Ossifying Fibromyxoid Tumor of the Shoulder: A Case Report.

Ossifying fibromyxoid tumor (OFMT) is a rare, slow-growing, mesenchymal tumor with intermediate malignant potential, predominantly affecting middle-aged individuals. Histologically, it presents as a fibrous capsule or pseudocapsule, with a complete or incomplete lamellar bone shell surrounding oval/polygonal cells within a fibromyxoid matrix. Advances in immunohistochemistry have facilitated OFMT identification, with S100 protein expression and INI-1 loss being notable features. CD10 expression is also reported in a small minority of cases. Recent studies highlight a translocation of the PHF-1 gene, proposing a possible etiology for tumorigenesis. Treatment involves wide excision, with long-term follow-up for recurrence or metastasis. In this case, a 61-year-old White male presented to the outpatient surgical office with a painless mass on his right shoulder. The patient reported that the mass first appeared three to four years prior and that it had been growing slowly since the initial presentation. On examination, the patient had a well-circumscribed, 1.5 x 1.5 cm, soft, nontender, nonmobile subcutaneous mass on his right shoulder. The mass was initially suspected to be a subcutaneous cyst based on physical exam, but surgical excision and histopathology established the diagnosis of OFMT that extended to the margins of the specimen. The patient underwent a wider excision for margins and has had a benign postoperative course. The patient was referred to dermatology and oncology for continuation of care. This case demonstrates the necessity for a thorough work-up, appropriate excision, and histopathologic examination to rule in diagnoses of lower incidence with the potential for a worse prognosis. Appropriate and timely diagnoses can guide proper screening for cancer recurrence and management.

Estimating ambient air pollutant concentrations outside and inside homes in the Subpopulations and Intermediate outcomes in COPD air pollution (SPIROMICS air) cohort.

BACKGROUND: Valid, high-resolution estimates of population-level exposure to air pollutants are necessary for accurate estimation of the association between air pollution and the occurrence or exacerbation of adverse health outcomes such as Chronic Obstructive Pulmonary Disease (COPD). OBJECTIVES: We produced fine-scale individual-level estimates of ambient concentrations of multiple air pollutants (fine particulate matter [PM2.5], NOX, NO2, and O3) at residences of participants in the Subpopulations and Intermediate Outcomes in COPD Air Pollution (SPIROMICS Air) study, located in seven regions in the US. For PM2.5, we additionally integrated modeled estimates of particulate infiltration based on home characteristics and measured total indoor concentrations to provide comprehensive estimates of exposure levels. METHODS: To estimate ambient concentrations, we used a hierarchical high-resolution spatiotemporal model that integrates hundreds of geographic covariates and pollutant measurements from regulatory and study-specific monitors, including ones located at participant residences. We modeled infiltration efficiency based on data on house characteristics, home heating and cooling practices, indoor smoke and combustion sources, meteorological factors, and paired indoor-outdoor pollutant measurements, among other indicators. RESULTS: Cross-validated prediction accuracy (R2) for models of ambient concentrations was above 0.80 for most regions and pollutants. Particulate matter infiltration efficiency varied by region, from 0.51 in Winston-Salem to 0.72 in Los Angeles, and ambient-source particles constituted a substantial fraction of total indoor PM2.5. CONCLUSION: Leveraging well-validated fine-scale approaches for estimating outdoor, ambient-source indoor, and total indoor pollutant concentrations, we can provide comprehensive estimates of short and long-term exposure levels for cohorts undergoing follow-up in multiple different regions.

Direct Numerical Solutions to Stochastic Differential Equations with Multiplicative Noise.

Inspired by path integral solutions to the quantum relaxation problem, we develop a numerical method to solve classical stochastic differential equations with multiplicative noise that avoids averaging over trajectories. To test the method, we simulate the dynamics of a classical oscillator multiplicatively coupled to non-Markovian noise. When accelerated using tensor factorization techniques, it accurately estimates the transition into the bifurcation regime of the oscillator and outperforms trajectory-averaging simulations with a computational cost that is orders of magnitude lower.

