搜索结果：Clinical and translational medicine

As an established driver of hypertension, obstructive sleep apnea (OSA) generates a significant cardiovascular burden when both disorders are present. This intersection not only compromises nocturnal hemodynamics but also hampers long-term clinical management. Yet, current health care delivery rarely integrates the simultaneous and continuous tracking of these dual burdens. While wearable technology provides a noninvasive, pragmatic toolset for synchronized physiological monitoring, research remains largely siloed within single-disease frameworks. Consequently, clinical evidence supporting wearable applications specifically for comorbid populations remains sparse. In this scoping review, we summarized the current applications of wearable technology for comorbid OSA and hypertension. The analysis primarily outlines device categories, monitored physiological indicators, prevalent clinical scenarios, and existing challenges. The search for relevant literature spanned PubMed, Web of Science, Embase, and IEEE Xplore, covering the period from January 2015 to February 2026. Eligible studies included adults and used wearable or portable technologies to objectively track sleep- or respiratory-related indicators and cardiovascular/blood pressure metrics. Study selection, data charting, and evidence synthesis were conducted using a 2-reviewer process and descriptive and narrative approaches. Our initial search yielded 739 records. Following title and abstract screening, we reviewed 54 full texts, ultimately finalizing a cohort of 13 eligible studies. Published between 2015 and 2026 across 9 countries, these articles capture data from 5596 participants. Most were observational studies and device validation studies. Evaluated device types included wrist-worn devices, fingertip contact devices, patch and single-lead devices, and multiparameter portable monitoring systems. The clinical applications mainly focused on screening and risk stratification for comorbid OSA and hypertension, monitoring of abnormal nocturnal blood pressure and hemodynamic changes, and cardiovascular risk assessment and remote longitudinal management. However, research remains sparse, and different devices vary greatly in reference standards, diagnostic thresholds, and validation pathways; therefore, their clinical translational value still requires further validation. Wearable devices may complement traditional assessment by providing continuous nocturnal and longitudinal data. However, at present, they are more suitable as auxiliary monitoring and risk warning tools in comorbidity management and cannot yet replace standard sleep studies or standard blood pressure monitoring. Future research should further shift from feasibility validation to large-sample, prospective, multicenter clinical studies in comorbid populations.

Information on the safety profile of disease-modifying therapies (DMTs) in multiple sclerosis (MS) is often lacking in routine clinical practice. Real-world data sources, such as patient registries, support pharmacovigilance to characterise safety signals, as recently recognised by regulatory agencies. In Italy, the "Italian Multiple Sclerosis and Related Disorders Register" (RISM) was officially launched in 2015 to collect demographic and clinical data from patients with MS. To describe the main characteristics of RISM as a research platform supporting the safety evaluation of MS therapies. RISM enables the systematic characterisation of clinical events occurring in treated patients and, over the years, has implemented procedures to ensure high-quality data collection. A study cohort including subjects who initiated a DMT between 2016 and 2025 is analysed using descriptive statistics. Clinical events recorded during the study period are reported as absolute numbers and frequencies. Between 2016 and 2025, a total of 24 259 subjects received at least one DMT, and 4419 of them (18.2%) experienced one or multiple clinical events. For descriptive purposes, the occurrence of infections and malignancies, which accounted for 29.4% and 3.7% of all the clinical events collected in RISM respectively, are reported and categorised. This article outlines the strengths and limitations of RISM in conducting safety studies and highlights the methodological and legal challenges associated with such platforms. Routinely collected healthcare data within RISM provide a comprehensive, patient-centred perspective for the long-term evaluation of DMT safety and can address relevant questions on drug policies and public health. Multiple sclerosis (MS) is a chronic condition that often requires long‐term treatment with therapies that are specific for MS. However, information about the safety of MS therapies in everyday clinical practice is still limited. The Italian Multiple Sclerosis and Related Disorders Register (RISM) was created in 2015 to collect information from clinical practice about people with MS across Italy. By gathering data from specialised MS centres, RISM helps better understand how MS therapies work and what side effects may occur over time. Data quality controls have been implemented with the aim to collect complete and accurate information. Between 2016 and 2025, RISM recorded 24 259 people who received at least one MS treatment. About 18% of them reported at least one clinical event, most often infections (29.4% of all events) or, less frequently, cancers (3.7%). This work describes how RISM can be used to monitor the safety of available MS therapies by analysing data collected in routine clinical practice, as well as the challenges of managing such large data collections. Information from RISM can guide clinicians, researchers, and relevant stakeholders in improving treatment safety and supporting better healthcare decisions for people living with MS.

