Full-length isoform concatenation sequencing to resolve cancer transcriptome complexity.

BACKGROUND: Cancers exhibit complex transcriptomes with aberrant splicing that induces isoform-level differential expression compared to non-diseased tissues. Transcriptomic profiling using short-read sequencing has utility in providing a cost-effective approach for evaluating isoform expression, although short-read assembly displays limitations in the accurate inference of full-length transcripts. Long-read RNA sequencing (Iso-Seq), using the Pacific Biosciences (PacBio) platform, can overcome such limitations by providing full-length isoform sequence resolution which requires no read assembly and represents native expressed transcripts. A constraint of the Iso-Seq protocol is due to fewer reads output per instrument run, which, as an example, can consequently affect the detection of lowly expressed transcripts. To address these deficiencies, we developed a concatenation workflow, PacBio Full-Length Isoform Concatemer Sequencing (PB_FLIC-Seq), designed to increase the number of unique, sequenced PacBio long-reads thereby improving overall detection of unique isoforms. In addition, we anticipate that the increase in read depth will help improve the detection of moderate to low-level expressed isoforms. RESULTS: In sequencing a commercial reference (Spike-In RNA Variants; SIRV) with known isoform complexity we demonstrated a 3.4-fold increase in read output per run and improved SIRV recall when using the PB_FLIC-Seq method compared to the same samples processed with the Iso-Seq protocol. We applied this protocol to a translational cancer case, also demonstrating the utility of the PB_FLIC-Seq method for identifying differential full-length isoform expression in a pediatric diffuse midline glioma compared to its adjacent non-malignant tissue. Our data analysis revealed increased expression of extracellular matrix (ECM) genes within the tumor sample, including an isoform of the Secreted Protein Acidic and Cysteine Rich (SPARC) gene that was expressed 11,676-fold higher than in the adjacent non-malignant tissue. Finally, by using the PB_FLIC-Seq method, we detected several cancer-specific novel isoforms. CONCLUSION: This work describes a concatenation-based methodology for increasing the number of sequenced full-length isoform reads on the PacBio platform, yielding improved discovery of expressed isoforms. We applied this workflow to profile the transcriptome of a pediatric diffuse midline glioma and adjacent non-malignant tissue. Our findings of cancer-specific novel isoform expression further highlight the importance of long-read sequencing for characterization of complex tumor transcriptomes.

Cerebral organoids containing an AUTS2 missense variant model microcephaly.

Variants in the AUTS2 gene are associated with a broad spectrum of neurological conditions characterized by intellectual disability, microcephaly, and congenital brain malformations. Here, we use a human cerebral organoid model to investigate the pathophysiology of a heterozygous de novo missense AUTS2 variant identified in a patient with multiple neurological impairments including primary microcephaly and profound intellectual disability. Proband cerebral organoids exhibit reduced growth, deficits in neural progenitor cell (NPC) proliferation and disrupted NPC polarity within ventricular zone-like regions compared to control cerebral organoids. We used CRISPR-Cas9-mediated gene editing to correct this variant and demonstrate rescue of impaired organoid growth and NPC proliferative deficits. Single-cell RNA sequencing revealed a marked reduction of G1/S transition gene expression and alterations in WNT-ß-catenin signalling within proband NPCs, uncovering a novel role for AUTS2 in NPCs during human cortical development. Collectively, these results underscore the value of cerebral organoids to investigate molecular mechanisms underlying AUTS2 syndrome.

Youth Caregivers of Adults in the United States: Prevalence and the Association Between Caregiving and Education.

A growing proportion of individuals adopt family caregiving roles. Family caregivers are the primary providers of long-term care in the United States yet limited federal policy supports exist, despite the known negative impacts of caregiving. There is also limited information about the prevalence of youth/young adult caregivers and the impacts of caregiving at formative ages in the United States. Our objective is to estimate the prevalence of youth caregivers and examine the association of caregiving with educational investments. We use the American Time Use Survey (2013-2019) to identify and describe youth caregivers (aged 15-18) and young adult caregivers (aged 19-22) and compare them with non-caregiving peers. We estimate that there are approximately 1,623,000 youth caregivers and 1,986,000 young adult caregivers, corresponding to 9.2% and 12.7% of these age groups, respectively. However, there is a wide range in the estimated prevalence per year, from approximately 364,000 to 2.8 million youth caregivers and from 353,000 to 2.2 million young adult caregivers, depending on caregiver definition. Unlike adult caregivers, we find that young men and women were nearly equally likely to provide care. We also find that non-White individuals are disproportionately represented as youth caregivers. Compared with non-caregiving peers, both youth and young adult caregivers are less likely to be enrolled in school and, among those enrolled in school, spend significantly less time on educational activities. Considering the association of caregiving among youth/young adults and education, policies supporting youth and young adult caregivers are critical.

