Evaluation of a Seizure Action Plan in an Adult Epilepsy Center.

Background: Seizure action plans (SAPs) provide valuable information for patients to manage seizure emergencies, but are underutilized in adult epilepsy centers. The purpose of this project was to implement a structured SAP for adult patients with epilepsy. Methods: A pre/postimplementation design was used. Provider SAP utilization rates were analyzed over a 16-week period. A pre and postimplementation survey assessed participant perceived impact of the SAP on knowledge and comfort associated with managing seizure emergencies. Provider barriers and facilitators were also assessed. Results: Average provider SAP utilization rate was 51.45%. A total of 204 participants completed the surveys, which showed a significant increase in knowledge and comfort for all items, p < 0.001. At postsurvey analysis, 98% of participants felt that all patients with epilepsy should have a SAP regardless of seizure burden. Discussion: Implementing a structured SAP increased provider utilization and patient and care partner knowledge and comfort of managing seizure emergencies.

Profiling the molecular and clinical landscape of glioblastoma utilizing the Oncology Research Information Exchange Network brain cancer database.

Background: Glioblastoma exhibits aggressive growth and poor outcomes despite treatment, and its marked variability renders therapeutic design and prognostication challenging. The Oncology Research Information Exchange Network (ORIEN) database contains complementary clinical, genomic, and transcriptomic profiling of 206 glioblastoma patients, providing opportunities to identify novel associations between molecular features and clinical outcomes. Methods: Survival analyses were performed using the Logrank test, and clinical features were evaluated using Wilcoxon and chi-squared tests with q-values derived via Benjamini-Hochberg correction. Mutational analyses utilized sample-level enrichments from whole exome sequencing data, and statistical tests were performed using the one-sided Fisher Exact test with Benjamini-Hochberg correction. Transcriptomic analyses utilized a student's t-test with Benjamini-Hochberg correction. Expression fold changes were processed with Ingenuity Pathway Analysis to determine pathway-level alterations between groups. Results: Key findings include an association of MUC17, SYNE1, and TENM1 mutations with prolonged overall survival (OS); decreased OS associated with higher epithelial growth factor receptor (EGFR) mRNA expression, but not with EGFR amplification or mutation; a 14-transcript signature associated with OS > 2 years; and 2 transcripts associated with OS < 1 year. Conclusions: Herein, we report the first clinical, genomic, and transcriptomic analysis of ORIEN glioblastoma cases, incorporating sample reclassification under updated 2021 diagnostic criteria. These findings create multiple avenues for further investigation and reinforce the value of multi-institutional consortia such as ORIEN in deepening our knowledge of intractable diseases such as glioblastoma.

Common mitochondrial deletions in RNA-Seq: evaluation of bulk, single-cell, and spatial transcriptomic datasets.

Common mitochondrial DNA (mtDNA) deletions are large structural variants in the mitochondrial genome that accumulate in metabolically active tissues with age and have been investigated in various diseases. We applied the Splice-Break2 pipeline (designed for high-throughput quantification of mtDNA deletions) to human RNA-Seq datasets and describe the methodological considerations for evaluating common deletions in bulk, single-cell, and spatial transcriptomics datasets. A robust evaluation of 1570 samples from 14 RNA-Seq studies showed: (i) the abundance of some common deletions detected in PCR-amplified mtDNA correlates with levels observed in RNA-Seq data; (ii) RNA-Seq library preparation method has a strong effect on deletion detection; (iii) deletions had a significant, positive correlation with age in brain and muscle; (iv) deletions were enriched in cortical grey matter, specifically in layers 3 and 5; and (v) brain regions with dopaminergic neurons (i.e., substantia nigra, ventral tegmental area, and caudate nucleus) had remarkable enrichment of common mtDNA deletions.

Strategies for Developing a Nurturing Environment for the next Generation of Nurses.

With the introduction of more complex health conditions and the changing landscape of the healthcare infrastructure, burnout is increasingly becoming a crisis for the nursing profession and for the public. Recruitment in nursing must consider the concept of a nurturing environment as a key driver of sustainability within the profession. Human beings cannot flourish in hostile and unwelcoming environments. Failure to thrive in nursing is a real phenomenon that is driven by multiple factors, including incivility, workplace bullying, and lack of support. Mitigation requires intentional, strategic interventions toward building nurturing environments in education and practice for the next generation of nurses.

Enhancing Spatial Transcriptomics Analysis by Integrating Image-Aware Deep Learning Methods.