Due to widespread availability and familiarity, unfractionated heparin (UFH) is the most used intravenous anticoagulant for many indications in hospitalised patients. UFH, however, is a high-risk medication with complex pharmacokinetics and pharmacodynamics that are highly variable between different patients and within the same patients over time. The traditional titration and monitoring approach uses a clot-based assay, the activated partial thromboplastin time (aPTT), titrated to one and a half to two and a half times the upper limit of the normal range. Alternate assays indirectly measuring the anti-Xa level have not been compared with the aPTT for the monitoring of heparin in a prospective study. The optimal laboratory test for monitoring and adjusting heparin is not known. Our pragmatic study developed within the learning healthcare infrastructure is designed to answer this clinical question by comparing two established protocols for monitoring heparin in our hospital through a pragmatic randomised clinical trial. The Comparison of Heparin Assay Monitoring Protocols (CHAMP) Trial is a single-centre, pragmatic, randomised trial conducted at Vanderbilt University Medical Centre (VUMC) beginning 26 June 2024. The CHAMP trial compares the aPTT protocol to the anti-Xa protocol for monitoring and titration of intravenous UFH for systemic anticoagulation in hospitalised adult patients. Admitted patients initiated on UFH protocols are assigned to either the aPTT or anti-Xa protocol in a randomised fashion. The primary outcome is time to reach the therapeutic anticoagulation range by coagulation assay. Secondary outcomes include the percent of measurements in the therapeutic range, the number of coagulation laboratory measurements over time, frequency of heparin rate changes while on the protocol and the incidence of thrombotic and clinically relevant bleeding events. The CHAMP trial is an ongoing pragmatic trial embedded into the current existing clinical workflow for heparin administration. The two protocols are considered clinically equivalent and already used in clinical practice, allowing for a waiver of consent approval (VUMC Institutional Review Board #232192). This waiver is critical to the implementation of the study due to the nature of scenarios and time constraints in which UFH is typically initiated. Partnering with nursing, pharmacy and clinical providers has been key to launching this study, which provides the first prospective, randomised, direct comparison of the two heparin laboratory protocols available for the monitoring and titration of intravenous UFH in hospitalised patients. After trial completion and data analysis, the findings of the CHAMP trial will be submitted to a peer-reviewed journal for consideration of publication for distribution to a broad clinical audience. The CHAMP study was registered on ClinicalTrials.gov (NCT identifier: NCT06329921) on 19 March 2024. The first patient was enrolled in the study on 26 June 2024, with enrolment of the planned 700 participants expected to occur over two years.

Pharmacotherapy for common mental disorders is frequently limited by adverse events and suboptimal adherence. While music therapy offers a promising nonpharmacological alternative, its clinical utility is currently constrained by limited accessibility, inconsistent efficacy, and a lack of mechanistic clarity. This study aims to describe the development of individualized (receptive) music therapy (IMT), an artificial intelligence (AI)-enabled, neuroscience-guided intervention, and to evaluate its efficacy, safety, and underlying neurobiological mechanisms in adults with major depressive disorder, generalized anxiety disorder, and primary insomnia. This multistage research program is being conducted at Peking Union Medical College Hospital and comprises four sequential studies: (1) a cross-sectional pilot study (n=20) to benchmark clinical and electroencephalography features, (2) a prospective cohort study (n=80) evaluating the efficacy and safety of nonindividualized receptive music therapy, (3) a pilot randomized clinical trial (n=300) comparing nonindividualized therapy with IMT over 8 weeks, and (4) a prospective validation study (n=60) of a treatment-response prediction model. Participants include adults aged 18 to 60 years with mild-to-moderate major depressive disorder, generalized anxiety disorder, or primary insomnia, along with healthy controls. In the nonindividualized arm, participants engage in daily 30-minute listening sessions using therapist-curated instrumental tracks designed to regulate mood. In the IMT arm, an AI generation pipeline creates bespoke instrumental tracks based on weekly participant preferences regarding tempo, instrumentation, and emotional valence. To equalize participant-researcher contact across arms and reduce attention and expectation bias, participants in the nonindividualized arm complete a weekly music-experience questionnaire matched in length and timing to the IMT arm's weekly preference assessment, and treatment credibility and outcome expectancy are measured at baseline in both arms. The primary outcomes are the response rate at 8 weeks (defined as ≥50% reduction in Montgomery-Åsberg Depression Rating Scale [MADRS], Hamilton Anxiety Rating Scale [HAMA], or Pittsburgh Sleep Quality Index [PSQI] scores) and changes in quantitative electroencephalography characteristics. Secondary outcomes include changes in MADRS, HAMA, and PSQI scores from baseline to 8 weeks. Ethical approval was obtained from the Ethics Review Committee of Peking Union Medical College Hospital (I-24PJ0689). Written informed consent will be obtained from all participants. The recruitment started on May 24, 2024, and the study is expected to be completed by December 2027. Results will be disseminated via peer-reviewed publications, conference presentations, and stakeholder communications. Authorship will follow the International Committee of Medical Journal Editors (ICMJE) criteria. The participant-level dataset will be available upon reasonable request. This protocol outlines a translational framework designed to address the "therapeutic ceiling" of traditional music therapy. By integrating generative AI with neurophysiological monitoring, this program aims to develop a scalable, precision-medicine approach to mental health care that is both clinically effective and biologically grounded.