Increasing Medicare Annual Wellness Visit Utilization: An RN-Led Model of Care Pilot.

Annual wellness visits (AWVs) are an important component of primary care as they provide preventive services and an opportunity to identify safety and health risk factors for Medicare beneficiaries. However, primary care practices are facing unprecedented demands with high patient volumes, multimorbidity, a rapidly growing aging population, and primary care provider (PCP) shortages. RN-led models of care are increasingly recognized as a major key to providing quality care while relieving PCP demands. This article describes the implementation of an RN-led model of care pilot in an urban family practice to increase Medicare AWV completion and alleviate PCP burden.

Infantile metastatic ependymoma with a novel molecular profile and favorable outcome to intensive chemotherapy without irradiation: Case-based review.

Ependymal tumors are the third most common brain tumor under 14 years old. Even though metastatic disease is a rare event, it affects mostly young children and carries an adverse prognosis. The factors associated with dissemination and the best treatment approach have not yet been established and there is limited published data on how to manage metastatic disease, especially in patients under 3 years of age. We provide a review of the literature on clinical characteristics and radiation-sparing treatments for metastatic ependymoma in children under 3 years of age treated. The majority (73%) of the identified cases were above 12 months old and had the PF as the primary site at diagnosis. Chemotherapy-based approaches, in different regimens, were used with radiation reserved for progression or relapse. The prognosis varied among the studies, with an average of 50%-58% overall survival. This study also describes the case of a 7-month-old boy with metastatic posterior fossa (PF) ependymoma, for whom we identified a novel SPECC1L-RAF1 gene fusion using a patient-centric comprehensive molecular profiling protocol. The patient was successfully treated with intensive induction chemotherapy followed by high-dose chemotherapy and autologous hematopoietic progenitor cell rescue (AuHSCR). Currently, the patient is in continuous remission 5 years after his diagnosis, without radiation therapy. The understanding of the available therapeutic approaches may assist physicians in their management of such patients. This report also opens the perspective of newly identified molecular alterations in metastatic ependymomas that might drive more chemo-sensitive tumors.

Manufacture and Characterization of Good Manufacturing Practice-Compliant SARS-COV-2 Cytotoxic T Lymphocytes.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 virus-specific cytotoxic T-cell lymphocytes (vCTLs) could provide a promising modality in COVID-19 treatment. We aimed to screen, manufacture, and characterize SARS-CoV-2-vCTLs generated from convalescent COVID-19 donors using the CliniMACS Cytokine Capture System (CCS). METHODS: Donor screening was done by stimulation of convalescent COVID-19 donor peripheral blood mononuclear cells with viral peptides and identification of interferonγ (IFN-γ)+ CD4 and CD8 T cells using flow cytometry. Clinical-grade SARS-CoV-2-vCTLs were manufactured using the CliniMACS CCS. The enriched SARS-CoV-2-vCTLs were characterized by T-cell receptor sequencing, mass cytometry, and transcriptome analysis. RESULTS: Of the convalescent donor blood samples, 93% passed the screening criteria for clinical manufacture. Three validation runs resulted in enriched T cells that were 79% (standard error of the mean 21%) IFN-γ+ T cells. SARS-CoV-2-vCTLs displayed a highly diverse T-cell receptor repertoire with enhancement of both memory CD8 and CD4 T cells, especially in CD8 TEM, CD4 TCM, and CD4 TEMRA cell subsets. SARS-CoV-2-vCTLs were polyfunctional with increased gene expression in T-cell function, interleukin, pathogen defense, and tumor necrosis factor superfamily pathways. CONCLUSIONS: Highly functional SARS-CoV-2-vCTLs can be rapidly generated by direct cytokine enrichment (12 hours) from convalescent donors. CLINICAL TRIALS REGISTRATION: NCT04896606.

