Search Results (491)

Background: Pneumococcal conjugate vaccines (PCVs) prevent severe disease in children, but high costs limit access. PCV10-SII (PNEUMOSIL), a 10-valent PCV prequalified by the World Health Organization (WHO) in 2019, offers a cost-effective alternative. This study assessed its safety and immunogenicity in Vietnamese children aged 6 weeks–24 months. Methods: An open-label, single-arm study enrolled 304 children in three age groups: 6 weeks–6 months (n = 151), >6–12 months (n = 76), and >12–24 months (n = 77). Participants received two or three doses. Safety was evaluated through immediate reactions, adverse events (AEs), serious adverse events (SAEs), and withdrawals. Immunogenicity was measured 28 days after the final dose using serotype-specific IgG geometric mean concentrations (GMCs), opsonophagocytic activity (OPA) titers, and seroresponse rates. The trial was approved by the IRB of the National Ethics Council (code: No. 75/CN-HĐĐĐ on date 4 June 2021) and was registered with ClinicalTrials.gov, NCT05140720. Results: Of 304 enrolled participants, 294 (96.7%) completed follow-up. No immediate adverse events or serious adverse events occurred. Unsolicited adverse events were reported in 17%, mainly respiratory, while serious adverse events occurred in 4%. Mild local/systemic reactions (e.g., injection site pain, crying) resolved without sequelae. Immunogenicity was strong, with GMCs 1.8–9.11 µg/mL, GMTs 277.8–22,342, and seroresponse rates >90% for 9 of 10 serotypes, serotype 6B demonstrated a slightly lower seroresponse rate of 88.6%. Conclusions: PCV10-SII demonstrated favorable safety and robust immunogenicity, supporting its inclusion in national immunization programs as an affordable option for pneumococcal disease prevention. Full article

Global demand for sustainable protein has intensified amid environmental, public health, and ethical concerns surrounding conventional animal agriculture. Edible mushrooms have emerged as promising next-generation protein sources, delivering 19–35% protein (dry weight) with complete essential amino acid profiles and digestibility rates of 60–80%. Beyond protein, mushrooms provide bioactive compounds, including β-glucans, ergothioneine, phenolic acids, and vitamin D₂, supporting immunomodulatory, antioxidant, and anti-inflammatory functions. Enzymatically derived bioactive peptides further demonstrate antihypertensive and antimicrobial activity. This review systematically examines mushroom protein properties, processing technologies, and product performance across three application categories: meat analogs, functional snacks, and beverages. Advanced processing technologies including high-moisture extrusion, ultrasonic-assisted extraction, and microencapsulation have improved bioactive preservation and digestibility. From an environmental perspective, mushroom cultivation requires 85–90% less water and land than animal agriculture, with 80% fewer greenhouse gas emissions. However, critical gaps remain: extraction efficiency varies 3-fold across studies, only 15–23% of commercial products are supported by clinical trials, and techno-economic analyses are largely absent. Standardized processing protocols, large-scale clinical validation, and harmonized quality standards are essential to establish mushrooms as viable, commercially scalable protein alternatives. Full article

Recent findings in nutritional epidemiology report an association between high dietary phosphorus intake and increased cancer risk. Building on the author’s analysis of breast cancer incidence in the Study of Women’s Health Across the Nation (SWAN), this paper presents a theoretical–conceptual model and a hypothesis to guide further population-study replication. To strengthen the initial SWAN analysis signal, a sensitivity analysis increased the number of controls in the nested case–control design from four to five per case. This adjustment modestly raised the relative risk (RR) of breast cancer incidence among middle-aged women consuming >1800 mg/day of dietary phosphorus (compared with 800–1000 mg/day) from RR: 2.30 to 2.38 (95% CI: 0.95–5.95; p = 0.06), improving statistical precision from the original p = 0.07. However, the result remains an exploratory pilot signal, not a confirmed association. Because clinical trials cannot ethically expose participants to potential harm from phosphate toxicity, a confirmed association relies on observational research. As in historical tobacco–cancer investigations, secondary analyses are needed across large cohort studies to examine dietary phosphorus intake and incidence of major cancer types. Relevant cohorts include the Nurses’ Health Study, Women’s Health Initiative, Health Professionals Follow-Up Study, National Health and Nutrition Examination Survey (NHANES) Epidemiologic Follow-Up Study, European Prospective Investigation into Cancer and Nutrition (EPIC), and the Canadian Study of Diet, Lifestyle and Health. Effect estimates can be synthesized using meta-analytic methods following PRISMA-P 2015 guidelines. Dietary phosphate modification may offer a cancer prevention strategy with substantial public health impact and clinical implications. Full article

