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Inside and Outside: The Transcendent, Boundaries, and the Trouble with Spaces
Full text link“Outsider art” is a term that was developed within gallery spaces during the 1970s. Outsider art as a category has often been plagued by the issue of balancing the work of artists, who often belong to vulnerable demographics like the mentally ill, and the dissemination of respectful thought surrounding their work. In this paper I compare and contrast the works of the two outsider artists, Oswald Tschirtner and Annie Hooper, and their subject matter, methods of creation, and interaction with the formal art world. In “Inside and Outside: The Transcendent, Boundaries, and the Trouble with Spaces”, I base my understanding of mental illness on Michel Foucault’s work “Madness and Civilization” [1961]. These theories show how mental illness interacts with art in both the sense of adding therapeutic value to the creators and how it adds monetary or social value for galleries. I analyze the way these gallery spaces can help or harm our understanding of art based on the dynamics of display practices. The goal of this paper aims to reexamine practices of how to utilize gallery spaces without fetishizing the artist
Availability, accessibility, and utilization of mental health services or support among university students in Africa: a mixed methods systematic review with meta-analysis and meta-synthesis
No full textBackground: The literature is replete with studies documenting the magnitude of mental illness among university students in Africa. However, it is unclear what mental health services or support (MHSS) are available to students and the extent to which they access and utilize them. We determined the availability, accessibility, and utilization of MHSS among university students in Africa and explored factors associated with the accessibility and utilization of MHSS.
Methods: We obtained data through a systematic search of five databases and included studies that reported on the availability, accessibility, or utilization of MHSS among university students in Africa. We extracted data on sociodemographic characteristics, MHSS focus (availability, accessibility, or utilization), mental health outcomes, and factors associated with MHSS accessibility and utilization. Quantitative data were meta-analyzed, and qualitative data were meta-synthesized.
Results and conclusion: We included 18 studies. More informal than formal sources of MHSS are available, accessible, and utilized by African university students. While parents and lecturers are often seen as the available informal sources of MHSS for university students in Africa, access to these services is hampered by instrumental-related barriers such as inadequate mental health literacy and financial constraints. These findings underscore the need for targeted, low-cost interventions, such as faculty training and peer counseling, that improve mental health literacy and access to services. Providing psychoeducation to parents can help them guide students toward appropriate help without being an obstructive force. Rather than adopting a one-size-fits-all approach, universities and policymakers can consider developing segmented mental health promotion campaigns that target specific student subpopulations (i.e., those with different religious, cultural, or ethnic backgrounds) with messages that resonate with their preferred help-seeking pathways. There is a need to prioritize policies that expand access to mental health insurance and services
The Impacts of Climate Change and Land Use on Urban Water Quality in Indianapolis
No full textIUIUrban water systems are increasingly vulnerable to microbial contamination driven by climate change, aging infrastructure, and intensified land use. This dissertation investigates long-term trends in E. coli concentrations in Indianapolis, Indiana, and explores the influence of climatic and environmental drivers on urban water quality using a combination of statistical analyses and machine learning models. Chapters 1 and 2 investigated the temporal and spatial trends of urban water quality in Indianapolis, with a focus on climate and land use as key drivers. In Chapter 1, long-term analysis of E. coli concentrations in the Pleasant Run watershed revealed a significant upward trend, with values exceeding the Indiana standard of 235 MPN/100 mL since 1998. Concentrations increased from 111 MPN/100 mL in 1999 to 911 MPN/100 mL in 2019. Precipitation and stream discharge explained 60% of the observed variability. Under the RCP 8.5 climate scenario, E. coli levels are projected to increase by up to 58% by the 2080s. Chapter 2 expanded the analysis to include nitrate, sulfate, and chloride concentrations across 12 sites in Pleasant Run and Fall Creek. Seasonal and spatial differences were observed, with E. coli peaking in summer and chloride in March due to road salt runoff. Key drivers included 7-day antecedent precipitation and snow, urban built-up area, tree cover, and NDVI. Together, the results underscore the combined influence of climate variability and land use patterns on urban water quality, highlighting the need for integrated, climate-informed management strategies. Chapter 3 applies machine learning approaches Random Forest, XGBoost, and LightGBM-based quantile regression to model non-linear patterns of E. coli concentrations in a weekly scale. These models capture complex interactions among environmental variables and outperform linear models in predictive accuracy. Quantile regression further provides probabilistic estimates, enabling risk-based assessments of high E. coli levels. Overall, this research demonstrates that urban water quality in Indianapolis is significantly impacted by climate variability and land use dynamics. The integration of long-term monitoring data with interpretable machine learning models offers valuable tools for predicting microbial risks and informing climate-resilient water quality management in urban environments
Gyral‐Sulcal Net: A Novel Brain Network Representation for Mild Cognitive Impairment Classification
Full text linkBackground:
Alzheimer's disease (AD), once established, cannot be reversed or cured. The diagnosis of mild cognitive impairment (MCI), often considered a precursor to AD, has become a more feasible goal. AD significantly affects individuals' brain structure and function. Therefore, it is crucial to incorporate features of brain structure and function simultaneously to provide a comprehensive diagnosis and effectively distinguish MCI from cognitively normal (CN) individuals. In this work, we propose a novel brain network representation, the Gyral‐Sulcal Net that provides finer‐scale brain structural landmarks along with corresponding functional features, to enhance the diagnostic accuracy of MCI from CN.