Fishers (Pekania pennanti) are forest structure specialists when resting and generalists when moving: behavior influences resource selection in a northern Rocky Mountain fisher population.

BACKGROUND: Studies of animal habitat selection are important to identify and preserve the resources species depend on, yet often little attention is paid to how habitat needs vary depending on behavioral state. Fishers (Pekania pennanti) are known to be dependent on large, mature trees for resting and denning, but less is known about their habitat use when foraging or moving within a home range. METHODS: We used GPS locations collected during the energetically costly pre-denning season from 12 female fishers to determine fisher habitat selection during two critical behavioral activities: foraging (moving) or resting, with a focus on response to forest structure related to past forest management actions since this is a primary driver of fisher habitat configuration. We characterized behavior based on high-resolution GPS and collar accelerometer data and modeled fisher selection for these two behaviors within a home range (third-order selection). Additionally, we investigated whether fisher use of elements of forest structure or other important environmental characteristics changed as their availability changed, i.e., a functional response, for each behavior type. RESULTS: We found that fishers exhibited specialist selection when resting and generalist selection when moving, with resting habitat characterized by riparian drainages with dense canopy cover and moving habitat primarily influenced by the presence of mesic montane mixed conifer forest. Fishers were more tolerant of forest openings and other early succession elements when moving than resting. CONCLUSIONS: Our results emphasize the importance of considering the differing habitat needs of animals based on their movement behavior when performing habitat selection analyses. We found that resting fishers are more specialist in their habitat needs, while foraging fishers are more generalist and will tolerate greater forest heterogeneity from past disturbance.

Cutting Edge: Hepatic Stellate Cells Drive the Phenotype of Monocyte-derived Macrophages to Regulate Liver Fibrosis in Metabolic Dysfunction-associated Steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by infiltration of monocyte-derived macrophages (MdMs) into the liver; however, the function of these macrophages is largely unknown. We previously demonstrated that a population of MdMs, referred to as hepatic lipid-associated macrophages (LAMs), assemble into aggregates termed hepatic crown-like structures in areas of liver fibrosis. Intriguingly, decreasing MdM recruitment resulted in increased liver fibrosis, suggesting that LAMs contribute to antifibrotic pathways in MASH. In this study, we determined that hepatic crown-like structures are characterized by intimate interactions between activated hepatic stellate cells (HSCs) and macrophages in a collagen matrix in a mouse model of MASH. MASH macrophages displayed collagen-degrading capacities, and HSCs derived from MASH livers promoted expression of LAM marker genes and acquisition of a collagen-degrading phenotype in naive macrophages. These data suggest that crosstalk between HSCs and macrophages may contribute to collagen degradation MASH.

IL-10 suppresses T cell expansion while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus macaques.

The regulation of inflammatory responses and pulmonary disease during SARS-CoV-2 infection is incompletely understood. Here we examine the roles of the prototypic pro- and anti-inflammatory cytokines IFNγ and IL-10 using the rhesus macaque model of mild COVID-19. We find that IFNγ drives the development of 18fluorodeoxyglucose (FDG)-avid lesions in the lungs as measured by PET/CT imaging but is not required for suppression of viral replication. In contrast, IL-10 limits the duration of acute pulmonary lesions, serum markers of inflammation and the magnitude of virus-specific T cell expansion but does not impair viral clearance. We also show that IL-10 induces the subsequent differentiation of virus-specific effector T cells into CD69+CD103+ tissue resident memory cells (Trm) in the airways and maintains Trm cells in nasal mucosal surfaces, highlighting an unexpected role for IL-10 in promoting airway memory T cells during SARS-CoV-2 infection of macaques.

The Association between Exposure to Fine Particulate Matter and MRI-Assessed Locus Coeruleus Integrity in the Vietnam Era Twin Study of Aging (VETSA).