Artificial intelligence (AI) is rapidly reshaping head and neck surgical oncology by augmenting decision-making across the full perioperative continuum. This state-of-the-art review aims to provide head and neck surgical oncologists with a conceptual framework for understanding and critically appraising AI tools entering clinical practice, summarizing how machine learning, deep learning, and generative AI are being integrated into contemporary surgical workflows. Preoperative applications include detection of occult nodal metastasis and extranodal extension. Intraoperative innovations include augmented reality-assisted navigation, real-time margin assessment, and improving visual clarity and tissue handling for robotic platforms. Postoperatively, AI can predict complications like free flap failure and oncologic outcomes. Large language models are being operationalized for clinician-facing applications such as documentation and inbox support, as well as patient-facing education. Despite promising results, broad clinical deployment remains limited by concerns about privacy, validation, reliability, safety, and ethics. Widespread adoption will require prospective clinical trials, robust governance, and human-centered workflows that ensure AI remains a safe, assistive copilot. Full article

The integration of emerging technologies and real-world data is transforming the landscape of hematologic clinical trials. Artificial intelligence (AI) offers remarkable capabilities for predictive modeling, patient stratification, and adaptive trial design, while circulating tumor DNA (ctDNA) provides a minimally invasive biomarker for disease monitoring, the early detection of relapse, and treatment response assessment. Concurrently, real-world evidence (RWE) complements traditional clinical trial data by capturing treatment effectiveness, safety, and patient outcomes in broader, heterogeneous populations. This review examines the synergistic potential of AI, ctDNA, and RWE to optimize trial design and decision-making in hematologic malignancies. We discuss methodological innovations, including AI-driven patient selection, ctDNA-guided adaptive interventions, and the incorporation of RWE for external control arms and post-marketing surveillance. Key challenges, such as data standardization, regulatory considerations, and ethical implications, are also addressed. By integrating these advanced tools, clinical trials in hematology can achieve greater efficiency, precision, and translatability, ultimately accelerating the development of personalized therapies and improving patient outcomes. Full article

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that severely affects cognitive, behavioral, and functional abilities, creating a substantial burden for family members who provide continuous care. Caregivers often experience role changes, occupational imbalance, emotional distress, and reduced quality of life, although some report personal growth. These experiences extend beyond active caregiving and include anticipatory grief during disease progression and grief after the relative’s death. Despite this continuum, few studies have examined caregiving, loss, and bereavement from an integrative perspective. This protocol describes a mixed-methods study aimed at exploring the lived experiences of family caregivers of individuals with AD, focusing on how evolving relational, occupational, and identity-related losses influence their well-being and adaptation. Methods: A parallel convergent mixed-methods design will be used. The quantitative component consists of a cross-sectional observational study including 66 caregivers recruited through purposive sampling across kinship categories (spouse/partner, adult child, grandchild) and care settings (home care with day-center attendance vs. institutionalized care). Data will be collected using the Zarit Burden Interview, Role Checklist, Short Form-36 Health Survey, and Occupational Balance Questionnaire. Descriptive and subgroup analyses will be conducted using SPSS (version 27). The qualitative component comprises a multiple-case study with approximately 36 participants across three groups: caregivers living with individuals with AD, caregivers of institutionalized relatives, and bereaved family members. Semi-structured interviews (45–80 min) will be conducted online or in person, transcribed verbatim, and analyzed thematically using MAXQDA (version 26). Integration will follow a concurrent approach, combining quantitative and qualitative results through joint narratives and displays to produce a comprehensive interpretation. Discussion: This study aims to deepen understanding of the caregiving–grief continuum in families affected by AD by integrating quantitative indicators of burden, health status, and occupational balance with qualitative accounts of adaptation and meaning-making. Findings are expected to support the development of holistic, evidence-based interventions that promote caregiver well-being throughout the care trajectory and during bereavement. Ethics and Dissemination: Ethical approval was granted by the Research Ethics Committee of Universidad Rey Juan Carlos (Code: 041220246522024; 15 October 2025). ClinicalTrials.gov Identifier: NCT07251738. Registered November 2025. Protocol version: Version 2. Full article

