Health disparities in ocular oncology.

Social determinants of health (SDH) play a crucial role in shaping health outcomes, including those in ophthalmology. Only a few studies have explored the impact of SDH in ocular oncology, looking at differences in disease presentation, treatment choices, and outcomes based on race, ethnicity, socioeconomic status (SES), and insurance status. Specifically, retinoblastoma exhibits disparities in survival rates, with lower-income countries experiencing substantially lower survival rates compared to high-income countries. Similarly, racial and SES disparities exist in the United States, impacting treatment choices and outcomes in children with retinoblastoma. Disparities in treatment modalities based on race and SES have been reported in uveal melanoma, with non-White and economically disadvantaged patients more likely to undergo primary enucleation. Ocular surface squamous neoplasia (OSSN) also exhibits racial and socioeconomic disparities in treatment outcomes. Black patients with OSSN face higher mortality risks, independent of tumor size, eye laterality, or tumor behavior. Given the rarity of the disease, currently, there is no data on disparities in the management of vitreoretinal lymphoma. When looking at data on primary central nervous system lymphoma as a surrogate of vitreoretinal lymphoma, management and survival outcomes vary based on factors such as race, socioeconomic status, and insurance status. This article aims to review the current literature on disparities in ocular oncology, highlighting the need for more granular data to better understand and bridge the existing gaps in care within ocular oncology.

Impact of COVID-19 on work loss in the United States- A retrospective database analysis.

OBJECTIVES: This study investigates the utilization of work absence benefits among United States (US) employees diagnosed with COVID-19, examining frequency, duration, cost, and types of work loss benefits used. METHODS: This retrospective analysis of the Workpartners Research Reference Database (RRDb) included employees eligible for short- and long-term disability (STD and LTD employer-sponsored benefits, respectively), and other paid work absence benefits from 2018 to 2022. Workpartners RRDb includes over 3.5 million employees from over 500 self-insured employers across the US. Employees were identified by codes from adjudicated medical and disability claims for COVID-19 (2020-2022) and influenza, as well as prescription claims for COVID-19 treatments. Associated payments were quantified for each absence reason. RESULTS: Approximately 1 million employees were eligible for employer-sponsored paid leave benefits between January 2018 and December 2022. The mean age was 37 years (22% >50 years), and 49.4% were females. COVID-19 was the 2nd most common reason for an STD claim (6.9% of all STD claims) and 13th for an LTD claim (1.7% of all LTD claims) from 2020-2022. The mean duration for COVID-19 STD claims was 24 days (N = 3,731, mean claim=$3,477) versus 10 days for influenza (N = 283, mean claim=$1,721). The mean duration for an LTD claim for COVID-19 was 153 days (N = 11, mean claim=$19,254). Only 21.5% of employees with STD claims in the COVID-19 cohort had prior COVID-19-associated medical or pharmacy claims; over half (range 53%-61%) had documented high risk factors for severe COVID-19. CONCLUSION: COVID-19 and influenza have the potential to cause work loss in otherwise healthy employees. In this analysis, COVID-19 was the second most frequent reason for an STD claim at the start of the pandemic and remained high (ranked 5th) in 2022. These results highlight the impact of COVID-19 on work loss beyond the acute phase. Comprehensively evaluating work loss implications may help employers prioritize strategies, such as vaccinations and timely treatments, to mitigate the impact of COVID-19 on employees and their companies.

COVID-19 results in short- and long-term symptoms that may affect employees' ability to work. Short- and long-term disability (STD and LTD, respectively), other work absences, and medical and pharmacy claims from the Workpartners Research Reference Database were analyzed for US adult (≥18 years) employees. COVID-19 claims were identified using the Center for Disease Control and Prevention recommended International Classification of Diseases codes during the analysis from 2020 to 2022. During 2020 to 2022, COVID-19 ranked as the second most frequent reason for STD claims and 13th most frequent among LTD claims. Influenza ranked 58th overall with no LTD claims (2018­2022). The average COVID-19 STD claim lasted 24 days and cost employers $3,477 per claim, and LTD claims averaged 153 days, costing $19,254. Only 21.5% of employees with STD claims in the COVID-19 cohort had prior COVID-19-associated medical or pharmacy claims, and over half (range 53%­61%) had a documented high-risk factor for severe COVID-19. Our results highlight the ongoing and substantial impact of COVID-19 on work absence benefit utilization beyond the acute phase. This analysis demonstrates the need for employers and researchers to review all available medical, pharmacy, and disability claims to assess the acute and long-term impact of COVID-19 on employees and prioritize mitigation strategies to reduce the burden of the virus to their employees.

