Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, represent a major global health burden and share convergent pathogenic mechanisms, such as mitochondrial dysfunction, oxidative stress, neuroinflammation, calcium imbalance, and neuronal loss. Despite advances in symptomatic management, effective disease-modifying therapies remain limited. This review aims to critically synthesize mechanistic, preclinical, and clinical evidence on α-lipoic acid and biotin as candidate neuroprotective agents in neurodegenerative diseases, with emphasis on shared signaling pathways, therapeutic potential, generally favorable safety profiles, and translational limitations. A narrative and integrative review was conducted, encompassing mechanistic studies, preclinical experimental models, and clinical trials and observational studies evaluating ALA and biotin in neurodegenerative diseases. The evidence was qualitatively analyzed with attention to biological plausibility, consistency across models, and clinical relevance. ALA and biotin modulate key cellular pathways implicated in neurodegeneration, including mitochondrial metabolism, redox homeostasis, inflammatory signaling, and neurovascular function. Preclinical studies consistently report beneficial effects on mitochondrial efficiency, oxidative stress, and neuroinflammatory markers. In contrast, clinical evidence remains heterogeneous, with more extensive evaluation of biotin in progressive multiple sclerosis and more limited or exploratory findings for ALA across neurodegenerative disorders. ALA and biotin exhibit mechanistic convergence across pathways relevant to neurodegeneration and generally favorable safety profiles. Although current evidence supports their biological plausibility as adjunctive or exploratory therapeutic strategies, clinical outcomes remain inconsistent and appear to be influenced by dosing regimens, disease stage at intervention, and endpoint selection. Well-designed clinical studies are required to define their efficacy, optimal dosing, and disease-specific applicability.
Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and -13 signaling, is approved for the treatment of eosinophilic esophagitis (EoE) based on phase III clinical trials. However, real-world data on dupilumab use for EoE are lacking. To assess the characteristics, treatment patterns, and outcomes among patients with EoE aged 12 years or older who receive treatment with dupilumab for EoE as prescribed under the US prescribing information. This study protocol describes a phase IV, prospective, observational, multicenter patient registry, EDESIA, which will enroll approximately 300 patients aged 12 years or older who initiate dupilumab treatment as part of routine care across approximately 50 sites in the USA. Baseline data collection will include demographics, disease characteristics, medical history, and prior/concomitant therapies. Data will be collected at baseline (day 1 of treatment) and at follow-up visits through 36 months. Key primary outcomes assessed will include details of food elimination diet, history of food impaction and esophageal dilation, histologic and endoscopic findings, and patient-reported outcomes. Adverse events will be monitored throughout the study. The EDESIA registry will be conducted in accordance with the Declaration of Helsinki, the International Council for Harmonization guidelines for Good Clinical Practice, and applicable regulatory requirements. The local institutional review board at each study center will approve the study. Written informed consent will be obtained from all patients and/or a parent/legal guardian. EDESIA will address the safety and tolerability of long-term weekly dupilumab treatment in patients with EoE, and inform future treatment guidelines. A US registry of EoE adolescent and adult patients treated with DUPIXENT® as standard of care (EDESIA), NCT06693531 (https://www.clinicaltrials.gov/study/NCT06693531). A study protocol of the baseline characteristics, treatment patterns, and long-term outcomes in patients with eosinophilic esophagitis initiating dupilumab in routine clinical practice Eosinophilic esophagitis (EoE) is a long-term inflammatory disease of the esophagus (the tube that carries food and liquids from your mouth to your stomach). EoE is becoming more common, affecting more people worldwide. Dupilumab, a type of medication called a biologic, was the first of its kind to be approved for the treatment of EoE. Based on results from two clinical trials, dupilumab is now approved in the USA and Europe for people with EoE aged 1 year or older, weighing at least 15 kg. Dupilumab has been shown to improve signs and symptoms of EoE in clinical trial settings. “Real-world” studies show how effective and safe a treatment is for patients in real-life situations outside of controlled clinical trials. The EDESIA patient registry will be the first large-scale, US-based, real-world study for patients with EoE. EDESIA will aim to recruit approximately 300 patients with EoE, across 50 clinics in the USA. Patients with EoE, aged 12 years or older, who are being treated with dupilumab will be invited to participate in the study. After starting dupilumab, patients will attend a check-in at month 3, month 6, and every 6 months thereafter, up to 36 months (3 years). Questionnaires completed by the patient and clinician-collected assessments will be carried out at each check-in. Procedures such as an endoscopy (a camera inserted into the esophagus) will be conducted, if required, as part of the patient’s standard care. Data collected throughout the study will be analyzed to assess the patient characteristics, treatment patterns, side effects, and outcomes. EDESIA will provide the largest US-specific, real-word data for the treatment of EoE with dupilumab to date. The data will build upon existing knowledge of the safety and effectiveness of dupilumab by providing new data on how dupilumab is prescribed and its effectiveness for the treatment of EoE in real-life situations.
