A Comparative Analysis of Healthcare Quality Perception Among Different Vulnerable Populations with and without Telehealth Utilization: A Cross-Sectional Study from the Health Information National Trends Survey.

OBJECTIVE: The COVID-19 pandemic led to a rapid expansion of telehealth utilization in medicine. However, the quality measures associated with telehealth use remain unclear, particularly among vulnerable populations. This study aims to investigate the impact of telehealth on individuals' perception of overall quality care among vulnerable patient populations. METHODS: This cross-sectional study utilized Health Information National Trends Survey data. The individuals' overall perception of healthcare quality was compared between populations that had at least one telehealth visit and non-telehealth users, who all had the option of utilizing telehealth. This comparison focused on vulnerable populations, considering differences in race and ethnicity (non-Hispanic white vs. non-Hispanic black/Hispanic individuals) and socioeconomic status (high vs. low). Multivariable logistic regressions were employed to ascertain the association between individuals' overall perceptions of quality care with and without telehealth utilization. RESULTS: A total of 2920 participants, representing an unweighted population of 114,608,302, were analyzed. The adjusted odds ratio (AOR) for at least one telehealth visit associated with individuals' overall perception of quality care among the entire survey population was 0.76 with a 95% CI of 0.51-1.13 (p = 0.173). The AOR was 0.83 (95% CI 0.39-1.77, p = 0.618) among the non-White population, and the AOR was 0.71 (95% CI 0.29-1.78, p = 0.462) among individuals with low SES. CONCLUSIONS: Although telehealth utilization has both its limitations and advantages compared to traditional clinical visits, no statistically significant differences in individuals' overall perception of quality care were identified among telehealth and non-telehealth users. These findings were also consistent across various vulnerable populations.

The influence of realistic 3D mantle viscosity on Antarctica's contribution to future global sea levels.

The response of the Antarctic Ice Sheet (AIS) to climate change is the largest uncertainty in projecting future sea level. The impact of three-dimensional (3D) Earth structure on the AIS and future global sea levels is assessed here by coupling a global glacial isostatic adjustment model incorporating 3D Earth structure to a dynamic ice-sheet model. We show that including 3D viscous effects produces rapid uplift in marine sectors and reduces projected ice loss for low greenhouse gas emission scenarios, lowering Antarctica's contribution to global sea level in the coming centuries by up to ~40%. Under high-emission scenarios, ice retreat outpaces uplift, and sea-level rise is amplified by water expulsion from Antarctic marine areas.

Clinical Effects of Psychedelic Substances Reported to United States Poison Centers: 2012 to 2022.

STUDY OBJECTIVE: Psychedelic substances use is increasing in the United States (US). The approval of new psychedelic drugs and legalization of natural psychedelic substances will likely further increase exposures and subsequent adverse events. The study objective is to describe the clinical effects, therapies, and medical outcomes of patients with psychedelic exposures reported to US poison centers. METHODS: We performed a retrospective, cross-sectional study on psychedelic exposures reported to the National Poison Data System from January 1, 2012, to December 31, 2022. We categorized exposures into groups: hallucinogenic amphetamines, lysergic acid diethylamide, tryptamines (such as N, N-dimethyltryptamine), phencyclidine, hallucinogenic mushrooms, hallucinogenic plants, and ketamine and ketamine analogs. We summarized effects, treatments, and outcomes and evaluated associations with logistic regression and odds ratios. RESULTS: Our sample included 54,605 cases. There were concomitant exposures in 41.1% (n=22,460) of cases. Hallucinogenic mushroom exposures increased most over the study period from 593 in 2012 to 1,440 in 2022. Overall, 27,444 (50.3%) psychedelic exposures had symptoms that required treatment, severe residual or prolonged symptoms, or death. Cardiovascular effects were common, especially with hallucinogenic amphetamine exposures (31.1%). Patients managed in or referred to a health care facility received medical therapies in 62.4% of cases, including sedation (32.9%) and respiratory interventions (10.3%). CONCLUSION: Over half of psychedelic exposures reported to US poison centers had symptoms that required treatment, severe residual or prolonged symptoms, or death. Increases in psychedelic use may lead to increased frequency of adverse events and health care utilization.

