Search Results (3,324)

Background/Objectives: Pemphigus is a rare blistering disease characterized by a chronic course, associated with significant mortality and morbidity. This review article aims to delve into three Pemphigus subtypes: Pemphigus Vulgaris, Pemphigus Foliaceus and Paraneoplastic Pemphigus, including the safety and efficacy of their treatment options. Methods: A thorough literature search was conducted using PubMed, EMBASE, Medline and Cochrane Library to collate data on pharmaceutical treatments of Pemphigus. Studies were selected based on predefined inclusion criteria, which included English language, peer-reviewed articles published in the date range January 2000 to May 2025. Eligible studies involved adults diagnosed with Pemphigus Vulgaris, Pemphigus Foliaceus or Paraneoplastic Pemphigus who were treated with Glucocorticoids, Mycophenolate mofetil, azathioprine or rituximab. The focus was on identifying adverse effects, complete remission and relapse rates. Results: The analysis revealed that glucocorticoid is the first-line treatment for Pemphigus. However, low remission rates of 34% along with steroid-related adverse effects indicate the use of Mycophenolate and azathioprine as steroid-sparing adjuvant therapies. Emerging treatments with rituximab have demonstrated 90% remission rates, indicating promising results with a comparatively mild side effect profile. Conclusions: The findings highlight the importance of ongoing evaluation of treatment modalities for Pemphigus subtypes to optimise remission rates and minimise adverse effects. Ultimately, studies often fail to isolate specific Pemphigus subtypes owing to the scarcity of literature. There is also a crucial need to address the lack of a standardised grading system for the side effects of glucocorticoids and long-term safety data for rituximab in further longitudinal research. Full article

(1) Background: Arteriovenous fistula (AVF) thrombosis represents a major cause of vascular access failure in patients undergoing maintenance hemodialysis. Identifying early biochemical markers associated with thrombosis may facilitate timely intervention and improve vascular outcomes. This study aimed to evaluate the association between baseline biochemical markers and the risk of AVF thrombosis and mortality during long-term follow-up. (2) Methods: We conducted a prospective observational study involving 249 chronic hemodialysis patients with functional AVFs. Baseline data included intact parathyroid hormone (iPTH), hemoglobin, phosphate, potassium, albumin, dialysis adequacy (Kt/V), age, diabetes status, and antivitamin K (AVK) therapy. Patients were followed for five years for the occurrence of AVF thrombosis and mortality. Statistical analysis was performed using one-way ANOVA with Levene’s test and Scheffé post hoc comparisons. (3) Results: iPTH levels were significantly higher in patients who developed AVF thrombosis (mean 494.6 pg/mL) than in those without thrombosis (mean 381.5 pg/mL; p = 0.047). Other variables, including hemoglobin, phosphate, Kt/V, age, diabetes, and AVK therapy, were not significantly associated with thrombosis. Mortality was more frequent among patients with diabetes mellitus and those receiving antivitamin K therapy; however, only the association with diabetes reached statistical significance. (4) Conclusions: Elevated iPTH was associated with AVF thrombosis. Routine monitoring may help identify high-risk patients and guide timely interventions. Full article

