. Methods: This retrospective single-center cohort study included 426 adults (199 females, 227 males) with PCR-confirmed symptomatic COVID-19 and at least two vaccine doses. Serial assessments were conducted at baseline, 18-, 24-, and 30-month post-infection. Parameters included fasting glucose, HbA1c, lipid profile, thyroid function, renal markers, CRP, D-dimer, fibrinogen, troponin, and hematologic indices. Statistical analyses assessed longitudinal changes and sex-stratified correlations. Results: Fasting glucose and HbA1c levels significantly declined over time, more prominently in males. Glucose correlated with age and BMI only in females. Lipid levels remained largely unchanged, although males had higher baseline triglycerides. Females showed rising TSH levels and persistently lower free T3; males exhibited higher creatinine, urea, and troponin levels throughout. Inflammatory markers declined significantly in both sexes, with males displaying higher CRP and troponin, and females showing sustained fibrinogen elevation and a temporary lymphocyte surge. D-dimer was elevated in females at the 30-month point. Conclusions: Sex-specific physiological recovery patterns were evident among vaccinated COVID-19 survivors. Males exhibited earlier metabolic and cardiac alterations, while females had more persistent endocrine and inflammatory shifts. These findings underscore the need for sex-tailored long-term monitoring strategies prioritizing early metabolic and cardiac screening in men and prolonged immunoendocrine surveillance in women. Full article

A greater understanding of health-promoting factors, such as hope, is crucial for preventing and enhancing the mental health of higher education students. The Herth Hope Index (HHI) is a 12-item tool that has been widely used to assess a comprehensive, non-temporal perception of hope. While this instrument has been used extensively in adult populations, most studies focus on clinical populations. Additionally, the HHI reveals inconsistencies in terms of scale dimensionality and items to be retained. Therefore, this study sought to assess the HHI’s psychometric characteristics in a sample of Portuguese Higher Education students. The person response validity, internal scale validity, unidimensionality, and uniform differential item functioning were assessed using a Rasch rating scale model. A total of 2227 higher education students participated during the e-survey activation period (spring semester of 2020). The mean age of the sample was 22.5 ± 6.2 years (range 18–59 years). Three of the twelve items (#3, #5, and #6) failed to satisfy the established criterion for goodness of fit. Following the elimination of these three items, the resultant nine-item scale exhibited satisfactory item fit to the model, appropriate unidimensionality (52.4% of the variance explained), enough person goodness of fit, sufficient separation, and the absence of differential item functioning. The 9-item version of the HHI had psychometric properties comparable to the original 12-item version. This study also underscores the importance of validated instruments for assessing hope-based interventions in academic contexts. Further research is necessary to explore the potential dimensions inherent to the hope concept and to identify variations in hope profiles among items influenced by cultural attributes. Full article

Nuclear processes are fundamental to the regulation of cellular, tissue, and organismal function, especially in complex multicellular systems. Central to these processes are lamins and lamin-associated proteins, which contribute to nuclear structure, gene expression, and chromatin organization. The discovery that mutations in genes coding for lamins and lamina-associated proteins give rise to rare disorders—collectively called laminopathies—has intensified interest in this field among cell biologists and medical scientists. While many practical and clinically relevant questions about phenotype development and potential treatments require mammalian models, key molecular mechanisms and interactions have also been effectively studied in both vertebrate and invertebrate systems. This review focuses on a discussion of Drosophila lamins, their major properties, functions, interactions and post-translational modifications, with comparison to mammalian lamins, and a discussion of the value of fly models in studies of lamins in muscle tissue development and function in comparison to mammalian lamin B-type and A/C-type. In this paper, we have discussed the overall impact of lamin Dm and lamin C level manipulations on overall phenotype, especially on larval and adult muscles. We have thoroughly discussed the conclusions, which may have been drawn from experiments with overexpression of lamin C mutants mimicking lamin A laminopathy mutations. We have presented and discussed the suggestion that the mechanisms underlying Drosophila muscle phenotype development are similar not only to human dystrophic laminopathies but also to classical human muscular dystrophies such as Duchenne muscular dystrophy and Hutchison–Gilford Progeria syndrome. We suggest that the activation of the stress response contributes to the laminopathic phenotype detected in Drosophila. Finely, this review discusses in depth the lamin Dm and lamin C interactomes, discrepancies between String-based interactome networks, and our map of interactomes based on manual verification of experimental data on Drosophila lamin interactions. Full article

