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Approximately two-thirds of Latinx college students attend Hispanic Serving Institutions (HSIs). Despite the growing number of HSIs, these institutions often fail to result in better educational outcomes and success for Latinx students. As such, more research is needed to explore factors that may hinder HSIs in their ability to support Latinx students. Whiteness--defined as the invasive system of White supremacy that permeates society--is systemically embedded throughout higher educational systems. However, little research has explored the specific ways that whiteness may influence the construction and maintenance of HSIs by senior administrators, staff, and faculty. To address this gap, the present study centered theories from critical whiteness studies (Nayak, 2007) and Garcia's (2018) decolonizing HSIs organizational framework to assess how whiteness operates at a recently designated HSI. We used a critical qualitative case study design that included thematic analysis of 14 student affairs staff, faculty, and senior administrator interviews and document analysis of public-facing institutional materials. Results indicated three predominant themes related to how whiteness is maintained by senior administrators, staff, and faculty, including "the rhetoric of all as a tool of White appeasement, the taxation of bodies of people of color," and "whiteness through good intentions." The study concludes with recommendations for identifying and disrupting whiteness at HSIs, including specific recommendations at the individual and institutional levels.

Abstract To fertilize eggs, sperm must pass through narrow, complex channels filled with viscoelastic fluids in the female reproductive tract. While it is known that the topography of the surfaces plays a role in guiding sperm movement, sperm have been thought of as swimmers, i.e., their motility comes solely from sperm interaction with the surrounding fluid, and therefore, the surfaces have no direct role in the motility mechanism itself. Here, we examined the role of solid surfaces in the movement of sperm in a highly viscoelastic medium. By visualizing the flagellum interaction with surfaces in a microfluidic device, we found that the flagellum stays close to the surface while the kinetic friction between the flagellum and the surface is in the direction of sperm movement, providing thrust. Additionally, the flow field generated by sperm suggests slippage between the viscoelastic fluid and the solid surface, deviating from the no-slip boundary typically used in standard fluid dynamics models. These observations point to hybrid motility mechanisms in sperm involving direct flagellum-surface interaction in addition to flagellum pushing the fluid. This finding signifies an evolutionary strategy of mammalian sperm crucial for their efficient migration through narrow, mucus-filled passages of the female reproductive tract.

The current study explored the experiences of Asian International Students (AISs) in terms of mental health, disclosure and help-seeking within Higher Education in Scotland, UK. A qualitative study using individual semi-structured interviews with AISs (n = 20) was used and an inductive thematic approach to analysis was conducted. Three major themes were developed: (1) Negative beliefs, stigma and fear of judgment, (2) Adaptation and acculturation difficulties and (3) Barriers in communication, social disconnection and loneliness. Supporting AISs involves challenging negative judgements surrounding mental health, increasing mental health literacy and addressing barriers that may inhibit disclosure and help-seeking behaviour. The need for culturally sensitive mental health practitioners and awareness of diverse understandings of mental health issues is essential to improving support for AISs.

Abstract Upon infecting its vertebrate host, the malaria parasite initially invades the liver where it undergoes massive replication, whilst remaining clinically silent. The coordination of host responses across the complex liver tissue during malaria infection remains unexplored. Here, we perform spatial transcriptomics in combination with single-nuclei RNA sequencing over multiple time points to delineate host-pathogen interactions across Plasmodium berghei-infected liver tissues. Our data reveals significant changes in spatial gene expression in the malaria-infected tissues. These include changes related to lipid metabolism in the proximity to sites of Plasmodium infection, distinct inflammation programs between lobular zones, and regions with enrichment of different inflammatory cells, which we term ‘inflammatory hotspots’. We also observe significant upregulation of genes involved in inflammation in the control liver tissues of mice injected with mosquito salivary gland components. However, this response is considerably delayed compared to that observed in P. berghei-infected mice. Our study establishes a benchmark for investigating transcriptome changes during host-parasite interactions in tissues, it provides informative insights regarding in vivo study design linked to infection and offers a useful tool for the discovery and validation of de novo intervention strategies aimed at malaria liver stage infection.