Background: Aortic stenosis (AS) is a prevalent acquired heart valve disease with increasing incidence, particularly among older adults. Gender-specific differences in AS presentation, comorbidities, and outcomes remain underexplored, necessitating further investigation to optimize personalized treatment strategies. Objective: To evaluate the clinical and demographic characteristics, comorbidities, and survival outcomes of patients with AS, stratified by gender and aortic valve morphology. Methods: A retrospective analysis of 145,454 echocardiographic examinations (2009–2018) at the Federal State Budgetary Institution “V.A. Almazov National Medical Research Centre” identified 84,851 patients meeting the inclusion criteria (Vmax ≥ 2.0 m/s, age ≥ 18 years). Patients were stratified by gender and valve morphology (bicuspid aortic valve [BAV] vs. tricuspid aortic valve [TAV]). Survival was assessed in 475 pts with AS over a 16-year period (2009–2025) using Kaplan–Meier analysis. Statistical comparisons utilized STATISTICA v. 10.0, with p-values derived from P-tests. Results: Of the cohort, 4998 men and 6322 women had AS. Men with AS were older (median 64 vs. 57 years, p < 0.0001) and had higher systolic blood pressure (140 vs. 130 mmHg, p < 0.0001) than men without AS. Women with AS were also older (median 70 vs. 58 years, p < 0.0001) with higher systolic (140 vs. 130 mmHg, p < 0.0001) and diastolic blood pressure (80 vs. 80 mmHg, p < 0.0001). Men with AS had higher rates of hyperlipidemia (HLP) (26.3% vs. 10.3%, p < 0.0001), while women with AS had increased coronary artery disease (CAD) (35.7% vs. 26.4%, p < 0.0001), diabetes mellitus (DM) (13.4% vs. 10.2%, p < 0.0001), and obesity (10.9% vs. 10.2%, p = 0.06). Chronic heart failure (CHF) was more frequently reported in patients with AS, regardless of gender, compared to patients without AS (in men 53.4% vs. 41.8%, p < 0.0001; in women 54.5% vs. 37.5%, p < 0.0001). BAV was associated with higher AS prevalence (54.5% in men, 66.4% in women). Survival analysis revealed higher mortality. Over the 16-year follow-up period, the mortality rate was 21.7%. Conclusions: Mortality in a representative AS cohort reached 21.7%, underscoring the progressive nature of the disease and its long-term impact. Survival was negatively affected by age over 68.5 years, as well as the presence of aortic regurgitation (AR), increased peak aortic jet velocity, and enlarged maximum aortic diameter. Aortic valve replacement demonstrates an insignificant effect on patient survival rates. Beta-blocker therapy in patients with varying degrees of aortic AS severity has not only demonstrated its safety but has also shown a positive effect on reducing mortality (improving survival). In contrast, the combination of angiotensin II receptor blockers (ARBs) with calcium channel blockers (CCBs) is quite dangerous for patients with AS and reduces their survival. Aortic valve replacement demonstrates an insignificant effect on patient survival rates. In contrast, the absence of fibrinolytic therapy and anticoagulant treatment is associated with an improved prognosis. Conversely, the administration of antiarrhythmic agents and statins is correlated with enhanced survival outcomes, potentially attributable to their influence on coexisting comorbidities. Further research is required to delineate their precise mechanisms and contributions. These results emphasize the importance of early identification, comprehensive risk assessment, and individualized management strategies in improving outcomes for patients with AS. Full article

Compound 221s (2,9) is a novel antihypertensive drug candidate synthesized utilizing danshensu, borneol, and proline by using the strategy of combinatorial molecular chemistry. This study aimed to systematically identify the safety of danshensu-derived compound 221s (2,9) by conducting an acute toxicity test and long-term toxicity study and to elucidate the in vivo metabolic pathways of 221s (2,9) in order to provide critical insights into the observed toxicity. In the acute toxicity study, a single oral dose of 221s (2,9) at 3000 mg/kg in mice produced no clinical signs of toxicity or mortality, indicating an MTD of 3000 mg/kg. In a subsequent 12-week repeated-dose toxicity study in rats, doses of 20, 40, and 80 mg/kg were well tolerated, with no adverse clinical observations or deaths. Notably, organ coefficient analysis revealed transient lung injury, which resolved following a 4-week recovery period. The metabolite identification study indicated that metabolism in rats is predominated by Phase II metabolites, potentially contributing to the low toxicity of 221s (2,9). Further investigation into the impact of the drug metabolic enzyme–transporter interplay on the in vivo disposition of 221s (2,9) is warranted. Full article