BACKGROUND: Increased exposure to ambient air pollution, especially fine particulate matter ≤2.5µm (PM2.5) is associated with poorer brain health and increased risk for Alzheimer's disease (AD) and related dementias. The locus coeruleus (LC), located in the brainstem, is one of the earliest regions affected by tau pathology seen in AD. Its diffuse projections throughout the brain include afferents to olfactory areas that are hypothesized conduits of cerebral particle deposition. Additionally, extensive contact of the LC with the cerebrovascular system may present an additional route of exposure to environmental toxicants. OBJECTIVE: Our aim was to investigate if exposure to PM2.5 was associated with LC integrity in a nationwide sample of men in early old age, potentially representing one pathway through which air pollution can contribute to increased risk for AD dementia. METHODS: We examined the relationship between PM2.5 and in vivo magnetic resonance imaging (MRI) estimates of LC structural integrity indexed by contrast to noise ratio (LCCNR) in 381 men [mean age=67.3; standard deviation (SD)=2.6] from the Vietnam Era Twin Study of Aging (VETSA). Exposure to PM2.5 was taken as a 3-year average over the most recent period for which data were available (average of 5.6 years prior to the MRI scan). We focused on LCCNR in the rostral-middle portion of LC due to its stronger associations with aging and AD than the caudal LC. Associations between PM2.5 exposures and LC integrity were tested using linear mixed effects models adjusted for age, scanner, education, household income, and interval between exposure and MRI. A co-twin control analysis was also performed to investigate whether associations remained after controlling for genetic confounding and rearing environment. RESULTS: Multiple linear regressions revealed a significant association between PM2.5 and rostral-middle LCCNR (ß=-0.16; p=0.02), whereby higher exposure to PM2.5 was associated with lower LCCNR. A co-twin control analysis found that, within monozygotic pairs, individuals with higher PM2.5 exposure showed lower LCCNR (ß=-0.11; p=0.02), indicating associations were not driven by genetic or shared environmental confounds. There were no associations between PM2.5 and caudal LCCNR or hippocampal volume, suggesting a degree of specificity to the rostral-middle portion of the LC. DISCUSSION: Given previous findings that loss of LC integrity is associated with increased accumulation of AD-related amyloid and tau pathology, impacts on LC integrity may represent a potential pathway through which exposure to air pollution increases AD risk. https://doi.org/10.1289/EHP14344.

Synthesis and antifungal evaluation of novel triazole derivatives bearing a pyrazole-methoxyl moiety.

Life-threatening invasive fungal infections pose a serious threat to human health. A series of novel triazole derivatives bearing a pyrazole-methoxyl moiety were designed and synthesized in an effort to obtain antifungals with potent, broad-spectrum activity that are less susceptible to resistance. Most of these compounds exhibited moderate to excellent in vitro antifungal activities against Candida albicans SC5314 and 10,231, Cryptococcus neoformans 32,609, Candida glabrata 537 and Candida parapsilosis 22,019 with minimum inhibitory concentration (MIC) values of ≤0.125 µg/mL to 0.5 µg/mL. Use of recombinant Saccharomyces cerevisiae strains showed compounds 7 and 10 overcame the overexpression and resistant-related mutations in ERG11 of S. cerevisae and several pathogenic Candida spp. Despite being substrates of the C. albicans and Candida auris Cdr1 drug efflux pumps, compounds 7 and 10 showed moderate potency against five fluconazole (FCZ)-resistant fungi with MIC values from 2.0 µg/mL to 16.0 µg/mL. Growth kinetics confirmed compounds 7 and 10 had much stronger fungistatic activity than FCZ. For C. albicans, compounds 7 and 10 inhibited the yeast-to-hyphae transition, biofilm formation and destroyed mature biofilm more effectively than FCZ. Preliminary mechanism of action studies showed compounds 7 and 10 blocked the ergosterol biosynthesis pathway at Erg11, ultimately leading to cell membrane disruption. Further investigation of these novel triazole derivatives is also warranted by their predicted ADMET properties and low cytotoxicity.

On-Field Evaluation of Mouthpiece-and-Helmet-Mounted Sensor Data from Head Kinematics in Football.