Abstract PARP inhibitor (PARPi) therapy has transformed outcomes for patients with homologous recombination DNA repair (HRR) deficient ovarian cancers, for example those with BRCA1 or BRCA2 gene defects. Unfortunately, PARPi resistance is common. Multiple resistance mechanisms have been described, including secondary mutations that restore the HR gene reading frame. BRCA1 splice isoforms △11 and △11q can contribute to PARPi resistance by splicing out the mutation-containing exon, producing truncated, partially functional proteins. However, the clinical impacts and underlying drivers of BRCA1 exon skipping are not fully understood. We analyzed nine ovarian and breast cancer patient derived xenografts (PDX) with BRCA1 exon 11 frameshift mutations for exon skipping and therapy response, including a matched PDX pair derived from a patient pre- and post-chemotherapy/PARPi. BRCA1 exon 11 skipping was elevated in PARPi resistant PDX tumors. Two independent PDX models acquired secondary BRCA1 splice site mutations (SSMs) that drive exon skipping, confirmed using qRT-PCR, RNA sequencing, immunoblotting and minigene modelling. CRISPR/Cas9-mediated disruption of splicing functionally validated exon skipping as a mechanism of PARPi resistance. SSMs were also enriched in post-PARPi ovarian cancer patient cohorts from the ARIEL2 and ARIEL4 clinical trials. Few PARPi resistance mechanisms have been confirmed in the clinical setting. While secondary/reversion mutations typically restore a gene’s reading frame, we have identified secondary mutations in patient cohorts that hijack splice sites to enhance mutation-containing exon skipping, resulting in the overexpression of BRCA1 hypomorphs, which in turn promote PARPi resistance. Thus, BRCA1 SSMs can and should be clinically monitored, along with frame-restoring secondary mutations.

Abstract Background Driving cessation is one of the most challenging life transitions, associated with multiple negative consequences for individuals living with late-onset dementia. This paper extends the literature as to date there is no published review that details the experiences of people living with young onset dementia (“YOD”). Methods A comprehensive search of the literature was conducted using the scoping review methodology. Results Ten studies were included for full text review of 1634 initially identified through database searching. The results of the included articles indicated areas of concern for people living with YOD and their family members including, loss of independence; role change; threat to self-identify; feelings of isolation, grief; acceptance; predictors of driving cessation. Conclusion There is a lack of robust evidence related to driving cessation and the experiences of people living with YOD. No published paper reported psychosocial interventions specifically targeted at supporting persons with YOD through driving cessation.

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.

Abstract There are hundreds of genes typically overexpressed in breast cancer cells and it's often assumed that their overexpression contributes to cancer progression. However, the precise proportion of these overexpressed genes contributing to tumorigenicity remains unclear. To address this gap, we undertook a comprehensive screening of a diverse set of seventy-two genes overexpressed in breast cancer. This systematic screening evaluated their potential for inducing malignant transformation and, concurrently, assessed their impact on breast cancer cell proliferation and viability. Select genes including ALDH3B1, CEACAM5, IL8, PYGO2, and WWTR1, exhibited pronounced activity in promoting tumor formation and establishing gene dependencies critical for tumorigenicity. Subsequent investigations revealed that CEACAM5 overexpression triggered the activation of signaling pathways involving β-catenin, Cdk4, and mTOR. Additionally, it conferred a growth advantage independent of exogenous insulin in defined medium and facilitated spheroid expansion by inducing multiple layers of epithelial cells while preserving a hollow lumen. Furthermore, the silencing of CEACAM5 expression synergized with tamoxifen-induced growth inhibition in breast cancer cells. These findings underscore the potential of screening overexpressed genes for both oncogenic drivers and tumor dependencies to expand the repertoire of therapeutic targets for breast cancer treatment.

Summary: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a spectrum of disease states ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), which can eventually lead to the development of cirrhosis and hepatocellular carcinoma. Macrophages have long been implicated in driving the progression from steatosis to end-stage disease, yet we still know relatively little about the precise involvement of these cells in MASLD progression and/or regression. Rather, there are a considerable number of conflicting reports regarding the precise roles of these cells. This confusion stems from the fact that, until recently, macrophages in the liver were considered a homogenous population. However, thanks to recent technological advances including multi-parameter flow cytometry, single-cell RNA sequencing and spatial proteogenomics, we now know that this is not the case. Rather hepatic macrophages, even in the healthy liver, are heterogenous, existing in multiple subsets with distinct transcriptional profiles and hence likely functions. This heterogeneity is even more prominent in MASLD, where the macrophage pool consists of multiple different subsets of resident and recruited cells. To probe the unique functions of these cells and determine if targeting macrophages may be a viable therapeutic strategy in MASLD, we first need to unravel this complexity and decipher which populations and/or activation states are present and what functions each of these may play in driving MASLD progression. In this review, we summarise recent advances in the field, highlighting what is currently known about the hepatic macrophage landscape in MASLD and the questions that remain to be tackled.