Cell-free fat extract (CEFFE), an adipose-derived biologic, offers a potent alternative to cell-based therapies by delivering a complex milieu of growth factors (e.g., VEGF, EGF, and BDNF) and regulatory proteins without the tumorigenic, immunogenic, or ethical challenges associated with stem cell applications. The objective of this study is to systematically evaluate CEFFE's regenerative efficacy across diverse tissue systems-including musculoskeletal, neural, reproductive, dermal, ocular, and systemic applications-while synthesizing its underlying molecular mechanisms, clinical outcomes, and translational challenges. A comprehensive literature review was conducted utilizing databases such as PubMed, Scopus, and Web of Science, focusing on preclinical and clinical studies published from January 2018 to May 2026. Over 55 articles were analyzed to evaluate CEFFE's efficacy, dosage-response patterns, and molecular pathways. CEFFE accelerates tissue repair through three conserved mechanistic axes: antiapoptotic survival (e.g., PI3K-Akt/mTOR activation and NRF2-mediated antiferroptosis), context-specific immunomodulation (e.g., Annexin A5-mediated M2 macrophage polarization and NLRP3 inflammasome disruption), and extracellular matrix remodeling alongside angiogenesis (e.g., TGF-β/Smad signaling). Emerging evidence highlights CEFFE's efficacy in novel domains such as intervertebral disc degeneration, corneal neurodegeneration, systemic sepsis, and as an IVF culture media supplement. Clinical trials confirm its safety and efficacy in dermatological applications (e.g., infraorbital aging and hyperpigmentation) and demonstrate superiority over standard treatments, such as hyaluronic acid, for early-to-mid-stage osteoarthritis. CEFFE represents a highly versatile and precise cell-free biologic capable of driving multitissue regeneration. To fully realize its clinical and commercial potential, future research must address donor variability by establishing standardized dosing protocols, implementing key-molecule quantification for batch consistency, and conducting large-scale, multicenter randomized controlled trials.

Cancer remains a leading cause of mortality worldwide, highlighting the need for therapeutic strategies that reduce systemic toxicity and drug resistance. Resveratrol (RES), a natural polyphenolic stilbenoid, possesses antioxidant, anti-inflammatory, pro-apoptotic, anti-metastatic, and chemosensitizing activities. However, its clinical translation is limited by poor aqueous solubility, chemical instability, rapid metabolic clearance, and consequently low systemic bioavailability. Nanotechnology-based drug delivery systems provide a promising strategy to address these limitations. This review summarizes recent advances in RES-loaded nanoformulations, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, micelles, inorganic nanocarriers, protein-based systems, and biomimetic vesicles. Their therapeutic performance is evaluated across prostate, lung, colorectal, breast, and other cancers, with attention to tumor targeting, controlled release, combination therapy, multidrug-resistance reversal, and modulation of cancer-relevant pathways such as NF-κB, p53, and PI3K/Akt/mTOR. Current oncology-related clinical evidence for RES is still largely based on conventional oral or micronized formulations. Translation of engineered RES nanocarriers therefore requires stronger evidence on scalable manufacturing, carrier-specific safety, heterogeneous tumor delivery, and biomarker-guided trial design. This review also introduces a semi-quantitative prioritization framework based on model-readiness, translational priority, and safety-alert scoring for future PBPK, PK-PD, nano-QSAR, and machine-learning analyses.