Background. Parkinson’s Disease (PD) is a neurological condition that can severely impair gait, often through changes to gait parameters including stride length, velocity, and variability. Therapeutic interventions such as Rhythmic Auditory Stimulation (RAS^®) target gait dysfunction in PD by using the regular beat of music or metronome clips to cue normalized walking patterns. Previous research has suggested that auditory cue properties (e.g., familiarity and groove) and individual factors (e.g., beat perception ability and susceptibility to dual-task interference) influence auditory cueing treatment efficacy in healthy young and older adults; however, optimization of rhythmic cueing across individuals with PD remains understudied. Methods. To address this, we explored the effects of familiarity, groove, beat perception ability, and synchronization instructions on gait in patients with PD during accelerated auditory cues. Individuals with idiopathic PD were randomized to walk freely or synchronized to music and metronome cues played 10% faster than their baseline walking cadence. Musical stimuli varied in self-reported familiarity and perceived groove and beat perception ability was assessed to classify participants as good or poor beat perceivers. Results. Overall, high-groove music and synchronized walking elicited faster gait patterns compared to low-groove music and free walking, respectively, as demonstrated by increased gait velocity and cadence. Familiarity and beat perception ability did not significantly affect gait in individuals with PD. Discussion. Altogether, our results indicate that high-groove music and synchronized walking lead to the greatest gait improvements during cueing, regardless of beat perception ability. Conclusion. Future studies and clinical interventions should consider stimulus type and synchronization instructions when implementing cueing therapies for gait dysfunction in PD in order to optimize treatment responses. Full article

Background/Objectives: Recently, concerns about age-related conditions, such as sarcopenia and chronic inflammation, have increased owing to the global acceleration of population aging. Notably, these conditions are interrelated and further exacerbate functional decline in older adults. Therefore, this study aimed to evaluate the efficacy of a novel bioactive compound, DuoX (a mixture of the postbiotic beLP1 and Cichorium intybus L.), in alleviating muscle wasting and chronic inflammation. Specifically, the mixture consisted of inulin-rich C. intybus L. root extract, known for its anti-inflammatory effects, and beLP1, a postbiotic previously shown to exert anti-sarcopenic effects. Methods: To assess the multifunctional effects of the DuoX, dexamethasone-induced sarcopenia models (C2C12 myotubes and an in vivo rat model) and a lipopolysaccharide-stimulated RAW 264.7 macrophage inflammation model were established. Results: Pretreatment with DuoX prevented the dexamethasone-induced reduction in myotube diameter and effectively inhibited muscle degradation by downregulating the expression of atrogin-1 caused by dexamethasone treatment. In rats with DEX-induced sarcopenia, DuoX prevented muscle weight loss, grip strength reduction, and the upregulation of atrogin-1 expression in vivo. In lipopolysaccharide-stimulated RAW 264.7 macrophages, DuoX significantly reduced nitric oxide production and cyclooxygenase-2 protein expression and suppressed p38 and ERK phosphorylation in the MAPK signaling pathway, thereby alleviating inflammatory responses. Conclusions: DuoX holds promise as a dual-functional candidate with both anti-sarcopenic and anti-inflammatory properties. Further preclinical and clinical studies are required to validate its therapeutic efficacy and safety in humans, which may contribute to the development of preventive strategies for healthy aging. Full article

Patient activation enhances self-management of chronic illnesses, and sleep quality is vital for health. The link between activation and sleep quality and the mediating role of chronic diseases remain underexplored. This study examined the association between patient activation and sleep quality, variations across chronic disease groups, and whether chronic diseases mediate this relationship. A population-based cross-sectional survey in South Tyrol (Italy) included 2090 adults (55.0% response rate). Patient activation was measured using the Patient Activation Measure (PAM-10), and sleep quality was measured using the Brief Pittsburgh Sleep Quality Index (B-PSQI). The presence and number of chronic diseases were self-reported. Bivariate analyses, multiple linear regression, and mediation analyses (PROCESS) were performed. Among the participants, 918 (44%) reported at least one chronic disease. These individuals had poorer sleep (B-PSQI mean: 5.05 ± 3.26 vs. 3.66 ± 2.65; p < 0.001) and lower patient activation (PAM-10: 54.4 ± 12.7 vs. 57.2 ± 12.5; p < 0.001) than those without. A negative correlation between PAM-10 and B-PSQI was observed (r = −0.12, p < 0.001), with stronger associations in patients with hypertension and mental illness. In adjusted regressions, chronic disease, female sex, and older age predicted poorer sleep, whereas higher PAM-10 scores predicted better sleep. Mediation analyses showed that chronic disease partially mediated the relationship between patient activation and sleep quality, accounting for 4.7% to 6.3% of the total effect. Conclusions: Higher patient activation correlates with better sleep quality, although this relationship is partly mediated by the chronic disease burden. Sleep disturbances persist across chronic conditions, despite good self-management. These findings highlight the importance of adopting strategies to manage chronic diseases and sleep disturbances, acknowledging that while patient activation is statistically associated with sleep quality, the strength of this relationship is limited. Full article