Spatial transcriptomics (ST) represents a pivotal advancement in biomedical research, enabling the transcriptional profiling of cells within their morphological context and providing a pivotal tool for understanding spatial heterogeneity in cancer tissues. However, current analytical approaches, akin to single-cell analysis, largely depend on gene expression, underutilizing the rich morphological information inherent in the tissue. We present a novel method integrating spatial transcriptomics and histopathological image data to better capture biologically meaningful patterns in patient data, focusing on aggressive cancer types such as glioblastoma and triple-negative breast cancer. We used a ResNet-based deep learning model to extract key morphological features from high-resolution whole-slide histology images. Spot-level PCA-reduced vectors of both the ResNet-50 analysis of the histological image and the spatial gene expression data were used in Louvain clustering to enable image-aware feature discovery. Assessment of features from image-aware clustering successfully pinpointed key biological features identified by manual histopathology, such as for regions of fibrosis and necrosis, as well as improved edge definition in EGFR-rich areas. Importantly, our combinatorial approach revealed crucial characteristics seen in histopathology that gene-expression-only analysis had missed.Supplemental Material: https://github.com/davcraig75/song_psb2014/blob/main/SupplementaryData.pdf.

To Tube or Not to Tube ... That Continues to Be the Question.

In the prehospital setting, "to tube, or not to tube" will persist as a probing question - long after this article is published. It is the hope of the authors simply to position a compilation of thoughts to consider in regards to alternate airways vs. endotracheal intubation. Ultimately, it's all about the right care, for the right patient, at the right time!

The Foundational Data Initiative for Parkinson Disease: Enabling efficient translation from genetic maps to mechanism.

The Foundational Data Initiative for Parkinson Disease (FOUNDIN-PD) is an international collaboration producing fundamental resources for Parkinson disease (PD). FOUNDIN-PD generated a multi-layered molecular dataset in a cohort of induced pluripotent stem cell (iPSC) lines differentiated to dopaminergic (DA) neurons, a major affected cell type in PD. The lines were derived from the Parkinson's Progression Markers Initiative study, which included participants with PD carrying monogenic PD variants, variants with intermediate effects, and variants identified by genome-wide association studies and unaffected individuals. We generated genetic, epigenetic, regulatory, transcriptomic, and longitudinal cellular imaging data from iPSC-derived DA neurons to understand molecular relationships between disease-associated genetic variation and proximate molecular events. These data reveal that iPSC-derived DA neurons provide a valuable cellular context and foundational atlas for modeling PD genetic risk. We have integrated these data into a FOUNDIN-PD data browser as a resource for understanding the molecular pathogenesis of PD.

Debakarn Koorliny Wangkiny: steady walking and talking using first nations-led participatory action research methodologies to build relationships.

Aboriginal participatory action research (APAR) has an ethical focus that corrects the imbalances of colonisation through participation and shared decision-making to position people, place, and intention at the centre of research. APAR supports researchers to respond to the community's local rhythms and culture. APAR supports researchers to respond to the community's local rhythms and culture. First Nations scholars and their allies do this in a way that decolonises mainstream approaches in research to disrupt its cherished ideals and endeavours. How these knowledges are co-created and translated is also critically scrutinised. We are a team of intercultural researchers working with community and mainstream health service providers to improve service access, responsiveness, and Aboriginal client outcomes. Our article begins with an overview of the APAR literature and pays homage to the decolonising scholarship that champions Aboriginal ways of knowing, being, and doing. We present a research program where Aboriginal Elders, as cultural guides, hold the research through storying and cultural experiences that have deepened relationships between services and the local Aboriginal community. We conclude with implications of a community-led engagement framework underpinned by a relational methodology that reflects the nuances of knowledge translation through a co-creation of new knowledge and knowledge exchange.

Spatial Transcriptomic Analysis of a Diverse Patient Cohort Reveals a Conserved Architecture in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive disease that disproportionately affects African American (AA) women. Limited targeted therapeutic options exist for patients with TNBC. Here, we employ spatial transcriptomics to interrogate tissue from a racially diverse TNBC cohort to comprehensively annotate the transcriptional states of spatially resolved cellular populations. A total of 38,706 spatial features from a cohort of 28 sections from 14 patients were analyzed. Intratumoral analysis of spatial features from individual sections revealed heterogeneous transcriptional substructures. However, integrated analysis of all samples resulted in nine transcriptionally distinct clusters that mapped across all individual sections. Furthermore, novel use of join count analysis demonstrated nonrandom directional spatial dependencies of the transcriptionally defined shared clusters, supporting a conserved spatio-transcriptional architecture in TNBC. These findings were substantiated in an independent validation cohort comprising 17,861 spatial features representing 15 samples from 8 patients. Stratification of samples by race revealed race-associated differences in hypoxic tumor content and regions of immune-rich infiltrate. Overall, this study combined spatial and functional molecular analyses to define the tumor architecture of TNBC, with potential implications in understanding TNBC disparities. SIGNIFICANCE: Spatial transcriptomics profiling of a diverse cohort of triple-negative breast cancers and innovative informatics approaches reveal a conserved cellular architecture across cancers and identify proportional differences in tumor cell composition by race.