Low copy numbers of complement C4 and C4A deficiency are risk factors for myositis, its subgroups and autoantibodies.

BACKGROUND: Idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterised by myositis-related autoantibodies plus infiltration of leucocytes into muscles and/or the skin, leading to the destruction of blood vessels and muscle fibres, chronic weakness and fatigue. While complement-mediated destruction of capillary endothelia is implicated in paediatric and adult dermatomyositis, the complex diversity of complement C4 in IIM pathology was unknown. METHODS: We elucidated the gene copy number (GCN) variations of total C4, C4A and C4B, long and short genes in 1644 Caucasian patients with IIM, plus 3526 matched healthy controls using real-time PCR or Southern blot analyses. Plasma complement levels were determined by single radial immunodiffusion. RESULTS: The large study populations helped establish the distribution patterns of various C4 GCN groups. Low GCNs of C4T (C4T=2+3) and C4A deficiency (C4A=0+1) were strongly correlated with increased risk of IIM with OR equalled to 2.58 (2.28-2.91), p=5.0×10-53 for C4T, and 2.82 (2.48-3.21), p=7.0×10-57 for C4A deficiency. Contingency and regression analyses showed that among patients with C4A deficiency, the presence of HLA-DR3 became insignificant as a risk factor in IIM except for inclusion body myositis (IBM), by which 98.2% had HLA-DR3 with an OR of 11.02 (1.44-84.4). Intragroup analyses of patients with IIM for C4 protein levels and IIM-related autoantibodies showed that those with anti-Jo-1 or with anti-PM/Scl had significantly lower C4 plasma concentrations than those without these autoantibodies. CONCLUSIONS: C4A deficiency is relevant in dermatomyositis, HLA-DRB1*03 is important in IBM and both C4A deficiency and HLA-DRB1*03 contribute interactively to risk of polymyositis.

The impact of funding models on the integration of Ontario midwives: a qualitative study.

BACKGROUND: Nearly 30 years post legalisation and introduction, midwifery is still not optimally integrated within the health system of Canada's largest province, Ontario. Funding models have been identified as one of the main barriers. METHODS: Using a constructivist perspective, we conducted a qualitative descriptive study to examine how antepartum, intrapartum, and postpartum funding arrangements in Ontario impact midwifery integration. We conceptualized optimal 'integration' as circumstances in which midwives' knowledge, skills, and model of care are broadly respected and fully utilized, interprofessional collaboration and referral support the best possible care for patients, and midwives feel a sense of belonging within hospitals and the greater health system. We collected data through semi-structured telephone interviews with midwives, obstetricians, family physicians, and nurses. The data was examined using thematic analysis. RESULTS: We interviewed 20 participants, including 5 obstetricians, 5 family physicians, 5 midwives, 4 nurses, and 1 policy expert. We found that while course-of-care-based midwifery funding is perceived to support high levels of midwifery client satisfaction and excellent clinical outcomes, it lacks flexibility. This limits opportunities for interprofessional collaboration and for midwives to use their knowledge and skills to respond to health system gaps. The physician fee-for-service funding model creates competition for births, has unintended consequences that limit midwives' scope and access to hospital privileges, and fails to appropriately compensate physician consultants, particularly as midwifery volumes grow. Siloing of midwifery funding from hospital funding further restricts innovative contributions from midwives to respond to community healthcare needs. CONCLUSIONS: Significant policy changes, such as adequate remuneration for consultants, possibly including salary-based physician funding; flexibility to compensate midwives for care beyond the existing course of care model; and a clearly articulated health human resource plan for sexual and reproductive care are needed to improve midwifery integration.

Implementing palliative care education into primary care practice: a qualitative case study of the CAPACITI pilot program.