Cytomegalovirus Retinitis in an Eye with Unilateral Retinoblastoma: A Case Report.

Introduction: Cytomegalovirus (CMV) retinitis in the setting of pediatric retinoblastoma is exceedingly unusual. Here, we present the first reported case of CMV retinitis in an enucleated eye with retinoblastoma after chemotherapy in the western hemisphere. Case Presentation: A 2-year-old Hispanic male without a family history of retinoblastoma presented with a 3-month history of right eye exotropia and squinting. Clinical examination revealed dense white vitreous opacities in the right eye. Ocular oncology evaluation unveiled an exudative retinal detachment with vitreous seeds, subretinal seeding, and a tumor emanating from the retina in the superonasal quadrant of the right eye. The patient was diagnosed with unilateral Group D retinoblastoma, and RB1 sequencing revealed a pathogenic variant with mosaicism. Treatment involved systemic chemotherapy, intravitreal chemotherapy, and cryotherapy. However, the patient developed a rhegmatogenous retinal detachment with diffuse vitreous hemorrhage and ultimately underwent right eye enucleation. Interestingly, histopathological analysis of the enucleated eye revealed concomitant CMV retinitis alongside retinoblastoma. After consultation with infectious disease, antiviral treatment was not initiated as the patient remained asymptomatic and maintained a recovered immune system. Repeat CMV PCR confirmed viral clearance. The patient received a prosthetic eye and continues to be monitored for retinoblastoma recurrence. Conclusion: Clinicians should be aware of the potential for CMV retinitis to develop in retinoblastoma patients receiving chemotherapy, which may complicate clinical decision-making and management. Timely identification of CMV retinitis in this setting may improve patient ocular outcomes and overall prognosis.

Progressive verbal apraxia of reading.

We identified a syndrome characterized by a relatively isolated progressive impairment of reading words that the patient was able to understand and repeat but without other components of speech apraxia. This cluster of symptoms fits a new syndrome designated Progressive Verbal Apraxia of Reading. A right-handed man (AB) came with a 2.5-year history of increasing difficulties in reading aloud. He was evaluated twice, 2 years apart, using multimodal neuroimaging techniques and quantitative neurolinguistic assessment. In the laboratory, reading difficulties arose in the context of intact visual and auditory word recognition as well as intact ability to understand and repeat words he was unable to read aloud. The unique feature was the absence of dysarthria or speech apraxia in tasks other than reading. Initial imaging did not reveal statistically significant atrophy. Structural magnetic resonance and FDG-PET imaging at the second assessment revealed atrophy and hypometabolism in the right posterior cerebellum, in areas shown to be part of his language network by task-based functional neuroimaging at initial assessment. This syndromic cluster can be designated Progressive Verbal Apraxia of Reading, an entity that has not been reported previously to the best of our knowledge. We hypothesize a selective disconnection of the visual word recognition system from the otherwise intact articulatory apparatus, a disconnection that appears to reflect the disruption of multisynaptic cerebello-cortical circuits.

NF-κB inhibitor alpha controls SARS-CoV-2 infection in ACE2-overexpressing human airway organoids.