Method:
Our study utilized structural T1‐weighted structural MRI (sMRI) and functional MRI (fMRI) data from 126 MCI subjects and 141 CN subjects from the ADNI dataset. After the cortical surface reconstruction, we constructed the Gyral‐Sulcal Net from sMRI and identify gyral and sulcal nodes. The fMRI signals from gyral and sulcal nodes located at the corresponding region of interest (ROI) were extracted. We then calculated a functional connectivity matrix with such ROIs at dimensions of 88 × 88. For group prediction, we developed a graph transformer attention network, where the topology of gyral and sulcal nodes, and the functional connectivity matrix served as the feature input. The overall framework is illustrated in Figure 1.
Result:
The proposed method achieved promising results. We conducted 10 experiments and 5‐fold cross validation (best for each fold) for MCI/CN classification. We achieved a mean accuracy of 73.80% with a standard deviation of 2.97%. The cross‐validation results are shown in Figure 2.
Conclusion:
We proposed a novel brain Gyral‐Sulcal Net for MCI/CN classification. The Gyral‐Sulcal Net integrates the brain's two primary folding patterns, gyri and sulci, into a unified finer‐scale anatomical network. It effectively combines structural and functional information as the node features. Based on the Gyral‐Sulcal Net, we developed a novel graph transformer network to leverage Gyral‐Sulcal Net for MCI/CN classification. Our approach achieved promising results, highlighting the great potential of the Gyral‐Sulcal Net in improving diagnostic accuracy
Socioeconomic and ethnic disparities in breast cancer-related lymphedema and quality-of-life after immediate lymphatic reconstruction
Full text linkPurpose: Breast cancer-related lymphedema (BCRL) disproportionately impacts patients facing socioeconomic challenges. The influence of socioeconomic disparities on preventive procedures such as immediate lymphatic reconstruction (ILR) is unclear. We sought to determine the impact of area deprivation index (ADI) on BCRL incidence and patient-reported outcomes (PROs) following ILR.
Methods: We retrospectively studied consecutive patients who underwent ILR following ALND between 2017 and 2024 across multiple hospitals within a hospital network. Patients were stratified into quartiles based on ADI (Q1 = least deprived, Q4 = most deprived). BCRL prevalence and condition-specific (LYMPH-Q) quality-of-life performance was compared and correlated across quartiles via multivariable regression, including subgroup analysis by ethnicity.
Results: We identified 172 patients with follow-up time of 23.1 ± 15.2 months. Patients residing in the most deprived neighborhoods (ADI Q4) demonstrated significantly higher BCRL rates compared to those from less deprived neighborhoods (Q1-3) (16.3% vs. 3.9%; p = 0.006). In multivariable regression, residence in the most deprived neighborhoods remained independently associated with a significantly higher risk of BCRL (OR 5.10, 95% CI 1.30-20.30; p = 0.021). Subgroup analysis revealed that Black patients in the highest ADI quartile reported significantly worse LYMPH-Q function scores (median 62.0 vs 100.0; p = 0.020), compared to Black patients residing in less deprived areas. ADI was not significantly associated with surgical complications or unplanned reoperations.