PURPOSE: Wearable sensors are used to measure head impact exposure in sports. The Head Impact Telemetry (HIT) System is a helmet-mounted system that has been commonly utilized to measure head impacts in American football. Advancements in sensor technology have fueled the development of alternative sensor methods such as instrumented mouthguards. The objective of this study was to compare peak magnitude measured from high school football athletes dually instrumented with the HIT System and a mouthpiece-based sensor system. METHODS: Data was collected at all contact practices and competitions over a single season of spring football. Recorded events were observed and identified on video and paired using event timestamps. Paired events were further stratified by removing mouthpiece events with peak resultant linear acceleration below 10 g and events with contact to the facemask or body of athletes. RESULTS: A total of 133 paired events were analyzed in the results. There was a median difference (mouthpiece subtracted from HIT System) in peak resultant linear and rotational acceleration for concurrently measured events of 7.3 g and 189 rad/s2. Greater magnitude events resulted in larger kinematic differences between sensors and a Bland Altman analysis found a mean bias of 8.8 g and 104 rad/s2, respectively. CONCLUSION: If the mouthpiece-based sensor is considered close to truth, the results of this study are consistent with previous HIT System validation studies indicating low error on average but high scatter across individual events. Future researchers should be mindful of sensor limitations when comparing results collected using varying sensor technologies.

Exercise mitigates reductive stress-induced cardiac remodeling in mice.

The endoplasmic reticulum (ER) regulates protein folding and maintains proteostasis in cells. We observed that the ER transcriptome is impaired during chronic reductive stress (RS) in cardiomyocytes. Here, we hypothesized that a prolonged moderate treadmill exercise mitigates the RS-induced ER dysfunction and cardiac remodeling in cardiac-specific constitutively active Nrf2 mice (CaNrf2-TG). RNA sequencing showed notable alterations in the ER transcriptome of TG hearts at 4, 12, and 24 weeks (16, 28, and 35 genes, respectively). Notably, the downregulation of ER genes was significant at 12 weeks, and further pronounced at 24 weeks, at which the cardiac pathology is evident. We also observed increased levels of ubiquitinated proteins in CaNrf2-TG hearts across all ages, along with VCP, a marker of ERAD function, at 24 weeks. These findings indicate that constitutive Nrf2 activation and RS impair protein-folding activity and augments ERAD function over time. Exercise intervention for 20 weeks (beginning at 6 weeks of age), reduced cardiomyocyte hypertrophy (from 448 µm2 to 280 µm2) in TG mice, through adaptive remodeling, and preserved the cardiac function. However, while exercise did not influence antioxidants or ER stress protein levels, it significantly improved ERAD function and autophagy flux (LC-I to LC-II) in the TG-EXE hearts. Collectively, our findings underscore the prophylactic potential of exercise in mitigating RS-associated pathology, highlighting its essential role in maintaining cellular proteostasis through ER-independent mechanisms.

Cognitive and Salience Network Connectivity Changes following a Single Season of Repetitive Head Impact Exposure in High School Football.

BACKGROUND AND PURPOSE: During a season of high school football, adolescents with actively developing brains experience a considerable number of head impacts. Our aim was to determine whether repetitive head impacts in the absence of a clinically diagnosed concussion during a season of high school football produce changes in cognitive performance or functional connectivity of the salience network and its central hub, the dorsal anterior cingulate cortex. MATERIALS AND METHODS: Football players were instrumented with the Head Impact Telemetry System during all practices and games, and the helmet sensor data were used to compute a risk-weighted exposure metric (RWEcp), accounting for the cumulative risk during the season. Participants underwent MRI and a cognitive battery (ImPACT) before and shortly after the football season. A control group of noncontact/limited-contact-sport athletes was formed from 2 cohorts: one from the same school and protocol and another from a separate, nearly identical study. RESULTS: Sixty-three football players and 34 control athletes were included in the cognitive performance analysis. Preseason, the control group scored significantly higher on the ImPACT Visual Motor (P = .04) and Reaction Time composites (P = .006). These differences increased postseason (P = .003, P < .001, respectively). Additionally, the control group had significantly higher postseason scores on the Visual Memory composite (P = .001). Compared with controls, football players showed significantly less improvement in the Verbal (P = .04) and Visual Memory composites (P = .01). A significantly greater percentage of contact athletes had lower-than-expected scores on the Verbal Memory (27% versus 6%), Visual Motor (21% versus 3%), and Reaction Time composites (24% versus 6%). Among football players, a higher RWEcp was significantly associated with greater increments in ImPACT Reaction Time (P = .03) and Total Symptom Scores postseason (P = .006). Fifty-seven football players and 13 control athletes were included in the imaging analyses. Postseason, football players showed significant decreases in interhemispheric connectivity of the dorsal anterior cingulate cortex (P = .026) and within-network connectivity of the salience network (P = .018). These decreases in dorsal anterior cingulate cortex interhemispheric connectivity and within-network connectivity of the salience network were significantly correlated with deteriorating ImPACT Total Symptom (P = .03) and Verbal Memory scores (P = .04). CONCLUSIONS: Head impact exposure during a single season of high school football is negatively associated with cognitive performance and brain network connectivity. Future studies should further characterize these short-term effects and examine their relationship with long-term sequelae.