As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that recapitulate the cell-intrinsic response to arising viral variants are needed. Here we describe an adult stem cell-derived human airway organoid model overexpressing the ACE2 receptor (ACE2-OE) that supports robust viral replication while maintaining 3D architecture and cellular diversity of the airway epithelium. ACE2-OE organoids were infected with SARS-CoV-2 variants and subjected to single-cell RNA-sequencing. Interferon-lambda was upregulated in cells with low-level infection while the NF-kB inhibitor alpha gene (encoding IkBa) was consistently upregulated in infected cells, and its expression positively correlated with infection levels. Confocal microscopy showed more IkBa expression in infected than bystander cells, but found concurrent nuclear translocation of NF-kB that IkBa usually prevents. Overexpressing a nondegradable IkBa mutant reduced NF-kB translocation and increased viral infection. These data demonstrate the functionality of ACE2-OE organoids in SARS-CoV-2 research and underscore that the strength of the NF-kB feedback loop in infected cells controls viral replication.

Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging.

DNA hydroxymethylation (5hmC), the most abundant oxidative derivative of DNA methylation, is typically enriched at enhancers and gene bodies of transcriptionally active and tissue-specific genes. Although aberrant genomic 5hmC has been implicated in age-related diseases, its functional role in aging remains unknown. Here, using mouse liver and cerebellum as model organs, we show that 5hmC accumulates in gene bodies associated with tissue-specific function and restricts the magnitude of gene expression changes with age. Mechanistically, 5hmC decreases the binding of splicing associated factors and correlates with age-related alternative splicing events. We found that various age-related contexts, such as prolonged quiescence and senescence, drive the accumulation of 5hmC with age. We provide evidence that this age-related transcriptionally restrictive function is conserved in mouse and human tissues. Our findings reveal that 5hmC regulates tissue-specific function and may play a role in longevity.

Distinct neurodevelopmental and epileptic phenotypes associated with gain- and loss-of-function GABRB2 variants.

BACKGROUND: Variants in GABRB2, encoding the ß2 subunit of the γ-aminobutyric acid type A (GABAA) receptor, can result in a diverse range of conditions, ranging from febrile seizures to severe developmental and epileptic encephalopathies. However, the mechanisms underlying the risk of developing milder vs more severe forms of disorder remain unclear. In this study, we conducted a comprehensive genotype-phenotype correlation analysis in a cohort of individuals with GABRB2 variants. METHODS: Genetic and electroclinical data of 42 individuals harbouring 26 different GABRB2 variants were collected and accompanied by electrophysiological analysis of the effects of the variants on receptor function. FINDINGS: Electrophysiological assessments of α1ß2γ2 receptors revealed that 25/26 variants caused dysfunction to core receptor properties such as GABA sensitivity. Of these, 17 resulted in gain-of-function (GOF) while eight yielded loss-of-function traits (LOF). Genotype-phenotype correlation analysis revealed that individuals harbouring GOF variants suffered from severe developmental delay/intellectual disability (DD/ID, 74%), movement disorders such as dystonia or dyskinesia (59%), microcephaly (50%) and high risk of early mortality (26%). Conversely, LOF variants were associated with milder disease manifestations. Individuals with these variants typically exhibited fever-triggered seizures (92%), milder degrees of DD/ID (85%), and maintained ambulatory function (85%). Notably, severe movement disorders or microcephaly were not reported in individuals with loss-of-function variants. INTERPRETATION: The data reveals that genetic variants in GABRB2 can lead to both gain and loss-of-function, and this divergence is correlated with distinct disease manifestations. Utilising this information, we constructed a diagnostic flowchart that aids in predicting the pathogenicity of recently identified variants by considering clinical phenotypes. FUNDING: This work was funded by the Australian National Health & Medical Research Council, the Novo Nordisk Foundation and The Lundbeck Foundation.

A mild increase in nutrient signaling to mTORC1 in mice leads to parenchymal damage, myeloid inflammation and shortened lifespan.

The mechanistic target of rapamycin complex 1 controls cellular anabolism in response to growth factor signaling and to nutrient sufficiency signaled through the Rag GTPases. Inhibition of mTOR reproducibly extends longevity across eukaryotes. Here we report that mice that endogenously express active mutant variants of RagC exhibit multiple features of parenchymal damage that include senescence, expression of inflammatory molecules, increased myeloid inflammation with extensive features of inflammaging and a ~30% reduction in lifespan. Through bone marrow transplantation experiments, we show that myeloid cells are abnormally activated by signals emanating from dysfunctional RagC-mutant parenchyma, causing neutrophil extravasation that inflicts additional inflammatory damage. Therapeutic suppression of myeloid inflammation in aged RagC-mutant mice attenuates parenchymal damage and extends survival. Together, our findings link mildly increased nutrient signaling to limited lifespan in mammals, and support a two-component process of parenchymal damage and myeloid inflammation that together precipitate a time-dependent organ deterioration that limits longevity.

