Citations

Background: Matching techniques such as direct covariate matching and propensity score matching (PSM) are increasingly used in anterior cruciate ligament reconstruction (ACLR) research to reduce bias in observational study designs. However, the rationale for covariate selection, consistency in methodological reporting, and patterns of matching practices remain unclear. Purpose: To systematically evaluate covariate matching practices in ACLR literature, including the types and number of covariates used, methodological transparency, and trends in matching strategies. Study Design: Systematic review. Methods: A systematic literature search of the PubMed, EMBASE, and Cochrane databases was conducted to evaluate covariate matching practices in the ACLR literature. A comprehensive search identified 798 unique studies, of which 97 met eligibility criteria. Data were extracted on study design, matching technique, covariate inclusion, reporting practices, and matching ratios. Descriptive and comparative statistics were used to summarize trends. Results: The 97 included studies encompassed 91,165 ACLRs. Most studies were retrospective (90.7%) and cohort in design (92.8%). PSM was used in 41 studies (42.3%), while 56 (57.7%) used direct matching. A total of 60 unique covariates were used across 76 different combinations. PSM studies used significantly more covariates than direct matching studies (6.17 ± 2.79 vs 3.75 ± 1.63; P < .0001), and database studies used more covariates than single-center studies (6.33 ± 2.89 vs 4.08 ± 1.96; P < .0001). The most commonly used covariates were age (96.9%), sex (84.5%), and body mass index (41.2%). Only 6 studies (6.2%) provided justification for covariate selection. The most frequent matching ratio was 1:1 (73.2%). While most studies reported descriptive statistics after matching (95.9%), only 10.3% did so before matching, and 13.4% failed to report prematching sample size. Conclusion: Matching practices in ACLR studies remain highly variable, with limited justification provided for covariate selection. PSM and database-based studies tend to incorporate a greater number of covariates, yet reporting of matching methodology is often inconsistent. To enhance the quality, reproducibility, and comparability of ACLR research, future studies should adopt standardized reporting practices for matching, including explicit descriptions of covariate selection, matching algorithms, balance diagnostics, and match ratios. These steps can serve as a foundation for a more unified research framework, enabling future studies to collectively generate higher quality, generalizable evidence for ACLR outcomes.

Immune-mediated epilepsies represent an etiologically unique category defined by immune activation within the central nervous system that initiates a pathophysiological cascade resulting in seizures, encephalopathy, and sometimes epileptogenesis with long-term epilepsy. Once considered rare and largely confined to paraneoplastic or postinfectious syndromes, immune-mediated and inflammatory mechanisms are now recognized across a broad spectrum ranging from acute autoimmune encephalitis with reversible seizures, new-onset refractory status epilepticus, or febrile illness-related refractory status epilepticus, to chronic autoimmune-associated epilepsy and drug-refractory structural epilepsies. This review integrates historical perspectives, mechanistic insights from animal and human studies, and contemporary clinical frameworks. It synthesizes advances in neuroimmunology, clinical phenotyping, diagnostics, immunomodulatory and antiseizure therapies, neuromodulation, and patient and family centered outcomes, and outlines future directions focused on biomarker-driven precision medicine, disease-modifying strategies, and interdisciplinary care models.

Abstract Provided herein are novel compounds as TREM2 agonists, pharmaceutical compositions, use of such compounds in treating Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Nasu-Hakola disease, and stroke, and processes for preparing such compounds.

Abstract Unvetted scientific claims about vaccines can spread rapidly and undermine decades of progress in immunization and public trust. A recent non-peer-reviewed analysis, promoted at political hearings, in the documentary “An Inconvenient Study,” and on social media, has been used to suggest that vaccinated children experience higher rates of chronic illness than unvaccinated peers. Despite standard regression models, critical flaws - uncontrolled confounding, exposure misclassification, unequal follow-up, and outcome multiplicity, invalidate causal inference. An independent group of international experts critically appraises this analysis and contrast its claims with the consistent evidence confirming vaccine safety and effectiveness. We also show how poorly designed studies can distort public discourse, amplify misinformation, and fuel vaccine hesitancy. We outline actions to strengthen research integrity, such as transparent data sharing, labeling of non-peer-reviewed content, and evidence-based communication. Safeguarding public health demands that vaccine evidence be methodologically sound, reviewed, and interpreted by qualified experts.