Not available.
Barth syndrome (BTHS; OMIM 302060) is an ultra-rare, life-limiting genetic disorder characterized by cardiomyopathy, skeletal muscle myopathy, neutropenia, gastrointestinal issues, and fatigue. Formal analyses of survival and clinical progression remain limited. Barth Syndrome Foundation has maintained an intake database (n = 502), representing > 80% of the known global population, as well as a patient-inputted registry for a subset of individuals (n = 162) with up to 11 years of longitudinal outcome data. We estimate the survival curve, identify factors associated with mortality, characterize clinical manifestations over time, and evaluate causes of death. Death disproportionately affected young children, with a 59% transplant-free survival rate for those age < 5. The risk of death plateaued between ages 5-25 before rising again. Heart transplantation (HR = 0.316, 95% CI: 0.162-0.619, p < 0.001) and living in a developed country (HR = 0.109, 95% CI: 0.018-0.659, p < 0.05) were associated with reduced risk of death. Clinical manifestations increased with age, with musculoskeletal/fatigue (66%) being most frequent. Top causes of death were cardiac-related complications, with cardiomyopathy/heart failure (51.3%), mostly in young children < 5, and arrhythmia/cardiac arrest (15%). This is the most comprehensive longitudinal assessment of BTHS survival, mortality risk, and clinical manifestation progression. Early childhood is a period of high mortality risk, driven in large part by heart failure. Although risk of death and hospitalizations plateaued between ages 5-25, the clinical burden of BTHS increases throughout the lifespan. Our results may guide clinical care, identify time windows for optimal intervention, and help clinicians better recognize BTHS clinical features.
This study analyzed the clinical and genetic characteristics of 73 pediatric patients with tuberous sclerosis complex (TSC). Through an examination of genotype-phenotype correlations, the research aimed to identify patterns in mutation characteristics to facilitate the optimization of diagnostic, therapeutic, and prognostic strategies. This retrospective study analyzed pediatric patients with TSC at Nanjing Medical University Children's Hospital between February 2018 and June 2025. Clinical data, including demographics and initial manifestations, were reviewed and peripheral blood samples were collected for whole-exome sequencing. Statistical analysis of categorical variables was performed using the chi-square test. Among the 73 pediatric TSC patients, 62 (85%) were diagnosed with epilepsy, with seizures being the initial manifestation in 56 (90%) of these cases. The observed seizure types included epileptic spasms (n = 25), generalized tonic-clonic seizure (n = 13), focal impaired consciousness seizure (n = 10), focal preserved consciousness seizure (n = 6), focal to bilateral tonic-clonic seizure (n = 5), tonic (n = 1), and absence (n = 1). Other common clinical features were hypopigmented macules (n = 44), cortical tubers (n = 34), intellectual disability (n = 24), and subependymal nodules (n = 22). Genetic testing identified TSC1 or TSC2 mutations in 68 patients (93%), corresponding to 71 distinct mutation sites. Fourteen variants (2 in TSC1, 12 in TSC2) were novel. The spectrum of mutations included nonsense, frameshift, missense, and splice-site types, with both de novo and inherited origins identified. The clinical phenotype of TSC is highly heterogeneous, with complex genotype-phenotype associations. The identification of 14 novel variants expands the known mutational spectrum of TSC, and the detailed genotype-phenotype analysis provides valuable insights for early diagnosis, genetic counseling, and personalized therapeutic strategies in pediatric populations. Early TSC1/TSC2 genetic testing is therefore crucial for diagnostic confirmation and enables personalized management strategies in cases of suspected TSC.