Pediatric patients require age-appropriate dosage forms because developmental differences in physiology, pharmacokinetics and swallowing ability can significantly affect therapeutic outcomes. Conventional dosage forms are often unsuitable for children and practices such as tablet splitting, crushing or extemporaneous preparation may lead to dose inaccuracy, altered stability, poor palatability and reduced adherence. These limitations highlight the need for innovative formulation strategies that provide precise dosing while improving acceptability and therapeutic effectiveness. In this context, three-dimensional (3D) printing has emerged as a promising platform for personalized pediatric drug delivery. This review critically examines recent advances in 3D printing technologies for pediatric drug delivery and provides a formulation-focused and translational perspective by integrating pediatric therapeutic needs with technology selection, polymer considerations and dosage form design flexibility. A comprehensive literature review was conducted to evaluate recent developments in pediatric pharmaceutical applications of 3D printing. Major technologies including fused deposition modeling, semi-solid extrusion, binder jet printing and inkjet printing were assessed with respect to formulation design, polymer selection, drug-polymer compatibility and pediatric suitability. Particular emphasis was placed on taste-masking approaches, personalized dosing capability and dosage adaptability for different pediatric age groups. Three-dimensional printing enables fabrication of diverse pediatric-friendly dosage forms including chewable gummies, mini-tablets, orodispersible films and confectionery-like formulations. Published studies demonstrated improved dose precision, effective taste masking, customizable drug release profiles and enhanced patient acceptability. Regulatory approval of Spritam further supports the clinical feasibility of this technology. However, challenges remain regarding printer calibration, reproducibility, limited pharmaceutical-grade printable materials, long-term stability and regulatory harmonization. Three-dimensional printing represents an important advancement in patient-centric pediatric pharmacotherapy by enabling precise control over dose, geometry, release kinetics and sensory attributes. This review highlights its practical potential and translational readiness for pediatric healthcare.

Based upon substantive professional engagement over two decades and the collective action of diverse professionals, this conceptual paper proposes that translational science (TS) is best understood as a meta-discipline. As with Science, Technology, Education, and Mathematics (STEM) or Information Sciences, meta-disciplines rely on coherent professional identities. Positioning TS in this way foregrounds the need to develop such identities across diverse contributors. TS team members often begin with deep domain-specific expertise followed by acquisition of cross-cutting translational capabilities that together support career and professional outcomes. Despite intensive workforce development efforts, no shared framework describes how Translational Science Professionals (TrSPros [We use TrSPro, "Translational Science Professional," to differentiate from the existing TSP, "Team Science Professional."]) develop professional identities. We adapt an established identity socialization model to TS, offering a heuristic for how contributors across roles become-and belong as-TrSPros. Prior studies in medicine link strong professional identity to job satisfaction, career well-being, resilience, and retention; building identities in TS should likewise increase the capacity and coherence of translation. This paper presents practical strategies and a research agenda to support intentional TrSPro identity development across Clinical and Translational Science Awards (CTSAs), their partnering organizations, and the broader TS ecosystem, strengthening the long-term sustainability of translational initiatives.

