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Background: Children with cerebral palsy (CP) regularly fall over and this has negative effects on their physical and psychosocial wellbeing (e.g., reduced activity participation). However, the reasons for falls are not well understood. The way in which children negotiate challenging walking environments (e.g., uneven surfaces), may reveal more about how falls occur as these environments require gait modifications to maintain stability. Stability in challenging walking environments has been explored for children with CP; however, it remains unclear how these lead to falls., Research Question: Do challenging walking environments that mimic those faced in the real-world, contribute to increased fall occurrence and fall risk in children with CP?, Methods: Five databases were searched, and 1386 records screened to include ambulatory children with CP, aged 5-18 years old, investigating dynamic walking in challenging environments, with outcomes of fall occurrence or fall risk. The full protocol for this review was registered on PROSPERO (CRD42021290456)., Results: Sixteen studies met the inclusion criteria. One study reported occurrence of stumbles, two reported no falls. Fifteen studies identified gait alterations used by children with CP in challenging environments. Twenty-four gait characteristics were identified to be indicative of cautious walking strategies and seven gait characteristics identified to increase fall risk, suggesting a potential link. However, limited evidence exists as to whether this reflects falls faced in the real-world., Significance: Investigations into stability over challenging walking environments for children with CP are lacking any measures of fall occurrence. Investigations into the mechanisms that may contribute to high fall risk, or fall avoidance when negotiating obstacles, uneven surfaces, steep declines and stairs may reveal further causes of real-world falls, and in doing so inform future fall prevention techniques. Finally, understanding the multifaceted causes of falls in real-world challenging environments from the perspectives of children with CP is key for future research., Competing Interests: Declaration of Competing Interest The authors declare no conflicting interests., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Background : The fourth universal definition of myocardial infarction (MI) introduced the differentiation of acute myocardial injury from MI. In this study, we developed a computational phenotype for distinct identification of acute myocardial injury and MI within electronic medical records (EMRs). Methods : Two cohorts were used from a Calgary-wide EMR system: a chart review of 3042 randomly selected inpatients from Dec 2014 to Jun 2015; and 11,685 episodes of care that included cardiac catheterization from Jan 2013 to Apr 2017. Electrocardiogram (ECG) reports were processed using natural language processing and combined with high-sensitivity troponin lab results to classify patients as having an acute myocardial injury, MI, or neither. Results : For patients with an MI diagnosis, only 64.0% (65.7%) in the catheterized cohorts (chart review cohort) had two troponin measurements within 6 h of each other. For patients with two troponin measurements within 6 h; of those with an MI diagnosis, our phenotype classified 25.2% (31.3%) with an acute myocardial injury and 62.2% (55.2%) with an MI in the catheterized cohort (chart review cohort); and of those without an MI diagnosis, our phenotype classified 12.9% (12.4%) with an acute myocardial injury and 10.0% (13.1%) with an MI in the catheterized cohort (chart review cohort). Conclusions : Patients with two troponin measurements within 6 h, identified by our phenotype as having either an acute myocardial injury or MI, will at least meet the diagnostic criteria for an acute myocardial injury (barring lab errors) and indicate many previously uncaptured cases. Myocardial infarctions are harder to be certain of because ECG report findings might be superseded by evidence not included in our phenotype, or due to errors with the natural language processing.

Background: Nonhuman animals are regularly enhanced genomically with CRISPR and other gene editing tools as scientists aim at better models for biomedical research, more tractable agricultural animals, or animals that are otherwise well suited to a defined purpose. This study investigated how genome editors and policymakers perceived ethical or policy benefits and drawbacks for animal enhancement and how perceived benefits and drawbacks are alike, or differ from, those for human genome editing., Methods: We identified scientists through relevant literature searches as well as conference presentations. Policymakers were identified through rosters of genome editing oversight groups (e.g., International Commission on the Clinical Use of Human Germline Genome Editing, World Health Organization) or efforts aimed at influencing policy (e.g., deliberative democracy groups). Interviews covered participants' views on ethical differences between interventions affecting somatic or germline cells and distinctions between using gene editing for disease treatment, prevention, and enhancement purposes., Results: Of the 92 participants interviewed, 81 were genome editing scientists, and 33 were policymakers, with 22 interviewees being both scientists and policymakers. Multiple areas were identified in which the ethical implications of genomic enhancements for nonhuman animals differ from those for human animals including with respect to experiential welfare; germline edits; environmental sustainability; and justice., Conclusions: Overall, respondents viewed that animal enhancement is unburdened by the ethical complexities of human enhancement. These views may be related to participant perceptions of animals' lesser moral status and because germline editing in animals is common practice.

Osteosarcoma is the most common type of bone cancer. Some patients eventually develop recurrent or metastatic diseases and treatment options are extremely limited. Discoidin domain receptor 1 (DDR1) is a unique collagen-activated tyrosine kinase that participates in various human diseases, including cancer. DDR1 promotes adhesion, proliferation, differentiation, migration, and metastasis of cancer cells. The purpose of this study is to assess the expression, clinical prognostic relationship and functional roles of DDR1 in osteosarcoma. The correlation between DDR1 expression in tumor tissues and clinicopathological features, and prognosis was assessed via immunohistochemical staining of a unique tissue microarray (TMA) constructed from osteosarcoma specimens. DDR1-specific siRNA and a highly selective DDR1 inhibitor, 7rh, were applied to determine the impact of DDR1 expression on osteosarcoma cell growth and proliferation. Furthermore, the effect of DDR1 inhibition on clonogenicity was evaluated using a clonogenic assay, and a 3D cell culture model was used to mimic DDR1 effects in an in vivo environment. The results demonstrate that higher DDR1 expression significantly correlates with recurrence, metastasis, and shorter overall survival in osteosarcoma patients. The expression of DDR1 is also inversely correlated to the response to neoadjuvant chemotherapy. Therapeutically, DDR1 knockdown with siRNA or selective inhibition with 7rh decreases the proliferation and growth of osteosarcoma cells. In conclusion, our study supports DDR1 expression as an independent predictor of poor prognosis and a promising therapeutic target for osteosarcoma., (© 2024 Federation of American Societies for Experimental Biology.)