Anesthesia Techniques for Vitreoretinal Surgery in the United States: A Report from the Multicenter Perioperative Outcomes Group Research Consortium.

PURPOSE: To explore the patterns of anesthesia use and their determinants during vitreoretinal (VR) surgeries in academic and community hospitals across the US, using data from the Multicenter Perioperative Outcomes Group (MPOG). DESIGN: A retrospective, multicenter, cohort study. METHODS: We queried the MPOG database of 107,066 patients undergoing VR surgeries. Patients (≥18 years) undergoing VR surgery with monitored anesthesia care (MAC) or general anesthesia (GA) from January 1, 2015 to December 31, 2021 were included. Patient-level, case-based, and institutional-level covariates were collected. We performed multivariable mixed-effects models to determine predictors of anesthesia type use. The primary outcome was the type of anesthesia (MAC or GA) used during VR surgeries. As a secondary outcome, MAC cases were further classified based on the additional use of sedation into MAC with or without sedation. RESULTS: We found that 67.45% of VR surgery cases received MAC, and 73.63% of institutions administered MAC to more than half of cases. Random effect modeling revealed that 47.76% of the variation in MAC use was attributed to institutions. A trend toward increased use of MAC with increasing age was observed. Patients diagnosed with chronic pulmonary disease, liver disease, or a history of drug abuse were less likely to receive MAC. Conversely, we found that patients with reported alcohol abuse disorder, diabetes with complications, and those with American Society of Anesthesiologists (ASA) physical status of 4 (vs. 1, 2, or 3) were more likely to use MAC. Compared to non-complex VR surgeries, there was a notably decreased likelihood of MAC use in complex PPV (P = .004), PPV + scleral buckle (SB) for retinal detachment (P < .0001), and primary SB surgery (P < .0001). CONCLUSIONS: Approximately 2/3 of VR anesthesia is under MAC, but GA is still preferred for SBs, complex vitrectomy, and younger patients. We show that large interinstitutional variation for using MAC in practice exists.

Long-Term Impacts on Clinical Practice Along the HIV Care Continuum: Addressing Workforce Gaps Through a Clinician Scholars Program.

The Clinician Scholars Program (CSP) was designed to expand the HIV care workforce by improving the clinical capacity of clinicians in underserved areas. This evaluation assessed program participants' long-term practice changes and system changes. The year-long program combined mentoring, training, and on-site clinical observation. Qualitative interviews (N = 46) were conducted with Scholars at least 2 years following CSP, supplemented by a 2023 survey. Multiple coders analyzed transcripts using open coding. Thematic analysis explored practice changes and efforts to move patients along the HIV care continuum. Findings indicate positive long-term impacts of CSP regarding the HIV care continuum and care system engagement. Over 90% of Scholars remained working in HIV care, with 75% maintaining or increasing patient loads and 72% making changes to their clinical practice. This training model appears to enhance care along the HIV care continuum and may be adaptable to other contexts that address complex chronic conditions.

ZBTB11 Depletion Targets Metabolic Vulnerabilities in K-Ras Inhibitor Resistant PDAC.