Small Molecules Targeting GRP78 Mitigate Anti- GRP78 Autoantibody-Mediated Tissue Factor Procoagulant Activity in Cultured Endothelial Cells.

BACKGROUND: The 78-kDa glucose-regulated protein (GRP78) expressed on the cell surface (csGRP78) has been reported to regulate tissue factor procoagulant activity (TF PCA) in lesion-resident endothelial cells (ECs), which is further enhanced by circulating anti-GRP78 autoantibodies that bind to the Leu98-Leu115 epitope in GRP78. OBJECTIVES: Determine the effects of the engagement of the anti-GRP78 autoantibody to cell surface GRP78 on endothelial cells and the underlying mechanisms that impact TF PCA. METHODS: Immunofluorescent staining was used to determine the presence of csGRP78 in TNFα-treated endothelial cells. An established TF PCA assay was used to evaluate human ECs following treatment with anti-GRP78 autoantibodies. The Fura 2-AM assay was used to quantify changes in intracellular Ca2+ levels. Small molecules predicted to bind csGRP78 were identified using artificial intelligence. ELISAs were used to assess the ability of these GRP78 binders to mitigate TF activity and interfere with the autoantibody/csGRP78 complex. RESULTS: In TNFα-treated ECs, anti-GRP78 autoantibodies increased TF PCA. This observation was further enhanced by ER-stress-induced elevation of csGRP78 levels. Anti-GRP78 autoantibody treatment increased intracellular Ca2+ levels. Sequestering the anti-GRP78 autoantibody with a conformational peptide or blocking with heparin molecules attenuated anti-GRP78 autoantibody-induced TF PCA. We identified B07*, a GRP78 binder that diminished anti-GRP78 autoantibody-induced TF PCA on ECs. CONCLUSIONS: These findings show how anti-GRP78 autoantibodies enhance TF PCA that contributes to thrombosis and identify novel GRP78 binders that represent a potential novel therapeutic strategy for treating and managing atherothrombotic disease.

Near-cure in patients with Gadolinium deposition disease undergoing intravenous DTPA chelation.

Purpose: To demonstrate and evaluate factors contributing to near-cures in patients with Gadolinium Deposition Disease (GDD) undergoing intravenous (IV) DTPA chelation. Methods: Patients who had undergone or are currently undergoing DTPA chelation for GDD were included in this report based on their medical records that showed their perceived improvement was at least 80% back to normal. A survey was developed that included factors commonly reported by patients treated in one clinic to determine if these 'near-cured' (pre-MRI baseline health) individuals possessed certain factors and lacked others. The anonymized survey was emailed to these individuals by the principal treating physician, the only investigator not blinded to the subjects. This report describes clinical documentation of patient status and their underlying factors in individuals treated by the primary author, and no research was performed. The survey was sent to sixteen individuals; Fourteen patients completed it (10 females; 41.1 ± 11.2 y/o). Results: The most common factor was the administration of ≤5 lifetime doses of a Gadolinium-Based Contrast Agents (GBCA) (12/14). Unconfounded agents triggering GDD were seen in nine subjects. Most subjects (12/14) initiated chelation in the first year after the causative GBCA, and most (11/14) underwent ≤10 chelations with DTPA. Good healthcare status prior to MRI was observed in 5 subjects. The majority (11/14) described their immune status as strong. Severe physical disability prior to chelation was seen in 1. Conclusion: Subjects with GDD can experience near-cure with IV DTPA chelation. Factors surveyed that predict near-cure include the start of chelation in the first year, few GBCA administrations, and good health status before MRI with GBCA injection. Nonetheless, a few patients with predictors of less successful outcomes still experienced near-cure.

Pulmonary artery banding and arch repair versus Norwood for unbalanced atrioventricular canal defect.