Diversity in Nursing Is Not Enough.

An introspective look.

Identifying Suicide Risk Factors in Lesbian, Gay, Bisexual, Transgender, and Queer Veterans.

The purpose of this article is to provide an overview of risk and protective factors for suicide in the lesbian (L), gay (G), bisexual (B), transgender (T), and queer (Q) veteran population, identify the tools and resources necessary to address their mental health needs and outline an evidence-based approach for community health care professionals to use as a guide for treatment and suicide prevention in this unique population. The importance of applying an intersectional lens to the multidimensional identity of LGTQ veterans is emphasized. Recommendations are provided for safety planning, follow-up, and treatment.

Public-Private Partnerships to Lower the Risk of Diabetes Among Black Women Using Cooperative Agreements: The National Diabetes Prevention Program and the Black Women's Health Imperative.

The National Diabetes Prevention Program (National DPP) is a partnership of public and private organizations working to build a nationwide delivery system for a lifestyle change program (LCP), which is proved to prevent or delay onset of type 2 diabetes in adults with prediabetes. Through this program, the Centers for Disease Control and Prevention (CDC) establishes partnerships with organizations to prevent or delay the onset of type 2 diabetes by using the evidence-based and audience-tailored LCP. The DP17-1705 cooperative agreement aims to expand the reach of the program in underserved areas and to populations currently underrepresented in the program relative to their risk. This article highlights a successful adaptation of the National DPP PreventT2 curriculum to address the needs of women who are Black funded by this cooperative agreement. The Change your Lifestyle, Change your Life (CYL2) program resulted from a partnership between CDC and the Black Women's Health Imperative. Successes and challenges associated with this program are highlighted. Lessons learned from these efforts can be used by practitioners to inform future type 2 diabetes prevention initiatives.

High prevalence of deleterious mutations in concomitant nonsyndromic cleft and outflow tract heart defects.

Our previous work demonstrating enrichment of outflow tract (OFT) congenital heart disease (CHD) in children with cleft lip and/or palate (CL/P) suggests derangements in common underlying developmental pathways. The current pilot study examines the underlying genetics of concomitant nonsyndromic CL/P and OFT CHD phenotype. Of 575 patients who underwent CL/P surgery at Children's Hospital Los Angeles, seven with OFT CHD, negative chromosomal microarray analysis, and no recognizable syndromic association were recruited with their parents (as available). Whole genome sequencing of blood samples paired with whole-blood-based RNA sequencing for probands was performed. A pathogenic or potentially pathogenic variant was identified in 6/7 (85.7%) probands. A total of seven candidate genes were mutated (CHD7, SMARCA4, MED12, APOB, RNF213, SETX, and JAG1). Gene ontology analysis of variants predicted involvement in binding (100%), regulation of transcription (42.9%), and helicase activity (42.9%). Four patients (57.1%) expressed gene variants (CHD7, SMARCA4, MED12, and RNF213) previously involved in the Wnt signaling pathway. Our pilot analysis of a small cohort of patients with combined CL/P and OFT CHD phenotype suggests a potentially significant prevalence of deleterious mutations. In our cohort, an overrepresentation of mutations in molecules associated with Wnt-signaling was found. These variants may represent an expanded phenotypic heterogeneity within known monogenic disease genes or provide novel evidence of shared developmental pathways. The mechanistic implications of these mutations and subsequent developmental derangements resulting in the CL/P and OFT CHD phenotype require further analysis in a larger cohort of patients.

A syndemic effect: Interrelationships between systemic racism, health disparities, and COVID-19.

ABSTRACT: This article discusses the interconnection between the syndemic effect of racial inequities and disparities as well as the impact of the COVID-19 pandemic on Black Americans. It also highlights meaningful reforms and priorities to achieve health equity in Black communities.

Comprehensive molecular profiling of UV-induced metastatic melanoma in Nme1/Nme2-deficient mice reveals novel markers of survival in human patients.