Conclusions: Neighborhood socioeconomic disadvantage significantly increases BCRL risk following ILR and is associated with significantly worse patient-reported functional outcomes among Black patients. Targeted interventions addressing neighborhood-level factors are critical to mitigate these disparities and ensure equitable outcomes
Multi-site video-based assessment with the NACC UDS-Version 3 battery: Design and participant experience in the V-Cog study
Full text linkIntroduction: Video-based cognitive testing is becoming more common. The 'VCog' study aims to evaluate the validity, feasibility, and acceptability of a standardized video-administered cognitive research battery.
Methods: Twelve Alzheimer's Disease Research Centers (ADRCs) administered, in randomized order, an in-person and video-adapted Uniform Data Set Version 3 (UDSv3) cognitive assessment battery to participants with normal cognition (n = 156), mild cognitive impairment (MCI; n = 230), and dementia (n = 77). Acceptability of technology and participant experience completing video testing was assessed.
Results: Of 463 participants (mean age 75.1 years, 52.5% female, and 25.5% non-White individuals), most rated video testing as easy (90.0%), convenient (95.3%) and would accept it in future visits (75.5%). Greater cognitive impairment was associated with more difficulty with setup and use of video. Staff rated most administrations as producing valid data (94.8%).
Discussion: Video-based research cognitive testing with an adapted UDSv3 battery is feasible and well-accepted among older adults with and without cognitive impairment.
Highlights: The COVID-19 pandemic increased the need for video-administered cognitive assessments in Alzheimer's Disease Research Centers (ADRCs) . Feasibility, acceptability, and validity of video cognitive testing were evaluated. Participant experience and examiner evaluations of data validity were positive. Video assessment may extend the ADRCs reach to otherwise unreachable participants
Macrophage peroxisomes guide alveolar regeneration and limit SARS-CoV-2 tissue sequelae
Full text linkPeroxisomes are vital but often overlooked metabolic organelles. We found that excessive interferon signaling remodeled macrophage peroxisomes. This loss of peroxisomes impaired inflammation resolution and lung repair during severe respiratory viral infections. Peroxisomes were found to modulate lipid metabolism and mitochondrial health in a macrophage type-specific manner and enhanced alveolar macrophage-mediated tissue repair and alveolar regeneration after viral infection. Peroxisomes also prevented excessive macrophage inflammasome activation and IL-1β release, limiting accumulation of KRT8high dysplastic epithelial progenitors following viral injury. Pharmacologically enhancing peroxisome biogenesis mitigated both acute symptoms and post-acute sequelae of COVID-19 (PASC) in animal models. Thus, macrophage peroxisome dysfunction contributes to chronic lung pathology and fibrosis after severe acute respiratory syndrome coronavirus 2 infection
Cell‐Based Phenotypic and Target Engagement Assays for the Identification of Small Molecules that Enhance Microglial Phagocytosis
Full text linkBackground:
Enhancement of microglial phagocytosis activity is being pursued as a potential therapeutic strategy for Alzheimer’s Disease (AD). Assays evaluating small molecule compound effects on microglial phagocytosis and target binding specificity in live cells may help drug discovery along this strategy, such as our projects seeking SHIP1 inhibitors and PLCG2 activators.
Methods:
We developed paired cell‐based assay platforms to evaluate small molecule effects on microglial phagocytosis activity and cell health as well as target engagement for specificity. The phenotypic high‐content imaging assay is used to evaluate microglial phagocytosis activity and cell health. Microglia (HMC3, BV2 or primary mouse microglia) are plated in 384‐well plates, treated with compounds on day 2, seeded with pHrodo labeled myelin/cell membrane debris on day 3, and cells stained with Hoechst 33342 DNA dye and imaged on day 4. Phagocytosis and cell health are evaluated by quantifying phagocytosis vesicle fluorescence, cell counting and average nuclear intensity. Target binding and specificity of compounds are assessed using a series of cell‐based thermal shift assays (CETSAs) that utilize the HiBiT/LgBiT reconstituted NanoLuc technology. Intact human (HEK293T or HMC3) cells stably overexpressing the full‐length target protein tagged with HiBiT (an 11‐amino acid tag) are plated in 96‐well PCR plates, treated with compounds for one hour, followed by brief heating at target specific Tm, cell lysis, addition of LgBiT and NanoLuc substrate, and luminescence reading. Alterations in the luminescence signal indicate compound binding to the HiBiT‐tagged target protein.