Background and Objectives: Total body irradiation (TBI) remains a cornerstone of conditioning for allogeneic haematopoietic stem-cell transplantation (HSCT). Whereas early research debated the need for irradiation, contemporary investigations focus on optimising dose, fractionation and delivery techniques. Material and Methods: We synthesised six decades of evidence, spanning from single-fraction cobalt treatments to modern helical tomotherapy and intensity-modulated total-marrow/lymphoid irradiation (TMI/TMLI). To complement the literature, we reported our institutional experience on 77 paediatric and adult recipients treated with conventional extended-source-to-skin-distance TBI at the University Hospital Policlinico “G. Rodolico–San Marco” between 2015 and 2025. Results: According to literature data, fractionated myeloablative schedules, typically 12 Gy in 6 fractions, provide superior overall survival and lower rates of severe graft-versus-host disease (GVHD) compared with historical single-dose regimens. Conversely, reduced-intensity protocols of 2–4 Gy broaden HSCT eligibility for older or comorbid patients with acceptable toxicity. Conformal planning reliably decreases mean lung dose without compromising engraftment, and early-phase trials are testing selective escalation to 16–20 Gy or omission of TBI in molecularly favourable cases. With regard to our institutional retrospective series, 92% of patients completed a 12-Gy regimen with only transient grade 1–2 nausea, fatigue or hypotension; all transplanted patients engrafted, and no grade ≥ 3 radiation pneumonitis occurred. Conclusions: Collectively, the published evidence and our experience support TBI as an irreplaceable component of HSCT conditioning and suggest that coupling it with advanced imaging, organ-sparing dosimetry and molecular response monitoring can deliver safer, more personalised therapy in the coming decade. Full article

In the absence of commercialized vaccines for most arboviruses, including dengue, chikungunya, and Zika, which are transmitted by Aedes aegypti, the management of vector populations to prevent disease transmission remains the cornerstone of arbovirus control strategies. Larviciding targets the early stages of the mosquito life cycle and subsequently reduces the capacity of adult population to transmit pathogens. Here, we report the susceptibility profile of Ae. aegypti larval populations from two West Africa cities, namely Niamey and Ouagadougou, to organophosphates larvicides. In Niamey, sampling was carried out using ovitraps at two sites, whereas in Ouagadougou, larvae were collected from three different types of larval containers at a single site. Temephos and fenitrothion were tested at six different concentrations each. Mosquito populations from Niamey and Ouagadougou were found susceptible to temephos and fenitrothion, with LD₅₀ < 0.015 mg/L and RR₅₀ < 5. However, Ae. aegypti populations from Ouagadougou showed reduced susceptibility to temephos compared to baseline data from 2016, as indicated by RR₅₀ values. This observation highlights the need for regular surveillance of larval susceptibility, as it may signal the emergence of temephos resistance in Ouagadougou. The acetylcholinesterase (AChE) mutation and the expression levels of metabolic genes Carboxy-/Cholinesterase (CCE) should be characterized to understand the molecular mechanisms underlying the observed phenotype response. Our results provide up-to-date data that could inform the potential deployment of these larvicides for the prevention and control of dengue and chikungunya outbreaks in Ouagadougou and Niamey. Full article

Background/Objectives: This study conducted a secondary and integrative analysis of qualitative data on adolescents and young adults (AYAs) with biliary atresia who survive with their native livers. These individuals struggle with independence and self-care due to prolonged parental involvement. Prior studies have insufficiently clarified how AYAs and parents jointly navigate daily responsibility transitions during this period. Therefore, we aimed to elucidate this process and develop a practical model to support nursing care. Methods: Semi-structured interview data from eight adolescent–parent dyads (one male and seven females, aged 17–25; one father and seven mothers, aged 40–60) were reanalyzed using the modified grounded theory approach. By reframing the analytical focus on dyadic interactions, four transition phases were identified, which were then integrated with the findings of two prior studies to construct an integrative process model. Results: The transition comprised four phases: (1) parent-led recuperation, (2) a vicious cycle of control and rebellion, (3) passing the axis of responsibility, and (4) aligning the parent–child rhythm to create a patient-centered life. The transition processes were shaped by changes in cognition and behavior. The model illustrates mutual adaptation through communication, negotiation, and reflection, identifying opportunities for nursing intervention. Conclusions: This process model offers a practical framework for nurses to assess readiness for care transitions, support transitional role shifts, and co-develop care strategies. The model provides insights into relationship-based communication and shared decision-making in transitional care by capturing the relational dynamics between AYAs and their parents. Full article