BACKGROUND: The outcomes of single ventricle palliation in unbalanced atrioventricular canal defect with coarctation of aorta (uAVC+CoA) have not been well studied. These patients have a propensity to develop systemic ventricle outflow tract obstruction following aortic arch repair with pulmonary artery banding (arch-PAB); which may adversely affect survival and Fontan candidacy. METHODS: A retrospective review was performed of patients who underwent single ventricle palliation for uAVC+CoA from 2000 to 2022. Patients were divided into two groups based on initial palliation - (1) arch-PAB and (2) Norwood procedure. Demographic and clinical characteristics were analyzed and compared, along with survival data. RESULTS: 41 patients underwent stage 1 palliation for uAVC+CoA. Arch-PAB was performed in 14 infants and Norwood in 27 infants. Arch-PAB patients had more chromosomal abnormalities (28.6 vs 7.4%, p<0.009) and less severe systemic ventricle outflow tract obstruction on baseline echocardiogram (0.0 vs. 70.4%, p<0.001). Survival to stage 3 palliation was lower for the arch-PAB group (28.6 vs. 66.6%, p=0.02). Arch-PAB remained a significant risk factor for mortality (HR 2.93 [CI 1.05-8.53], p=0.04) after adjusting for chromosomal abnormalities and atrioventricular valve regurgitation. Following arch-PAB, systemic ventricle outflow tract obstruction was diagnosed in 13/14 patients. Echocardiography underestimated the degree of outflow tract obstruction in 10/13 arch-PAB patients. CONCLUSIONS: Arch-PAB has worse outcomes than Norwood for uAVC+CoA. Almost all patients develop systemic ventricle outflow tract obstruction following arch-PAB. Outflow tract obstruction is underestimated by echocardiogram, and requires a high index of suspicion along with advanced imaging to ensure timely diagnosis and management.

Cardiac Myxomas in Carney Complex: Single Institution Multi Decade Experience.

BACKGROUND: We present our surgical experience with cardiac myxomas in the setting of Carney Complex (CNC). METHODS: We searched our institutional data explorers to identify patients diagnosed with CNC. We gathered clinical, surgical, and recurrence data from electronic medical records. In total, 38 patients with Carney Complex were documented from 1970 through 2023. RESULTS: There were 24 (63.1%) patients who developed cardiac myxomas in the setting of Carney Complex. The median age of onset for cardiac myxoma occurrence was 39.0 years (interquartile range[IQR], 25.0-56.0). The majority were females (62.5%), and all underwent surgery. A total of 42 (52.7%) myxomas were extracted from the left atrium, 12 (15.0%) from the right ventricle, 11 (13.7%) from the right atrium, and 6 (7.5%) from the left ventricle. Among the 24 myxoma patients, 54.1%(n=13) experienced at least one myxoma recurrence. The median time for the first myxoma recurrence was 7.5 years (IQR,3.8-10.0). There were 27 (52.9%) recurrences from the same chamber, 11 (29.4%) from different chambers, and 9 (17.6%) had undocumented localizations. The freedom from tumor recurrence was 100% (95%CI;100.0-100.0), 66.7% (95%CI; 44.7%-99.5%) and 16.7% (95%CI; 4.7%-59.1%) at 1, 5 and 10 years respectively. The long-term survival was 100.0% at 10 and 15 years. CONCLUSIONS: Nearly two-thirds of CNC patients in this study (63.1%) developed cardiac myxomas, and more than half (54.1%) experienced recurring instances. Consistent monitoring through echocardiograms is essential for detecting asymptomatic first-time occurrences or recurrences. Surgical removal remains the key treatment method for managing cardiac myxomas associated with CNC.

Design of the SPIROMICS Study of Early COPD Progression: SOURCE Study.

The biological mechanisms leading some tobacco-exposed individuals to develop early-stage chronic obstructive pulmonary disease (COPD) are poorly understood. This knowledge gap hampers development of disease-modifying agents for this prevalent condition. Accord-ingly, with National Heart, Lung and Blood Institute support, we initiated the SPIROMICS Study of Early COPD Progression (SOURCE), a multicenter observational cohort study of younger individuals with a history of cigarette smoking and thus at-risk for, or with, early-stage COPD. Our overall objectives are to identify those who will develop COPD earlier in life, characterize them thoroughly, and by contrasting them to those not developing COPD, define mechanisms of disease progression. SOURCE utilizes the established SPIROMICS clinical network. Its goal is to enroll n=649 participants, ages 30-55 years, all races/ethnicities, with ≥10 pack-years cigarette smoking, in either Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups 0-2 or with Preserved Ratio Impaired Spirometry (PRISm); and an additional n=40 never-smoker controls. Participants undergo baseline and three-year follow-up visits, each including high-resolution computed tomography; respiratory oscillometry and spirometry (pre- and post-bronchodilator administration), exhaled breath condensate (baseline only); and extensive biospecimen collection, including sputum induction. Symptoms, interim healthcare utilization, and exacerbations are captured every six months via follow-up phone calls. An embedded bronchoscopy sub-study involving n=100 participants (including all never-smokers) will allow collection of lower airway samples for genetic, epigenetic, genomic, immunological, microbiome, mucin analyses, and basal cell culture. SOURCE should provide novel insights into the natural history of lung disease in younger individuals with a smoking history, and its biological basis.

