Indiana University South Bend

The COVID-19 pandemic caused widespread social disruption, with stigma emerging as a significant challenge for individuals who survived infection. This qualitative study explored the forms, drivers, and impacts of COVID-19-related stigma among survivors in Eastern Nepal. In-depth interviews were conducted with 15 COVID-19 survivors who had reported stigma in a preceding cross-sectional survey. Due to pandemic-related restrictions, interviews were conducted over the phone. Data were analysed thematically following the process outlined by Braun and Clarke. COVID-19 stigma was multifaceted, including social rejection, internalized stigma, and discriminatory practices by community members. Key drivers of stigma included self-directed fear of infection and death, misinformation and limited awareness about COVID-19 transmission and prevention, and a fragile health system and policy responses. Although COVID-19-related stigma may have declined as the pandemic evolved, the findings illustrate how stigma can emerge rapidly during health emergencies that can have social consequences related to trust, disclosure, and help-seeking behavior in future crisis. The study highlights the importance of outbreak preparedness strategies that integrate clear communication, strengthened health system capacity, and social protection measures to mitigate stigma and its harms during future public health crises.

Background Cardiovascular health remains susceptible to inaccurate information, which can harm health outcomes. This scoping review addresses a gap in comprehensive analyses by synthesising evidence on the prevalence, spread, impact and correction strategies related to cardiovascular health misinformation across diverse populations and settings. Methods Following Joanna Briggs Institute guidelines, we searched MEDLINE, EMBASE, Global Index Medicus, Web of Science. A dual-reviewer process, using Covidence, screened articles in two phases (title/abstract, full-text) based on predefined inclusion criteria. Data extraction was performed by two reviewers, and results were synthesised narratively, presented by tables and figures. Results From 6348 screened articles, 22 were included. The review reveals widespread misinformation concerning smoking, nutrition, blood pressure, weight management, alcohol consumption and diabetes care. Specific examples include misleading claims about e-cigarette safety and the downplaying of alcohol’s harms. A substantial proportion of social media posts falsely discourage salt reduction (reaching 1.5 million followers) and a significant number of diet/exercise vlogs (36.7%) and YouTube videos on myocardial infarction (one-third) contain inaccuracies, often originating from unreliable sources. Instagram, Facebook, YouTube and X were identified as key platforms for dissemination. Conclusion This review demonstrates that cardiovascular health misinformation is widespread and shaped by both platform dynamics and user-level factors. Addressing this challenge requires coordinated strategies that strengthen digital literacy, enhance visibility of evidence-based content and reduce the reach of misinformation. Collaborative efforts between public health agencies, clinical institutions and technology platforms are essential to ensure that trustworthy cardiovascular disease-related information reaches the public.

We introduce ARB-Dropout, an efficient single-pass alternative to Monte Carlo (MC) Dropout for uncertainty estimation in deep neural networks. ARB-Dropout adaptively determines per-input dropout rates from gradient variance and analytically propagates the resulting epistemic variance through the network, eliminating the need for multiple stochastic forward passes. By integrating this analytic epistemic estimate with heteroscedastic aleatoric noise from a dedicated output head, ARB-Dropout produces well-calibrated predictive distributions with lower Expected Calibration Error (ECE) and Negative Log-Likelihood (NLL) than MC Dropout, while maintaining comparable accuracy. Experiments on CIFAR-10, CIFAR-100, SVHN, and STL-10 demonstrate that ARBDropout offers substantial inference-time speedups and robust uncertainty estimates, making it well-suited for real-time, uncertainty-aware applications.

A former college president offers advice for administrators navigating unprecedented challenges.

Central sensitization (CS) is a neural mechanism associated with the development and perpetuation of chronic pain. The purpose of this study was to examine the severity and prevalence of central sensitization and examine its relationships with demographics and pain indicators among veterans with chronic pain. This study used a cross-sectional design. Data for the Central Sensitization Inventory Part A (CSI-A), Pain Catastrophizing Scale, and Brief Pain Inventory-Short Form were manually extracted from paper forms and hospital electronic health records. Descriptive statistics, Kendall Tau correlation coefficient, and independent samples t test were used for data analysis. The sample consisted of 184 veterans, predominantly men (87%) with a mean age of 60 years. The mean CSI-A score was 45.06 ± 17.06 and 62.5% of veterans (n = 115) were identified as having CS (CSI-A ≥ 40), with 23.9% (n = 44) identified as having severe CS (CSI-A = 50–59). A significant but weak negative correlation was obtained between CSI-A score and age (τb = ‐0.121, P = .016) and a significant positive weak to moderate correlation was obtained between CSI-A score and severity of pain (τb = 0.209, P < .001), pain interference (τb = 0.333, P < .001), and pain catastrophizing (τb = 0.385, P < .001). Women veterans had a significantly higher mean CSI-A score compared to men (55.38 ± 13.23 vs 43.51 ± 17.06, tdf = 182 = 3.260, P = .001). These findings highlight the high prevalence of CS among veterans with chronic pain, particularly in women, emphasizing the need to assess CS to improve chronic pain management in this population.