Abstract Purpose : Inclusive design seeks to ensure that digital health interventions (DHIs) are accessible, acceptable, and useful for older adults by addressing functional, health-related, and socio-cultural needs. This study aimed to identify factors influencing the inclusivity of DHIs for older adults and to compare perspectives derived from the literature, expert interviews, and a focus group with older adults. By triangulating these perspectives, we sought to establish a common set of factors to inform inclusive design guidelines for DHIs targeting older adults. Methods : Inclusive design criteria were identified and triangulated using three complementary sources: a scoping literature review, semi-structured expert interviews, and a focus group with older adults. Convergences and divergences across these sources were analyzed to determine shared and context-specific priorities for inclusive DHI design. Results : Older adults emphasized the importance of emotional reassurance, analog alternatives, and personal contact with healthcare professionals to reduce anxiety and strengthen feelings of safety and trust. Experts highlighted healthcare system integration, co-design processes, regulatory compliance, sustainable financing models, and ethical considerations such as privacy protection and the avoidance of stigmatization. The literature most frequently emphasized equity-related factors, including affordability and insurance coverage, interoperability across devices and platforms, and tailoring content to individual needs. Across all three sources, there was strong convergence regarding the importance of usability, accessibility, personalization, and user support. Conclusions : The findings demonstrate that inclusive DHI design for older adults requires attention not only to usability and accessibility, but also to emotional, ethical, and systemic dimensions. The convergence across literature, expert, and user perspectives suggests that usability, accessibility, personalization, and ongoing user support constitute foundational requirements for inclusive design guidelines for DHIs aimed at older adults.

Abstract Provided herein are novel 6,5-bicyclic compounds as 5-HT2A receptor agonists, pharmaceutical compositions, use of such compounds in treating depression, anxiety, substance abuse, and headaches, and processes for preparing such compounds.

Peritoneal coccidioidomycosis is a rare, disseminated manifestation of Coccidioides infection with limited representation in the literature. We report 37 proven or probable cases from a single institution, including 12 patients (32%) with immunosuppression. Thirty-six patients received antifungal therapy, all of whom demonstrated clinical response. Among 11 (29.7%) patients who completed and stopped therapy after a median duration of 26 months, 2 (5%) experienced a relapse and were successfully retreated. Nine patients (24%) had no known relapse. Thirteen patients (35%) required modification of antifungal regimens, primarily due to azole adverse effects. Treatment approaches and median duration of therapy (57 months) were similar between immunosuppressed and non-immunosuppressed groups. No deaths were attributable to infection. Overall, outcomes were favorable, with strong clinical responses to azole therapy. Patients without identifiable immunologic deficits or additional sites of dissemination, when managed with antifungal therapy and close clinical, radiologic, and serologic monitoring, may achieve good prognosis, particularly when indefinite azole therapy is not feasible.

Abstract INTRODUCTION Neurodegenerative diseases often involve overlapping alpha‐synuclein (asyn), amyloid beta, and tau proteinopathies, yet the mechanisms, impact, and directionality of their interactions remain unclear. METHODS We induced brain‐wide neuronal asyn/tau pathologies via viral expression of wild‐type asyn, mutant asyn E46K , mutant tau A152T , or both asyn E46K /tau A152T in adult amyloidosis knock‐in mice and controls, either post‐plaque deposition (6 months old) or pre‐plaque (3 months old). Open‐field behavior was assessed baseline and 3 and 6 months post‐transduction, followed by neuropathology and neuroinflammation analyses. RESULTS Post‐plaque induction in amyloid mice increased asyn/tau total and phosphorylated levels and exacerbated amyloid‐related hyperlocomotion/anxiety. Pre‐plaque induction produced robust phosphorylated pathologies irrespective of amyloid, while causing similar amyloid‐dependent behavioral synergy. Tau pathology drove LGALS3 + inflammatory glial responses in white‐matter fibers. DISCUSSION Amyloid context gates vulnerability, with certain synergies manifesting across stages. White‐matter gliosis is a novel mechanism of tau A152T risk. Together, our data argue for the development of stage‐aware, multitarget interventions and biomarkers.

Scattered tubular-like cells (STCs) are dedifferentiated renal tubular cells that repair other damaged kidney cells. This study shows that renovascular disease (RVD) induces site-specific 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) modifications in DNA associated with transcriptional changes and impaired proliferative capacity of swine STCs, which could be mitigated in RVD-STCs treated with an epigenetic modulator. Therefore, our observations may contribute to the development of novel approaches to preserve the reparative capacity of STCs in individuals with RVD.

ABSTRACT Pathogenic variants in AMMECR1 have been associated with a rare multisystem disorder characterized by midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis (MFHIEN). To date, most reported cases involve copy number variants or presumed loss‐of‐function alterations, with only a single prior report describing a missense variant supported by functional studies. Here, we report a patient with a heterozygous de novo AMMECR1 missense variant, NM_015365.3:c.649G>A p.(Val217Met) presenting with clinical features consistent with MFHIEN, including midface hypoplasia, partial hearing impairment, nephrocalcinosis, and elliptocytosis identified on peripheral blood smear. Comparative review of the literature highlights that while previously reported missense variants in AMMECR1 demonstrated altered intranuclear protein distribution and reduced expression in functional assays, clinical evidence supporting pathogenicity of non‐truncating variants remains limited. The phenotypic overlap between our patient and prior report strengthens the association between missense variations and the MFHIEN phenotype. Our findings support the pathogenic relevance of missense variation in AMMECR1 and emphasize the importance of integrating detailed phenotyping, including hematologic evaluation, with genomic data in the diagnosis of rare multisystem disorders. Additional cases and functional studies are needed to clarify genotype–phenotype correlations and underlying disease mechanisms.