DNA methylation analysis reveals local changes in resistant and susceptible soybean lines in response to Phytophthora sansomeana.

Phytophthora sansomeana is an emerging oomycete pathogen causing root rot in many agricultural species including soybean. However, as of now, only one potential resistance gene has been identified in soybean, and our understanding of how genetic and epigenetic regulation in soybean contributes to responses against this pathogen remains largely unknown. In this study, we performed whole genome bisulfite sequencing (WGBS) on two soybean lines, Colfax (resistant) and Williams 82 (susceptible) in response to P. sansomeana at two time points: 4 and 16 hours post inoculation to compare their methylation changes. Our findings revealed that there were no significant changes in genome-wide CG, CHG (H = A, T, or C), and CHH methylation. However, we observed local methylation changes, specially an increase in CHH methylation around genes and transposable elements (TEs) after inoculation, which occurred earlier in the susceptible line and later in the resistant line. After inoculation, we identified differentially methylated regions (DMRs) in both Colfax and Williams 82, with a predominant presence in TEs. Notably, our data also indicated that more TEs exhibited changes in their methylomes in the susceptible line compared to the resistant line. Furthermore, we discovered 837 DMRs within or flanking 772 differentially expressed genes (DEGs) in Colfax and 166 DMRs within or flanking 138 DEGs in Williams 82. These DEGs had diverse functions, with Colfax primarily showing involvement in metabolic process, defense response, plant and pathogen interaction, anion and nucleotide binding, and catalytic activity, while Williams 82 exhibited a significant association with photosynthesis. These findings suggest distinct molecular responses to P. sansomeana infection in the resistant and susceptible soybean lines.

Born This Way? National Collective Narcissism, Implicit Homophobia, and Homosexual Essentialism in Populist Poland.

Prejudice toward the LGBT community has become prevalent in Poland under the ultraconservative populist government. The results of three studies conducted between 2018 and 2019 (N1 = 879, N2 = 324, and N3 = 374) indicate that Polish collective narcissism-the belief that the exaggerated greatness of the nation is not recognized by others-is associated with implicit homophobia assessed as the intuitive disapproval of gay men and automatic evaluative preference of heterosexuality over homosexuality. Those associations were to a large extent explained by the relationships between collective narcissism and (1) the belief that groups defined by sexual orientations are essentially distinct; (2) the belief that homosexuality is a personal choice, not genetically determined or culturally universal. The experimental results of Study 3 indicated that inducing the belief that non-normative sexuality is genetically determined and culturally universal reduced automatic preference for heterosexuality over homosexuality (but not intuitive disapproval of gay men) across levels of collective narcissism (contrary to predictions). The obtained results complete the picture of the association of narcissistic beliefs about the nation and homophobia emerging from previous studies. National narcissism is linked not only to explicit but also to latent, implicit homophobia likely to be triggered by increased presence of national narcissism in public discourse. Moreover, national narcissism is linked to implicit homophobia, especially via the agentic belief that sexual orientation is a matter of choice. Changing this belief reduces implicit homophobia also among national narcissists.

Organizational characteristics of highly specialized units for people with dementia and severe challenging behavior.

