Citations

Objective Macrophages are highly plastic immune cells that maintain tissue homeostasis through their roles in immune surveillance, repair, and remodeling. Emerging evidence reveals that macrophages, residing in tissues with widely varying stiffness, are profoundly influenced by the mechanical properties of their microenvironment. Methods Relevant publications on macrophage mechanoregulation published up to January 2026 were identified through systematic searches of PubMed, EMBASE, and Web of Science using combinations of keywords related to macrophages, mechanosensing, mechanotransduction, and mechanical stimuli (e.g., stiffness, stretch, and shear stress). Articles were screened based on relevance to macrophage biology and mechanistic insights. Results Mechanical cues are sensed through mechanosensors such as Piezo1, TRPV4, and integrins, which integrate these signals to regulate immune surveillance, inflammation, tissue repair, and remodeling. Dysregulation of these pathways contributes to the pathogenesis of multiple diseases, including fibrosis, atherosclerosis, and neurodegeneration. Conclusion Macrophage mechanobiology represents a critical regulatory axis in tissue homeostasis and disease. Targeting mechanosensing pathways offers promising therapeutic opportunities to modulate inflammation and enhance tissue regeneration.

Abstract In 2011, a workgroup of the Alzheimer's Association Research Roundtable introduced recommendations for detecting and monitoring amyloid‐related imaging abnormalities (ARIA) in Alzheimer's disease (AD) clinical trials. Since then, anti‐amyloid immunotherapies have received regulatory approval for AD treatment and are beginning to enter clinical practice, underscoring the importance of informing healthcare providers, researchers, and patients about ARIA's implications in real‐world settings. In response, the Alzheimer's Association convened a new workgroup to review current knowledge of ARIA, including underlying mechanisms, clinical presentations, associated risk factors, mitigation strategies, radiologic detection methods, patients’ perspectives in treatment decision‐making, and outstanding challenges. Here, we outline key insights from this workgroup, highlighting that effective ARIA detection and monitoring in clinical practice requires adherence to robust protocols to mitigate risks and enhance patient safety. Limited availability of clinical and pathologic data on predictors of symptomatic and severe ARIA underscores the importance of continued real‐world data collection.

53BP1 nuclear bodies are dynamic structures with properties resembling biomolecular condensates, but the molecular determinants that govern 53BP1 higher-order assembly at DNA double-strand breaks (DSBs) remain to be established. Here, we show that 53BP1 condensation is stimulated by phosphatidylinositol 3-phosphate (PI(3)P) in vitro through a highly specific interaction with its C-terminal tandem BRCT domain (tBRCT). Consequently, mutational inactivation of the 53BP1 tBRCT domain compromised PI(3)P binding and suppressed 53BP1 optodroplet formation in vivo. We further show that rapid 53BP1 clustering following DNA damage precedes its stable assembly on DSB-flanking chromatin, requires its tBRCT, and is suppressed by sequestration of nuclear PI(3)P. Taken together, our findings identify PI(3)P binding as a mechanism that promotes the formation and maturation of 53BP1 condensate-like assemblies on damaged chromatin.

Background: The National SCI Model Systems (SCIMS) Database was established in 1973 to study longitudinal data from persons with traumatic SCI (TSCI). The SCIMS provides an ideal platform to explore the feasibility of a parallel data collection effort to understand the characteristics of individuals with nontraumatic SCI (NTSCI). In the current data collection cycle (2021-2026), all SCIMS centers gathered data specific to NTSCI. Objectives: To (1) describe the demographic and injury-specific characteristics of participants with NTSCI and (2) assess neurological changes from admission to discharge. Methods: The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination data of participants with NTSCI who were enrolled at an SCIMS center were extracted from the medical records at admission and discharge from inpatient rehabilitation. Data from 178 participants with NTSCI were analyzed. Results: Among the 93 participants who had adequate ISNCSCI data on admission, only 8.6% had neurological complete injuries. More participants had paraplegia ( n = 58, 62.4%) than tetraplegia ( n = 35, 37.6%). For participants with full ISNCSCI data at both admission and discharge ( n = 47), there were significant improvements in the lower extremity motor score and pinprick and light touch scores on discharge. Conclusion: On admission to acute rehabilitation, more people with NTSCI had paraplegia than tetraplegia, and neurological incomplete injuries were more common. People with NTSCI experienced significant improvement in ISNCSCI neurological variables by the time of discharge from rehabilitation.