This review aims to assess the clinical performance and application results of oral wearable devices in in vivo trials. Following a systematic search of PubMed, Cochrane, Embase, and Scopus databases up to 15 October 2025, and strict screening in accordance with PRISMA 2020 guidelines, 13 in vivo human trials were finally included for analysis. These were analyzed across four clinical functions: diagnosis, treatment, monitoring, and prevention. These devices have evolved from bulky prototypes into miniaturized, wireless systems with diverse diagnostic and therapeutic functions. Their applications now extend beyond common conditions like caries and bruxism to postoperative recovery and pediatric dental anxiety intervention. The findings show that some devices already offer practical value for clinical screening and auxiliary diagnosis. They demonstrate significant potential in early disease detection and medical cost control. However, development still faces many challenges. Technical issues include limited battery life, insufficient mechanical durability, and wireless transmission constraints within the oral environment. Furthermore, clinical evidence levels remain low, indications are narrow, and dedicated ethical and regulatory frameworks are lacking. Inconsistent regulatory standards, production costs, and clinician adoption hurdles slow its commercial development. In the future, the integration of AI, breakthroughs in energy harvesting, and the creation of digital health platforms will be key to overcoming technical bottlenecks. Full article

This review examines the current state of development and application of artificial intelligence (AI) tools for monitoring nutrition and physical activity in individuals with obesity, with a focus on the physiological complexity of energy balance and the role of chrono-nutrition. Energy intake and expenditure are dynamically coupled and circadian-regulated: meal timing and movement patterns influence insulin sensitivity, thermogenesis, and Non-Exercise Activity Thermogenesis within the same day. Traditional monitoring methods suffer from recall bias and low granularity, while isolated sensors operate in data silos, limiting accuracy. Effective solutions require multimodal, continuous, and temporally aligned data streams. Current AI models exhibit critical limitations in obesity-specific contexts: inaccurate gait and energy expenditure estimates due to biomechanical differences, dietary models underestimating glycemic variability, poor performance on mixed dishes, sauces, and culturally diverse foods, and a lack of validation against gold standards such as doubly labelled water (DLW) and weighed food records. This review proposes a paradigm shift toward obesity-specific AI design, including enriched datasets and multimodal integration. Physical activity monitoring faces similar challenges: systematic measurement bias in wearables, sensor placement issues, and algorithms trained on normal-weight cohorts. In the GLP-1/GIP era, if transparency, ethical safeguards, and equitable access are ensured, AI will act as a catalyst for personalized care, remote monitoring, trial optimization, and next-generation drug discovery. In conclusion, the integration of AI with rigorous validation procedures and inclusive sampling strategies is essential to achieve reliable, fair, and clinically relevant monitoring approaches for obesity management. Full article