Over 95% of pancreatic ductal adenocarcinomas (PDAC) harbor oncogenic mutations in K-Ras. Upon treatment with K-Ras inhibitors, PDAC cancer cells undergo metabolic reprogramming towards an oxidative phosphorylation-dependent, drug-resistant state. However, direct inhibition of complex I is poorly tolerated in patients due to on-target induction of peripheral neuropathy. In this work, we develop molecular glue degraders against ZBTB11, a C2H2 zinc finger transcription factor that regulates the nuclear transcription of components of the mitoribosome and electron transport chain. Our ZBTB11 degraders leverage the differences in demand for biogenesis of mitochondrial components between human neurons and rapidly-dividing pancreatic cancer cells, to selectively target the K-Ras inhibitor resistant state in PDAC. Combination treatment of both K-Ras inhibitor-resistant cell lines and multidrug resistant patient-derived organoids resulted in superior anti-cancer activity compared to single agent treatment, while sparing hiPSC-derived neurons. Proteomic and stable isotope tracing studies revealed mitoribosome depletion and impairment of the TCA cycle as key events that mediate this response. Together, this work validates ZBTB11 as a vulnerability in K-Ras inhibitor-resistant PDAC and provides a suite of molecular glue degrader tool compounds to investigate its function.

Multifractal fluctuations in zebrafish (Danio rerio) polarization time series.

In this work, we study the polarization time series obtained from experimental observation of a group of zebrafish (Danio rerio) confined in a circular tank. The complex dynamics of the individual trajectory evolution lead to the appearance of multiple characteristic scales. Employing the Multifractal Detrended Fluctuation Analysis (MF-DFA), we found distinct behaviors according to the parameters used. The polarization time series are multifractal at low fish densities and their average scales with ρ - 1 / 4 . On the other hand, they tend to be monofractal, and their average scales with ρ - 1 / 2 for high fish densities. These two regimes overlap at critical density ρ c , suggesting the existence of a phase transition separating them. We also observed that for low densities, the polarization velocity shows a non-Gaussian behavior with heavy tails associated with long-range correlation and becomes Gaussian for high densities, presenting an uncorrelated regime.

Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer.

Importance: Benefits of prostate cancer (PCa) screening with prostate-specific antigen (PSA) alone are largely offset by excess negative biopsies and overdetection of indolent cancers resulting from the poor specificity of PSA for high-grade PCa (ie, grade group [GG] 2 or greater). Objective: To develop a multiplex urinary panel for high-grade PCa and validate its external performance relative to current guideline-endorsed biomarkers. Design, Setting, and Participants: RNA sequencing analysis of 58 724 genes identified 54 markers of PCa, including 17 markers uniquely overexpressed by high-grade cancers. Gene expression and clinical factors were modeled in a new urinary test for high-grade PCa (MyProstateScore 2.0 [MPS2]). Optimal models were developed in parallel without prostate volume (MPS2) and with prostate volume (MPS2+). The locked models underwent blinded external validation in a prospective National Cancer Institute trial cohort. Data were collected from January 2008 to December 2020, and data were analyzed from November 2022 to November 2023. Exposure: Protocolized blood and urine collection and transrectal ultrasound-guided systematic prostate biopsy. Main Outcomes and Measures: Multiple biomarker tests were assessed in the validation cohort, including serum PSA alone, the Prostate Cancer Prevention Trial risk calculator, and the Prostate Health Index (PHI) as well as derived multiplex 2-gene and 3-gene models, the original 2-gene MPS test, and the 18-gene MPS2 models. Under a testing approach with 95% sensitivity for PCa of GG 2 or greater, measures of diagnostic accuracy and clinical consequences of testing were calculated. Cancers of GG 3 or greater were assessed secondarily. Results: Of 761 men included in the development cohort, the median (IQR) age was 63 (58-68) years, and the median (IQR) PSA level was 5.6 (4.6-7.2) ng/mL; of 743 men included in the validation cohort, the median (IQR) age was 62 (57-68) years, and the median (IQR) PSA level was 5.6 (4.1-8.0) ng/mL. In the validation cohort, 151 (20.3%) had high-grade PCa on biopsy. Area under the receiver operating characteristic curve values were 0.60 using PSA alone, 0.66 using the risk calculator, 0.77 using PHI, 0.76 using the derived multiplex 2-gene model, 0.72 using the derived multiplex 3-gene model, and 0.74 using the original MPS model compared with 0.81 using the MPS2 model and 0.82 using the MPS2+ model. At 95% sensitivity, the MPS2 model would have reduced unnecessary biopsies performed in the initial biopsy population (range for other tests, 15% to 30%; range for MPS2, 35% to 42%) and repeat biopsy population (range for other tests, 9% to 21%; range for MPS2, 46% to 51%). Across pertinent subgroups, the MPS2 models had negative predictive values of 95% to 99% for cancers of GG 2 or greater and of 99% for cancers of GG 3 or greater. Conclusions and Relevance: In this study, a new 18-gene PCa test had higher diagnostic accuracy for high-grade PCa relative to existing biomarker tests. Clinically, use of this test would have meaningfully reduced unnecessary biopsies performed while maintaining highly sensitive detection of high-grade cancers. These data support use of this new PCa biomarker test in patients with elevated PSA levels to reduce the potential harms of PCa screening while preserving its long-term benefits.