Background: LUAD, the most common subtype of lung cancer, particularly in non-smokers, is significantly influenced by air pollution from fine particulate matter (PM). One suspected method by which PM contributes to cancer progression is through angiogenesis, which promotes tumor growth and metastasis. This study was conducted to explore the impact of long-term PM exposure on the progression of LUAD, focusing on angiogenesis promotion. Methods: We conducted an integrative bioinformatics analysis incorporating epidemiological and transcriptomic datasets from public repositories (TCGA and GEO) to evaluate differential VEGFA expression in LUAD tissues and its relationship to regional PM exposure. In vitro and in vivo assays using PM-adapted NSCLC cell lines and murine xenograft models served as secondary confirmatory experiments supporting the computational results. Results: Epidemiological analysis revealed a strong positive correlation between long-term PM exposure and lung adenocarcinoma mortality across U.S. states (r = 0.7638, p < 0.0001), underscoring a population-level impact. Bioinformatics analysis identified a significant upregulation of VEGFA in NSCLC tumors from regions with high PM levels, with VEGFA overexpression also associated with poorer patient survival. Gene ontology and pathway enrichment analyses implicated angiogenesis-related processes. These findings were supported by experimental models, in which long-term PM exposure on human and murine LUAD cell lines (A549, H1299, and LLC) induced VEGFA and p-ERK overexpression. Furthermore, PM-exposed cells enhanced angiogenesis processes, as evidenced by increased endothelial cell tube formation and migration in vitro, and promoted tumor vascularization in a xenograft model. These pro-angiogenesis effects were abrogated following inhibition of the MAPK signaling pathway or blockade of VEGFA. Conclusions: Our findings reveal a compelling molecular link between PM exposure and NSCLC progression, centered on VEGFA-driven angiogenesis and urging the need to reduce ambient PM exposure to mitigate its oncogenic impact. Full article

Background: Novel and accessible biomarkers may add to the existing risk stratification schemes in patients with acute coronary syndrome (ACS). The platelet-to-lymphocyte ratio (PLR) and glucose-to-lymphocyte ratio (GLR) have emerged as potential indicators of systemic inflammation and metabolic stress, both of which are pivotal in ACS pathophysiology. The aim of this study was to investigate the prognostic significance of the PLR and GLR in patients with ACS. Methods: We performed a retrospective cohort study of patients hospitalized with ACS between 2017 and 2023 at Hippokration Hospital of Thessaloniki, Greece. PLR and GLR were calculated from admission blood samples. The primary endpoint was all-cause mortality. Logistic and Cox regression models were used to investigate the associations of PLR and GLR with all-cause mortality. Receiver operating characteristic (ROC) analysis, Kaplan–Meier survival curves, and restricted cubic spline (RCS) modeling were also applied. Results: In total, 853 patients (median age: 65 years, 72.3% males) were included. Higher PLR and GLR were independently associated with increased risk of long-term mortality [adjusted Odds Ratio (aOR) for PLR: 1.007, 95% CI: 1.005–1.008; and for GLR: aOR = 1.006, 95% CI: 1.003–1.008]. The optimal cut-off values were 191.92 for PLR and 66.80 for GLR. Kaplan–Meier and Cox regression analyses confirmed significantly reduced survival in patients with GLR and PLR values exceeding these thresholds. RCS analysis revealed non-linear relationships, with mortality risk rising sharply at higher levels of both markers. PLR showed superior prognostic performance (AUC: 0.673, 95% CI: 0.614–0.723) compared to GLR (AUC: 0.602, 95% CI: 0.551–0.653). Conclusions: While PLR demonstrated greater predictive accuracy, both PLR and GLR were consistently associated with mortality and may provide complementary prognostic information. Incorporating those ratios into routine clinical assessment may improve risk stratification, particularly in resource-limited settings or for patients without traditional risk factors. Full article

Background/Objectives: To investigate the associations between educational attainment and 20-year cardiovascular disease (CVD) incidence, mortality, lifetime risk, and burden, and to explore the mediating role of healthy and sustainable dietary habits through a sex-specific lens. Methods: A total of 3042 CVD-free adults from the ATTICA Study were included at the 2001/2002 baseline. Educational level was treated as both continuous and ordinal variable. Adherence to the EAT–Lancet diet pattern (EAT-LDP) was assessed at baseline. Participants were followed for 20 years, with complete data on CVD outcomes available for 1988 individuals. Generalized structural equation and nested Cox regression models were used to estimate the direct and indirect effects between education attainment and 20-year CVD incidence. Moderation analysis was also conducted by incorporating interaction terms in Cox models. Results: An inverse educational gradient in CVD risk and burden was observed, particularly among females for lifetime risk estimates. Each additional year of education was associated with higher EAT-LDP adherence (β = 0.45, 95% CI: 0.40–0.50) and increased odds of physical activity (OR: 1.01, 95% CI: 1.00–1.01). These behaviors mediated part of the relationship between education and long-term CVD incidence. Among females, the cardioprotective role of EAT-LDP adherence was more evident at lower educational levels, suggesting potential effect modification. Conclusions: Educational disparities in long-term CVD outcomes are partly mediated by sustainable dietary habits. These findings highlight the need for gender-responsive and equity-focused strategies in cardiovascular prevention. Full article