Objective: This exploratory study presents an international, multi-stakeholder snapshot of perceptions regarding real-world data and real-world evidence in health technology assessment. The aim is to identify perceived opportunities, barriers, and enabling conditions rather than to generate generalizable conclusions. Methods: A 21-item, expert-validated questionnaire was distributed via LimeSurvey to diverse health technology assessment stakeholders, including academia, industry, health technology assessment agencies, healthcare providers, policymakers, patients, and payers. The survey explored perceptions of value, methodological and regulatory challenges, and future outlooks for RWD/RWE use in HTA. Ethical approval was obtained by the University of West Attica Ethics Committee, and pilot testing was conducted prior to dissemination. Data were analyzed using descriptive statistics, consistent with the study’s exploratory intent and acknowledging that results are preliminary and not statistically generalizable. Results: Thirty-two completed responses demonstrated preliminary stakeholder support for integrating real-world data and real-world evidence into health technology assessment. Respondents represented academia, industry, HTA agencies, healthcare providers, policymakers, and patient/advocacy groups; however, no payer responses were obtained. Respondents emphasized the value of real-world data in complementing clinical trials by capturing real-world effectiveness, patient diversity, and long-term outcomes, especially in rare diseases and cancer. Key challenges included poor data quality, confounding biases, and regulatory barriers. Stakeholders highlighted the importance of standardization, transparency, and international collaboration. Opportunities included better decision-making, personalized healthcare, and improved post-market monitoring, with strong calls for robust infrastructure, clear methodologies, patient involvement, and supportive health policy frameworks. Conclusions: Real-world data and evidence enhance health technology assessment by supporting better decisions and personalized care. However, issues like data quality, methods, and trust must be addressed through standardization, strong infrastructure, and collaboration to ensure effective and impactful implementation in healthcare, while acknowledging these insights are based on a small exploratory sample. Full article

End-stage kidney disease (ESKD) is a global health challenge, with kidney transplant demand outstripping supply. Allotransplantation remains the gold standard for treatment but organ scarcity leads to prolonged waiting times and high mortality. Xenotransplantation, using genetically modified porcine kidneys, offers a novel and potentially sustainable solution. Genetic engineering and immunosuppression advances have enabled xenotransplantation to transition from a theoretical possibility to feasible solution. This review explores the evolution of xenotransplantation, the scientific advancements in overcoming immunological barriers, and emerging clinical data. Furthermore, we discuss emerging approaches such as central immune tolerance induction, the ongoing risks of cross-species infection, and the ethical and environmental considerations inherent to scaling up porcine organ donation. With the commencement of the first formal clinical trials, progress in the field could transform kidney transplantation, though questions remain regarding long-term outcomes and societal impact. Full article

Background and Objectives: Effective postoperative analgesia is essential for enhanced recovery after bariatric surgery. The erector spinae plane block (ESPB) has emerged as a promising regional anesthesia technique, but its impact on postoperative pain control, opioid requirement, patient and surgeon satisfaction, and stress response in obese patients undergoing sleeve gastrectomy remains unclear. This study aimed to evaluate the effects of bilateral ESPB on postoperative analgesia requirements, pain scores, patient and surgeon satisfaction, hemodynamic stability, postoperative stress response, and perioperative hematologic and biochemical parameters in ASA II–III patients with a body mass index (BMI) > 30 undergoing sleeve gastrectomy. Study design was a prospective, randomized, single-blind clinical trial. Materials and Methods: After obtaining ethics committee approval (Şanlıurfa Harran University Hospital, date: 23 January 2023; decision no: HRÜ/23.02.09) and written/verbal informed consent, 60 patients aged 18–65 years, BMI > 30, ASA II–III scheduled for elective sleeve gastrectomy were included. Patients were randomized into two groups: those receiving bilateral ESPB (Group E, n = 30) and those without ESPB (Group C, n = 30). Demographic characteristics, ASA scores, comorbidities, and surgical duration were recorded. Preoperative venous samples were collected into hemogram (WBC, lymphocyte, neutrophil) and biochemistry tubes (CRP, cortisol, glucose). Standard monitoring (ECG, SpO₂, NIBP) was applied intraoperatively, and vital parameters (HR, MAP) were recorded throughout. Postoperatively, HR, MAP, Numerical Rating Scale (NRS) scores at 0, 2, 4, 8, and 24 h, opioid requirement, patient and surgeon satisfaction (Likert scale), postoperative hemogram and biochemistry values, and side effects or complications were documented. All patients received dexketoprofen as baseline analgesia, with tramadol HCl administered as rescue analgesic. Results: All 60 patients completed the study. There were no statistically significant differences between the groups regarding age, BMI, or surgery duration. Comorbidities were similar between groups. Intraoperative and postoperative HR and MAP values showed no significant differences. Postoperative NRS scores at the 0, 2, 8, and 24 hours were significantly lower in Group E compared with Group C. Both patient and surgeon satisfaction scores were higher in Group E. Rescue analgesic (tramadol HCl) consumption in the postoperative ward was significantly reduced in Group E. Cortisol levels, particularly at the 24th postoperative hour, showed a significantly smaller increase in Group E, suggesting a reduced surgical stress response. No significant differences were found between the groups regarding postoperative side effects or complications. Conclusions: Preoperative bilateral ESPB is an effective component of multimodal analgesia in sleeve gastrectomy. The block significantly reduces postoperative pain intensity, lowers NRS scores, improves patient and surgeon satisfaction, and decreases opioid requirements. Additionally, ESPB appears to attenuate the postoperative stress response, as reflected by smaller increases in cortisol levels. These findings support the routine incorporation of ESPB in perioperative pain management strategies for gastric sleeve surgery. Full article