Thirty-day unplanned readmission following coronary artery bypass grafting (CABG) affects 10%-20% of patients and is a key quality indicator, particularly in low- and middle-income countries (LMICs) where access to cardiac rehabilitation is limited. Existing risk models are static, lack real-time engagement, and no validated large language model (LLM)-based clinical decision support (CDS) system exists for post-CABG readmission prevention. This protocol describes the development, validation, and evaluation of Smart CABGuard, a nurse-led, LLM-based CDS chatbot with continuous remote electrocardiographic (ECG) monitoring, to predict and prevent postoperative complications, and 30-day unplanned readmission after isolated CABG. This multiphase translational study is conducted at Amrita Institute of Medical Sciences, Kochi, India, following TRIPOD-LLM (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis-Large Language Model) and CONSORT (Consolidated Standards of Reporting Trials) AI reporting guidelines. Phase I uses an ambispective design (retrospective: January 2020 to December 2024; prospective needs survey: June 2025 to January 2026) to develop a logistic regression-based Complication Risk Index (CRI), assessed via receiver operating characteristic area under the curve, Brier score, and decision curve analysis. Phase II refines Smart CABGuard by integrating a frozen Mistral-7B LLM (low-rank adaptation fine-tuned), the CRI engine, explainable AI, and single-lead ECG telemetry (Amrita Spandanam device), with a usability threshold of ≥80%. Phase III is a prospective, parallel-group, open-label randomized controlled trial (RCT). Adults aged ≥18 years undergoing isolated CABG with smartphone access are randomized 1:1 via permuted block randomization, with allocation concealment. The intervention arm receives Smart CABGuard-assisted care (daily chatbot check-ins, CRI-based risk stratification, ECG monitoring, and nurse-led triage) for approximately 24 days postdischarge plus standard care; the control arm receives standard care with structured telephone follow-up for outcome ascertainment only. Outcome assessors and statisticians are blinded; analyses follow the intention-to-treat principle. The primary outcome is 30-day all-cause unplanned readmission. Based on a baseline rate of 10.71%, a 50% relative reduction, α=.10, and 80% power, the target sample size is 800 patients (400 per arm, including 10% attrition). Ethics approval was granted by the Institutional Ethics Committee of Amrita Institute of Medical Sciences on April 16, 2025. Funding was awarded by Sigma Theta Tau International Honor Society of Nursing, Small Grants Program (grant 21650) in June 2025. Phase I data extraction commenced in May 2025 and is projected to be completed by April 2026; the patient needs survey (June 2025 to January 2026) is ongoing. Phase II usability evaluation is projected from May to July 2026. Phase III recruitment is anticipated from August 2026 to September 2027. Results are expected to be published in early 2028. Smart CABGuard is the first RCT protocol of an LLM-based nurse-led CDS system for post-CABG readmission prevention in an LMIC setting, aiming to establish the usefulness, safety, and feasibility of AI-augmented postoperative surveillance.

Personalized vaccines provide the advantage of patient-specific antigen selection to optimize immune responses, a strategy extensively explored in oncology through neoantigen-targeted peptide, mRNA, and dendritic cell platforms. Peptide vaccines provide simplicity and stability though often elicit limited cytotoxic T-cell responses. What is more, mRNA vaccines lead to rapid, multiplexed neoantigen delivery, endogenous antigen processing and eventually improved immunogenic coverage. Dendritic cell-based vaccines have the potency to prime potent T-cells although this technology requires labor-intensive manufacturing and extensive production timelines. Integration with immune checkpoint inhibitors, adoptive cell therapies, and oncolytic viruses further enhances efficacy, suggesting that rational combinations may be more effective than single modalities. Recent advances in sequencing, computational epitope prediction, and bioinformatics pipelines have facilitated neoantigen prioritization and DC vaccine design, enabling more rapid and precise personalization. Hybrid vaccination strategies, such as ex-vivo mRNA-electroporated dendritic cells and in-vivo DC-targeted platforms, bridge the gap between manufacturing feasibility and potent immune activation. Emerging technologies, including AI-driven neoepitope prediction, receptor-targeted antigen delivery, biomaterial-based modulation, and distributed mRNA manufacturing, seem to be promising approaches to accelerate personalized vaccine development in future. From another point of view, lessons learned from the COVID-19 pandemic accelerated the development, large-scale deployment, and validation of mRNA vaccine platforms for infectious diseases. Host HLA diversity, prior immune history, and viral evolution create heterogeneity in immune responses, highlighting opportunities for semi-personalized or adaptive strategies. In this review, we provide a landscape of personalized vaccines, with a focus on DC-based platforms, and explore translational lessons for viral pathogens. A conceptual framework linking cancer immunotherapy and infectious disease preparedness is proposed, emphasizing hybrid personalization approaches, rapid manufacturing, and AI-enabled epitope selection. This perspective highlights how convergence of immunology, computational biology, and advanced vaccine technologies could expand the scope of personalized vaccination, from oncology to future epidemic and pandemic scenarios as well as the current challenges.