BACKGROUND: CAPACITI is a virtual education program that teaches primary care teams how to provide an early palliative approach to care. After piloting its implementation, we conducted an in-depth qualitative study with CAPACITI participants to assess the effectiveness of the components and to understand the challenges and enablers to virtual palliative care education. METHODS: We applied a qualitative case study approach to assess and synthesize three sources of data collected from the teams that participated in CAPACITI: reflection survey data, open text survey data, and focus group transcriptions. We completed a thematic analysis of these responses to gain an understanding of participant experiences with the intervention and its application in practice. RESULTS: The CAPACITI program was completed by 22 primary care teams consisting of 159 participants across Ontario, Canada. Qualitative data was obtained from all teams, including 15 teams that participated in focus groups and 21 teams that provided reflection survey data on CAPACITI content and how it translated into practice. Three major themes arose from cross-analysis of the data: changes in practice derived from involvement in CAPACITI, utility of specific elements of the program, and barriers and challenges to enacting CAPACITI in practice. Importantly, participants reported that the multifaceted approach of CAPACITI was helpful to them building their confidence and competence in applying a palliative approach to care. CONCLUSIONS: Primary care teams perceived the CAPACITI facilitated program as effective towards incorporating palliative care into their practices. CAPACITI warrants further study on a national scale using a randomized trial methodology. Future iterations of CAPACITI need to help mitigate barriers identified by respondents, including team fragmentation and system-based challenges to encourage interprofessional collaboration and knowledge translation.

Sleep Disturbances Associated With Posttraumatic Stress Disorder.

Sleep disturbances, namely insomnia and recurrent nightmares, are ubiquitous following trauma exposure and are considered hallmarks of posttraumatic stress disorder (PTSD). Other sleep disorders frequently co-occur with PTSD. This article describes research examining sleep problems most common in PTSD, including prevalence and clinical characteristics. Sleep disturbances are often robust to trauma-focused treatment; thus, evidence for psychological and pharmacological interventions for insomnia and nightmares in PTSD are discussed. Given the high prevalence of sleep problems in PTSD, more work is needed to empirically study putative mechanisms linking trauma exposure and sleep, as well as how to best target these symptoms in patients with PTSD.

The power of story: Bringing 2SLGBTQ+ digital stories into gerontology settings.

Two-spirit, lesbian, gay, bisexual, trans, and queer or questioning (2SLGBTQ+) older adults are underrepresented in gerontology research and education, impacting the preparedness of health and social care students and professionals working with the diverse aging population. To address this lack of representation of 2SLGBTQ+ older adults in gerontology education, this study explored the use of digital stories as tools for knowledge mobilization and social justice. Digital stories are short videos that pair audio recordings with visuals, including videos, photographs, or artwork. To conduct the study, the research team worked alongside 2SLGBTQ+ older adults to create a suite of three digital stories. These stories were presented at various educational and professional settings in gerontology, and survey and open-feedback responses (n = 147) were gathered from the audience on their perceived impact. Viewers included students, researchers, decision-makers, stakeholders, and citizens. Content analysis was used to analyze the data. From the analysis, digital stories showed the potential to increase viewers' awareness and understanding of 2SLGBTQ+ aging experiences. The format was particularly significant in their learning and enhancing the connection to the content and the storytellers. The findings also suggest that digital stories showed the potential to impact policy and practice for 2SLGBTQ+ communities.

Minority Student Perspectives of Barriers, Supports, and Christian Virtues in an Undergraduate Christian Nursing Program.

ABSTRACT: Diversity and inclusion are critical priorities in nursing education programs. Literature has focused on minority student experiences of barriers and supports-but not through a Christian worldview. This qualitative study using a phenomenological-hermenuetic approach gave voice to the experiences of 15 self-identified minority student graduates from a Christian baccalaureate nursing program. Data analysis revealed opportunities for growth in providing a supportive climate within the program and how Christian virtues of hospitality, humility, and reconciliation can be employed to achieve this goal.

Patient-Specific Sarcoma Organoids for Personalized Translational Research: Unification of the Operating Room with Rare Cancer Research and Clinical Implications.