Abstract Understanding tree transpiration variability is vital for assessing ecosystem water‐use efficiency and forest health amid climate change, yet most landscape‐level measurements do not differentiate individual trees. Using canopy temperature data from thermal cameras, we estimated the transpiration rates of individual trees at Harvard Forest and Niwot Ridge. PT‐JPL model was used to derive latent heat flux from thermal images at the canopy‐level, showing strong agreement with tower measurements (R2 = 0.70–0.96 at Niwot, 0.59–0.78 at Harvard at half‐hourly to monthly scales) and daily RMSE of 33.5 W/m2 (Niwot) and 52.8 W/m2 (Harvard). Tree‐level analysis revealed species‐specific responses to drought, with lodgepole pine exhibiting greater tolerance than Engelmann spruce at Niwot and red oak showing heightened resistance than red maple at Harvard. These findings show how ecophysiological differences between species result in varying responses to drought and demonstrate that these responses can be characterized by deriving transpiration from crown temperature measurements.

Summary: Neuroblastoma, a rare embryonic tumor arising from neural crest development, is responsible for 15% of pediatric cancer-related deaths. Recently, several single-cell transcriptome studies were performed on neuroblastoma patient samples to investigate the cell of origin and tumor heterogeneity. However, these individual studies involved a small number of tumors and cells, limiting the conclusions that could be drawn. To overcome this limitation, we integrated seven single-cell or single-nucleus datasets into a harmonized cell atlas covering 362,991 cells across 61 patients. We use this atlas to decipher the transcriptional landscape of neuroblastoma at single-cell resolution, revealing associations between transcriptomic profiles and clinical outcomes within the tumor compartment. In addition, we characterize the complex immune-cell landscape and uncover considerable heterogeneity among tumor-associated macrophages. Finally, we showcase the utility of our atlas as a resource by expanding it with additional data and using it as a reference for data-driven cell-type annotation.

Abstract Dryland ecosystems cover 40% of our planet's land surface, support billions of people, and are responding rapidly to climate and land use change. These expansive systems also dominate core aspects of Earth's climate, storing and exchanging vast amounts of water, carbon, and energy with the atmosphere. Despite their indispensable ecosystem services and high vulnerability to change, drylands are one of the least understood ecosystem types, partly due to challenges studying their heterogeneous landscapes and misconceptions that drylands are unproductive “wastelands.” Consequently, inadequate understanding of dryland processes has resulted in poor model representation and forecasting capacity, hindering decision making for these at‐risk ecosystems. NASA satellite resources are increasingly available at the higher resolutions needed to enhance understanding of drylands' heterogeneous spatiotemporal dynamics. NASA's Terrestrial Ecology Program solicited proposals for scoping a multi‐year field campaign, of which Adaptation and Response in Drylands (ARID) was one of two scoping studies selected. A primary goal of the scoping study is to gather input from the scientific and data end‐user communities on dryland research gaps and data user needs. Here, we provide an overview of the ARID team's community engagement and how it has guided development of our framework. This includes an ARID kickoff meeting with over 300 participants held in October 2023 at the University of Arizona to gather input from data end‐users and scientists. We also summarize insights gained from hundreds of follow‐up activities, including from a tribal‐engagement focused workshop in New Mexico, conference town halls, intensive roundtables, and international engagements.