Chromosome 16p11.2 deletion syndrome is a genetic syndrome that includes difficulties in speech, language, and motor coordination. Arbaclofen, a selective GABA-B receptor agonist, has improved motor functioning and memory in mouse models. Prior clinical trials of arbaclofen in fragile X syndrome and autism spectrum disorder suggested benefit for social communication. L16hthouse (NCT04271332) is a multi-site, double-blind, randomized, placebo-controlled phase 2 trial to evaluate safety, efficacy, and tolerability of arbaclofen compared in 60 youths with 16p11.2 deletion syndrome (5 to 17:11 years) randomized on a 1:1 ratio. Primary outcomes included speech articulation, measured by the Goldman Fristoe Test of Articulation 3 (GFTA-3). Secondary outcomes included objective dysarthria indices, memory, motor control, and cognitive function, assessed with both standardized clinical measures and novel, computer-based assessments with automated scoring. Exploratory outcomes included attention, autism traits, and electrophysiological responses. L16hthouse is the first randomized trial in 16p11.2 deletion syndrome and uses an array of novel outcome measures to assess potential benefit in this population. In addition to providing potential insights about the safety, efficacy, and tolerability of arbaclofen, L16hthouse will provide an initial assessment of how these developmental outcome measures perform in a clinical trial across a broad age range.Clinical trial registration number: NCT04271332; 2020-02-13. The methods are described for a multi-site, double-blind, randomized controlled Phase 2 trial to evaluate the safety, efficacy, and tolerability of arbaclofen for youth with 16p11.2 deletion syndrome. The primary outcome measure was speech articulation, a key difficulty for youth with 16p11.2 deletion syndrome. The outcomes of this trial, combined with the parallel Canadian ARBA and European AIMS-CT-01 trials, will contribute to the evidence base of arbaclofen as a treatment for neurological and psychiatric conditions.
The human leukocyte antigen (HLA) system underpins allorecognition and shapes the response to infection, autoimmunity, and treatment response. Technological advances from serology to next-generation sequencing now enable full-gene characterization and four-field HLA nomenclature, while artificial intelligence (AI) and machine learning are transforming the data generation, interpretation, and clinical use. This review summarizes the progress on the technical developments in the HLA era, which could be evaluated in three perspectives. First, we survey AI for antigen processing and T-cell recognition, including HLA–peptide binding, presentation, and T cell receptor (TCR)–epitope models, and outline their effects on applications like neoantigen discovery, vaccine design, and tolerance induction. Since there are still persistent gaps in immunogenicity prediction and coverage of rare alleles, secondly, we evaluated HLA imputation from the single nucleotide polymorphism (SNP) arrays and low-coverage whole-genome sequencing, highlighting deep learning models that improve accuracy for common and low-frequency alleles, and the critical role of diverse reference panels. Third, we assessed the AI-enabled transplant decision support: survival and graft-versus-host disease forecasting from registry data, donor ranking beyond simple allele match, and crossmatch compatibility prediction. We integrate emerging biology, non-classical HLA molecules, allele-specific expression, and HLA loss of heterozygosity, as key modulators of immune activation and evasion with implications for donor selection, infectious diseases, vaccinology, inflammatory disease, and cancer therapy. To accelerate safe clinical translation, we need to have standards for data governance, fairness auditing, validation and calibration, explainability, robustness, monitoring, and human oversight. By bridging core HLA principles with recent biological insights and AI innovations, we outline a path toward reproducible and equitable clinical translation to immunogenomics in transplantation, infectious, inflammatory, oncologic diseases, and precision vaccinology.