Background: Physical inactivity is highly prevalent among individuals with spinal cord injury (SCI), contributing to secondary health conditions and reduced quality of life (QOL). Objectives: To examine the independent associations between adherence to SCI cardiorespiratory fitness guidelines and health and psychosocial outcomes, while controlling for relevant covariates. Method: We conducted a multisite, cross-sectional study of adults with traumatic SCI stratified by self-reported leisure-time physical activity: no activity (28%), some activity (41%), and met guidelines (26%). Multivariable regression models analyzed associations between physical activity (PA) group and outcomes of hospitalization, self-perceived health, resilience (SCI-QOL Resilience), pain, depression (PHQ-8), QOL (SWLS), and social integration (CHART-SF). Results: The study included 361 participants (no activity, 28%; some activity, 41%; met guidelines, 26%). Meeting PA guidelines was associated with better self-perceived health (odds ratio [OR] 2.79, P < .001) and higher resilience (β = 1.78, P = .04) compared to the No Activity group. However, hospitalization risk was unexpectedly higher for both the Some Activity (risk ratio [RR] 1.93, P = .005) and Met Guidelines (RR 1.75, P = .03) groups. After adjusting for covariates, PA was not significantly associated with pain, depression, QOL, or social integration; instead, higher income was consistently associated with better outcomes in these domains. Conclusion: Adherence to SCI exercise guidelines is associated with enhanced self-perceived health and resilience. However, PA alone was not associated with broader psychosocial outcomes in this model, where socioeconomic factors such as income appeared to play a significant explanatory role.

Background: The Spinal Cord Injury Model Systems (SCIMS) began studying traumatic SCI (TSCI) in 1970. The National Institute of Disability, Independent Living and Rehabilitation Research (NIDILRR) provided pilot funding during the 2021-2026 SCIMS funding cycle to perform an initial study of individuals with nontraumatic spinal cord injury (NTSCI). Objectives: To describe the demographic and etiological profiles and inpatient rehabilitation outcomes of the SCIMS NTSCI pilot cohort. Methods: This was a descriptive study of adults with NTSCI admitted to SCIMS centers who consented to medical records abstraction and completed survey questionnaires near the completion of inpatient rehabilitation. Results: One hundred eighty-seven people with NTSCI consented to participate and provided data. The etiology of patients’ NTSCI was degenerative vertebral causes ( n = 67), tumor-malignant ( n = 29), tumor-benign/unknown ( n = 16), vascular ( n = 28), infection ( n = 26), and other NTSCI causes ( n = 21). The average age was 59.2 years. Over 40% of the population was age 60-74 years. The population was 35% female, 59.5% non-Hispanic White, 21.6% non-Hispanic Black, and 11.4% Hispanic. Age, sex, race, and ethnicity distributions did not differ significantly across etiology groups. Only symptom onset time ( P = .002) and marital status ( P = .005) were significantly different between groups. Vascular disorders onset was less than a day in 60% of cases. Greater than 60% of tumor-malignant, vascular, and other NTSCI individuals were married or living with a partner. Conclusion: The US SCIMS program can recruit a population of NTSCI research participants that is consistent with previously published results. Ongoing study of NTSCI through the US SCIMS could provide important data akin to that available regarding TSCI.

Background: Previous studies suggest that internalized HIV stigma (IHS) results in HIV viral nonsuppression via directly increasing depression, which then reduces adherence leading to nonsuppression; however, the dynamics between IHS and mental health are likely more complex. We sought to better understand IHS-mental health dynamics using data from a longitudinal clinical cohort of people with HIV (PWH) receiving healthcare across 10 US primary care clinics. Methods: Among 8,506 PWH who had ≥2 timepoints in which IHS, depression, and anxiety were measured, we examined changes over time in both two-state (i.e., impact of IHS on depression or anxiety and vice versa) and four-state combinations of depression-IHS (i.e., no depression or IHS, depression/no IHS, no depression/IHS, both depression/IHS) and anxiety-IHS. Transition probabilities between states and factors influencing transitions were identified using multistate Markov models. Results: The impact of IHS on the transition rates of mental health measures (i.e., depression, anxiety) and vice versa were almost the same, suggesting that each influences the other. Over 50% of PWH remained in the same IHS-depression or IHS-anxiety state. PWH with IHS had almost twice the rate of transitioning from no depression/anxiety to having depression/anxiety compared to PWH without IHS; with similar results for the depression or anxiety with no IHS to reporting IHS transition. Conclusions: We demonstrate that IHS and mental health dynamics are more complex than previously suspected and that the associations are bidirectional, which has implications for both future analyses and optimal management of these conditions among PWH.