Background/Objectives: Cancer is a major public health burden in Serbia and a factor influencing long-term disaster readiness by straining health system capacity. This study examined spatial and temporal trends in incidence and mortality for eight major cancers among women in Central Serbia (1999–2021) to inform targeted prevention and preparedness strategies. Methods: Standardised rates from national datasets were analysed using the Mann–Kendall trend test and Sen’s slope estimator. Geographic disparities were mapped in ArcGIS Pro 3.2. Mortality trends were assessed only for statistically reliable series. Results: Breast cancer incidence increased in six counties, while cervical cancer declined in several areas, likely reflecting screening success. Colorectal, bladder, pancreatic, and lung and bronchus cancers showed rising incidence; lung and bronchus cancer mortality increased in 16 counties, indicating growing demand for chronic respiratory care. These shifts may reduce surge capacity during disasters by increasing the baseline burden on healthcare infrastructure. Regional disparities highlight uneven system resilience. Conclusions: Aligning cancer control measures—especially for high-burden cancers like lung—with emergency preparedness frameworks is essential to strengthen health system resilience, particularly in resource-limited regions. Full article

Background: The rate of long-term outcomes, including arrhythmic episodes following implantable cardioverter–defibrillator (ICD) device replacements, is often unknown. Thus, the aim of this manuscript was to evaluate the risk of ICD or cardiac resynchronization therapy–defibrillator (CRT-D) therapies in remotely monitored patients following device replacement. Methods: Data from 134 patients who underwent ICD/CRT-D replacement or upgrade were analyzed. Kaplan–Meier estimates, as well as Cox proportional hazards regression, were used to present long-term outcomes and predictors of study endpoints, these being all-cause mortality, and appropriate and inappropriate ICD/CRT-D therapies. Results: Among the cohort, 51.5% of patients received ICDs and 48.5% received CRT-Ds; the median (quartile 1–quartile 3) LVEF at replacement was 23.0% (18.0–28.0%). In 11 (8.2%) patients, the LVEF at replacement was higher than 35%. During the median (Q1–Q3) follow-up of 3.0 (1.4–5.0) years, 32.1% experienced appropriate and 6.0% experienced inappropriate therapies. The all-cause mortality rate was 38.0%, and appropriate antitachycardia pacing (ATP), a reduced baseline LVEF, and no history of myocardial infarction were independent predictors of death (odds ratios of 1.87 for appropriate ATP, 0.88 per 1% of the LVEF and 0.54 for a history of MI, respectively). The rate of appropriate device therapies was numerically lower in patients whose LVEF improved (19.8% vs. 33.3% and 0% vs. 6.5%, for appropriate and inappropriate therapies). An LVEF of >35% at replacement did not influence the analyzed outcomes. Conclusions: In patients who underwent ICD/CRT-D replacement, an improvement in LVEF was not identified as either a predictor of improved survival or of a lower risk of needing device therapies. Further stratification models are needed to evaluate the arrhythmic risk in patients after generator replacements. Full article

Cardiovascular disease is a leading cause of global mortality. Percutaneous coronary intervention, which involves the placement of stents to restore blood flow in narrowed arteries, is a widely used treatment. However, traditional stents, such as bare metal stents and drug-eluting stents, can lead to long-term complications such as restenosis, inflammation, and thrombosis. Biodegradable metallic vascular stents, with their superior mechanical properties, excellent biocompatibility, and gradual degradation in vivo, hold significant potential for the treatment of coronary artery disease. This review provides a comprehensive overview of the current research status and challenges. Firstly, it outlines the design principles and performance evaluation methods for biodegradable stents, which focus on mechanical properties, chemical characteristics, corrosion behavior, and biocompatibility. Furthermore, it summarizes the material features, degradation mechanisms, and metabolic behavior of three primary biodegradable metals—magnesium alloys, iron alloys, and zinc alloys—and discusses critical issues such as the degradation rate of different alloys and the development of zinc alloys. Finally, based on the current achievements and challenges of studies on biodegradable metal-based stents, this article proposes some optimization strategies and research prospects. Full article