The association between frailty and outcomes following ruptured abdominal aortic aneurysm repair.

OBJECTIVE: Endovascular aortic repair (EVAR) is a less invasive method than the more physiologically stressful open surgical repair (OSR) for patients with anatomically appropriate abdominal aortic aneurysms (AAAs). Early postoperative outcomes are associated with both patients; physiologic reserve and the physiologic stresses of the surgical intervention. Among frail patients with reduced physiologic reserve, the stress of an aortic rupture in combination with the stress of an operative repair are less well tolerated, raising the risk of complications and mortality. This study aims to evaluate the difference in association between frailty and outcomes among patients undergoing minimally invasive EVAR and the physiologically more stressful OSR for ruptured AAAs (rAAAs). METHODS: Our retrospective cohort study included adults undergoing rAAA repair in the Vascular Quality Initiative from 2010 to 2022. The validated Risk Analysis Index (RAI) (robust, ≤20; normal, 21-29; frail, 30-39; very frail, ≥40) quantified frailty. The association between the primary outcome of 1-year mortality and frailty status as well as repair type were compared using multivariable Cox models generating adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Interaction terms evaluated the association's moderation. RESULTS: We identified 5806 patients (age, 72 ± 9 years; 77% male; EVAR, 65%; robust, 6%; normal, 48%; frail, 36%; very, frail 10%) with a 53% observed 1-year mortality rate following rAAA repair. OSR (aHR, 1.43; 95% CI, 1.19-1.73) was associated with increased 1-year mortality when compared with EVAR. Increasing frailty status (frail aHR, 1.26; 95% CI, 1.00-1.59; very frail aHR, 1.64; 95% CI, 1.26-2.13) was associated with increased 1-year mortality, which was moderated by repair type (P-interaction < .05). OSR was associated with increased 1-year mortality in normal (aHR, 1.49; 95% CI, 1.20-1.87) and frail (aHR, 1.51; 95% CI, 1.20-1.89), but not among robust (aHR, 0.88; 95% CI, 0.59-1.32) and very frail (aHR, 1.29; 95% CI, 0.97-1.72) patients. CONCLUSIONS: Frailty and OSR were associated with increased adjusted risk of 1-year mortality following rAAA repair. Among normal and frail patients, OSR was associated with an increased adjusted risk of 1-year mortality when compared with EVAR. However, there was no difference between OSR and EVAR among robust patients who can well tolerate the stress of OSR and among very frail patients who are unable to withstand the surgical stress from rAAA regardless of repair type.

Exploratory factor analysis of the Illness Intrusiveness Rating Scale for parents of children with atypical genital appearance due to differences of sex development (DSD).

OBJECTIVE: Illness intrusiveness refers to the subjective cognitive appraisal of a chronic health condition interfering in daily, valued activities and may be highly relevant for parents of children with atypical genital appearance due to differences of sex development (DSD). However, a measure of illness intrusiveness has not been validated for this population. The current study aimed to evaluate the factor structure of the Illness Intrusiveness Scale for Parents (IIS-P) and examine convergent validity. METHODS: Participants included 102 parents (Mage = 33.39 years, SD = 6.48; 58% mothers) of 65 children (<2 years old) diagnosed with DSD participating in a larger, longitudinal study. Parents completed the IIS-P as well as self-report measures of stigma, and anxious and depressive symptoms. An exploratory factor analysis (EFA) was conducted. RESULTS: EFA results supported a 1-factor intrusiveness solution (α = .93), as well as a 2-factor solution measuring intrusiveness on daily living (α = .92) and community connectedness (α = .85). The 1-factor solution and both factors of the 2-factor solution demonstrated significant convergent validity with stigma as well as anxious and depressive symptoms. CONCLUSIONS: Support emerged for both 1- and 2-factor solutions of the IIS-P in parents of children with DSD. The decision to evaluate illness intrusiveness as a total score or to examine the subscales of daily living and community connectedness should be tailored to the unique aims of researchers and clinicians. Future research should conduct a confirmatory factor analysis with both 1- and 2-factor models with larger, more diverse samples of caregivers.