Hypnosis has traditionally been conceptualized as a clinical technique for reducing physiological symptoms (e.g., pain, nausea) and psychological symptoms (e.g., anxiety, intrusive thoughts), yet emerging neuroscientific evidence suggests it operates through the fundamental mechanisms of emotional regulation and self-integration. This integrative review synthesizes research on clinical hypnosis from cognitive neuroscience, affective science, and clinical practice to examine how hypnotic phenomena modulate large-scale brain networks—particularly the default mode network (DMN), executive control network (ECN), and salience network (SaN)—to reorganize emotional experience and self-referential processing. We propose a formal mechanistic model in which hypnotic induction produces heightened experiential plasticity through coordinated network reconfiguration, enabling adaptive emotion regulation and reduced dissociative fragmentation. Central to this framework is the construct of Fundamental Peace (FP), operationalized as a dynamic neuro-experiential state characterized by: (1) flexible attentional control without effortful suppression; (2) emotional coherence across self-states; (3) reduced self-referential rigidity; (4) compassionate self-awareness. Unlike equanimity (affective neutrality) or well-being (positive evaluation), Fundamental Peace represents integrated regulatory capacity under changing conditions. Key findings from neuroimaging studies demonstrate that hypnotic states consistently reduce DMN activity, enhance ECN-SaN coupling, and modulate connectivity patterns associated with self-referential processing. Meta-analytic evidence from 85 controlled experimental trials shows robust pain reduction effects, while clinical studies document improvements in trauma-related dissociation and emotional dysregulation. We critically evaluate this framework against alternative theories (dissociated control, cold control, predictive processing, social-cognitive models), specify testable predictions, and assess evidence quality across neuroimaging and clinical domains. Implications for trauma treatment, clinical implementation, and future research integrating causal inference methods are discussed, alongside ethical and cultural considerations. Full article

Background/Objectives: Necrotizing enterocolitis (NEC) is an inflammatory disease with an incidence of about one in 1000 live births, much higher in premature and low birth weight newborns. Intestinal dysbiosis is an important element in the pathogenesis of NEC, and for this reason, experimental models have been used to administer fecal microbiota transplants (FMTs) for prophylaxis and treatment of NEC with very satisfactory results. The primary endpoint of the study is safety, defined as the incidence of adverse events (AEs) and serious adverse events (SAEs) occurring from the time of intervention until hospital discharge, classified according to severity and assessed for relatedness to the intervention. Methods: This prospective, single-arm, open-label clinical study will include 20 infants born between 24 0/7 and 36 6/7 weeks of gestation. FMTs will be administered twice as a deep rectal infusion via a Foley catheter. The donors of the material from which the FMT will be prepared will be women in the third trimester of pregnancy. The safety of the therapy will be assessed by comparison with a control group, i.e., 20 patients who will meet the same inclusion criteria and will not meet any of the exclusion criteria, subject to the same hospital observation but without undergoing any medical/therapeutic intervention other than the collection of biological material. Discussion: The study will provide data on the safety and initial efficacy of FMT in this group of patients, which will allow for further research into the use of this method in the prevention of infections and NEC. Ethics: The study protocol was approved by the Bioethics Committee of the Medical University of Warsaw, Warsaw, Poland (KB/52/2025). All procedures will follow the principles of the Declaration of Helsinki. The results of the study will be submitted for knowledge translation in peer-reviewed journals and presented at national and international pediatric society conferences. Clinical Trial Registration: The study is registered at ClinicalTrials.gov: ID: NCT06333405. Full article