How an IJES Working Group Grappled with the Complexities of Three Letters-DEI-With the Goal to Broaden Inclusion and Representation in Exercise Science Research.

A self-study of International Journal of Exercise Science (IJES) publications from 2008 through 2021 revealed a sex-data gap in participant and corresponding author representation. This finding prompted the creation of the IJES Working Group for Opportunity, Representation, and Diverse Perspectives. We are a collaborative team of authors, reviewers, and editors, spanning both rural and urban teaching- and research-focused institutions, who assembled regularly starting in September 2023. The goal was to contemplate potential challenges and opportunities around diversity, equity, and inclusion (DEI), elicit discourse, and broaden inclusion and representation in exercise science research. Our group identified six main challenges/opportunities: 1) Mixed Definitions and Applications of DEI Principles; 2) Competing Lifeviews and Worldviews; 3) Oversight and Enforcement of DEI Principles in IJES; 4) Oversight and Enforcement of DEI Principles in the Broader Field; 5) IJES is a Home for Developing Scholars; and 6) Lag Time for Creating Change in IJES. As a growing international journal, we depend on a diverse group of authors, reviewers, editors, and readers to achieve our mission. Accordingly, the Working Group encourages impactful, inclusive research that broadens representation within exercise science.

The 2024 International Journal of Exercise Science Position Stand on Inclusion.

The International Journal of Exercise Science (IJES) Working Group for Opportunity, Representation, and Diverse Perspectives was tasked with developing a position stand to provide guidance in critical areas of inclusion. We present to authors, reviewers, and all readership IJES ideals to utilize in practice. Key points are presented, followed by a deeper look with greater explanation into the areas of inclusive language, diversity and inclusion in research, and accessibility. The same approach is presented for the areas of age, disability status, gender identity and sexual orientation, race, and ethnicity with attention to Indigenous Communities, religion, socioeconomic status, and neurodiversity. Person-first language is encouraged, with the acknowledgment that the preference of different community members may vary. IJES is committed to maintaining an environment that is welcoming to all identities so that they feel valued, respected, and included.

Priming antibody responses to the fusion peptide in rhesus macaques.

Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to prime and elicit antibody responses against the conserved fusion peptide (FP). GC responses and antibody specificities were tracked longitudinally using lymph node fine-needle aspirates and electron microscopy polyclonal epitope mapping (EMPEM), respectively, to show antibody responses to the FP/N611 glycan hole region were primed, although exhibited limited neutralization breadth. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.

Association of Gaseous Ambient Air Pollution and Dementia-Related Neuroimaging Markers in the ARIC Cohort, Comparing Exposure Estimation Methods and Confounding by Study Site.