Objective: Large language models such as ChatGPT have demonstrated significant potential in question-answering within ophthalmology, but there is a paucity of literature evaluating its ability to generate clinical assessments and discussions. The objectives of this study were to (1) assess the accuracy of assessment and plans generated by ChatGPT and (2) evaluate ophthalmologists’ abilities to distinguish between responses generated by clinicians versus ChatGPT. Design: Cross-sectional mixed-methods study. Subjects: Sixteen ophthalmologists from a single academic center, of which 10 were board-eligible and 6 were board-certified, were recruited to participate in this study. Methods: Prompt engineering was used to ensure ChatGPT output discussions in the style of the ophthalmologist author of the Medical College of Wisconsin Ophthalmic Case Studies. Cases where ChatGPT accurately identified the primary diagnoses were included and then paired. Masked human-generated and ChatGPT-generated discussions were sent to participating ophthalmologists to identify the author of the discussions. Response confidence was assessed using a 5-point Likert scale score, and subjective feedback was manually reviewed. Main Outcome Measures: Accuracy of ophthalmologist identification of discussion author, as well as subjective perceptions of human-generated versus ChatGPT-generated discussions. Results: Overall, ChatGPT correctly identified the primary diagnosis in 15 of 17 (88.2%) cases. Two cases were excluded from the paired comparison due to hallucinations or fabrications of nonuser-provided data. Ophthalmologists correctly identified the author in 77.9% ± 26.6% of the 13 included cases, with a mean Likert scale confidence rating of 3.6 ± 1.0. No significant differences in performance or confidence were found between board-certified and board-eligible ophthalmologists. Subjectively, ophthalmologists found that discussions written by ChatGPT tended to have more generic responses, irrelevant information, hallucinated more frequently, and had distinct syntactic patterns (all P < 0.01). Conclusions: Large language models have the potential to synthesize clinical data and generate ophthalmic discussions. While these findings have exciting implications for artificial intelligence-assisted health care delivery, more rigorous real-world evaluation of these models is necessary before clinical deployment. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Background: Traditional healing practices are prevalent in rural and mountainous areas of India where Western medicine is not accessible. WHO guidelines recommend integration of traditional and Western medicine to meet rural primary care needs. We explored three dimensions of rural patients' decision-making and satisfaction with their medical care: pregnancy-related concerns, pediatric care for children under five, and acute injuries. Methods: We conducted a qualitative study using a phenomenological approach in India's Spiti Valley between August and October 2023. Sixteen individuals, age 18 years and older, participated in one-on-one interviews. The interviews were transcribed from Hindi into English, reviewed for accuracy by a native speaker, and imported into Dedoose software. Data were analyzed using inductive coding. Findings: Multiparous women aged 35–44 were concerned about pregnancy complications, leading them to choose Western medicine despite access and cost barriers. Pediatric illness requiring urgent care at night was a concern for women with children under five. Those in the injuries group reported having to travel for care beyond basic first aid. Overall, concerns were about limited access to some services locally, as well as costs of travel, medical procedures, and medications when services were obtained beyond the local area. Interpretation: All participants considered their traditional healer their first point of contact for medical care. A number of Western medical services were not available locally. These findings suggest a need to strengthen access to and integration of Western and traditional medical care in rural settings in India.

BackgroundTo monitor the progress of lymphatic filariasis (LF) elimination programmes, field surveys to assess filarial antigen (Ag) prevalence require access to reliable, user-friendly rapid diagnostic tests. We aimed to evaluate the performance of the new Q Filariasis Antigen Test (QFAT) with the currently recommended Filariasis Test Strip (FTS) for detecting the Ag of Wuchereria bancrofti, the causative agent of LF, under field laboratory conditions.Methodology/principal findingsDuring an LF survey in Samoa, 344 finger-prick blood samples were tested using FTS and QFAT. Microfilariae (Mf) status was determined from blood slides prepared from any sample that reported Ag-positive by either Ag-test. Each test was re-read at 1 hour and the next day to determine the stability of results over time. Overall Ag-positivity by FTS was 29.0% and 30.2% by QFAT. Concordance between the two tests was 93.6% (kappa = 0.85). Of the 101 Mf slides available, 39.6% were Mf-positive, and all were Ag-positive by both tests. Darker test line intensities from Ag-positive FTS were found to predict Mf-positivity (compared to same/lighter line intensities). QFAT had significantly higher reported test result changes than FTS, mostly reported the next day, but fewer changes were reported between 10 minutes to 1hour. The field laboratory team preferred QFAT over FTS due to the smaller blood volume required, better usability, and easier readability.Conclusion/significanceQFAT could be a suitable and user-friendly diagnostic alternative for use in the monitoring and surveillance of LF in field surveys based on its similar performance to FTS under field laboratory conditions.