INTRODUCTION: Sarcoma clinical outcomes have been stagnant for decades due to heterogeneity of primaries, lack of comprehensive preclinical models, and rarity of disease. We hypothesized that engineering hydrogel-based sarcoma organoids directly from the patient without xenogeneic extracellular matrices (ECMs) or growth factors is routinely feasible and allows rare tumors to remain viable as avatars for personalized research. METHODS: Surgically resected sarcomas (angiosarcomas, leiomyosarcoma, gastrointestinal stromal tumor, liposarcoma, myxofibrosarcoma, dermatofibrosarcoma protuberans [DFSP], and pleiomorphic abdominal sarcoma) were dissociated and incorporated into a hyaluronic acid and collagen-based ECM hydrogel and screened for chemotherapy efficacy. A subset of organoids was enriched with a patient-matched immune system for screening of immunotherapy efficacy (iPTOs). Response to treatment was assessed using LIVE/DEAD staining and metabolic assays. RESULTS: Sixteen sarcomas were biofabricated into three-dimensional (3D) patient-specific sarcoma organoids with a 100% success rate. Average time from organoid development to initiation of drug testing was 7 days. Enrichment of organoids with immune system components derived from either peripheral blood mononuclear cells or lymph node cells was performed in 10/16 (62.5%) patients; 4/12 (33%) organoids did not respond to chemotherapy, while response to immunotherapy was observed in 2/10 (20%) iPTOs. CONCLUSIONS: A large subset of sarcoma organoids does not exhibit response to chemotherapy or immunotherapy, as currently seen in clinical practice. Routine development of sarcoma hydrogel-based organoids directly from the operating room is a feasible platform, allowing for such rare tumors to remain viable for personalized translational research.

Family Caregivers of Veterans Experience Clinically Significant Levels of Distress Prepandemic and During Pandemic: Implications for Caregiver Support Services.

BACKGROUND: Of the 26.4 million family caregivers in the United States, nearly 40% report high levels of emotional strain and subjective burden. However, for the 5 million caregivers of Veterans, little is known about the experiences of caregivers of Veterans during the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: The aim was to examine pandemic-related changes of caregiver well-being outcomes. RESEARCH DESIGN, SUBJECTS, AND MEASURES: Using a pre/post design and longitudinal data of individual caregivers captured pre-COVID-19 and during COVID-19, we use multilevel generalized linear mixed models to examine pandemic-related changes to caregiver well-being (n=903). The primary outcome measures include Zarit Subjective Burden, Center for Epidemiologic Studies Short Depression Scale, perceived financial strain, life chaos, and loneliness. RESULTS: During the pandemic, we observe slight improvements for caregivers across well-being measures except for perceived financial strain. Before the pandemic, we observed that caregivers screened positive for clinically significant caregiver burden and probable depression. While we do not observe worsening indicators of caregiver well-being during the COVID-19 pandemic, the average predicted values of indicators of caregiver well-being remain clinically significant for caregiving subjective burden and depression. CONCLUSIONS: These findings illuminate pandemic-related impacts of caregivers receiving support through the Veterans Affairs (VA) pre-COVID and during the COVID-19 pandemic while caring for a population of frail, older care-recipients with a high burden of mental illness and other chronic conditions. Considering the long-term impacts of the pandemic to increase morbidity and the expected increased demand for caregivers in an aging population, these consistently high levels of distress despite receiving support highlight the need for interventions and policy reform to systematically support caregivers more broadly.

The Landscape of State Policies Supporting Family Caregivers as Aligned With the National Academy of Medicine Recommendations.

Policy Points In the absence of federal policy, states adopted policies to support family caregivers, but availability and level of support varies. We describe, compare, and rank state policies to support family caregivers as aligned with National Academy of Medicine recommendations. Although the landscape of state policies supporting caregivers has improved over time, few states provide financial supports as recommended, and benefit restrictions hinder accessibility for all types of family caregivers. Implementing policies supporting family caregivers will become more critical over time, as the reliance on family caregivers as essential providers of long-term care is only expected to grow as the population ages. CONTEXT: In the United States in 2020, approximately 26 million individuals provided unpaid care to a family member or friend. On average, 60% of caregivers were employed, and they provided 20.4 hours of care per week on top of employment. Although a handful of patchwork laws exist to aid family caregivers, systematic supports, including comprehensive training, respite, and financial support, remain limited. In the absence of federal supports, states have adopted policies to provide assistance, but they vary in availability and level of support provided. Our objectives were to describe, compare, and rank state policies to support family caregivers over time. METHODS: We used publicly available data from the AARP Long-Term Services and Supports State Scorecard, the National Academy for State Health Policy, and Tax Credits for Workers and Families for all 50 states and the District of Columbia (2015-2019). FINDINGS: We found that states had increased supports to family caregivers over this five-year period, although significant variability in adoption and implementation of policies persists. Approximately 20% of states had enacted policies that exceed the federal Family and Medical Leave Act requirements, and 18% offered paid family leave. However, most states had not improved spousal impoverishment protections for Medicaid beneficiaries. For example, from 2016 to 2019, 24% of states provided fewer or no protections, while 71% of states did not improve spousal impoverishment protections over time. Access to training for caregivers varied based on eligibility criteria (e.g., select populations and/or only co-residing caregivers). CONCLUSIONS: Overall, state approaches to support family caregivers vary by eligibility and scope of services. Substantial gaps in support of caregivers, particularly economic supports, persist. Although the landscape of state policies supporting caregivers has improved over time, few states provide financial supports as recommended by the National Academy of Medicine, and benefit restrictions hinder accessibility for all family caregivers.