Results:
Implementation of these assays into our drug discovery team’s workflow has streamlined compound selection, improving efficiency in identifying and optimizing lead compounds that enhance microglial phagocytosis via selective interaction with and modulation of targeted proteins, e.g. inhibition of SHIP‐1 or activation of PLCG2, in live cells. Active compounds for each project were discovered with these assays.
Conclusions:
This combination of phenotypic and target engagement cell‐based assays is widely applicable to drug discovery projects. Our studies demonstrated the feasibility of combining phenotypic assays with target engagement assays to ensure compound specificity for drug discovery projects. This strategy can be useful when specific signaling measurement is unavailable or difficult to implement for some targets
Effect of varenicline on major adverse liver outcomes in alcohol‐associated liver disease: An exploratory analysis
Full text linkBackground: Varenicline, a partial agonist of the α4β2 nicotinic acetylcholine receptor, is effective for smoking cessation and has shown promise in treating alcohol use disorder (AUD). However, its impact on patients with concurrent alcohol-associated liver disease (ALD) remains understudied. We aimed to evaluate the association between varenicline use and long-term clinical outcomes in this population.
Methods: We conducted a retrospective cohort study using the TriNetX federated network of deidentified electronic health records. Adults with diagnoses of both ALD and AUD were included. Patients prescribed varenicline were compared to those receiving FDA-approved AUD pharmacotherapies (acamprosate or naltrexone), using 1:1 propensity score matching based on demographics, comorbidities, medications, and laboratory values. The primary outcome was major adverse liver outcomes (MALO); secondary outcomes included all-cause mortality and other liver-related complications. Hazard ratios (HRs) were estimated using Cox proportional hazards models over a five-year follow-up period.
Results: A total of 1278 patients were included after matching. Varenicline use was associated with lower all-cause mortality (14.4% vs. 17.4%; HR 0.75, 95% CI 0.57-0.99) and a significantly reduced risk of hepatic encephalopathy (3.5% vs. 6.7%; HR 0.47, 95% CI 0.28-0.79). Although overall MALO rates were similar between groups (17.3% vs. 17.6%; HR 0.89, 95% CI 0.66-1.20), subgroup analyses revealed reduced MALO incidence among females and all-cause mortality among individuals aged ≥65 years.
Conclusion: In this real-world cohort study, varenicline use was associated with improved survival and a lower risk of hepatic encephalopathy compared to standard AUD pharmacotherapies in patients with co-occurring ALD and AUD. These findings support further investigation of varenicline as a potential therapeutic option, ideally through randomized controlled trials
Impact of the Veterans Affairs National Telestroke Program's Subacute Telestroke Service on Interhospital Transfers
No full textBackground and Purpose: Telestroke improves access to acute ischemic stroke (AIS) expertise, aids in decision-making, and reduces interhospital transfers. Few studies have examined subacute inpatient telestroke services, which focus on inpatient stroke workup and management. Methods: In this retrospective cohort study of patients with emergency department (ED) diagnosis of AIS from 10/2021-6/2024, we sought to determine the impact of a novel subacute telestroke program on ED transfer rates at participating hospitals. For intervention sites (that implemented the subacute teleconsult program), the period prior to subacute consult "go-live" date was considered the pre-implementation period. Control sites (without the subacute program) were considered preimplementation prior to 5/22/2023 (when approximately half of intervention sites had initiated the subacute program). Logistic regression with generalized estimating equations evaluated the association between implementation time-period and odds of ED transfer in intervention and control sites, adjusting for age, NIHSS, sex, race, and an intervention by time-period interaction term. Results: 1266 patients met eligibility criteria (N = 544 patients from 11 control sites and N = 722 patients from 11 intervention sites). The ED transfer rate was lower within intervention sites post-implementation (pre: 25.7% to post: 22.5%) and higher in control sites (pre: 25.9% to post: 27.1%). These comparisons were statistically nonsignificant in the multivariable analysis. Conclusions: There was a reduction in interhospital transfers after implementation of a subacute telestroke consultation service, but results were nonsignificant in adjusted models. Future analyses should evaluate whether receipt of a subacute telestroke encounter at the patient-level is associated with reduced interhospital transfer for stroke