The few existing typology studies on women who have sexually offended (WWSO) have largely been limited by small sample sizes, have not included scale scores from risk assessments, or used recidivism within their typology (instead of using typologies to predict recidivism). In our sample of 241 WWSO, we conducted a latent profile analysis and observed four, distinct profiles: "low-risk WWSO," characterized by fewer criminal history incidents and lower risk-assessment scores; "problem-endorsing WWSO," with higher probability of endorsing various life problems such as educational/employment and emotional/personal issues; "antisocial WWSO" with more criminal history incidents, alcohol/drug problems, and higher scores on psychopathy; and "combined WWSO" with characteristics of both the problem-endorsing and antisocial profiles. This last profile showed elevations in general and/or violent recidivism risk, but relatively low recidivism. There were no cases of sexual recidivism in our sample following an average 30-month follow-up period. Membership in the antisocial profile predicted general and/or violent recidivism and suggests that WWSO typologies may be useful in predicting non-sexual recidivism for this population., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

To maintain genome stability, proliferating cells must enact a program of telomere maintenance. While most tumors maintain telomeres through the action of telomerase, a subset of tumors utilize a DNA-templated process termed Alternative Lengthening of Telomeres or ALT. ALT is associated with mutations in the ATRX/DAXX/H3.3 histone chaperone complex, which is responsible for deposition of non-replicative histone variant H3.3 at heterochromatic regions of the genome including telomeres. We wished to better understand the role DAXX plays in ALT suppression, and to determine which disease-associated DAXX mutations are unable to suppress ALT. To answer this question, we have leveraged the G292 cell line, in which ATRX is wild type but DAXX has undergone a fusion event with the non-canonical kinesin KIFC3. Restoration of wild-type DAXX in G292 localizes ATRX and abrogates ALT. Using this model system, we tested the ability of a panel of disease-associated DAXX missense variants to suppress ALT. Missense mutations in the ATRX binding domain, the histone binding domain, and the C-terminal SUMO interaction motif reduce the ability of DAXX to suppress ALT. Unexpectedly, we find that mutations in the DAXX histone binding domain lead to failure of ATRX localization. We conclude that a key function of DAXX in ALT suppression is the localization of ATRX to nuclear foci., Competing Interests: Competing Interests: The authors declare no competing interests.

The association between current use of oral contraceptives (OCs) among women younger than 50 years (n = 306 541), and hormone therapy (HT) among women aged 50 years or older (n = 323 203), and coronavirus 2019 (COVID-19) infection and hospitalization was evaluated in this population-based cohort. Current OC/HT use was recorded monthly using prescription dispensing data. COVID-19 infections were identified from March 2020 through February 2021. COVID-19 infections and hospitalizations were identified through diagnosis codes and laboratory tests. We used weighted generalized estimating equations models to estimate multivariable adjusted odds ratios (aORs) for COVID-19 infection associated with time-varying OC/HT use. Among women with COVID-19, logistic regression models were used to evaluate OC/HT use and COVID-19 hospitalization. Over 12 months, 11 727 (3.8%) women younger than 50 years and 8661 (2.7%) women aged 50 years or older experienced COVID-19 infections. There was no evidence of an association between OC use and infection (aOR = 1.05; 95% CI, 0.97-1.12). There was a modest association between HT use and infection (aOR = 1.19; 95% CI, 1.03-1.38). Women using OCs had a 39% lower risk of hospitalization (aOR = 0.61; 95% CI, 0.38-1.00), but there was no association of HT use with hospitalization (aOR = 0.89; 95% CI, 0.51-1.53). These findings do not suggest a meaningfully greater risk of COVID-19 infection associated with OC or HT use. OC use may be associated with lower COVID-19 hospitalization risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Suicide is a leading cause of death among Black emerging adults. The concurrent effect of the COVID-19 pandemic and racial discrimination were projected to exacerbate suicide vulnerability for Black Americans. The purpose of the present study was to utilize a risk-resilience model to examine the effects of racial discrimination and COVID-related stress on suicide risk for Black emerging adults, as well as the moderating effect of three central components of radical healing: critical consciousness, resilience, and cultural authenticity. Study participants included 521 Black emerging adults between the ages of 18 and 29 (51.6% male; M age = 24.6, SD = 2.6) who completed measures evaluating symptoms of racial discrimination, COVID-related stress, suicide risk, and psychological well-being. After controlling for age, gender, socioeconomic status, and general stress, structural equation modeling analyses revealed unique and interactive effects of racial discrimination, COVID-related stress, and culturally relevant protective factors on suicide risk for Black emerging adults. These findings provide preliminary insight into novel risk and protective factors that influence suicide risk for Black emerging adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Second-generation persons experience unique interpersonal stressors that contribute to overall risk for suicide. However, studies to date have yet to examine complex associations for interpersonal risks and suicide ideation in this growing population. Consistent with the interpersonal theory of suicide, the purpose of this study was to examine the potential moderating effects of acculturative stress (familial and general) in the association of perceived burdensomeness and suicide ideation among second-generation Asian American and Latinx young adults. Second-generation Asian American ( n = 146) and Latinx ( n = 139) university students completed self-measures of perceived burdensomeness, acculturative stress, suicide ideation, and depressive symptoms. Regression analyses revealed that the association for perceived burden and suicide ideation was most robust at higher levels of familial acculturative stress for Asian American study participants. Other models demonstrated likely clinical significance but did not reach statistical significance. In one example, perceived burdensomeness was associated with suicide ideation for second-generation Latinx study participants but, unexpectedly, at low (not high) levels of familial acculturative stress. General acculturative stress was not associated with suicide ideation for Asian American or Latinx university students in multivariate models. The current findings provide insight into interpersonal and contextual factors that contribute to suicide ideation for vulnerable second-generation Asian American and Latinx young adults. Further research is needed to assess shame, parental acculturative stress, and potential buffers such as peer support in risk/resilience models. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

While somatic cell editing to treat disease is widely accepted, the use of human genome editing for "enhancement" remains contested. Scientists and policy-makers routinely cite the prospect of enhancement as a salient ethical challenge for human genome editing research. If preventive genome editing projects are perceived as pursuing human enhancement, they could face heightened barriers to scientific, public, and regulatory approval. This article outlines what we call "preventive strengthening research" (or "PSR") to explore, through this example, how working to strengthen individuals' resistance to disease beyond what biomedicine considers to be the human functional range may be interpreted as pursuing human enhancement. Those involved in developing guidance for PSR will need to navigate the interface between preventive goals and enhancement implications. This article identifies and critiques three of these ideas in the interest of anticipating the wider emergence of PSR and the need for a normative approach for its pursuit. All three "candidate criteria" merit attention, but each also faces challenges that will need to be addressed as further research policy is developed., (© 2024 The Hastings Center.)

Background: Hospital inpatient data, coded using the International Classification of Diseases (ICD), is widely used to monitor diseases, allocate resources and funding, and evaluate patient outcomes. As such, hospital data quality should be measured before use; however, currently, there is no standard and international approach to assess ICD-coded data quality., Objective: To develop a standardized method for assessing hospital ICD-coded data quality that could be applied across countries: Data quality indicators (DQIs)., Research Design: To identify a set of candidate DQIs, we performed an environmental scan, reviewing gray and academic literature on data quality frameworks and existing methods to assess data quality. Indicators from the literature were then appraised and selected through a 3-round Delphi process. The first round involved face-to-face group and individual meetings for idea generation, while the second and third rounds were conducted remotely to collect online ratings. Final DQIs were selected based on the panelists' quantitative and qualitative feedback., Subjects: Participants included international experts with expertise in administrative health data, data quality, and ICD coding., Results: The resulting 24 DQIs encompass 5 dimensions of data quality: relevance, accuracy and reliability; comparability and coherence; timeliness; and Accessibility and clarity. These will help stakeholders (eg, World Health Organization) to assess hospital data quality using the same standard across countries and highlight areas in need of improvement., Conclusions: This novel area of research will facilitate international comparisons of ICD-coded data quality and be valuable to future studies and initiatives aimed at improving hospital administrative data quality., Competing Interests: L.O.-V. received partial financial support, provided by the Libin Cardiovascular Institute of Alberta. The remaining authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