BACKGROUND: People with dementia and severe challenging behavior in the Netherlands can be temporarily admitted to highly specialized units when their behavior is not manageable in regular dementia special care units (DSCUs). With scarce evidence available for the treatment of these patients, treatment in these units is in a pioneering phase. To gain more insight into these units, this study investigated organizational characteristics, i.e. admission and discharge characteristics, staffing, the physical environment, and the management of severe challenging behavior. METHODS: Three data collection methods were used: 1) a digital questionnaire to be completed by the unit manager, 2) an interview with the physician responsible for medical care and often another practitioner, and 3) an observation of the physical environment for which the OAZIS-dementia questionnaire was used. Descriptive analysis was used for quantitative data and thematic analysis for qualitative data, after which data was interpreted together. Thirteen units participated, with their sizes ranging from 10 to 28 places. RESULTS: Patients were mainly admitted from regular DSCUs, home or mental health care, and discharged to regular DSCUs. A multidisciplinary team comprising at least an elderly care physician or geriatrician, psychologist, and nursing staff member and other therapists as needed provided the treatment. Nursing staff hours per patient considerably differed among units. Nursing staff played a central role in the treatment. Competences such as reflectiveness on one's own behavior, and being able to cope with stressful situations were described as relevant for nursing staff. Investing in a stable nursing staff team was described as important. The units varied in whether their work-up was more intuitive or methodological. In the diagnostic phase, observation together with an extensive analysis of the patient's biography was essential. The units used a broad variety of interventions, and all paid attention to sensory stimuli. In the observation of the physical environment, the safety scored well and domesticity relatively low. CONCLUSION: Highly specialized units show strong heterogeneity in organizational characteristics and management, which can be understood in the light of the pioneering phase. Despite this, similarities were found in nursing staff roles, frequent multidisciplinary evaluation, and attention to sensory stimuli.

A single-nucleus transcriptomic atlas of medium spiny neurons in the rat nucleus accumbens.

Neural processing of rewarding stimuli involves several distinct regions, including the nucleus accumbens (NAc). The majority of NAc neurons are GABAergic projection neurons known as medium spiny neurons (MSNs). MSNs are broadly defined by dopamine receptor expression, but evidence suggests that a wider array of subtypes exist. To study MSN heterogeneity, we analyzed single-nucleus RNA sequencing data from the largest available rat NAc dataset. Analysis of 48,040 NAc MSN nuclei identified major populations belonging to the striosome and matrix compartments. Integration with mouse and human data indicated consistency across species and disease-relevance scoring using genome-wide association study results revealed potentially differential roles for MSN populations in substance use disorders. Additional high-resolution clustering identified 34 transcriptomically distinct subtypes of MSNs definable by a limited number of marker genes. Together, these data demonstrate the diversity of MSNs in the NAc and provide a basis for more targeted genetic manipulation of specific populations.

The COVID-19 thrombus: distinguishing pathological, mechanistic, and phenotypic features and management.

A heightened risk for thrombosis is a hallmark of COVID-19. Expansive clinical experience and medical literature have characterized small (micro) and large (macro) vessel involvement of the venous and arterial circulatory systems. Most events occur in patients with serious or critical illness in the hyperacute (first 1-2 weeks) or acute phases (2-4 weeks) of SARS-CoV-2 infection. However, thrombosis involving the venous, arterial, and microcirculatory systems has been reported in the subacute (4-8 weeks), convalescent (> 8-12 weeks) and chronic phases (> 12 weeks) among patients with mild-to-moderate illness. The purpose of the current focused review is to highlight the distinguishing clinical features, pathological components, and potential mechanisms of venous, arterial, and microvascular thrombosis in patients with COVID-19. The overarching objective is to better understand the proclivity for thrombosis, laying a solid foundation for screening and surveillance modalities, preventive strategies, and optimal patient management.

Interfacial Ice Density Fluctuations Inform Surface Ice-Philicity.