Mitochondrial complex III (CIII) deficiency, resulting from abnormalities in its subunits or assembly factors, presents with diverse clinical manifestations. LYRM7-associated CIII deficiency is rare and typically presents with progressive neurodegeneration. We report a case series of LYRM7-associated CIII deficiency in two brothers, highlighting inflammatory demyelinating-like presentations, intrafamilial variability, and atypical disease progression. We present an investigational case series highlighting continuing challenges in diagnosing and managing LYRM7-associated mitochondrial complex III deficiency. Whole-exome sequencing (WES) was performed for diagnostic evaluation, followed by confirmatory Sanger sequencing and literature review of previously reported cases. Two brothers from a consanguineous family presented with ataxia, visual impairment, and progressive neurological deterioration including spasticity, seizures, cognitive decline, and motor weakness. Patient 1 (P1) experienced recurrent ataxic episodes beginning at 7 years of age, initially suspected to represent an inflammatory demyelinating disorder, while patient 2 (P2) demonstrated a more aggressive disease course with rapid neurological deterioration and early mortality at 8 years of age. Neuroimaging revealed cystic white matter changes suggestive of mitochondrial leukodystrophy and longitudinally extensive transverse myelitis (LETM) in both patients, differing from typical inflammatory demyelinating patterns. Genetic testing confirmed a pathogenic LYRM7 variant. Notably, intrafamilial clinical variability and the inflammatory-like presentation in P1- including LETM and optic neuritis mimicking neuromyelitis optica spectrum disorder (NMOSD)- distinguished our cases from previously reported patients. These findings expand the phenotypic spectrum of LYRM7-associated CIII deficiency and highlight diagnostic challenges. This case series expand the clinical spectrum of LYRM7-associated complex III deficiency and highlights relapsing inflammatory-like presentations as a potential diagnostic pitfall. Our findings emphasize the importance of considering mitochondrial disorders in children presenting with recurrent demyelinating-like episodes, atypical progression, or familial patterns. Early genetic diagnosis is essential for accurate diagnosis, counseling, and management of mitochondrial disorders.
T cell-engaging bispecific antibodies (T-BsAbs) have revolutionized immunotherapy for hematologic malignancies, showing promise in lymphoid cancers and myeloma. However, their application in myeloid malignancies like acute myeloid leukemia (AML) faces challenges due to myelotoxicity and limited target specificity. Here, we review the current landscape of T-BsAb development for myeloid diseases, detailing target antigens, antibody engineering strategies, and clinical trial outcomes. We discuss advances in bispecific antibody formats designed to enhance efficacy and reduce toxicity, alongside emerging therapeutic combinations. Our synthesis highlights the complexity of targeting myeloid malignancies while sparing normal hematopoietic cells. These insights underscore the potential of refined T-BsAb approaches to improve treatment specificity and efficacy in AML and related disorders, informing future therapeutic strategies and clinical development.
Subsyndromal generalized anxiety is highly prevalent and associated with impaired well-being, elevated stress, and functional limitations, yet affected individuals often do not meet criteria for guideline-based treatment. Scalable, low-threshold digital interventions that target psychophysiological regulation may help address this gap. Guided self-hypnosis and aromatherapy using essential oils have each demonstrated anxiolytic and relaxation-promoting effects. Combining these approaches may enhance efficacy and allow for conditioning of relaxation responses via olfactory cues. This study protocol describes a randomized controlled trial evaluating the efficacy and conditioning potential of a digital self-hypnosis intervention combined with essential oil inhalation in adults with subsyndromal generalized anxiety. A total of N = 630 participants will be randomized into six groups. Four groups enter the primary efficacy analysis: (1) self-hypnosis + bergamot essential oil, (2) self-hypnosis + lavender essential oil, (3) self-hypnosis without essential oil, and (4) a minimal-intervention control. The intervention is delivered online over six weeks (Phase 1), followed by a two-week conditioning phase without hypnosis (Phase 2), in which stimulus-specific effects of the essential oils are tested. The primary outcome is subjective relaxation, measured by the Multidimensional Mood Questionnaire (MDBF) at baseline, post-intervention (6 weeks), and post-conditioning (8 weeks). Secondary outcomes include anxiety symptoms, perceived stress, sleep quality, well-being, and worry. In a voluntary subsample, heart rate variability (HRV) and pulse wave variability (PWV) will be assessed as physiological correlates of relaxation. In addition, the questionnaires are expanded to include open-ended questions, enabling an exploratory assessment of participants' experiences, attitudes, and reflections on the intervention and its potential for sustainability. This approach complements quantitative results with qualitative insights and may reveal new perspectives for future research. This study is expected to provide evidence on the efficacy of essential oil-enhanced digital hypnosis for subsyndromal anxiety and will examine whether repeated pairing of hypnosis and olfactory stimulation induces conditioned relaxation responses. If effective, this multimodal, low-intensity intervention could represent a scalable preventive approach for individuals with increased anxiety who are not receiving formal treatment and have been medically diagnosed.Clinical Trial Registration: https://www.drks.de/search/de/trial/DRKS00039047/details, Identifier DRKS00039047.