If we assume that nonhuman animals experience pain or distress, then ethically justifying human-centered research with only nonhuman animals as subjects likely requires that the research's benefits to humans must, at least, outweigh harms suffered by the nonhuman animals. Yet this reasoning does not seem to account well for the ethical view that nonhuman animals are morally valuable in their own right. This commentary on a case considers this ethical tension and discusses how clinician-researchers should navigate it. This commentary also suggests why clinician-researchers' reasoning about the nature and scope of their obligations to nonhuman animals extends beyond governing regulations and federal oversight, which is silent on or ambiguous about nonhuman animals as morally valuable in their own right., (Copyright 2024 American Medical Association. All Rights Reserved.)

Objective: Effective management of hypertension requires not only medical intervention but also significant patient self-management. The challenge, however, lies in the diversity of patients' personal barriers to managing their condition. The objective of this research is to identify and categorize personalized barriers to hypertension self-management using the TASKS framework (Task, Affect, Skills, Knowledge, Stress). This study aims to enhance patient-centered strategies by aligning support with each patient's specific needs, recognizing the diversity in their unique circumstances, beliefs, emotional states, knowledge levels, and access to resources. This research is based on observations from a single study focused on eight patients, which may have been a part of a larger project., Results: The analysis of transcripts from eight patients and the Global Hypertension Practice Guidelines revealed 69 personalized barriers. These barriers were distributed as follows: emotional barriers (49%), knowledge barriers (24%), logical barriers (17%), and resource barriers (10%). The findings highlight the significant impact of emotional and knowledge-related challenges on hypertension self-management, including difficulties in home blood pressure monitoring and the use of monitoring tools. This study emphasizes the need for tailored interventions to address these prevalent barriers and improve hypertension management outcomes., (© 2024. The Author(s).)

Background: Many studies have described barriers to gender-affirming surgery (GAS) in Canada; however, few have explored why these barriers persist. To address this knowledge gap, we sought to describe documents related to public health insurance (Medicare) for GAS to identify the types of procedures covered, variations in coverage across provinces and territories, and changes in policy over time., Methods: We conducted a descriptive cross-sectional study using an environmental scan approach. We queried 23 government websites, the Google search engine, and an online legal database between July 2022 and April 2024 to gather gray literature documents related to GAS and Medicare. Variables from relevant documents were compiled to create a present, at-glance overview of GAS Medicare coverage for all provinces and territories and a timeline of policy changes across Canada.  RESULTS: Eight provinces and three territories had documents or websites related to GAS Medicare coverage (85%). We identified 15 GAS procedures that were covered variably across Canada. Yukon (n = 14) covered the most types of GAS, while Quebec and Saskatchewan covered the least (n = 6). Mastectomy and genital surgeries were covered across Canada, but other GAS were rarely covered. Five provinces and territories provided coverage for travel-related costs. Our GAS Medicare timeline showed differential expansion of GAS coverage in Canada over the last 25 years. CONCLUSIONS : We provide previously unreported information regarding GAS Medicare coverage in Canada. We hope our findings will help patients and healthcare providers navigate a complicated public healthcare system. We also highlight barriers within GAS Medicare documents and make recommendations to alleviate those barriers., (© 2024. The Author(s).)

DNA methyltransferase inhibitors (DNMTi), most commonly cytidine analogs, are compounds that decrease 5'-cytosine methylation. DNMTi are used clinically based on the hypothesis that cytosine demethylation will lead to re-expression of tumor suppressor genes. 5-Aza-4'-thio-2'-deoxycytidine (Aza-TdCyd or ATC) is a recently described thiol-substituted DNMTi that has been shown to have anti-tumor activity in solid tumor models. In this study, we investigated the therapeutic potential of ATC in a murine transplantation model of myelodysplastic syndrome. ATC treatment led to the transformation of transplanted wild-type bone marrow nucleated cells into lymphoid leukemia, and healthy mice treated with ATC also developed lymphoid leukemia. Whole-exome sequencing revealed 1,000 acquired mutations, almost all of which were C>G transversions in a specific 5'-NCG-3' context. These mutations involved dozens of genes involved in human lymphoid leukemia, such as Notch1, Pten, Pax5, Trp53, and Nf1. Human cells treated in vitro with ATC showed 1,000 acquired C>G transversions in a similar context. Deletion of Dck, the rate-limiting enzyme for the cytidine salvage pathway, eliminated C>G transversions. Taken together, these findings demonstrate a highly penetrant mutagenic and leukemogenic phenotype associated with ATC. Significance: Treatment with a DNA methyltransferase inhibitor generates a distinct mutation signature and triggers leukemic transformation, which has important implications for the research and clinical applications of these inhibitors., (©2024 American Association for Cancer Research.)

Sarcomas include various subtypes comprising two significant groups - soft tissue and bone sarcomas. Although the survival rate for some sarcoma subtypes has improved over time, the current methods of treatment remain efficaciously limited, as recurrent, and metastatic diseases remain a major obstacle. There is a need for better options and therapeutic strategies in treating sarcoma. Cyclin dependent kinase 9 (CDK9) is a transcriptional kinase and has emerged as a promising target for treating various cancers. The aberrant expression and activation of CDK9 have been observed in several sarcoma subtypes, including rhabdomyosarcoma, synovial sarcoma, osteosarcoma, Ewing sarcoma, and chordoma. Enhanced CDK9 expression has also been correlated with poorer prognosis in sarcoma patients. As a master regulator of transcription, CDK9 promotes transcription elongation by phosphorylation and releasing RNA polymerase II (RNAPII) from its promoter proximal pause. Release of RNAPII from this pause induces transcription of critical genes in the tumor cell. Overexpression and activation of CDK9 have been observed to lead to the expression of oncogenes, including MYC and MCL-1, that aid sarcoma development and progression. Inhibition of CDK9 in sarcoma has been proven to reduce these oncogenes' expression and decrease proliferation and growth in different sarcoma cells. Currently, there are several CDK9 inhibitors in preclinical and clinical investigations. This review aims to highlight the recent discovery and results on the transcriptional role and therapeutic potential of CDK9 in sarcoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Traditional distinctions between treatment and enhancement goals for human genome editing (HGE) have animated oversight considerations, yet these categories have been complicated by the addition of prevention as a possible target for HGE applications. To assess the role these three categories might play in continued HGE governance efforts, we report on interviews with genome editing scientists and governance group members. While some accepted traditional distinctions between treatment and enhancement and rejected the latter as unacceptable, others argued that the concept of enhancement is largely irrelevant or not as morally problematic as suggested. Others described how preventive goals for HGE create gray zones where prevention and enhancement may be difficult to distinguish, which may stymie uses of HGE. We conclude by discussing the governance implications of these various understandings of treatment, prevention, and enhancement as HGE research moves beyond the treatment of serious disease to embrace longer range preventive goals.