The propensity of a surface to nucleate ice or bind to ice is governed by its ice-philicity─its relative preference for ice over liquid water. However, the relationship between the features of a surface and its ice-philicity is not well understood, and for surfaces with chemical or topographical heterogeneity, such as proteins, their ice-philicity is not even well-defined. In the analogous problem of surface hydrophobicity, it has been shown that hydrophobic surfaces display enhanced low water-density (vapor-like) fluctuations in their vicinity. To interrogate whether enhanced ice-like fluctuations are similarly observed near ice-philic surfaces, here we use molecular simulations and enhanced sampling techniques. Using a family of model surfaces for which the wetting coefficient, k, has previously been characterized, we show that the free energy of observing rare interfacial ice-density fluctuations decreases monotonically with increasing k. By utilizing this connection, we investigate a set of fcc systems and find that the (110) surface is more ice-philic than the (111) or (100) surfaces. By additionally analyzing the structure of interfacial ice, we find that all surfaces prefer to bind to the basal plane of ice, and the topographical complementarity of the (110) surface to the basal plane explains its higher ice-philicity. Using enhanced interfacial ice-like fluctuations as a measure of surface ice-philicity, we then characterize the ice-philicity of chemically heterogeneous and topologically complex systems. In particular, we study the spruce budworm antifreeze protein (sbwAFP), which binds to ice using a known ice-binding site (IBS) and resists engulfment using nonbinding sites of the protein (NBSs). We find that the IBS displays enhanced interfacial ice-density fluctuations and is therefore more ice-philic than the two NBSs studied. We also find the two NBSs are similarly ice-phobic. By establishing a connection between interfacial ice-like fluctuations and surface ice-philicity, our findings thus provide a way to characterize the ice-philicity of heterogeneous surfaces.

Genome sequence of Heterobasidion occidentale, a fungus that causes annosus root and butt rot among conifer trees in North America.

We report an annotated draft genome of Heterobasidion occidentale, a fungus (Basidiomycota, Agaricomycetes) that has pathogenic and saprophytic lifestyles. This fungus belongs to the H. annosum (Fr.) Bref. sensu lato species complex that comprises several root rot pathogens. Heterobasidion occidentale causes annosus root and butt rot primarily in true fir (Abies spp.) and spruce (Picea spp.) species throughout western North America.

A critical review of the use of R2 in risk equalization research.

Nearly all empirical studies that estimate the coefficients of a risk equalization formula present the value of the statistical measure R2. The R2-value is often (implicitly) interpreted as a measure of the extent to which the risk equalization payments remove the regulation-induced predictable profits and losses on the insured, with a higher R2-value indicating a better performance. In many cases, however, we do not know whether a model with R2 = 0.30 reduces the predictable profits and losses more than a model with R2 = 0.20. In this paper we argue that in the context of risk equalization R2 is hard to interpret as a measure of selection incentives, can lead to wrong and misleading conclusions when used as a measure of selection incentives, and is therefore not useful for measuring selection incentives. The same is true for related statistical measures such as the Mean Absolute Prediction Error (MAPE), Cumming's Prediction Measure (CPM) and the Payment System Fit (PSF). There are some exceptions where the R2 can be useful. Our recommendation is to either present the R2 with a clear, valid, and relevant interpretation or not to present the R2. The same holds for the related statistical measures MAPE, CPM and PSF.

Integrative Multiomics in the Lung Reveals a Protective Role of Asporin in Pulmonary Arterial Hypertension.

BACKGROUND: Integrative multiomics can elucidate pulmonary arterial hypertension (PAH) pathobiology, but procuring human PAH lung samples is rare. METHODS: We leveraged transcriptomic profiling and deep phenotyping of the largest multicenter PAH lung biobank to date (96 disease and 52 control) by integration with clinicopathologic data, genome-wide association studies, Bayesian regulatory networks, single-cell transcriptomics, and pharmacotranscriptomics. RESULTS: We identified 2 potentially protective gene network modules associated with vascular cells, and we validated ASPN, coding for asporin, as a key hub gene that is upregulated as a compensatory response to counteract PAH. We found that asporin is upregulated in lungs and plasma of multiple independent PAH cohorts and correlates with reduced PAH severity. We show that asporin inhibits proliferation and transforming growth factor-ß/phosphorylated SMAD2/3 signaling in pulmonary artery smooth muscle cells from PAH lungs. We demonstrate in Sugen-hypoxia rats that ASPN knockdown exacerbated PAH and recombinant asporin attenuated PAH. CONCLUSIONS: Our integrative systems biology approach to dissect the PAH lung transcriptome uncovered asporin as a novel protective target with therapeutic potential in PAH.