Acute respiratory distress syndrome (ARDS) has traditionally been managed with population-based, protocolized mechanical ventilation strategies designed to limit ventilator-induced lung injury. While these approaches have improved outcomes, they fail to account for the pronounced biological, mechanical, radiological, and temporal heterogeneity that characterizes ARDS. Accumulating evidence shows that patients differ markedly in functional lung size, recruitability, chest wall mechanics, inflammatory burden, and tolerance to ventilatory stress, making uniform ventilatory targets physiologically imprecise and, at times, harmful. This narrative review examines the evolution from conventional lung-protective ventilation toward a precision-based paradigm that aligns ventilatory support with individual patient physiology. We conceptualize ARDS not as a static syndrome but as a dynamic spectrum, viewing the injured lung as a heterogeneous mechanical system susceptible to regionally amplified stress and strain. Within this framework, we discuss key principles underlying precision ventilation, including functional lung size (the “baby lung”), driving pressure, mechanical power, patient–ventilator interaction, spontaneous breathing-associated injury, and the time-dependent evolution of lung mechanics. We synthesize current evidence supporting mechanical, biological, and radiological subphenotyping as complementary strategies to individualize ventilatory management, while critically appraising their current limitations. This review also evaluates bedside tools that may operationalize precision ventilation in clinical practice, including esophageal pressure monitoring, lung ultrasound, and electrical impedance tomography, and examines the role of artificial intelligence as a clinician-directed decision-support aid rather than a prescriptive substitute for physiological reasoning. Implications for clinical trial design, ethical considerations, and future directions toward predictive and adaptive ventilation strategies are also addressed. Precision mechanical ventilation represents a shift from rigid thresholds toward proportional, physiology-guided intervention across the disease trajectory. By integrating evolving lung mechanics, ventilatory load, and patient effort over time, this approach provides a coherent framework for safer and more effective mechanical ventilation in ARDS while preserving the core principles of lung protection. Full article

Background/Objectives: Dichorionic triamniotic (DCTA) triplet pregnancies are associated with increased rates of placenta-specific complications primarily attributed to vascular anastomoses in the monochorionic (MC) pair. Selective fetal reduction to twins (of one of the MC pair) is a complex and not a widely available procedure. Multifetal reduction (MFR) to singleton pregnancy can reduce adverse pregnancy outcomes but is controversial due to medico-legal and socio-ethical issues. The aim of this study is to identify the rate of miscarriage < 24 weeks or preterm birth < 34 weeks following MFR to singleton pregnancy in DCTA triplets and compare the results with expectant management. Methods: This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the Prospective Register of Systematic Reviews System (ID: CRD42023422585). Results: Overall, from 21 citations of relevance, 6 studies with a total of 548 DCTA triplet pregnancies fulfilled the inclusion/exclusion criteria. In comparison with expectant management (n = 336), meta-analysis demonstrated that MFR to singleton pregnancy (n = 212) was associated with a lower rate (9.4% vs. 48.5%) of preterm birth (RR = 0.19, 95%CI 0.07–0.51), whereas the rate of miscarriage (14.6% vs. 9.2%) did not significantly increase (RR = 1.53, 95%CI 0.91–2.55). Conclusions: In DCTA triplet pregnancies, MFR to singleton pregnancy was associated with a reduced preterm birth rate and not associated with an increased miscarriage rate. Given the fact that the MC pair is reduced only to lower the rate of preterm birth, appropriate counselling and justification are important. In the absence of randomized controlled trials, data from systematic reviews are the best available evidence for counseling on the different management options. Full article