Background/Objectives: Developmental coordination disorder (DCD) commonly co-occurs with attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and specific learning disorder (SLD), affecting academics, mental health, and lifestyle. Although screeners such as the Adolescents and Adults Coordination Questionnaire (AAC-Q) are widely used elsewhere, recognition and support for DCD in Japan remain limited. This study examined associations among DCD traits, ADHD/ASD-related difficulties, learning difficulties, mental health difficulties, and lifestyle factors in university students. Methods: We conducted a web-based survey of 16,295 students; responses from 527 were analyzed. The instruments used for the analysis included the AAC-Q, short forms of ADHD and ASD Difficulty Scales, the 7-item Learning Difficulty Scale for Postsecondary Students and 10-item Scale for Childhood Learning Difficulties, and the University Personality Inventory (UPI). Nonparametric and Spearman’s rank correlations were performed. Results: DCD traits were observed at 7.4% (AAC-Q ≥ 32). This is a screen-positive proportion only. AAC-Q scores correlated strongly with ADHD difficulties (r = 0.65), moderately to strongly with ASD difficulties (r = 0.55), and moderately with mental health difficulties measured by the UPI (r = 0.41). Conclusions: These findings suggest that identifying DCD traits at university entry may be associated with greater student self-understanding and improved access to appropriate support. They support targeted DCD screening alongside ADHD/ASD screening at university entry, rather than universal screening. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a modulator of infection severity, yet its impact on the immune response in severe community-acquired pneumonia (sCAP) remains poorly understood. In this prospective cohort study of 108 adults with sCAP, we evaluated the prevalence and prognostic impact of MASLD and performed pathogen-stratified immune profiling of cytokines and semaphorins on hospital days 1 and 5. MASLD was present in 50% of patients and independently associated with early respiratory failure (OR 3.8) and vasopressor-dependent shock (OR 4.0), despite similar sCAP severity at baseline. MASLD patients exhibited distinct immune profiles, including elevated baseline serum levels of SEMA3A, SEMA7A, IL-2, IL-10, IL-17A, CXCL10, and TGF-β1, and reduced SEMA5A. By day 5, the MASLD group exhibited a greater decline in pro-inflammatory mediators compared to non-MASLD patients but failed to upregulate reparative mediators such as SEMA4D and TGF-β1, unlike the non-MASLD group. These kinetics may suggest a maladaptive immune response in MASLD, potentially consistent with early immune exhaustion. Immunokinetic patterns were pathogen-specific, including transient increase in IL-17A and IL-10 in Legionella and Mycoplasma infections, and CXCL10, IL-2, IL-17A, TGF-β1 and IL-10 in influenza. Serum IL-10, CXCL10, SEMA3F, SEMA4D and SEMA7A correlated with organ failure and sCAP complications. These findings underscore the clinical importance of the lung–liver axis and suggest that semaphorins could serve as valuable prognostic biomarkers for identifying high-risk patients. Full article

It is widely accepted that chronic inflammation constitutes a significant mechanism that promotes the biological aging process. The pineal gland is regarded as being closely related to the control of the “life clock”. The present study aimed to determine the inflammation associated with pinealectomy in the rat hippocampus and to investigate the extent to which age stage impacts the severity of this inflammation. We evaluated the expression of the Akt/NF-kB signaling pathway in neurons and gliosis level in the dorsal hippocampus (dHipp) of rats subjected to sham surgery or pinealectomy at 3, 14, or 18 months of age. The assessment was conducted using immunohistochemistry. Removal of the pineal gland resulted in significant, region-specific increases in NF-kB expression in neurons of the dHipp in the youngest and middle-aged groups. However, the change in expression of the phosphorylated form of Akt (pAkt1) in neurons went in the opposite direction in these two age groups, and there were also regional differences. Pinealectomy triggered microgliosis in both young and old rats, but middle-aged rats were resistant to microglia activation. Conversely, astrogliosis was observed in young adult and middle-aged groups with melatonin deficiency in certain regions of the dHipp. It is noteworthy that young adult rats demonstrated the highest degree of vulnerability to inflammation associated with the loss of melatonin as a hormone. In contrast, middle-aged rats with pinealectomy exhibited a complex and partial adaptive response. These findings emphasize the dynamic and age-dependent nature of neuroinflammation following pinealectomy, underscoring the developmental stage as a critical determinant of inflammatory susceptibility. Full article