Objectives: Normative beliefs around gender and sexuality place individuals in the Two Spirit, lesbian, gay, bisexual, trans, and queer (2SLGBTQ) community at risk for poorer health outcomes within the health care system compared with their heterosexual and cisgender counterparts, particularly within gendered areas of care including family planning and fertility intentions. The purpose of this research was to explore the effect that the normative beliefs of heteronormativity and cisnormativity had on the experiences of 2SLGBTQ people engaged in family planning, and to begin to understand how health care providers can provide appropriate, safe, and holistic care. Methods: We conducted a qualitative study using case study methodology and completing semi-structured interviews with 11 participants with diverse genders and sexualities. Findings: For members of the 2SLGBTQ community, family planning is greatly affected by ideals of normal, intersections of identities, health care systems, and community. They may face additional emotional labor and intentional decision-making when related to family planning. Heteronormativity and cisnormativity greatly impact the health care that is received. Conclusions: The findings contribute information in the limited field of research related to the 2SLGBTQ community and may support health care providers in providing holistic care.

Machine learning models hold great promise with medical applications, but also give rise to a series of ethical challenges. In this survey we focus on training data, model interpretability and bias and the related issues tied to privacy, autonomy, and health equity., Competing Interests: Acknowledgments: The authors report no relevant conflicts of interest., (Copyright ©2024 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.)

Neuropsychiatric genome-wide association studies (GWASs), including those for autism spectrum disorder and schizophrenia, show strong enrichment for regulatory elements in the developing brain. However, prioritizing risk genes and mechanisms is challenging without a unified regulatory atlas. Across 672 diverse developing human brains, we identified 15,752 genes harboring gene, isoform, and/or splicing quantitative trait loci, mapping 3739 to cellular contexts. Gene expression heritability drops during development, likely reflecting both increasing cellular heterogeneity and the intrinsic properties of neuronal maturation. Isoform-level regulation, particularly in the second trimester, mediated the largest proportion of GWAS heritability. Through colocalization, we prioritized mechanisms for about 60% of GWAS loci across five disorders, exceeding adult brain findings. Finally, we contextualized results within gene and isoform coexpression networks, revealing the comprehensive landscape of transcriptome regulation in development and disease.

Diversified crop rotations have been suggested to reduce grain yield losses from the adverse climatic conditions increasingly common under climate change. Nevertheless, the potential for climate change adaptation of different crop rotational diversity (CRD) remains undetermined. We quantified how climatic conditions affect small grain and maize yields under different CRDs in 32 long-term (10-63 years) field experiments across Europe and North America. Species-diverse and functionally rich rotations more than compensated yield losses from anomalous warm conditions, long and warm dry spells, as well as from anomalous wet (for small grains) or dry (for maize) conditions. Adding a single functional group or crop species to monocultures counteracted yield losses from substantial changes in climatic conditions. The benefits of a further increase in CRD are comparable with those of improved climatic conditions. For instance, the maize yield benefits of adding three crop species to monocultures under detrimental climatic conditions exceeded the average yield of monocultures by up to 553 kg/ha under non-detrimental climatic conditions. Increased crop functional richness improved yields under high temperature, irrespective of precipitation. Conversely, yield benefits peaked at between two and four crop species in the rotation, depending on climatic conditions and crop, and declined at higher species diversity. Thus, crop species diversity could be adjusted to maximize yield benefits. Diversifying rotations with functionally distinct crops is an adaptation of cropping systems to global warming and changes in precipitation., (Global Change Biology© 2024 His Majesty the King in Right of Canada and The Authors. Global Change Biology published by John Wiley & Sons Ltd. Reproduced with the permission of the Minister of Agriculture & Agri-Food Canada. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Accumulating evidence suggests that cardiovascular disease (CVD) is associated with an altered gut microbiome. Our understanding of the underlying mechanisms has been hindered by lack of matched multi-omic data with diagnostic biomarkers. To comprehensively profile gut microbiome contributions to CVD, we generated stool metagenomics and metabolomics from 1,429 Framingham Heart Study participants. We identified blood lipids and cardiovascular health measurements associated with microbiome and metabolome composition. Integrated analysis revealed microbial pathways implicated in CVD, including flavonoid, γ-butyrobetaine, and cholesterol metabolism. Species from the Oscillibacter genus were associated with decreased fecal and plasma cholesterol levels. Using functional prediction and in vitro characterization of multiple representative human gut Oscillibacter isolates, we uncovered conserved cholesterol-metabolizing capabilities, including glycosylation and dehydrogenation. These findings suggest that cholesterol metabolism is a broad property of phylogenetically diverse Oscillibacter spp., with potential benefits for lipid homeostasis and cardiovascular health., Competing Interests: Declaration of interests R.J.X. is a member of the Scientific Advisory Boards at Nestlé and Magnet Biomedicine, a founder of Jnana and Celsius Therapeutics, and a board member of MoonLake Immunotherapeutics. A provisional patent application describing potential treatments for CVD using the isolates and related compositions described in this study has been filed. The authors listed on that application are R.J.X., C.L., M.S., A.M.T.M, and D.R.P., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Non-alcoholic fatty liver disease (NAFLD) describes a spectrum of chronic fattening of liver that can lead to fibrosis and cirrhosis. Diabetes has been identified as a major comorbidity that contributes to NAFLD progression. Health systems around the world make use of administrative data to conduct population-based prevalence studies. To that end, we sought to assess the accuracy of diabetes International Classification of Diseases (ICD) coding in administrative databases among a cohort of confirmed NAFLD patients in Calgary, Alberta, Canada., Methods: The Calgary NAFLD Pathway Database was linked to the following databases: Physician Claims, Discharge Abstract Database, National Ambulatory Care Reporting System, Pharmaceutical Information Network database, Laboratory, and Electronic Medical Records. Hemoglobin A1c and diabetes medication details were used to classify diabetes groups into absent, prediabetes, meeting glycemic targets, and not meeting glycemic targets. The performance of ICD codes among these groups was compared to this standard. Within each group, the total numbers of true positives, false positives, false negatives, and true negatives were calculated. Descriptive statistics and bivariate analysis were conducted on identified covariates, including demographics and types of interacted physicians., Results: A total of 12,012 NAFLD patients were registered through the Calgary NAFLD Pathway Database and 100% were successfully linked to the administrative databases. Overall, diabetes coding showed a sensitivity of 0.81 and a positive predictive value of 0.87. False negative rates in the absent and not meeting glycemic control groups were 4.5% and 6.4%, respectively, whereas the meeting glycemic control group had a 42.2% coding error. Visits to primary and outpatient services were associated with most encounters., Conclusion: Diabetes ICD coding in administrative databases can accurately detect true diabetic cases. However, patients with diabetes who meets glycemic control targets are less likely to be coded in administrative databases. A detailed understanding of the clinical context will require additional data linkage from primary care settings., (© 2024. The Author(s).)