Detection of brain somatic variation in epilepsy-associated developmental lesions.

OBJECTIVE: Epilepsy-associated developmental lesions, including malformations of cortical development and low-grade developmental tumors, represent a major cause of drug-resistant seizures requiring surgical intervention in children. Brain-restricted somatic mosaicism has been implicated in the genetic etiology of these lesions; however, many contributory genes remain unidentified. METHODS: We enrolled 50 children who were undergoing epilepsy surgery into a translational research study. Resected tissue was divided for clinical neuropathologic evaluation and genomic analysis. We performed exome and RNA sequencing to identify somatic variation and we confirmed our findings using high-depth targeted DNA sequencing. RESULTS: We uncovered candidate disease-causing somatic variation affecting 28 patients (56%), as well as candidate germline variants affecting 4 patients (8%). In agreement with previous studies, we identified somatic variation affecting solute carrier family 35 member A2 (SLC35A2) and mechanistic target of rapamycin kinase (MTOR) pathway genes in patients with focal cortical dysplasia. Somatic gains of chromosome 1q were detected in 30% (3 of 10) of patients with Type I focal cortical dysplasia (FCD)s. Somatic variation in mitogen-activated protein kinase (MAPK) pathway genes (i.e., fibroblast growth factor receptor 1 [FGFR1], FGFR2, B-raf proto-oncogene, serine/threonine kinase [BRAF], and KRAS proto-oncogene, GTPase [KRAS]) was associated with low-grade epilepsy-associated developmental tumors. RNA sequencing enabled the detection of somatic structural variation that would have otherwise been missed, and which accounted for more than one-half of epilepsy-associated tumor diagnoses. Sampling across multiple anatomic regions revealed that somatic variant allele fractions vary widely within epileptogenic tissue. Finally, we identified putative disease-causing variants in genes not yet associated with focal cortical dysplasia. SIGNIFICANCE: These results further elucidate the genetic basis of structural brain abnormalities leading to focal epilepsy in children and point to new candidate disease genes.

PTEN somatic mutations contribute to spectrum of cerebral overgrowth.

Phosphatase and tensin homologue (PTEN) regulates cell growth and survival through inhibition of the mammalian target of rapamycin (MTOR) signalling pathway. Germline genetic variation of PTEN is associated with autism, macrocephaly and PTEN hamartoma tumour syndromes. The effect of developmental PTEN somatic mutations on nervous system phenotypes is not well understood, although brain somatic mosaicism of MTOR pathway genes is an emerging cause of cortical dysplasia and epilepsy in the paediatric population. Here we report two somatic variants of PTEN affecting a single patient presenting with intractable epilepsy and hemimegalencephaly that varied in clinical severity throughout the left cerebral hemisphere. High-throughput sequencing analysis of affected brain tissue identified two somatic variants in PTEN. The first variant was present in multiple cell lineages throughout the entire hemisphere and associated with mild cerebral overgrowth. The second variant was restricted to posterior brain regions and affected the opposite PTEN allele, resulting in a segmental region of more severe malformation, and the only neurons in which it was found by single-nuclei RNA-sequencing had a unique disease-related expression profile. This study reveals brain mosaicism of PTEN as a disease mechanism of hemimegalencephaly and furthermore demonstrates the varying effects of single- or bi-allelic disruption of PTEN on cortical phenotypes.

Characterizing the Prevalence of Obesity Misinformation, Factual Content, Stigma, and Positivity on the Social Media Platform Reddit Between 2011 and 2019: Infodemiology Study.