"Euclidean Vision" is a short poem that evaluates geometry from a humanistic perspective, focusing partly on its pleasures. Geometry gives us the pleasing assurance of certainty. It does this through the radical abstraction of space and form, which makes possible a completeness of mathematical vision based on axioms. It's this purity that guarantees a knowledge that "can go on forever." In the end, the poem points to the wonderful freedom that geometry and other mathematical disciplines give us in the midst of difficult and confusing lives. In its beauty and universality, geometry stands as an eternal aspect of the human project. Because we can see that mathematics transcends history and cultures, we may feel inspired to work together to protect the viability of our shared world.

One-to-many facial identification is documented to achieve high accuracy in the case where both the probe and the gallery are ‘mugshot quality’ images. However, an increasing number of documented instances of wrongful arrest following one-to-many facial identification have raised questions about its accuracy. Probe images used in one-to-many facial identification are often cropped from frames of surveillance video and deviate from ‘mugshot quality’ in various ways. This paper systematically explores how the accuracy of one-to-many facial identification is degraded by the person in the probe image choosing to wear dark sunglasses. We show that sunglasses degrade accuracy for mugshot-quality images by an amount similar to strong blur or noticeably lower resolution. Further, we demonstrate that the combination of sunglasses with blur or lower resolution results in even more pronounced loss in accuracy. These results have important implications for developing objective criteria to qualify a probe image for the level of accuracy to be expected if it used for one-to-many identification. To ameliorate the accuracy degradation caused by dark sunglasses, we show that it is possible to recover about 38% of the lost accuracy by synthetically adding sunglasses to all the gallery images, without model re-training. We also show that the frequency of wearing-sunglasses images is very low in existing training sets, and that increasing the representation of wearing-sunglasses images can greatly reduce the error rate. The image set assembled for this research is available at https://cvrl.nd.edu/projects/data/ to support replication and further research.

Abstract Background: The human epidermal growth factor receptor 2 (HER2) is overexpressed in esophageal adenocarcinoma (EAC) and is a major target for EAC therapies. Lapatinib blocking HER1 and HER2 pathways, fails to improve patient survival. The molecular mechanisms of this lapatinib resistance are still unclear. We therefore explored the role of the glycolytic enzyme pyruvate kinase M2 (PKM2), a key regulator of the Warburg effect, in the lapatinib resistance mechanism of EAC cells. Methods: HER2/pHER2 expression status was evaluated by Western blot analysis in a panel of EAC cell lines (Flo-1, ESO26, OE19, OE33, SK-GT-2, ESO51, OACM5.1C, and LPR-OE19). The lapatinib-resistant OE19 (LPR-OE19) cell line was established from the OE19 cell line by intermittent exposure to increasing concentrations of lapatinib for a period over six months. We investigated the cell growth/migration inhibition and apoptotic signaling effects of treating HER2-overexpressing OE19, LPR-OE19, and OE33 cell lines with lapatinib, PKM2 inhibitor shikonin, and a chemotherapeutic agent nanoparticle albumin-bound paclitaxel (nab-paclitaxel) either alone or in combinations. Lactate production and cellular localization of PKM2/HSP40 were also detected. In addition, we explored the in-vivo antitumor efficacy following lapatinib, shikonin, and nap-paclitaxel mono and combination therapies in murine subcutaneous cell lines and patient-derived xenograft models of human EAC. Results: LPR-OE19 cells showed significantly reduced sensitivity to lapatinib-induced cell growth/migration inhibition and apoptosis compared to parent OE19 cells. Augmented cell growth/migration inhibition and apoptosis were observed in LPR-OE19 cells compared to parent OE19 cells when lapatinib was combined with shikonin. Knockdown of PKM2 in LPR-OE19 cells abolished the reduced sensitivity of lapatinib-induced cell growth inhibition and abolished the augmented cell growth inhibition response when lapatinib and shikonin were combined. Knockdown of HSP40 in OE19 cells enhanced PKM2 expression. LPR-OE19 cells showed enhanced lactate production compared to parent OE19 cells. PKM2 and HSP40 co-localize with each other in the cell nucleus, suggesting that PKM2 bound to molecular chaperone HSP40. In subcutaneous xenografts, shikonin displayed a remarkable tumor regression compared to that of control as monotherapy, and shikonin in combination with either lapatinib or nab-paclitaxel showed a significant enhancement effect of tumor regression. Conclusions: These data suggest that combination therapy of the PKM2 inhibitor shikonin with lapatinib or nab-paclitaxel should be tested as a potent option for lapatinib-resistant HER2-positive EAC patients and could be a novel treatment strategy for specific EAC. In addition, we suggest targeting HSP40-PKM2 interaction as an innovative therapeutic approach to overcome lapatinib resistance in EAC. Citation Format: Annie Ritter, Md Sazzad Hassan, Elizabeth Heffernan, Niranjan Awasthi, Urs von Holzen. PKM2 inhibition overcomes lapatinib resistance in HER2 overexpressing esophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3080.