Objective: To examine purpose in life (PIL) and ethnic identity (EI) as buffers to suicide ideation for Asian American, Hispanic, and Black emerging adults who perceive racial discrimination., Method: Two-hundred eighty-nine undergraduate students enrolled at a large university in the southwestern region of the United States (40.8% Asian American, 32.5% Hispanic, 26.6% Black; 61.2% women; mean age = 20.47, SD = 1.83) reported on experiences of racial discrimination, PIL, EI, and suicidal thoughts. Covariates were intrinsic religiosity, gender, and age., Results: Regression analysis showed that EI was not a significant moderator for the association between perceived racial discrimination (PRD) and suicidal ideation (β = -.08, p = .13; 95% confidence interval (CI) [-.19, .03]). However, PIL was a significant moderator (β = -.11, p = .025; CI [-.20, -.01]). A hierarchical regression showed that PIL as a moderator explained additional variance (ΔR2 = 0.11, p < .001) in suicide ideation above and beyond EI., Conclusions: These findings provide some insight into how life purpose might ameliorate the impact of social stressors above and beyond a positive cultural identity for young racial/ethnic minority adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Imprisonment may sometimes be a justified form of punishment. Yet the U.S. carceral system suffers from appalling problems of justice-in who is put into prisons, in how imprisoned people are treated, and in downstream personal and community health impacts. Medical personnel working in prisons and jails take on risky work for highly vulnerable and underserved patients. They are to be lauded for their professional commitments. Yet at the same time, prison care undercuts the ability of medical personnel to uphold their own professional standards and sometimes fails in even basic health protection. Doctors in prisons are stuck between their commitment to vulnerable patients and complicity in a system that requires their participation to uphold its constitutionality. Medical ethics is frayed in prisons, and the problem deserves our attention., (© 2024 The Hastings Center.)

Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: support from the Patient-Centered Outcomes Research Institute, Novo Nordisk Foundation, and Kaiser Permanente for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Background: Liposarcoma is the most commonly diagnosed subtype of soft tissue sarcoma. As these tumors often arise near vital organs and neurovascular structures, complete resection can be challenging; consequently, recurrence rates are high. Additionally, available chemotherapeutic agents have shown limited benefit and substantial toxicities. There is, therefore, a clear and unmet need for novel therapeutics for liposarcoma. Discoidin domain receptor tyrosine kinase 1 (DDR1) is involved in adhesion, proliferation, differentiation, migration, and metastasis in several cancers. However, the expression and clinical importance of DDR1 in liposarcoma are unknown., Questions/purposes: The purposes of this study were to assess (1) the expression, (2) the association between DDR1 and survival, and (3) the functional roles of DDR1 in liposarcoma., Methods: The correlation between DDR1 expression in tumor tissues and clinicopathological features and survival was assessed via immunohistochemical staining of a liposarcoma tissue microarray. It contained 53 samples from 42 patients with liposarcoma and 11 patients with lipoma. The association between DDR1 and survival in liposarcoma was analyzed by Kaplan-Meier plots and log-rank tests. The DDR1 knockout liposarcoma cell lines were generated by CRISPR-Cas9 technology. The DDR1-specific and highly selective DDR1 inhibitor 7RH was applied to determine the impact of DDR1 expression on liposarcoma cell growth and proliferation. In addition, the effect of DDR1 inhibition on liposarcoma growth was further accessed in a three-dimensional cell culture model to mimic DDR1 effects in vivo., Results: The results demonstrate elevated expression of DDR1 in all liposarcoma subtypes relative to benign lipomas. Specifically, high DDR1 expression was seen in 55% (23 of 42) of liposarcomas and no benign lipomas. However, DDR1 expression was not found to be associated with poor survival in patients with liposarcoma. DDR1 knockout or treatment of 7RH showed decreased liposarcoma cell growth and proliferation., Conclusion: DDR1 is aberrantly expressed in liposarcoma, and it contributes to several markers of oncogenesis in these tumors., Clinical Relevance: This work supports DDR1 as a promising therapeutic target in liposarcoma., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)

Alberta has rich clinical and health services data held under the custodianship of Alberta Health and Alberta Health Services (AHS), which is not only used for clinical and administrative purposes but also disease surveillance and epidemiological research. Alberta is the largest province in Canada with a single payer centralised health system, AHS, and a consolidated data and analytics team supporting researchers across the province. This paper describes Alberta's data custodians, data governance mechanisms, and streamlined processes followed for research data access. AHS has created a centralised data repository from multiple sources, including practitioner claims data, hospital discharge data, and medications dispensed, available for research use through the provincial Data and Research Services (DRS) team. The DRS team is integrated within AHS to support researchers across the province with their data extraction and linkage requests. Furthermore, streamlined processes have been established, including: 1) ethics approval from a research ethics board, 2) any necessary operational approvals from AHS, and 3) a tripartite legal agreement dictating terms and conditions for data use, disclosure, and retention. This allows researchers to gain timely access to data. To meet the evolving and ever-expanding big-data needs, the University of Calgary, in partnership with AHS, has built high-performance computing (HPC) infrastructure to facilitate storage and processing of large datasets. When releasing data to researchers, the analytics team ensures that Alberta's Health Information Act's guiding principles are followed. The principal investigator also ensures data retention and disposition are according to the plan specified in ethics and per the terms set out by funding agencies. Even though there are disparities and variations in the data protection laws across the different provinces in Canada, the streamlined processes for research data access in Alberta are highly efficient., Competing Interests: Statement of conflicts of interest: The authors declare there are no conflicts of interest.