BACKGROUND: Reddit is a popular social media platform that has faced scrutiny for inflammatory language against those with obesity, yet there has been no comprehensive analysis of its obesity-related content. OBJECTIVE: We aimed to quantify the presence of 4 types of obesity-related content on Reddit (misinformation, facts, stigma, and positivity) and identify psycholinguistic features that may be enriched within each one. METHODS: All sentences (N=764,179) containing "obese" or "obesity" from top-level comments (n=689,447) made on non-age-restricted subreddits (ie, smaller communities within Reddit) between 2011 and 2019 that contained one of a series of keywords were evaluated. Four types of common natural language processing features were extracted: bigram term frequency-inverse document frequency, word embeddings derived from Bidirectional Encoder Representations from Transformers, sentiment from the Valence Aware Dictionary for Sentiment Reasoning, and psycholinguistic features from the Linguistic Inquiry and Word Count Program. These features were used to train an Extreme Gradient Boosting machine learning classifier to label each sentence as 1 of the 4 content categories or other. Two-part hurdle models for semicontinuous data (which use logistic regression to assess the odds of a 0 result and linear regression for continuous data) were used to evaluate whether select psycholinguistic features presented differently in misinformation (compared with facts) or stigma (compared with positivity). RESULTS: After removing ambiguous sentences, 0.47% (3610/764,179) of the sentences were labeled as misinformation, 1.88% (14,366/764,179) were labeled as stigma, 1.94% (14,799/764,179) were labeled as positivity, and 8.93% (68,276/764,179) were labeled as facts. Each category had markers that distinguished it from other categories within the data as well as an external corpus. For example, misinformation had a higher average percent of negations (ß=3.71, 95% CI 3.53-3.90; P<.001) but a lower average number of words >6 letters (ß=-1.47, 95% CI -1.85 to -1.10; P<.001) relative to facts. Stigma had a higher proportion of swear words (ß=1.83, 95% CI 1.62-2.04; P<.001) but a lower proportion of first-person singular pronouns (ß=-5.30, 95% CI -5.44 to -5.16; P<.001) relative to positivity. CONCLUSIONS: There are distinct psycholinguistic properties between types of obesity-related content on Reddit that can be leveraged to rapidly identify deleterious content with minimal human intervention and provide insights into how the Reddit population perceives patients with obesity. Future work should assess whether these properties are shared across languages and other social media platforms.

Needs assessment of nurse researchers through a research lifecycle framework.

Objective: Health sciences librarian roles are evolving to better meet the needs of faculty. This study explores nursing faculty needs at the University of British Columbia through the research lifecycle framework of planning, conducting, disseminating, and assessing the impact of their research. Methods: A mixed methods survey study with Likert scale, multiple-choice, or ordinal ranking-scale questions and six open-response questions was conducted. The format was a web-based Qualtrics survey; participants had approximately three weeks to respond. Results: Nursing faculty identified the dissemination phase as benefiting most from library support prioritizing reference management and archiving research data as the top needs in that phase. Assessing impact skills such as citation analysis and Altmetrics training was ranked second. The Planning phase was ranked third with systematic review and literature review support most needed. The Conducting phase was identified as the phase where they needed the least support. Conclusion: Understanding the needs of researchers and enhancing scholar productivity is vital to offering responsive library research services. Across the research lifecycle, nursing faculty identified reference management, data management, metrics evaluation, systematic reviews, and literature reviews as the key areas for which they need support.

Physician experiences with medical assistance in dying: Qualitative study in northwestern Ontario.

OBJECTIVE: To explore physician experiences with medical assistance in dying (MAID). DESIGN: An exploratory qualitative research approach using thematic analysis. SETTING: Six communities in northwestern Ontario. PARTICIPANTS: Twenty-three physicians who perform, refer patients for, or are otherwise affected by MAID. METHODS: One semistructured focus group and one-to-one interviews, transcribed and analyzed thematically. MAIN FINDINGS: The legislation of MAID added a layer of complexity to the work of physicians in northwestern Ontario, as MAID requires physician leadership, knowledge, time, and careful implementation. Four themes were identified from the interviews that unpacked this additional layer of complexity: relationships, motivation, time and resources, and getting others on board. CONCLUSION: The logistics of health care delivery in northwestern Ontario communities are complex and layered, which contributes to the burden of physicians as they work to provide MAID.