Nitric oxide (NO) functions as a master integrative regulator of cardiovascular-kidney-metabolic (CKM) homeostasis, yet it displays a profound Janus face, defined by concentration- and context-dependent roles in both health and disease. This narrative review examines NO signaling from a life-course perspective, beginning with fetal programming, during which the NO-asymmetric dimethylarginine (ADMA) axis orchestrates placental development and nephron endowment. Perturbations during this critical window-such as maternal ADMA elevation-can imprint a maladaptive trajectory toward adult-onset hypertension and chronic kidney disease. In adulthood, this initially silent dysregulation of NO signaling is amplified by Western dietary patterns and environmental pollutants, culminating in the clinical manifestation of the CKM triad. This pathological transition is driven by eNOS uncoupling and ADMA accumulation, which shift redox balance toward peroxynitrite formation and precipitate mitochondrial bioenergetic failure. Moreover, while constitutive NO production is essential for vascular homeostasis, pathological induction of inducible NOS generates excessive NO fluxes that promote insulin resistance and tissue injury. With advancing age, a progressive loss of NO resilience further exacerbates multi-organ vulnerability. To mitigate the cumulative burden of CKM disease, this review highlights developmental reprogramming strategies-such as perinatal L-citrulline supplementation and ADMA-lowering interventions-as interventions to restore physiological NO signaling. Integrating such early-life strategies with contemporary pharmacological therapies offers a coherent framework for maintaining NO bioavailability and extending health span across the life course.
Ventricular fibrillation in paediatric recipients of left ventricular assist devices is rare but potentially fatal; however, because systemic perfusion may be temporarily maintained by the mechanical support, haemodynamic deterioration may be delayed, leading to underrecognition and presentation in the outpatient setting rather than as an immediate in-hospital emergency. We report three paediatric left ventricular assist device recipients who developed outpatient malignant ventricular arrhythmias, each representing a distinct mechanistic category: structural, mechanical, and endocrine. Clinical presentation, diagnostic findings, and therapeutic responses were reviewed to highlight pathophysiologic heterogeneity and inform individualised management. The first patient, with biopsy-proven arrhythmogenic right ventricular dysplasia, experienced recurrent ventricular fibrillation refractory to multiple antiarrhythmic agents, ultimately requiring heart transplantation. The second patient presented with ventricular fibrillation secondary to mechanical suction and interventricular septal contact; defibrillation and left ventricular assist device speed reduction restored a stable rhythm with no recurrence. The third patient developed polymorphic ventricular arrhythmias during amiodarone-induced thyrotoxicosis and succumbed to refractory electrical storm and multi-organ failure despite intensive endocrine and antiarrhythmic therapy. Outpatient ventricular fibrillation in paediatric left ventricular assist device recipients may result from diverse mechanisms, including myocardial structural disease, mechanical pump heart interaction, and systemic endocrine disturbances. Mechanism-guided management combining antiarrhythmic, mechanical, and metabolic interventions is essential for optimal outcomes. Continuous rhythm surveillance and readiness for immediate defibrillation are key to improving survival in this vulnerable group.
This special article synthesizes transformative insights from a recent international neonatal cell therapy symposium (held in Noosa, Australia) where leading experts convened to explore regenerative solutions for serious perinatal and neonatal conditions. The discussions highlighted pioneering cell-based therapies targeting preterm brain injury, bronchopulmonary dysplasia, fetal growth restriction, hypoplastic left heart syndrome and congenital diaphragmatic hernia; neonatal conditions that present both neonatal challenges and long-term morbidities, demanding innovation beyond conventional medical, surgical and supportive care. Advances in regenerative medicine, particularly those leveraging umbilical cord blood-derived cells, mesenchymal stromal cells from various sources, amniotic fluid and human amnion epithelial derived cells and extracellular vesicles, are redefining therapeutic possibilities through paracrine signaling, immunomodulation, and tissue repair to counteract shared mechanisms of inflammation, oxidative stress, apoptosis, and impaired regeneration. This article integrates the symposium's key clinical and translational perspectives, emphasizing system-specific developments across cardiovascular, pulmonary, neurological, and systemic domains, with a particular focus on scalable production strategies, and the importance of multidisciplinary collaboration. IMPACT: Synthesizes global evidence from preclinical and clinical studies to define the current translational trajectory of cell therapies across major neonatal conditions. Highlights integrative frameworks combining advanced preclinical modeling, clinical trials, scalable manufacturing and stakeholder collaboration to accelerate translation in neonatal regenerative medicine.