Summary: High-grade serous ovarian cancers (HGSOCs) with homologous recombination deficiency (HRD) are initially responsive to poly (ADP-ribose) polymerase inhibitors (PARPi), but resistance ultimately emerges. HGSOC with CCNE1 amplification (CCNE1amp) are associated with resistance to PARPi and platinum treatments. High replication stress in HRD and CCNE1amp HGSOC leads to increased reliance on checkpoint kinase 1 (CHK1), a key regulator of cell cycle progression and the replication stress response. Here, we investigated the anti-tumor activity of the potent, highly selective, orally bioavailable CHK1 inhibitor (CHK1i), SRA737, in both acquired PARPi-resistant BRCA1/2 mutant and CCNE1amp HGSOC models. We demonstrated that SRA737 increased replication stress and induced subsequent cell death in vitro. SRA737 monotherapy in vivo prolonged survival in CCNE1amp models, suggesting a potential biomarker for CHK1i therapy. Combination SRA737 and PARPi therapy increased tumor regression in both PARPi-resistant and CCNE1amp patient-derived xenograft models, warranting further study in these HGSOC subgroups.

Background: Heart failure with a preserved ejection fraction (HFpEF) is common in the elderly (≥75 years) and associated with arterial stiffness. The mean age of HFpEF presentation is lower (40–55 years) in sub-Saharan Africa. No clinical study has been conducted on HFpEF in identifying and characterising this phenotype at a younger age, moreover in a South African black population where the risk of HFpEF is two times higher than in other ethnic groups. This study investigated the characteristics of HFpEF in a black South African population, the biochemical markers that predict HFpEF and cardiac structural changes in this HF phenotype. Methods: Sixty-six participants with HFpEF and 213 controls were enrolled. All participants gave informed consent and completed a standardised questionnaire. Echocardiographic, anthropometric, central haemodynamic measurements, pulse wave velocity (PWV) and biomarker analysis were done. Results: The mean age of HFpEF participants was 54.88 ± 13.51 years. Most of the participants (76 %) were between 20 and 64 years, while only 24 % were older. HFpEF participants were hypertensive, and more obese with increased incidence of alcohol consumption. PWV was increased in HFpEF (9.97 ± 2.78 m/s) when compared to participants without HFpEF (6.11 ± 2.18 m/s), p

Breast cancer remains a leading cause of death worldwide. The Apiaceae plant family includes many culinary spices that have been shown to have medicinal properties. Many phytochemicals exhibit potent bioactivities but often suffer from poor uptake and oral bioavailability. Bovine milk and colostrum exosomes are a compelling drug delivery platform that could address this issue; these natural nanoparticles can be loaded with hydrophilic and lipophilic small molecules and biologics, resulting in lower doses needed to inhibit cancer growth. Ethanolic extracts of eight Apiaceae spices were examined for phytochemical content and antiproliferative potential. Acid hydrolysis (AH) was employed to remove glycosides, asses its impacts on extract efficacy, and evaluate its effects on exosome loading and subsequent formulation efficacy. Antiproliferative activity was assessed through MTT assays on T-47D, MDA-MB-231, and BT-474 breast cancer cells; all extracts exhibited broad antiproliferative activity. AH enhanced the bioactivity of cumin, caraway, and fennel in T-47D cells. Celery, cumin, anise, and ajwain showed the highest activity and were assayed in exosomal formulations, which resulted in reduced doses required to inhibit cellular proliferation for all extracts except AH-cumin. Apiaceae spice extracts demonstrated antiproliferative activities that can be improved with AH and further enhanced with exosomal delivery.

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability worldwide. There is a direct relationship between increasing levels of LDL-C and increased risk of ASCVD. Guidance from the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) recommends that high-risk ASCVD patients maintain an LDL-C 1.8 mmol/L (70 mg/dL). Methodology: An ASCVD risk reduction approach was initiated in a primary care clinic in December 2021. Of those patients who underwent review between December 2021 and July 2023, 102 patients were started on inclisiran treatment in a real-world setting. These patients were retrospectively reviewed to determine the initial effects of using inclisiran after the first dose as part of the patients’ ASCVD risk reduction management. Results: After 1 injection of Inclisiran, the patients’ mean decrease in LDL-C was 2.00 mmol/L (77.3 mg/dL) after a mean of 87 days. This represented a mean reduction of 61.7% (SD = 19.8) in their LDL-C measurements. The addition of inclisiran resulted in 79.4% of patients achieving an LDL-C target of