Background: Metastatic pancreatic cancer (mPC) is an aggressive disease with high morbidity and mortality, and long-term survival rates remain poor. New therapeutic options that demonstrate statistically significant improvements in overall survival (OS) and progression-free survival (PFS) are still being sought. Although many first-line (FL) treatment studies exist in the literature, there are almost no prospective studies on second-line (SL) therapy. Methods: The aim of this clinical study was to retrospectively analyze the medical history of 251 patients diagnosed with mPC, treated first-line (FL) with GEM-NAB between February 2017 and January 2025. After disease progression, 109 patients received SL treatment. We also present a multivariate analysis based on routinely collected data (demographic, clinical, and laboratory parameters) evaluating their impact on OS and PFS. Results: The median age was 66 years (range 37–84 years). The median PFS was 2.33 months (95% CI 1.69–2.97). Specifically, the mPFS was 4.1 months (95% CI 1.31–6.90) for FOLFIRINOX; 2.8 months (95% CI 2.30–3.30) for FOLFIRI; 2.37 months (95% CI 1.66–3.08) for NALIRI; 1.47 months (95% CI 1.18–1.75) for FOLFOX 6; and 0.93 months (95% CI 0.00–2.64) for GEM-cisplatin. The median OS was 5.03 months (95% CI 3.75–6.31). Seven patients achieved a partial response (overall response rate 6%). The most frequent adverse events (AEs) included anemia, fatigue, peripheral neuropathy, neutropenia, and thrombocytopenia. Conclusions: As a result, SL treatments were compared, and some statistically significant difference was found between them in PFS time for chemotherapy FOLFIRINOX and GEM + cisplatin. The most frequent AEs occurred during treatment with FOLFIRINOX chemotherapy. Full article

Objectives: This study aims to evaluate the association between antibiotic prophylaxis (particularly cephalosporins) and clinical outcomes in elderly hip fracture patients. Methods: We analyzed 4044 elderly hip fracture patients (2008–2022) from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database using inverse probability treatment weighting (IPTW). Cox proportional hazards models assessed mortality risk, while logistic regression evaluated infection and Intensive Care Unit (ICU) admission risks. Dose–response and subgroup analyses were performed for significant findings. Results: In total, 166 patients received no antibiotics, 2589 received Cephalosporin monotherapy, 403 received non-cephalosporin therapy, and 886 received Cephalosporin combination therapy. After IPTW adjustment, monotherapy showed significantly lower mortality risk versus combination therapy at all timepoints (hazard ratio (HR) for 28-day mortality: 0.46, 95% confidence interval (95% CI): 0.28–0.75; HR for 90-day mortality: 0.60, 95% CI: 0.44–0.82; HR for 180-day mortality: 0.67, 95% CI: 0.51–0.87; HR for 1-year mortality: 0.71, 95% CI: 0.57–0.89). The SII cut-off values were 1310.1 for 28-day mortality, 2077.5 for both 90-day and 180-day mortality, 1742.2 for 1-year mortality, 2199.7 for ICU admission, and 1930.7 for infection. Subgroup analyses showed that males and internal fixation patients derived more benefits after cephalosporin monotherapy treatment at all time nodes. Patients with multiple injuries had a lower risk of 28-day mortality, while high-comorbidity patients (CCI ≥ 5) and those with osteoporosis exhibited particular advantages with cephalosporin monotherapy. Conclusions: Cephalosporin monotherapy appears non-inferior to combination therapy for elderly hip fracture patients, potentially reducing long-term mortality risk, especially in males, internal fixation cases, and patients with CCI ≥ 5 and osteoporosis. Full article

The possible protective effect of obesity in the outcomes of chronic kidney disease (CKD) patients is an understudied field. We aimed to evaluate the prognostic value of vascular calcification (VC) on long-term outcomes in obese and non-obese CKD patients. We conducted a single-centre, prospective observational study of 150 CKD patients. Patients were divided into two groups using body mass index (BMI) scores (BMI ≥ 30 kg/m² and BMI < 30 kg/m²). Lateral lumbar X-rays (Kauppila score), the ankle–brachial index (ABI), and echocardiography were used for assessing VC. By the 11.2-year follow-up, 70 patients had died (47%). Twenty-four patients had had CV complications: stroke, myocardial infarction, decompensated heart failure, amputation caused by atherosclerosis, and aortic rupture. Among obese patients (BMI ≥ 30 kg/m²), only LVH was a significant predictor of CV complications (p = 0.01) and mortality (p = 0.004). In patients with BMI < 30 kg/m², predictors of CV complications and mortality were ABI (p = 0.03; p = 0.009), LVH (p = 0.02 for CV complications) and heart valve lesions (p = 0.009; p = 0.004). There were no differences in the measured parameters of VC between the obese and non-obese groups. Moreover, no significant differences were found comparing patients with and without obesity according to the studied parameters; we found no significant differences in complications and mortality. VC in patients with CKD is a significant complication that negatively impacts outcomes. Obesity does not have a protective effect in long-term outcomes in CKD patients. Full article