Abstract Background: Inhibition of the heat shock protein 90 (HSP90) chaperone activity with small molecules is an attractive therapeutic approach for cancer treatment because more than 300 client proteins are involved in aggressive cancer growth and metastasis. To date, ∼20 inhibitors have undergone clinical trials, however, all have failed due to pan-inhibitory activities and insufficient isoform selectivity. In this study, we have investigated isoform selective HSP90β inhibitors, NDNB21, NDNB25 and NDNB11.82 on esophageal adenocarcinoma (EAC), which is one of the most aggressive human cancers with increasing incidence in the United States. A major target for EAC therapies is the human epidermal growth factor receptor 2 (HER2), which is a well-known client protein of HSP90. In this research, we tested the effect of NDNB21 and NDNB25 on HER2 overexpressing EAC cell lines, including one cell line that acquired lapatinib resistance either alone or in combination with HER2/MET targeting by lapatinib/capmatinib. Methods: We first evaluated HER2/pHER2 and MET/pMET expression status by Western blot analysis in a panel of EAC cell lines (Flo-1, ESO26, OE19, OE33, SK-GT-2, ESO51, OACM5.1C, and LPR-OE19). Lapatinib-resistant OE19 (LPR-OE19) cell line was established from OE19 cells by intermittent exposure to increasing concentrations of lapatinib for a period over six months. Lapatinib is a potent EGFR/HER2 inhibitor and capmatinib is a potent c-MET inhibitor. Antiproliferative activities were measured by WST-1 assay and Western blot analyses were performed to evaluate apoptosis. Results: NDNB21 and NDNB25 dose-dependently inhibited in-vitro cell proliferation of HER2 overexpressing EAC cell lines with NDNB11.82 maintaining much lower potency. All three HER2 overexpressing EAC cell lines showed significant sensitivity to NDNB21 and NDNB25 mediated inhibition of cell proliferation with IC50 values between 16 nM to 2 µM and degree of sensitivities are OE19&amp;gt;LPR-OE19&amp;gt;OE33. NDNB21 and NDNB25 dose-dependently induced apoptosis as measured by the expression of cleavage of poly ADP-ribose polymerase (cleaved PARP). Treatment with increasing doses of NDNB21/NDNB25 resulted in a dose-dependent decrease in HER2, p-HER2, AKT, and p-AKT. Coadministration of NDNB21 or NDNB25 with lapatinib effectively inhibited HER2 phosphorylation and significantly enhanced inhibition of cell proliferation in OE19/LPR-OE19 but not in OE33. The OE33 cells with the strongest expression of phosphorylated MET showed reduced sensitivity to HER2 targeted NDNB21/NDNB25/lapatinib induced cell death compared to that of OE19/LPR-OE19. OE33 showed enhanced cell death when HER2 targeted NDNB25 were combined with MET inhibitor capmatinib. Conclusions: In conclusion, our data shows that NDNB21/NDNB25 exhibited potent apoptotic activity against HER2-positive EAC cells either alone or in combination. Citation Format: Md Sazzad Hassan, Erin Garzella, Annie Ritter, Elizabeth Heffernan, Aktar Ali, Brian Blagg, Urs von Holzen. Effects of novel isoform selective HSP90 beta inhibitors alone and in combinations against experimental esophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3035.