Hepatocyte growth factor-overexpressing mice that harbor a deletion of the Ink4a/p16 locus (HP mice) form melanomas with low metastatic potential in response to UV irradiation. Here we report that these tumors become highly metastatic following hemizygous deletion of the Nme1 and Nme2 metastasis suppressor genes (HPN mice). Whole-genome sequencing of melanomas from HPN mice revealed a striking increase in lung metastatic activity that is associated with missense mutations in eight signature genes (Arhgap35, Atp8b4, Brca1, Ift172, Kif21b, Nckap5, Pcdha2, and Zfp869). RNA-seq analysis of transcriptomes from HP and HPN primary melanomas identified a 32-gene signature (HPN lung metastasis signature) for which decreased expression is strongly associated with lung metastatic potential. Analysis of transcriptome data from The Cancer Genome Atlas revealed expression profiles of these genes that predict improved survival of patients with cutaneous or uveal melanoma. Silencing of three representative HPN lung metastasis signature genes (ARRDC3, NYNRIN, RND3) in human melanoma cells resulted in increased invasive activity, consistent with roles for these genes as mediators of the metastasis suppressor function of NME1 and NME2. In conclusion, our studies have identified a family of genes that mediate suppression of melanoma lung metastasis, and which may serve as prognostic markers and/or therapeutic targets for clinical management of metastatic melanoma.

Our journey, our story: a study protocol for the evaluation of a co-design framework to improve services for Aboriginal youth mental health and well-being.

INTRODUCTION: Mainstream Australian mental health services are failing Aboriginal young people. Despite investing resources, improvements in well-being have not materialised. Culturally and age appropriate ways of working are needed to improve service access and responsiveness. This Aboriginal-led study brings Aboriginal Elders, young people and youth mental health service staff together to build relationships to co-design service models and evaluation tools. Currently, three Western Australian youth mental health services in the Perth metropolitan area and two regional services are working with local Elders and young people to improve their capacity for culturally and age appropriate services. Further Western Australian sites will be engaged as part of research translation. METHODS AND ANALYSIS: Relationships ground the study, which utilises Indigenous methodologies and participatory action research. This involves Elders, young people and service staff as co-researchers and the application of a decolonising, strengths-based framework to create the conditions for engagement. It foregrounds experiential learning and Aboriginal ways of working to establish relationships and deepen non-Aboriginal co-researchers' knowledge and understanding of local, place-based cultural practices. Once relationships are developed, co-design workshops occur at each site directed by local Elders and young people. Co-designed evaluation tools will assess any changes to community perceptions of youth mental health services and the enablers and barriers to service engagement. ETHICS AND DISSEMINATION: The study has approval from the Kimberley Aboriginal Health Planning Forum Kimberley Research Subcommittee, the Western Australian Aboriginal Health Ethics Committee, and the Curtin University Human Research Ethics Committee. Transferability of the outcomes across the youth mental health sector will be directed by the co-researchers and is supported through Aboriginal and non-Aboriginal organisations including youth mental health services, peak mental health bodies and consumer groups. Community reports and events, peer-reviewed journal articles, conference presentations and social and mainstream media will aid dissemination.

Best Practices for Using Telehealth in Hospice and Palliative Care.

Hospice and palliative care providers throughout the United States have continued to provide compassionate patient- and family-centered care during the COVID-19 (coronavirus disease 2019) pandemic while adapting to the need for scrupulous infection control measures and the accelerated use of telehealth. Prior to the pandemic, hospice and palliative care adopted telehealth slowly compared with other specialties, but its rapidly increasing utilization during the COVID-19 pandemic has long-term implications for access to primary and specialty palliative care, particularly for patients in rural communities and populations experiencing inequitable access to services. Telehealth also shows great promise for leveraging technology to provide care more effectively and efficiently. As more provider organizations become equipped with telehealth infrastructure, and as advocacy for broader reimbursement of these services grows, telehealth services for hospice and palliative care are expected to continue. This article highlights the work of expert clinicians from multiple hospice and palliative care organizations to develop best practices for conducting telehealth visits in inpatient and community settings. The authors propose that best practices be compiled and considered to ensure quality-driven, evidence-based clinical practice guidelines with interprofessional applicability.

Single-cell sequencing of genomic DNA resolves sub-clonal heterogeneity in a melanoma cell line.

We performed shallow single-cell sequencing of genomic DNA across 1475 cells from a cell-line, COLO829, to resolve overall complexity and clonality. This melanoma tumor-line has been previously characterized by multiple technologies and is a benchmark for evaluating somatic alterations. In some of these studies, COLO829 has shown conflicting and/or indeterminate copy number and, thus, single-cell sequencing provides a tool for gaining insight. Following shallow single-cell sequencing, we first identified at least four major sub-clones by discriminant analysis of principal components of single-cell copy number data. Based on clustering, break-point and loss of heterozygosity analysis of aggregated data from sub-clones, we identified distinct hallmark events that were validated within bulk sequencing and spectral karyotyping. In summary, COLO829 exhibits a classical Dutrillaux's monosomic/trisomic pattern of karyotype evolution with endoreduplication, where consistent sub-clones emerge from the loss/gain of abnormal chromosomes. Overall, our results demonstrate how shallow copy number profiling can uncover hidden biological insights.