Background/Objectives: Acute ischemic stroke is a leading cause of mortality and long-term disability globally, with limited reliable early predictors of functional outcomes and survival. This study aimed to assess the prognostic value of two novel predictors: the hypoperfusion intensity ratio calculated from mean transit time and time-to-drain maps (HIR-MTT–TTD), derived from computed tomography perfusion (CTP) imaging parameters, and the Inflammation–Coagulation Index (ICI), which integrates systemic inflammatory (C-reactive protein and white blood cell count) and hemostatic (D-dimer) markers. Methods: This prospective, single-center observational study included 60 patients with acute ischemic stroke treated with intravenous thrombolysis and underwent pre-treatment CTP imaging. HIR-MTT–TTD evaluated collateral status and perfusion deficit severity, while ICI integrated C-reactive protein (CRP), white blood cell (WBC) count, and D-dimer levels. Functional outcomes were assessed using the National Institutes of Health Stroke Scale (NIHSS), Barthel Index, and modified Rankin Scale (mRS) at 24 h, 3 months, and 1 year. Results: Of 60 patients, 53.3% achieved functional independence (mRS 0–2) at 1 year. Unadjusted Cox models showed HIR-MTT–TTD (HR = 6.25, 95% CI: 1.48–26.30, p = 0.013) and ICI (HR = 1.08, 95% CI: 1.00–1.17, p = 0.052) were associated with higher 12-month mortality, worse mRS, and lower Barthel scores. After adjustment for age, BMI, smoking status, and sex, these associations became non-significant (HIR-MTT–TTD: HR = 2.83, 95% CI: 0.37–21.37, p = 0.314; ICI: HR = 1.07, 95% CI: 0.96–1.19, p = 0.211). Receiver operating characteristic (ROC) analysis indicated moderate predictive value, with ICI (AUC = 0.756, 95% CI: 0.600–0.867) outperforming HIR-MTT–TTD (AUC = 0.67, 95% CI: 0.48–0.83) for mortality prediction. Conclusions: The study introduces promising prognostic tools for functional outcomes. Elevated HIR-MTT–TTD and ICI values were independently associated with greater initial stroke severity, poorer functional recovery, and increased 1-year mortality. These findings underscore the prognostic significance of hypoperfusion intensity and systemic thrombo-inflammation in acute ischemic stroke. Combining the use of the presented indices may enhance early risk stratification and guide individualized treatment strategies. Full article

Fine particulate matter (PM_2.5) has been associated with mortality at low concentrations, with higher per-unit risk at lower exposure levels, and no threshold of effect. We examined characteristics of Medicare decedents living in zip codes at the lowest end of the U.S. PM_2.5 exposure distribution to determine whether there is a demographic, health or exposure profile of beneficiaries for whom even low PM_2.5 exposure is associated with increased mortality. The study included 2,773,647 decedent cases and 27,736,470 non-decedent controls, matched on decile of long-term PM_2.5 exposure from among 36 million Medicare fee-for-service beneficiaries enrolled 2015–2016. Outcomes of the study included all-cause and cause-specific mortality, stratified by decile and beneficiary characteristics. Increased PM_2.5-related mortality within the lowest exposure decile was found only among Native American beneficiaries, with odds ratios of 1.11 (95% CI, 1.01–1.21) and 1.21 (95% CI, 1.11–1.32) per 1 µg/m³ increase in PM_2.5, for those eligible and ineligible for Medicaid, respectively, and was driven by significant increases in selected kidney and cardiovascular outcomes, diabetes, and chronic obstructive pulmonary disease. These results may reflect particular sensitivity to PM_2.5; factors varying with PM_2.5 at the zip code level, including constituent exposures or social determinants of health; or inaccuracies in exposure estimates. Full article