Background: Abstracting cerebrovascular disease (CeVD) from inpatient electronic medical records (EMRs) through natural language processing (NLP) is pivotal for automated disease surveillance and improving patient outcomes. Existing methods rely on coders' abstraction, which has time delays and under-coding issues. This study sought to develop an NLP-based method to detect CeVD using EMR clinical notes., Methods: CeVD status was confirmed through a chart review on randomly selected hospitalized patients who were 18 years or older and discharged from 3 hospitals in Calgary, Alberta, Canada, between January 1 and June 30, 2015. These patients' chart data were linked to administrative discharge abstract database (DAD) and Sunrise ™ Clinical Manager (SCM) EMR database records by Personal Health Number (a unique lifetime identifier) and admission date. We trained multiple natural language processing (NLP) predictive models by combining two clinical concept extraction methods and two supervised machine learning (ML) methods: random forest and XGBoost. Using chart review as the reference standard, we compared the model performances with those of the commonly applied International Classification of Diseases (ICD-10-CA) codes, on the metrics of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)., Result: Of the study sample (n = 3036), the prevalence of CeVD was 11.8% (n = 360); the median patient age was 63; and females accounted for 50.3% (n = 1528) based on chart data. Among 49 extracted clinical documents from the EMR, four document types were identified as the most influential text sources for identifying CeVD disease ("nursing transfer report," "discharge summary," "nursing notes," and "inpatient consultation."). The best performing NLP model was XGBoost, combining the Unified Medical Language System concepts extracted by cTAKES (e.g., top-ranked concepts, "Cerebrovascular accident" and "Transient ischemic attack"), and the term frequency-inverse document frequency vectorizer. Compared with ICD codes, the model achieved higher validity overall, such as sensitivity (25.0% vs 70.0%), specificity (99.3% vs 99.1%), PPV (82.6 vs. 87.8%), and NPV (90.8% vs 97.1%)., Conclusion: The NLP algorithm developed in this study performed better than the ICD code algorithm in detecting CeVD. The NLP models could result in an automated EMR tool for identifying CeVD cases and be applied for future studies such as surveillance, and longitudinal studies., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Soluble human lectins are critical components of innate immunity. Genetic models suggest that lectins influence host-resident microbiota, but their specificity for commensal and mutualist species is understudied. Elucidating lectins' roles in regulating microbiota requires an understanding of which microbial species they bind within native communities. To profile human lectin recognition, we developed Lectin-Seq. We apply Lectin-Seq to human fecal microbiota using the soluble mannose-binding lectin (MBL) and intelectin-1 (hItln1). Although each lectin binds a substantial percentage of the samples (10 to 20%), the microbial interactomes of MBL and hItln1 differ markedly in composition and diversity. MBL binding is highly selective for a small subset of species commonly associated with humans. In contrast, hItln1's interaction profile encompasses a broad range of lower-abundance species. Our data uncover stark differences in the commensal recognition properties of human lectins.

Introduction: As the number of U.S. veterans over age 65 has increased, interest in whether military service affects late-life health outcomes has grown. Whether military employment is associated with increased risk of cognitive decline and dementia remains unclear., Materials and Methods: We used data from 4,370 participants of the longitudinal Adult Changes in Thought (ACT) cohort study, enrolled at age 65 or older, to examine whether military employment was associated with greater cognitive decline or higher risk of incident dementia in late life. We classified persons as having military employment if their first or second-longest occupation was with the military. Cognitive status was assessed at each biennial Adult Changes in Thought study visit using the Cognitive Abilities Screening Instrument, scored using item response theory (CASI-IRT). Participants meeting screening criteria were referred for dementia ascertainment involving clinical examination and additional cognitive testing. Primary analyses were adjusted for sociodemographic characteristics and APOE genotype. Secondary analyses additionally adjusted for indicators of early-life socioeconomic status and considered effect modification by age, gender, and prior traumatic brain injury with loss of consciousness TBI with LOC., Results: Overall, 6% of participants had military employment; of these, 76% were males. Military employment was not significantly associated with cognitive change (difference in modeled 10-year cognitive change in CASI-IRT scores in SD units (95% confidence interval [CI]): -0.042 (-0.19, 0.11), risk of dementia (hazard ratio [HR] [95% CI]: 0.92 [0.71, 1.18]), or risk of Alzheimer's disease dementia (HR [95% CI]: 0.93 [0.70, 1.23]). These results were robust to additional adjustment and sensitivity analyses. There was no evidence of effect modification by age, gender, or traumatic brain injury with loss of consciousness., Conclusions: Among members of the Adult Changes in Thought cohort, military employment was not associated with increased risk of cognitive decline or dementia. Nevertheless, military veterans face the same high risks for cognitive decline and dementia as other aging adults., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Little is known about whether diabetes increases the risk of COVID-19 infection and whether measures of diabetes severity are related to COVID-19 outcomes., Objective: Investigate diabetes severity measures as potential risk factors for COVID-19 infection and COVID-19 outcomes., Design, Participants, Measures: In integrated healthcare systems in Colorado, Oregon, and Washington, we identified a cohort of adults on February 29, 2020 (n = 1,086,918) and conducted follow-up through February 28, 2021. Electronic health data and death certificates were used to identify markers of diabetes severity, covariates, and outcomes. Outcomes were COVID-19 infection (positive nucleic acid antigen test, COVID-19 hospitalization, or COVID-19 death) and severe COVID-19 (invasive mechanical ventilation or COVID-19 death). Individuals with diabetes (n = 142,340) and categories of diabetes severity measures were compared with a referent group with no diabetes (n = 944,578), adjusting for demographic variables, neighborhood deprivation index, body mass index, and comorbidities., Results: Of 30,935 patients with COVID-19 infection, 996 met the criteria for severe COVID-19. Type 1 (odds ratio [OR] 1.41, 95% CI 1.27-1.57) and type 2 diabetes (OR 1.27, 95% CI 1.23-1.31) were associated with increased risk of COVID-19 infection. Insulin treatment was associated with greater COVID-19 infection risk (OR 1.43, 95% CI 1.34-1.52) than treatment with non-insulin drugs (OR 1.26, 95% 1.20-1.33) or no treatment (OR 1.24; 1.18-1.29). The relationship between glycemic control and COVID-19 infection risk was dose-dependent: from an OR of 1.21 (95% CI 1.15-1.26) for hemoglobin A1c (HbA1c) < 7% to an OR of 1.62 (95% CI 1.51-1.75) for HbA1c ≥ 9%. Risk factors for severe COVID-19 were type 1 diabetes (OR 2.87; 95% CI 1.99-4.15), type 2 diabetes (OR 1.80; 95% CI 1.55-2.09), insulin treatment (OR 2.65; 95% CI 2.13-3.28), and HbA1c ≥ 9% (OR 2.61; 95% CI 1.94-3.52)., Conclusions: Diabetes and greater diabetes severity were associated with increased risks of COVID-19 infection and worse COVID-19 outcomes., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Purpose: To investigate whether associations between diabetic retinopathy (DR) and dementia and Alzheimer's disease (AD) remain significant after controlling for several measures of diabetes severity., Design: Retrospective cohort study., Methods: Adult Changes in Thought (ACT) is a prospective cohort study of adults aged ≥65 years, randomly selected and recruited from the membership rolls of Kaiser Permanente Washington, who are dementia free at enrollment and followed biennially until incident dementia. The ACT participants were included in this study if they had type 2 diabetes mellitus at enrollment or developed it during follow-up, and data were collected through September, 2018 (3516 person-years of follow-up). Diabetes was defined by ≥ 2 diabetes medication fills in 1 year. Diagnosis of DR was based on International Classification of Diseases Ninth and Tenth Revision codes. Estimates of microalbuminuria, long-term glycemia, and renal function from longitudinal laboratory records were used as indicators of diabetes severity. Alzheimer's disease and dementia were diagnosed using research criteria at expert consensus meetings., Results: A total of 536 participants (median baseline age 75 [interquartile range 71-80], 54% women) met inclusion criteria. Significant associations between DR >5 years duration with dementia (hazard ratio 1.81 [95% CI 1.23, 2.65]) and AD (1.80 [1.15, 2.82]) were not altered by adjustment for estimates of microalbuminuria, long-term glycemia, and renal function (dementia: 1.69 [1.14, 2.50]; AD: 1.73 [1.10, 2.74])., Conclusions: Among people with type 2 diabetes, DR itself appears to be an important biomarker of dementia risk in addition to glycemia and renal complications., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Persons with military involvement may be more likely to have Parkinson's disease (PD) risk factors. As PD is rare, case finding remains a challenge, contributing to our limited understanding of PD risk factors. Here, we explore the validity of case-finding strategies and whether military employment is associated with PD., Materials and Methods: We identified Adult Changes in Thought (ACT) study participants reporting military employment as their longest or second longest occupation. We used self-report and prescription fills to identify PD cases and validated this case-finding approach against medical record review., Results: At enrollment, 6% of 5,125 eligible participants had military employment and 1.8% had prevalent PD; an additional 3.5% developed PD over follow-up (mean: 8.3 years). Sensitivity of our case-finding approach was higher for incident (80%) than prevalent cases (54%). Specificity was high (>97%) for both. Military employment was not associated with prevalent PD. Among nonsmokers, point estimates suggested an increased risk of incident PD with military employment, but the result was non-significant and based on a small number of cases., Conclusions: Self-report and prescription medications can accurately identify incident PD cases relative to the reference method of medical record review. We found no association between military employment and PD.