BACKGROUND: Evidence linking gaseous air pollution to late-life brain health is mixed. OBJECTIVE: We explored associations between exposure to gaseous pollutants and brain magnetic resonance imaging (MRI) markers among Atherosclerosis Risk in Communities (ARIC) Study participants, with attention to the influence of exposure estimation method and confounding by site. METHODS: We considered data from 1,665 eligible ARIC participants recruited from four US sites in the period 1987-1989 with valid brain MRI data from Visit 5 (2011-2013). We estimated 10-y (2001-2010) mean carbon monoxide (CO), nitrogen dioxide (NO2), nitrogen oxides (NOx), and 8- and 24-h ozone (O3) concentrations at participant addresses, using multiple exposure estimation methods. We estimated site-specific associations between pollutant exposures and brain MRI outcomes (total and regional volumes; presence of microhemorrhages, infarcts, lacunes, and severe white matter hyperintensities), using adjusted linear and logistic regression models. We compared meta-analytically combined site-specific associations to analyses that did not account for site. RESULTS: Within-site exposure distributions varied across exposure estimation methods. Meta-analytic associations were generally not statistically significant regardless of exposure, outcome, or exposure estimation method; point estimates often suggested associations between higher NO2 and NOx and smaller temporal lobe, deep gray, hippocampal, frontal lobe, and Alzheimer disease signature region of interest volumes and between higher CO and smaller temporal and frontal lobe volumes. Analyses that did not account for study site more often yielded significant associations and sometimes different direction of associations. DISCUSSION: Patterns of local variation in estimated air pollution concentrations differ by estimation method. Although we did not find strong evidence supporting impact of gaseous pollutants on brain changes detectable by MRI, point estimates suggested associations between higher exposure to CO, NOx, and NO2 and smaller regional brain volumes. Analyses of air pollution and dementia-related outcomes that do not adjust for location likely underestimate uncertainty and may be susceptible to confounding bias. https://doi.org/10.1289/EHP13906.

Injury Risk Predictions in Lunar Terrain Vehicle (LTV) Extravehicular Activities (EVAs): A Pilot Study.

Extravehicular activities will play a crucial role in lunar exploration on upcoming Artemis missions and may involve astronauts operating a lunar terrain vehicle (LTV) in a standing posture. This study assessed kinematic response and injury risks using an active muscle human body model (HBM) restrained in an upright posture on the LTV by simulating dynamic acceleration pulses related to lunar surface irregularities. Linear accelerations and rotational displacements of 5 lunar obstacles (3 craters; 2 rocks) over 5 slope inclinations were applied across 25 simulations. All body injury metrics were below NASA's injury tolerance limits, but compressive forces were highest in the lumbar (250-550N lumbar, tolerance: 5300N) and lower extremity (190-700N tibia, tolerance: 1350N) regions. There was a strong association between the magnitudes of body injury metrics and LTV resultant linear acceleration (ρ = 0.70-0.81). There was substantial upper body motion, with maximum forward excursion reaching 375 mm for the head and 260 mm for the chest. Our findings suggest driving a lunar rover in an upright posture for these scenarios is a low severity impact presenting low body injury risks. Injury metrics increased along the load path, from the lower body (highest metrics) to the upper body (lowest metrics). While upper body injury metrics were low, increased body motion could potentially pose a risk of injury from flail and occupant interaction with the surrounding vehicle, suit, and restraint hardware.

Silver-Doped Titanium Oxide Layers for Improved Photocatalytic Activity and Antibacterial Properties of Titanium Implants.

Titanium has a long history of clinical use, but the naturally forming oxide is not ideal for bacterial resistance. Anodization processes can modify the crystallinity, surface topography, and surface chemistry of titanium oxides. Anatase, rutile, and mixed phase oxides are known to exhibit photocatalytic activity (PCA)-driven bacterial resistance under UVA irradiation. Silver additions are reported to enhance PCA and reduce bacterial attachment. This study investigated the effects of silver-doping additions to three established anodization processes. Silver doping showed no significant influence on oxide crystallinity, surface topography, or surface wettability. Oxides from a sulfuric acid anodization process exhibited significantly enhanced PCA after silver doping, but silver-doped oxides produced from phosphoric-acid-containing electrolytes did not. Staphylococcus aureus attachment was also assessed under dark and UVA-irradiated conditions on each oxide. Each oxide exhibited a photocatalytic antimicrobial effect as indicated by significantly decreased bacterial attachment under UVA irradiation compared to dark conditions. However, only the phosphorus-doped mixed anatase and rutile phase oxide exhibited an additional significant reduction in bacteria attachment under UVA irradiation as a result of silver doping. The antimicrobial success of this oxide was attributed to the combination of the mixed phase oxide and higher silver-doping uptake levels.