Severe, rapidly progressive polyhydramnios with a structurally normal fetus remains a diagnostic challenge. We describe 2 consecutive pregnancies in the same mother that were complicated by massive polyhydramnios culminating in extreme preterm delivery and intra-uterine fetal demise. Trio whole-exome sequencing identified a previously unreported hemizygous MAGED2 variant (c.1330G>A; p.Gly444Ser), confirming antenatal Bartter syndrome (ABS, type V). This case underscores 3 practical messages: (1) an X-linked MAGED2 defect should be considered early when polyhydramnios recurs without anatomical anomalies and standard chromosomal microarray is normal; (2) timely genomic testing enables targeted counseling, antenatal management (eg, indomethacin) and discussion of pre-implantation diagnosis; and (3) dismissing genetic etiologies on the basis of mild maternal factors (eg, well-controlled gestational diabetes) risks missed diagnoses.
Necrotizing Enterocolitis (NEC) is a serious gastrointestinal disease primarily affecting preterm neonates. Despite improvements in neonatal care, NEC continues to contribute significantly to neonatal mortality, particularly in low-resource settings. In Ethiopia, NEC-related mortality rates vary from 45% to 89%, reflecting both the severity of the disease and inconsistencies in existing evidence. Moreover, little is known about the predictors of NEC-related mortality in the local context. This underscores the need for a locally derived predictive model to support early risk stratification and guide clinical decision-making. A prospective cohort study was conducted among 251 neonates hospitalized with Necrotizing Enterocolitis. Data were analyzed using R, a multivariable analysis was performed to identify predictors of mortality, and a nomogram was developed. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plot. Bootstrapping was used to validate all accuracy measures. A decision curve analysis was used to evaluate the clinical and public health utility of our model. NEC mortality rate was 51% (95%CI: 45.00-57.34). Out born delivery, lower gestational age, disease onset ⩽3 days, delayed first feeding beyond 48 hours of postnatal age, abdominal wall erythema, stage III NEC, severe thrombocytopenia, clinical deterioration within 48 hours of diagnosis, and hospital-acquired infection were Key predictors remained in the reduced model. The AUC of the original model was 0.965 (95%CI: 0.943, 0.982), whereas the nomogram model has an AUC of 0.959 (95%CI: 0.942, 0.982). Our decision curve analysis for the model provides a higher net benefit across ranges of threshold probabilities. Our model has excellent discrimination and calibration performance. Similarly, the nomogram model has excellent model ability with an insignificant loss of accuracy from the original. The models can have the potential to improve care and treatment outcomes in the clinical settings.
The incidence of respiratory diseases is increasing worldwide and imposes a significant health burden. Due to the complex etiology and diverse inducements of these diseases, existing therapies often struggle to control disease progression and reduce recurrence rates. Therefore, the medical community continues to explore novel strategies derived from natural medicines. As a precious traditional fungus, Cordyceps has long been used for nourishing the lungs in Asia. Extensive reports demonstrate that Cordyceps exhibits considerable potential in the treatment of respiratory diseases. This review seeks to comprehensively summarize the biologically active ingredients and underlying mechanisms of Cordyceps in the treatment of respiratory diseases. The aim is to offer valuable insights for future development of Cordyceps. The literature search is conducted in PubMed, Web of Science, Science Direct, and CNKI for publications from 2007 to 2025. The keywords include "Cordyceps", "respiratory diseases", "chronic obstructive pulmonary disease", "pulmonary fibrosis", "pneumonia", "cordycepin", "polysaccharide", "ergosterol", and other related terms. Both Chinese and English terms are used for the CNKI database. Literature consisting of original research and reviews on Cordyceps active ingredients for respiratory diseases is included. Non-respiratory system research, non-peer-reviewed literature, and repetitive literature are excluded. After eligibility screening, 194 studies are included in the final analyses. Nucleosides, polysaccharide and sterols emerge as the principal ingredients in Cordyceps, which exhibit significant function against respiratory diseases. The mechanisms mainly involve alleviating oxidative stress, inhibiting inflammatory reaction, modulating immune response and others. Up to now, Cordyceps does not show obvious toxic side effects in preclinical and clinical studies. Cordyceps is a promising fungal source. This review comprehensively analyzed the biologically active ingredients and elucidated the underlying mechanisms of Cordyceps in the treatment of respiratory diseases. The paper would provide evidence for clinical use of Cordyceps and lay a foundation for its future development.