Transferability of questionnaires across languages and cultures requires a systematic process to preserve content integrity and ensure validity and reliability. The aim of this study was to translate, culturally adapt and face validate the US-developed patient-reported outcome (PRO) measure 'Type 1 Diabetes and Life' (T1DAL) for use in a Danish population of parents of children under the age of 11 years living with type 1 diabetes. The process followed the 10-step International Society for Pharmacoeconomics and Outcomes Research good practice principles for the translation and cultural adaptation of PRO measures, thereby establishing content validity and cross-cultural validity in accordance with COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) recommendations. Following approval from the developer of the original questionnaire, two independent forward translations were conducted by bilingual native Danish speakers. These translations were then synthesised into a reconciled version, which were then back translated by two bilingual native English speakers. Discrepancies between the original and the reconciled versions were reviewed, leading to small linguistic and cultural adjustments. This process included discussions around the response categories on the Likert-scale and items reflecting the US healthcare context-particularly those related to insurance-dependent access, which are less relevant in Denmark.Cognitive debriefings regarding the updated Danish version with 12 parents resulted in a Danish version demonstrating strong semantic, conceptual and experiential equivalence. Additionally, minor linguistic and cultural adjustments were made to enhance clarity and contextual appropriateness. Cognitive debriefing confirmed the questionnaire's acceptability and comprehensibility across a diverse range of respondents. Applying ISPOR principles emphasised the importance of cultural adaptation that extends beyond linguistic translation to preserve the original questionnaire's integrity and meaningfulness and resulted in a conceptually equivalent and culturally adapted Danish version of the original T1DAL questionnaire, suitable for use in Danish clinical and research settings. H-25016032.

Hematological malignancies remain one of the leading causes of morbidity and mortality despite advances in targeted therapies, immunotherapy, and stem cell transplantation. Emerging evidence indicates that treatment efficacy and toxicity depend not only on the choice of therapy but also on its timing relative to the patient's internal circadian rhythm. The circadian clock orchestrates fundamental processes in hematopoiesis and immunity, such as stem-cell proliferation, leukocyte trafficking, DNA repair, and drug metabolism, while its disruption promotes malignant transformation, therapeutic resistance, and systemic toxicity. This narrative review synthesizes current understanding of circadian regulation in hematopoietic and immune systems, the mechanistic and preclinical foundations of chronotherapy in blood cancers, and the limited but growing body of clinical evidence linking treatment timing with outcome in leukemia, lymphoma, and transplantation. The review also examines practical challenges, including inter-individual variability, disease-induced circadian disruption, and hospital workflow constraints, while highlighting emerging technologies, such as transcriptomic clocks, wearable biosensors, and AI-driven scheduling algorithms, that are poised to enable personalized, time-aware therapy. By integrating temporal precision into existing therapeutic frameworks, chronotherapy may represent a promising investigational dimension of precision medicine in hematological oncology. However, its clinical value remains to be defined through prospective studies that incorporate validated circadian biomarkers, predefined timing windows, and clinically meaningful efficacy and toxicity endpoints.

Chronic and treatment-resistant dermatologic disorders remain difficult to manage with current therapies because of incomplete efficacy, tolerability limitations, and long-term safety concerns. GZ21T is a topical formulation of curcumin, harmine, and isovanillin that has emerged as a potential novel therapy for inflammatory and neoplastic skin disease. To review the preclinical evidence, proposed mechanism of action, safety data, and future clinical potential of GZ21T in atopic dermatitis, mycosis fungoides, and actinic keratoses. A focused literature review was performed using published preclinical and early translational studies evaluating GZ17-6.02 and topical GZ21T in dermatologic disease models, including atopic dermatitis, mycosis fungoides, and actinic keratoses. Studies were included if they reported mechanistic, efficacy, or safety outcomes relevant to dermatologic application; non-dermatologic studies were used selectively to contextualize safety and pharmacology. Across preclinical models, topical GZ21T reduced inflammation, pruritus, lesion burden, and tumor growth while promoting autophagy and suppressing pro-survival signaling pathways including MAPK, PI3K-AKT, mTOR-related pathways, Wnt, and ERBB signaling. In mycosis fungoides models, GZ17-6.02 increased apoptosis and enhanced tumor cell killing, including in combination with standard agents such as bexarotene. Safety data to date suggest favorable local tolerability, minimal systemic absorption in preclinical topical studies, and reversible liver enzyme elevations in oral phase 1 testing of GZ17-6.02. GZ21T represents a promising topical, multimodal therapeutic approach for inflammatory and premalignant or malignant skin disease. Further clinical studies are needed to confirm efficacy, define long-term safety, and establish its role relative to current standard therapies.