Multielectron Dynamics in the Condensed Phase: Quantum Structure-Function Relationships.

Quantum information promises dramatic advances in computing last seen in the digital revolution, but quantum hardware is fragile, noisy, and resource intensive. Chemistry has a role in developing new materials for quantum information that are robust to noise, scalable, and operable in ambient conditions. While molecular structure is the foundation for understanding mechanism and reactivity, molecular structure/quantum function relationships remain mostly undiscovered. Using singlet fission as a specific example of a multielectron process capable of producing long-lived spin-entangled electronic states at high temperatures, I describe how to exploit molecular structure and symmetry to gain quantum function and how some principles learned from singlet fission apply more broadly to quantum science.

Source-Specific Air Pollution and Loss of Independence in Older Adults Across the US.

Importance: Air pollution is a recognized risk factor associated with chronic diseases, including respiratory and cardiovascular conditions, which can lead to physical and cognitive impairments in later life. Although these losses of function, individually or in combination, reduce individuals' likelihood of living independently, little is known about the association of air pollution with this critical outcome. Objective: To investigate associations between air pollution and loss of independence in later life. Design, Setting, and Participants: This cohort study was conducted as part of the Environmental Predictors Of Cognitive Health and Aging study and used 1998 to 2016 data from the Health and Retirement Study. Participants included respondents from this nationally representative, population-based cohort who were older than 50 years and had not previously reported a loss of independence. Analyses were performed from August 31 to October 15, 2023. Exposures: Mean 10-year pollutant concentrations (particulate matter less than 2.5 µm in diameter [PM2.5] or ranging from 2.5 µm to 10 µm in diameter [PM10-2.5], nitrogen dioxide [NO2], and ozone [O3]) were estimated at respondent addresses using spatiotemporal models along with PM2.5 levels from 9 emission sources. Main Outcomes and Measures: Loss of independence was defined as newly receiving care for at least 1 activity of daily living or instrumental activity of daily living due to health and memory problems or moving to a nursing home. Associations were estimated with generalized estimating equation regression adjusting for potential confounders. Results: Among 25 314 respondents older than 50 years (mean [SD] baseline age, 61.1 [9.4] years; 11 208 male [44.3%]), 9985 individuals (39.4%) experienced lost independence during a mean (SD) follow-up of 10.2 (5.5) years. Higher exposure levels of mean concentration were associated with increased risks of lost independence for total PM2.5 levels (risk ratio [RR] per 1-IQR of 10-year mean, 1.05; 95% CI, 1.01-1.10), PM2.5 levels from road traffic (RR per 1-IQR of 10-year mean, 1.09; 95% CI, 1.03-1.16) and nonroad traffic (RR per 1-IQR of 10-year mean, 1.13; 95% CI, 1.03-1.24), and NO2 levels (RR per 1-IQR of 10-year mean, 1.05; 95% CI, 1.01-1.08). Compared with other sources, traffic-generated pollutants were most consistently and robustly associated with loss of independence; only road traffic-related PM2.5 levels remained associated with increased risk after adjustment for PM2.5 from other sources (RR per 1-IQR increase in 10-year mean concentration, 1.10; 95% CI, 1.00-1.21). Other pollutant-outcome associations were null, except for O3 levels, which were associated with lower risks of lost independence (RR per 1-IQR increase in 10-year mean concentration, 0.94; 95% CI, 0.92-0.97). Conclusions and Relevance: This study found that long-term exposure to air pollution was associated with the need for help for lost independence in later life, with especially large and consistent increases in risk for pollution generated by traffic-related sources. These findings suggest that controlling air pollution could be associated with diversion or delay of the need for care and prolonged ability to live independently.