Best practice recommendations and guidelines for the assessment and management of suicidality within the emergency department (ED) have recently been updated. Despite national efforts to improve the management of suicidality in the ED, evidence-based practices remain underused with varied uptake among EDs and clinical team members. Given that the ED is a common point of entry for many people with suicidality, implementation of evidence-based strategies are needed to increase access to these strategies and improve patient outcomes. To generate insights about the feasibility of implementing evidence-based practices for suicidality management, we developed a semi-structured interview guide focused on factors expected to influence the implementation process using a novel application of the Organizational Readiness for Innovation Implementation Framework. Working from a list or 80 EDs in the state of Indiana, we recruited emergency physicians, nurses, physician assistants, and social workers to participate in interviews. Interviews lasted approximately 45-60 minutes and were recorded, transcribed, and qualitatively analyzed using a multistage thematic analysis process. We conducted 11 interviews with ED clinical team members from eight EDs in Indiana, representing 10% of the 80 EDs invited to participate in our study. Identified barriers to effective implementation included a general lack of resources, resistance to change among clinical team members, and competing demands in the ED setting. Facilitators included openness to attending training, openness to implementing change in the ED, and leadership support. Openness to change and commitment to change appeared to be driven by discontent with current processes and a desire to improve patient experiences. Considering mixed attitudes toward suicidality management and questions about whether these services are within the scope of clinicians who work in the ED, efforts to increase uptake of evidence-based practices may involve a multifaceted approach that involves identifying and training team members who are open and ready for change, while simultaneously establishing stronger relationships between ED clinical team members and behavioral health clinicians with specialized training who can provide consultative services in the ED.
Background: RASopathies represent a clinically and genetically diverse group of syndromes resulting from germline mutations in genes regulating the RAS/mitogen-activated protein kinase (MAPK) signaling cascade. Methods: The aim of this study was to describe the clinical features and genetic variants identified in patients with genetically confirmed Noonan syndrome (NS) in a limited cohort from Romania. A total of 25 patients with positive genetic testing for NS-associated genes were included. Genetic testing was performed primarily using next-generation sequencing. Results: A total of twenty-six variants were identified in twenty-five patients, as one patient carried two pathogenic variants in the PTPN11 gene (c.188A>G and c.922A>G). Of these variants, twenty-four (92.31%) were classified as pathogenic and two (7.69%) as variants of uncertain significance (VUS). Pathogenic variants were found in different genes, including PTPN11, LZTR1, SOS1, and RAF1, with PTPN11 being the most frequently affected gene. Males predominated (17/25), with a male-to-female ratio of approximately 2:1. Two patients inherited the pathogenic variant from an affected parent. Cardiovascular involvement was present in 21 patients (84%), with pulmonary valve stenosis (PVS) being the most common finding (48%), followed by hypertrophic cardiomyopathy (16%). Additional cardiac anomalies included atrial septal defect, valvular regurgitation, dysplastic valves, coarctation of the aorta, and sinotubular junction narrowing. Short stature was observed in 64% of patients, and craniofacial dysmorphism was present in 96%. Cutaneous, ectodermal, dental, ophthalmologic, and auditory manifestations were variably observed. Conclusions: Although based on a limited cohort from Romania, this study provides insights into clinical features suggestive of NS. Our findings highlight the genetic heterogeneity of NS and emphasize the importance of comprehensive genetic testing for confirming diagnosis, guiding clinical management, and supporting family counseling.