This chapter includes an extensive examination of the neuroanatomical and neurophysiological basis of dreaming and is primarily concerned with the phenomenology of rapid eye movement (REM) sleep. Relying on integrated findings from neuroimaging, electrophysiology, and neurochemical studies, the chapter describes that dreaming results from the interaction of brain regions such as the brainstem, thalamus, limbic system, and prefrontal cortex. The chapter underscores the central contribution of pontine cholinergic mechanisms to the generation of REM, combined with thalamocortical integration, to define perceptual and narrative features of dreams. Limbic activation in the amygdala and hippocampus is responsible for the emotional intensity and memory-related features of dream content, and relative prefrontal deactivation helps minimize logical constraint and promotes associative reasoning. Oscillatory dynamics, particularly theta and gamma activity, are considered important underpinnings of dream vividness and perceptual integration. With its focus on clinical conditions, including post-traumatic stress disorder (PTSD), depression, and REM sleep behavior disorder, the chapter provides a translational perspective beyond simple mechanistic models associated with the brain. The modulation of acetylcholine, serotonin, and norepinephrine is proposed to be one of the most important mechanisms of regulation with therapeutic potential. The chapter also addresses new domains such as dream neuropharmacology, neuromodulation, ethical implications, and cross-cultural perspectives of dream interpretation. More generally, it places dreaming as a neurobiologically driven, functionally relevant phenomenon with significance for emotional regulation, memory consolidation, and clinical intervention in sleep medicine.

People with cystic fibrosis (PwCF) have historically been counselled to eat a high-energy, high-fat diet to prevent malnutrition. The widespread availability of novel drug therapy has led to increased weight and body composition changes in this population, necessitating dietary and lifestyle changes to promote optimal health and well-being. The objective of our study was to understand the attitudes, perspectives, and practices related to nutrition issues in the context of elexacaftor-tezacaftor-ivacaftor (ETI) use. Semi-structured interviews were conducted with PwCF on topics of body image, perceptions of nutrition status, dietary changes, and CF care team relationships in the context of ETI. Interviews were analysed by two independent coders using inductive thematic analysis. Ten adult PwCF were interviewed. Participants were predominantly white (80%), and half were female. Body mass index ranged from 18.9 to 37.1 kg/m2. Three global themes were identified: finding balance, a new normal, and working together. Participants discussed pre and post-ETI diet experiences, body image changes and perceptions, and interactions with CF care teams and other mechanisms of support. Perspectives on nutrition status changes on ETI were diverse in our sample and reflect participants' adjustment to a redefined standard of health and nutrition in this new era of CF care. Findings indicate opportunities for partnership strategies with the CF care team, and for providing updated educational resources and personalised nutritional counselling to support the individual needs of PwCF as they navigate dietary and health behaviour changes.

Adipose tissue is a readily accessible source of stromal vascular fraction (SVF) and adipose-derived stem/stromal cells, widely used in regenerative medicine. Current harvesting and processing standards are derived almost exclusively from elective surgical settings performed under controlled physiological conditions. However, expanding applications in trauma and neurosurgery increasingly require adipose tissue procurement in emergency settings, where systemic inflammation, hypoperfusion, and time constraints may alter tissue biology. The biological impact of emergency harvesting remains insufficiently characterized, yet this knowledge is critical for optimizing SVF-based regenerative medicine strategies in emergency surgical environments. To evaluate how emergency adipose procurement may influence SVF quality, cellular yield, viability, and translational feasibility, and to propose an acute-care-adapted framework for clinical integration. A comprehensive search of PubMed, EMBASE, and Scopus (inception-January 2026) identified studies addressing harvesting techniques, donor-site variability, enzymatic vs mechanical isolation, time-to-processing effects, cryopreservation, contamination risk, and clinical outcomes. Data were synthesized narratively with emphasis on variables relevant to emergency settings. Harvesting parameters-including cannula diameter and negative pressure-influence total nucleated cell yield and viability. Enzymatic digestion increases cell recovery by approximately 1.5- to 3-fold compared with mechanical fractionation but requires laboratory infrastructure and a longer processing time. Mechanical techniques enable rapid point-of-care application yet produce stromal vascular tissue with greater heterogeneity. Processing delays reduce viable cell counts. Emergency physiology introduces additional upstream modifiers, including cytokine activation and microvascular perturbation, that remain largely unstudied in SVF research. Emergency adipose harvesting challenges elective-based assumptions underlying current SVF standards. Context-specific comparative studies and standardized emergency-adapted protocols are required to ensure biological robustness and clinical safety in acute surgical environments.