Suicide risk prediction models can identify individuals for targeted intervention. Discussions of transparency, explainability, and transportability in machine learning presume complex prediction models with many variables outperform simpler models. We compared random forest, artificial neural network, and ensemble models with 1500 temporally defined predictors to logistic regression models. Data from 25,800,888 mental health visits made by 3,081,420 individuals in 7 health systems were used to train and evaluate suicidal behavior prediction models. Model performance was compared across several measures. All models performed well (area under the receiver operating curve [AUC]: 0.794-0.858). Ensemble models performed best, but improvements over a regression model with 100 predictors were minimal (AUC improvements: 0.006-0.020). Results are consistent across performance metrics and subgroups defined by race, ethnicity, and sex. Our results suggest simpler parametric models, which are easier to implement as part of routine clinical practice, perform comparably to more complex machine learning methods., (© 2023. The Author(s).)

Genomic regulatory elements active in the developing human brain are notably enriched in genetic risk for neuropsychiatric disorders, including autism spectrum disorder (ASD), schizophrenia, and bipolar disorder. However, prioritizing the specific risk genes and candidate molecular mechanisms underlying these genetic enrichments has been hindered by the lack of a single unified large-scale gene regulatory atlas of human brain development. Here, we uniformly process and systematically characterize gene, isoform, and splicing quantitative trait loci (xQTLs) in 672 fetal brain samples from unique subjects across multiple ancestral populations. We identify 15,752 genes harboring a significant xQTL and map 3,739 eQTLs to a specific cellular context. We observe a striking drop in gene expression and splicing heritability as the human brain develops. Isoform-level regulation, particularly in the second trimester, mediates the greatest proportion of heritability across multiple psychiatric GWAS, compared with eQTLs. Via colocalization and TWAS, we prioritize biological mechanisms for ~60% of GWAS loci across five neuropsychiatric disorders, nearly two-fold that observed in the adult brain. Finally, we build a comprehensive set of developmentally regulated gene and isoform co-expression networks capturing unique genetic enrichments across disorders. Together, this work provides a comprehensive view of genetic regulation across human brain development as well as the stage-and cell type-informed mechanistic underpinnings of neuropsychiatric disorders., Competing Interests: M.J.G. and D.H.G. receive grant funding from Mitsubishi Tanabe Pharma America.

Objective: Despite external ventricular drain (EVD) procedures being commonplace in neurosurgical practice, suboptimal placement rates remain high, and complications are not uncommon. The angle of the EVD catheter insertion and the accuracy of the drill hole placement are major factors determining successful EVD placement that are dependent on the drill bit morphology. The standard cylindrical 2-fluted twist drill bit creates a relatively deep and narrow drill hole that requires precise positioning, has limited visibility of the drill hole bottom and restricted catheter angular adjustment range, and poses the risk of inadvertent dural puncture. To overcome the standard problems associated with EVD drill bit morphology, the authors propose novel cone-shaped drill bits for EVD placement., Methods: Conical drill bits of 30° and 45° were designed, manufactured, and tested in a simulated laboratory setting as well as in three human cadavers with intact skull, dura mater, and brain. Drill bit performance was rated by neurosurgical trainees across various domains using Likert scale-type questions., Results: In the laboratory, maximum drilling temperatures adjacent to the drill hole were recorded and compared for the standard drill bit and the 30° and 45° conical drill bits and were not significantly different (p = 0.631 and p = 0.326, respectively). The maximum temperature recorded directly underneath the drilling site for the 45° drill bit was significantly higher than the temperature of the standard drill bit (p = 0.043). The differences between the standard and 30° drill bits were not significant (p = 0.783). Upon cadaver testing, the drilling times with 30° and 45° conical drill bits were significantly longer than those with the standard drill bit (p = 0.036 and p = 0.002, respectively). Likert scale scores were significantly higher for the conical 30° (median [IQR] 4.7 [3.3-5]) and 45° (4 [2-5]) drill bits than for the standard drill bit (1.7 [1-2.5], p < 0.0001), indicating significantly better performance. Conical drill bits used as a "rescue" strategy allowed for an EVD catheter angular adjustment range 6 to 9 times greater than that for the standard drill bit and resulted in a zero inadvertent dural puncture rate., Conclusions: The 30° conical drill bit can be safely used on its own or as a rescue tool to potentially achieve improved confidence, visualization, targeting, and precision of EVD placement while essentially eliminating the possibility of unintentional dural puncture with minimal increase in the total procedure time.

COVID-19 inequities have been well-documented. We evaluated whether higher rates of severe COVID-19 in racial and ethnic minority groups were driven by higher infection rates by evaluating if disparities remained when analyses were restricted to people with infection. We conducted a retrospective cohort study of adults insured through Kaiser Permanente (Colorado, Northwest, Washington), follow-up in March-September 2020. Laboratory results and hospitalization diagnosis codes identified individuals with COVID-19. Severe COVID-19 was defined as invasive mechanical ventilation or mortality. Self-reported race and ethnicity, demographics, and medical comorbidities were extracted from health records. Modified Poisson regression estimated adjusted relative risks (aRRs) of severe COVID-19 in full cohort and among individuals with infection. Our cohort included 1,052,774 individuals, representing diverse racial and ethnic minority groups (e.g., 68,887 Asian, 41,243 Black/African American, 93,580 Hispanic or Latino/a individuals). Among 7,399 infections, 442 individuals experienced severe COVID-19. In the full cohort, severe COVID-19 aRRs for Asian, Black/African American, and Hispanic individuals were 2.09 (95% CI: 1.36, 3.21), 2.02 (1.39, 2.93), and 2.09 (1.57, 2.78), respectively, compared to non-Hispanic Whites. In analyses restricted to individuals with COVID-19, all aRRs were near 1, except among Asian Americans (aRR 1.82 [1.23, 2.68]). These results indicate increased incidence of severe COVID-19 among Black/African American and Hispanic individuals is due to higher infection rates, not increased susceptibility to progression. COVID-19 disparities most likely result from social, not biological, factors. Future work should explore reasons for increased severe COVID-19 risk among Asian Americans. Our findings highlight the importance of equity in vaccine distribution., (© 2022. W. Montague Cobb-NMA Health Institute.)