The perinatal period is a high-risk time for stroke, with possible lifelong effects. We aimed at identifying factors associated with long-term neurological outcomes and post-stroke epilepsy in patients with neonatal arterial ischemic stroke (NAIS). We analyzed patients with NAIS from the Italian Registry of Infantile Thrombosis (RITI). Associations between clinical variables and outcomes (neurological deficits and epilepsy at last follow-up) were evaluated using univariate logistic regression. Among the 181 patients included (56.2% male), seizures were the most common initial symptom (79.4%). Stroke was left-sided in 62.0%, and bilateral in 15.0%; multiple lesions were reported in 32.5%. The middle cerebral artery territory was most frequently involved. One patient had a new infarction during hospitalization, and one died. At follow-up (median 21 months), no further recurrences or deaths occurred; neurological deficits were reported in 38.8%, and post-stroke epilepsy in 12.0% (among these latter, prior acute seizures occurred in 86.7%). At univariate regression, factors significantly associated with long-term neurological deficits were higher maternal age (p = 0.031); urgent cesarean (p < 0.001); lower gestational age (p = 0.033); neurological deficits at discharge (p < 0.001); seizures at last follow-up (p = 0.008). Factors significantly associated with post-stroke epilepsy were need for acute-phase assisted ventilation (p = 0.001); radiological brainstem involvement (p = 0.037); and longer admission duration (p = 0.050).  Mortality and recurrence after NAIS are rare, but neurological deficits occur in about 40%, and epilepsy in 12%. Perinatal and clinical factors may predict adverse outcomes and epilepsy. • The perinatal period is a high-risk window for neonatal arterial ischemic stroke (NAIS), with seizures as the most common presenting symptom. Mortality and recurrent strokes after NAIS are rare, but long-term neurological deficits and post-stroke epilepsy are recognized complications. • In this registry-based cohort, specific perinatal and clinical factors-such as higher maternal age, urgent cesarean delivery, lower gestational age, neurological deficits at discharge, and seizures at follow-up-were significantly associated with long-term neurological impairments. • Risk factors for post-stroke epilepsy were identified, including need for acute-phase assisted ventilation, radiological brainstem involvement, and longer hospital stays, providing new insights for early prognostication and follow-up strategies.
Febrile seizures (FS) are the most common seizures in childhood, yet identifying children at risk of developing epilepsy after the first FS remains challenging. We aimed to evaluate the prognostic potential of machine learning (ML) algorithms applied to post-febrile seizure electroencephalography (EEG) recordings. We retrospectively reviewed 104 children (69 boys; mean age at first febrile seizure: 39.4 ± 18.2 months) who presented with their first febrile seizure between January 2018 and December 2021. Clinical data and EEG recordings obtained during N2 sleep were collected. EEG analysis was performed using separate preprocessing pipelines. For conventional EEG analysis, recordings were band-pass filtered between 1 and 40 Hz, and artifact-free segments were analyzed using Python-based pipelines (YASA, MNE) to extract 34 time-domain. The 34 extracted electrophysiological features were calculated across different bipolar EEG channels and evaluated together with aggregated inter-channel measures, resulting in a total of 93 input attributes used for ML model development. High-frequency oscillations (HFOs) were analyzed using a distinct pipeline applied to wideband EEG data before low-pass filtering. Six machine learning algorithms-J48 Consolidated Decision Tree, Random Forest, Gradient Boosting, Extreme Gradient Boosting, k-nearest neighbor, and Support Vector Machine-were trained using 10 × 7 repeated cross-validation. Model performance was evaluated using sensitivity, specificity, accuracy, area under the receiver operating characteristic curve (ROC AUC), and F1-score. Over a median follow-up of 4.2 months, 13 patients (12.5%) developed epilepsy, and all diagnoses were made within 9 months. XGBoost achieved the highest accuracy (0.89) and specificity (0.95) but had low sensitivity (0.46). J48 achieved the highest sensitivity (0.87) and ROC AUC (0.79), with a specificity of 0.71. Incorporating clinical features, including recurrent seizures, increased sensitivity to 0.95. The most relevant predictors were patient history, frequency band power, particularly increased power in lower frequency bands, and high-frequency oscillations counts. ML-based analysis of initial EEG after a first febrile seizure may assist in early epilepsy risk stratification. J48 provided superior sensitivity, and combining electroencephalography-derived biomarkers with clinical data further enhanced predictive performance. Prospective, multicenter studies are warranted to confirm these findings.