To evaluate the efficacy and safety of antithrombotic treatment for migraine prevention in participants with patent foramen ovale (PFO). Investigator initiated, multicentre, prospective, randomised, active controlled, open label clinical trial with blinded outcome assessment and hierarchical hypothesis testing. Secondary and tertiary care hospitals across 39 centres in China. 1000 adults aged 18-64 years with a diagnosis of migraine for more than one year, experiencing at least four migraine days per month, and with PFO confirmed by echocardiography. All participants completed a 12 week screening period before randomisation during which eligibility was confirmed and baseline headache data were prospectively recorded. Participants with previous stroke, transient ischaemic attack, intracranial haemorrhage, non-PFO right-to-left shunt, or contraindications to study drugs were excluded. Of the randomised participants, 984 (75.1% female) were included in the full analysis set. After the screening phase, participants were randomised in a 1:1:1:1 ratio to receive aspirin (300 mg once daily), clopidogrel (75 mg once daily), rivaroxaban (20 mg once daily), or metoprolol (25 mg twice daily) for 12 weeks. No additional preventive migraine treatments were permitted during the intervention period. The primary outcome was the proportion of participants achieving a &#x2265;50% reduction in monthly migraine days or attacks from baseline to weeks 9-12. Safety outcomes included bleeding and other adverse events. For the primary endpoint, aspirin, clopidogrel, and rivaroxaban were all non-inferior to metoprolol. Responder rates were 61.7% (148/240) with aspirin, 66.8% (157/235) with clopidogrel, 78.4% (185/236) with rivaroxaban, and 61.8% (144/233) with metoprolol. Rivaroxaban further showed a statistically higher responder rate than metoprolol, with an absolute difference of 16.2% (98.33% confidence interval 6.0 to 26.4; P<0.001). Among secondary endpoints, rivaroxaban was associated with greater reductions in migraine days and attacks, higher rates of complete migraine cessation, and greater improvements in migraine specific quality-of-life scores than metoprolol. No major bleeding events occurred. The antithrombotic agents evaluated in this trial (aspirin, clopidogrel, and rivaroxaban) were all non-inferior to metoprolol for responder rate in participants with PFO and migraine. Rivaroxaban also showed superior responder rates over metoprolol without an increase in major bleeding events. ClinicalTrials.gov NCT05546320.

Long-acting injectable buprenorphine (LAIB) is increasingly used in the Criminal Justice System (CJS) for treating people with opioid use disorder; however, little is known about these patients' experiences. We aimed to understand the perspectives of participants commenced on LAIB in prison as a part of the Understanding NSW Long-Active Opioids in Custody-Treatment (UNLOC-T) study. Results of an open-ended survey administered by UNLOC-T researchers underwent analysis. Participants were adults, recruited November 2018-July 2019, with moderate-severe opioid use disorder and &#x2265;&#x2009;6&#x2009;months remaining on their sentence. We conducted a thematic analysis using a pragmatic, descriptive coding approach. Sixty-seven participants were included, of which 82% were male. Five primary themes were identified that described participants' experiences and highlighted issues that can directly inform service delivery: medication effectiveness, social and relational considerations, dosing frequency, financial aspects, and health and wellbeing. There was considerable variation in participant perspectives within themes. Perspectives on LAIB are diverse, suggesting a need to individualise treatment and ensure person-centered care. While LAIB offers benefits to warrant including it as a treatment option, challenges remain. Future research into LAIB in the CJS would allow for triangulation, as well as further exploration of ongoing acceptability in the post-release period. Our findings could help to improve the way LAIB is offered as a treatment option or delivered to people in the CJS. There are also lessons for prescribers in counselling and tailoring treatment, and broader policy considerations around access to treatment formulations and patient autonomy.

Allo-HSCT represents a curative option for various hematological disorders. However, aGVHD remains the leading cause of non-relapse mortality following transplantation. The gastrointestinal tract is the most severely affected and prognostically unfavorable target organ in aGVHD, driven by donor T-cell-mediated epithelial damage, microbiota dysbiosis-driven immune amplification, and a self-perpetuating cycle of barrier disruption. Recent multi-omics studies have identified key pathogenic mechanisms, including microbiota-driven MHC-II expression and immunomodulation by microbial metabolites. Biomarker-driven risk stratification using the MAGIC algorithm has shifted management toward precision medicine, while targeted agents such as ruxolitinib, vedolizumab, and microbiota-directed interventions are reshaping therapeutic strategies. Novel interventional modalities, including FMT, recombinant LCN2, and specific bile acids, have forged innovative avenues that synergize microbiota-directed approaches with immunomodulation for the prevention and treatment of GI-aGVHD. This review systematically delineates the latest advances in the pathogenesis, risk stratification, and therapeutic strategies for GI-aGVHD, and envisions future directions for precision medicine centered on personalized microbiota-immune interventions.