Exploring the preservation of a parasitic trace in decapod crustaceans using finite elements analysis.

The fossil record of parasitism is poorly understood, due largely to the scarcity of strong fossil evidence of parasites. Understanding the preservation potential for fossil parasitic evidence is critical to contextualizing the fossil record of parasitism. Here, we present the first use of X-ray computed tomography (CT) scanning and finite elements analysis (FEA) to analyze the impact of a parasite-induced fossil trace on host preservation. Four fossil and three modern decapod crustacean specimens with branchial swellings attributed to an epicaridean isopod parasite were CT scanned and examined with FEA to assess differences in the magnitude and distribution of stress between normal and swollen branchial chambers. The results of the FEA show highly localized stress peaks in reaction to point forces, with higher peak stress on the swollen branchial chamber for nearly all specimens and different forces applied, suggesting a possible shape-related decrease in the preservation potential of these parasitic swellings. Broader application of these methods as well as advances in the application of 3D data analysis in paleontology are critical to understanding the fossil record of parasitism and other poorly represented fossil groups.

Characterization of environmental airborne hydrocarbon contaminants by surface-enhanced Raman scattering.

This paper explores the unintentional contamination of Surface-Enhanced Raman Scattering (SERS) substrates by ambient hydrocarbon contaminants and their contribution to SERS spectra. Previous studies have identified amorphous carbon as a potential complicating factor in data analysis in SERS experiments, although its origin has been elusive. Our work showed that ambient hydrocarbon contamination and its decomposition products can be detected by SERS on a gold substrate. We propose that ambient air itself is a source of amorphous carbon contamination on SERS substrates. This understanding is crucial for the correct interpretation of SERS data and highlights the need for careful consideration of potential environmental contaminants in SERS analysis.

Threats to social safety and neuro-inflammatory mechanisms underlying sexual orientation disparities in depression symptom severity: A prospective cohort study of young adults.

Sexual minority individuals have a markedly elevated risk of depression compared to heterosexuals. We examined early threats to social safety and chronically elevated inflammation as mechanisms contributing to this disparity in depression symptoms, and compared the relative strength of the co-occurrence between chronic inflammation and depression symptoms for sexual minorities versus heterosexuals. To do so, we analyzed data from a prospective cohort of sexual minority and heterosexual young adults (n = 595), recruited from a nationally representative sample, that included assessments of early threats to social safety in the form of adverse childhood interpersonal events, three biomarkers of inflammation (i.e., CRP, IL-6, TNF-α) measured at two time points, and depression symptoms over four years. In pre-registered analyses, we found that sexual minorities experienced more adverse childhood interpersonal events, were more likely to display chronically elevated inflammation, and reported more severe depression symptoms than heterosexuals. Adverse childhood interpersonal events and chronically elevated inflammation explained approximately 23 % of the total effect of the association between sexual orientation and depression symptom severity. Further, there was an increased coupling of chronically elevated inflammation and depression symptoms among sexual minorities compared to heterosexuals. These results provide novel longitudinal, population-based evidence for the role of chronically elevated inflammation in linking threats to social safety during childhood with depression symptom severity in young adulthood, consistent with the primary tenets of the social signal transduction theory of depression. Our study extends this theory to the population level by finding that members of a stigmatized population (i.e., sexual minorities) experience a greater risk of depression because of their greater exposure to adverse childhood interpersonal events and the subsequent link to chronic inflammation, highlighting potential biopsychosocial intervention targets.