Citations

Purpose of review Circadian clocks are increasingly recognized as fundamental regulators of innate immune function, yet their relevance to allergy and clinical immunology has only recently been clarified. This review summarizes emerging evidence linking circadian regulation of innate immune cells to allergic inflammation and highlights the translational potential of circadian-informed therapeutic strategies. Recent findings Core clock components are rhythmically expressed in macrophages, mast cells, neutrophils and innate lymphoid cells, where they regulate inflammatory signalling, immunometabolism and activation thresholds. Disruption of these rhythms exaggerates cytokine production, inflammasome activation and mast cell mediator release, contributing to diurnal patterns of allergic disease such as nocturnal asthma. Human and experimental studies demonstrate that circadian misalignment driven by shift work, irregular sleep and mistimed feeding amplifies innate inflammation and worsens allergic outcomes. Summary Circadian regulation represents an underappreciated dimension of innate immunity in allergic disease. Aligning immunomodulatory therapies, vaccination, and lifestyle interventions with endogenous immune rhythms offers a rational approach to improving efficacy and reducing inflammatory burden. Future studies should prioritize time-stratified clinical trials and direct circadian phenotyping in allergic populations.

ABSTRACT The novel HLA‐A*26:268 allele is characterised by a single nucleotide substitution in exon 7.

Abstract Anterior and posterior cruciate ligament (ACL and PCL) reconstruction poses the risk of residual anterior or posterior tibial translation, respectively. As a result, patients may have residual knee instability and laxity, which can contribute to poor outcomes and graft failure. Ultimately, minimizing anterior and posterior tibial translation through proper ACL and PCL graft tensioning has the potential to improve clinical and functional outcomes in the setting of ACL and PCL reconstruction surgery. This technique aims to show a reproducible method for “setting” anterior and posterior tibial translation in the setting of ACL and PCL reconstructions.

Abstract Objective . Penile vibro-elastography (PVE) is complicated by reverberant shear wavefields from the cylindrical geometry of the corpus cavernosum (CC), which bias shear wave speed (SWS) estimates. This study evaluated local phase velocity imaging with wavefield-based filtering (LPVI-WBF) for CC stiffness assessment in post-prostatectomy erectile dysfunction (ED), compared against phase gradient (PG) and time-of-flight (TOF) methods. Approach . Six patients with post-prostatectomy ED underwent PVE at four longitudinal visits (902 acquisitions). SWS was estimated in flaccid and erect states at 100, 150, and 200 Hz using LPVI-WBF, PG, and TOF. Wavefield composition was quantified via the standing wave index. Simulations evaluated accuracy and frequency stability under clean and reverberant conditions. Main results . Reverberant components dominated penile acquisitions, with traveling wave energy absent in 59% of acquisitions and mean standing wave fraction of 57 ± 17%. LPVI-WBF was the only method producing physiologically consistent estimates, with erect SWS exceeding flaccid (3.59 ± 0.48 vs 3.25 ± 0.58 m s −1 , p < 0.0001). PG and TOF yielded reversed results ( E < F, p < 0.0001). The dispersion exponent was near-zero for LPVI-WBF ( α = 0.048, p = 0.21), consistent with weakly viscoelastic tissue, while PG ( α = 0.184) and TOF ( α = 0.321) showed significant frequency dependence from reverberant contamination. Simulations confirm PG accuracy in clean wavefields but collapse under reverberant ones. Significance . LPVI-WBF produced SWS estimates consistent with expected CC biomechanics across all patients and frequencies, a criterion PG and TOF failed to satisfy. Phantom validation and multi-directional wavefield simulation are needed to establish accuracy.

VEXAS syndrome is a clonal hemato-inflammatory disorder impacting older, predominantly male patients, characterized by systemic inflammation and progressive bone marrow failure. It is caused by somatic mutations in UBA1, an X-linked gene, essential for initiating cellular ubiquitination. Loss-of-function mutations, most commonly M41 missense variants, lead to decreased expression of the cytoplasmic isoform, UBA1b, resulting in accumulation of misfolded proteins and activation of the endoplasmic reticulum stress pathway. Patients classically present with systemic and often refractory inflammation, requiring chronic glucocorticoid treatment and targeted immunosuppressive therapies. A central hallmark of this syndrome is progressive bone marrow failure and associated cytopenia, with a diagnosis of myelodysplastic syndromes (MDS) being reported in approximately 30-50% of patients while only 1% of unselected MDS patients have UBA1 mutations. This review examines current literature on distinct MDS features reported in VEXAS syndrome. We first summarize the defects and alterations in the hematopoietic system from UBA1 mutations, including associated peripheral blood and bone marrow findings. Next, we describe the histological and molecular characteristics of patients with VEXAS syndrome, with and without MDS, and review potential treatment strategies, including responses to hypomethylating agents. Finally, we highlight that VEXAS-associated MDS is a challenging diagnosis but one with unique clinical, laboratory, and morphological features, including prognostic implications.

Abstract Studies have reported conflicting findings regarding the contribution of germline variants or somatic genomic drivers to racial disparities in multiple myeloma. To comprehensively investigate somatic drivers in relation to inherited genetics in multiple myeloma, we combined newly sequenced whole-genome sequencing data with publicly available datasets (total n = 1,286). Overall, we did not identify germline or somatic genomic differences that explain the different risk of developing multiple myeloma between patients with genetic similarity to African (AFR) or European (EUR) reference populations. A difference in the detectability and timing of APOBEC-associated and germinal center mutational activity was observed. Integrating epidemiologic data and mutational signature-based temporal estimates, we challenge the assumption that individuals in the AFR group develop multiple myeloma at a younger age. Finally, we demonstrate that, with equal access to efficacious therapies, patients in the AFR and EUR groups have equivalent clinical outcomes. Significance: Multiple myeloma is reported to occur at higher rates in individuals who self-identify as non-Hispanic Black. In this large dataset, genomic drivers occur at the same rate among ancestry groups, except for APOBEC mutagenesis. With equivalent therapy, clinical outcomes did not differ for patients grouped by genetic ancestry similarity.

Aging selectively impacts the function of type IIx/IIb fibers in the diaphragm muscle. We show that sarcopenia reduces maximum specific force, maximum shortening velocity, and peak power output, whereas endurance during repetitive contractions is preserved. These findings explain why higher force airway clearance behaviors decline with age, whereas fatigue-resistant breathing behavior remains resilient.