Risk prediction models are frequently used to identify individuals at risk of developing hypertension. This study evaluates different machine learning algorithms and compares their predictive performance with the conventional Cox proportional hazards (PH) model to predict hypertension incidence using survival data. This study analyzed 18,322 participants on 24 candidate features from the large Alberta's Tomorrow Project (ATP) to develop different prediction models. To select the top features, we applied five feature selection methods, including two filter-based: a univariate Cox p-value and C-index; two embedded-based: random survival forest and least absolute shrinkage and selection operator (Lasso); and one constraint-based: the statistically equivalent signature (SES). Five machine learning algorithms were developed to predict hypertension incidence: penalized regression Ridge, Lasso, Elastic Net (EN), random survival forest (RSF), and gradient boosting (GB), along with the conventional Cox PH model. The predictive performance of the models was assessed using C-index. The performance of machine learning algorithms was observed, similar to the conventional Cox PH model. Average C-indexes were 0.78, 0.78, 0.78, 0.76, 0.76, and 0.77 for Ridge, Lasso, EN, RSF, GB and Cox PH, respectively. Important features associated with each model were also presented. Our study findings demonstrate little predictive performance difference between machine learning algorithms and the conventional Cox PH regression model in predicting hypertension incidence. In a moderate dataset with a reasonable number of features, conventional regression-based models perform similar to machine learning algorithms with good predictive accuracy., (© 2023. The Author(s).)

Background: Prior studies into the association of head trauma with neuropathology have been limited by incomplete lifetime neurotrauma exposure characterization., Objective: To investigate the neuropathological sequelae of traumatic brain injury (TBI) in an autopsy sample using three sources of TBI ascertainment, weighting findings to reflect associations in the larger, community-based cohort., Methods: Self-reported head trauma with loss of consciousness (LOC) exposure was collected in biennial clinic visits from 780 older adults from the Adult Changes in Thought study who later died and donated their brain for research. Self-report data were supplemented with medical record abstraction, and, for 244 people, structured interviews on lifetime head trauma. Neuropathology outcomes included Braak stage, CERAD neuritic plaque density, Lewy body distribution, vascular pathology, hippocampal sclerosis, and cerebral/cortical atrophy. Exposures were TBI with or without LOC. Modified Poisson regressions adjusting for age, sex, education, and APOE ɛ4 genotype were weighted back to the full cohort of 5,546 participants., Results: TBI with LOC was associated with the presence of cerebral cortical atrophy (Relative Risk 1.22, 95% CI 1.02, 1.42). None of the other outcomes was associated with TBI with or without LOC., Conclusion: TBI with LOC was associated with increased risk of cerebral cortical atrophy. Despite our enhanced TBI ascertainment, we found no association with the Alzheimer's disease-related neuropathologic outcomes among people who survived to at least age 65 without dementia. This suggests the pathophysiological processes underlying post-traumatic neurodegeneration are distinct from the hallmark pathologies of Alzheimer's disease.

Objective: The associations between posttraumatic stress disorder (PTSD) symptom severity, alcohol use, and alcohol use motives are well-established. Emotion regulation difficulties have been implicated in the association between PTSD symptoms and alcohol use. A dearth of empirical work, however, has examined these associations among Black/African American college students, a population with high prevalence of exposure to potentially traumatic events, PTSD symptomatology, and alcohol-related consequences., Methods: This study examined PTSD symptoms, emotion regulation difficulties, and alcohol use severity and motives among a sample of Black/African American trauma-exposed college students ( N  = 282; 77.4% identified as female; M age  = 22.36, SD  = 4.71)., Results: PTSD symptom severity was related to alcohol use and coping and conformity motives for alcohol use through heightened emotion regulation difficulties. Findings were significant above and beyond the effects of trauma load (i.e., number of potentially traumatic event types experienced)., Conclusions: This study extends past work to an understudied population and contributes to groundwork for culturally informed interventions.

Background: The ethical use both of human and non-human animals in research is predicated on the assumption that it is of a high quality and its projected benefits are more significant than the risks and harms imposed on subjects. Yet questions remain about whether and how IRBs and IACUCs should consider the scientific value of proposed research studies., Methods: We draw upon 45 interviews with IRB and IACUC members and researchers with oversight experience about their perceptions of their own roles in reviewing the quality and value of scientific protocols. Interview transcripts were memoed to highlight specific findings, which were then used to identify key themes through an iterative process., Results: IRB and IACUC members expressed broad trust in the need for and value of research, and they often assumed that protocols had social value or that prior review, especially when associated with funding, affirmed both the rigor and merit of those protocols. Some oversight members also took an explicit stance against scientific review by stating that such review is not within the regulatory mandates governing their parts in the oversight system. Yet other interviewees expressed uneasiness about the current paradigm for evaluating the quality and overall value of science, suggesting that IRB and IACUC members perceive gaps in the oversight systems., Conclusions: These findings reveal many similarities in how IRB and IACUC members understand the roles and limitations of their respective oversight committees. We conclude with a discussion of how the lack of a clear mandate regarding scientific review within US federal regulations may undermine ethical engagement of whether human and animal research is scientifically justified, resulting in a "mission lapse" wherein no organizational body is clearly responsible for ensuring that the research being conducted has the potential to advance science and benefit society.

Background: Prognostic information for patients with hypertension is largely based on population averages. The purpose of this study was to compare the performance of four machine learning approaches for personalized prediction of incident hospitalization for cardiovascular disease among newly diagnosed hypertensive patients., Methods: Using province-wide linked administrative health data in Alberta, we analyzed a cohort of 259,873 newly-diagnosed hypertensive patients from 2009 to 2015 who collectively had 11,863 incident hospitalizations for heart failure, myocardial infarction, and stroke. Linear multi-task logistic regression, neural multi-task logistic regression, random survival forest and Cox proportional hazard models were used to determine the number of event-free survivors at each time-point and to construct individual event-free survival probability curves. The predictive performance was evaluated by root mean squared error, mean absolute error, concordance index, and the Brier score., Results: The random survival forest model has the lowest root mean squared error value at 33.94 and lowest mean absolute error value at 28.37. Machine learning methods provide similar discrimination and calibration in the personalized survival prediction of hospitalizations for cardiovascular events in patients with hypertension. Neural multi-task logistic regression model has the highest concordance index at 0.8149 and lowest Brier score at 0.0242 for the personalized survival prediction., Conclusions: This is the first personalized survival prediction for cardiovascular diseases among hypertensive patients using administrative data. The four models tested in this analysis exhibited a similar discrimination and calibration ability in predicting personalized survival prediction of hypertension patients., (© 2022. The Author(s).)