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We examine the connection between diffuse ionized gas (DIG), H  ii regions, and field O and B stars in the nearby spiral M101 and its dwarf companion NGC 5474 using ultra-deep H α narrow-band imaging and archival GALEX UV imaging. We find a strong correlation between DIG H α surface brightness and the incident ionizing flux leaked from the nearby H  ii regions, which we reproduce well using simple cloudy simulations. While we also find a strong correlation between H α and co-spatial far-ultraviolet (FUV) surface brightness in DIG, the extinction-corrected integrated UV colours in these regions imply stellar populations too old to produce the necessary ionizing photon flux. Combined, this suggests that H  ii region leakage, not field OB stars, is the primary source of DIG in the M101 Group. Corroborating this interpretation, we find systematic disagreement between the H α- and FUV-derived star formation rates (SFRs) in the DIG, with SFRH α FUV everywhere. Within H  ii regions, we find a constant SFR ratio of 0.44 to a limit of ∼10−5 M⊙ yr−1. This result is in tension with other studies of star formation in spiral galaxies, which typically show a declining SFRH α/SFRFUV ratio at low SFR. We reproduce such trends only when considering spatially averaged photometry that mixes H  ii regions, DIG, and regions lacking H α entirely, suggesting that the declining trends found in other galaxies may result purely from the relative fraction of diffuse flux, leaky compact H  ii regions, and non-ionizing FUV-emitting stellar populations in different regions within the galaxy. [ABSTRACT FROM AUTHOR]

Aims: Drug disposition in children may vary from adults due to age‐related variation in drug metabolism. Microdose studies present an innovation to study pharmacokinetics (PK) in paediatrics; however, they should be used only when the PK is dose linear. We aimed to assess dose linearity of a [14C]midazolam microdose, by comparing the PK of an intravenous (IV) microtracer (a microdose given simultaneously with a therapeutic midazolam dose), with the PK of a single isolated microdose. Methods: Preterm to 2‐year‐old infants admitted to the intensive care unit received [14C]midazolam IV as a microtracer or microdose, followed by dense blood sampling up to 36 hours. Plasma concentrations of [14C]midazolam and [14C]1‐hydroxy‐midazolam were determined by accelerator mass spectrometry. Noncompartmental PK analysis was performed and a population PK model was developed. Results: Of 15 infants (median gestational age 39.4 [range 23.9–41.4] weeks, postnatal age 11.4 [0.6–49.1] weeks), 6 received a microtracer and 9 a microdose of [14C]midazolam (111 Bq kg−1; 37.6 ng kg−1). In a 2‐compartment PK model, bodyweight was the most significant covariate for volume of distribution. There was no statistically significant difference in any PK parameter between the microdose and microtracer, nor in the area under curve ratio [14C]1‐OH‐midazolam/[14C]midazolam, showing the PK of midazolam to be linear within the range of the therapeutic and microdoses. Conclusion: Our data support the dose linearity of the PK of an IV [14C]midazolam microdose in children. Hence, a [14C]midazolam microdosing approach may be used as an alternative to a therapeutic dose of midazolam to study developmental changes in hepatic CYP3A activity in young children. [ABSTRACT FROM AUTHOR]

Pang X, Zhang L, Bai F, et al. Drug Des Devel Ther. 15;9:6043–6054.The authors have advised there is an error in theWestern blot bands shown in Figure 6 on page 6050, pSmad2 at 2 weeks.Each band shown in Figure 6 represents one animal, and six or seven animals were used for each group. The statistical difference was calculated from the protein analysis using every animal tissue sample. Once the overall group statistical difference was found, three bands were chosen to represent the difference more closely between the control (Con) and curcumin (Cur) groups. The authors acknowledge the error in using the same bands in lanes two and three to show pSmad 2 at 2 weeks in the Con group. The data have been newly and independently validated from additional samples, and the results have demonstrated symmetrical expression of pSmad2 in the Con group as shown in the correct Figure 6 below.The authors apologize for this error.Read the original article

Xue-Fen Pang,1 Li-Hui Zhang,2 Feng Bai,1 Ning-Ping Wang,3 Ron E Garner,3 Robert J McKallip,4 Zhi-Qing Zhao1,3 1Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Cardiology, Shanxi Academy of Medical Sciences and Shanxi Dayi Hospital, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Basic Biomedical Sciences, Mercer University School of Medicine, Savannah, GA, USA; 4Division of Basic Biomedical Sciences, Mercer University School of Medicine, Macon, GA, USA Abstract: Curcumin is known to improve cardiac function by balancing degradation and synthesis of collagens after myocardial infarction. This study tested the hypothesis that inhibition of myocardial fibrosis by curcumin is associated with modulating expression of angiotensin II (Ang II) receptors and angiotensin-converting enzyme 2 (ACE2). Male Sprague Dawley rats were subjected to Ang II infusion (500 ng/kg/min) using osmotic minipumps for 2 and 4 weeks, respectively, and curcumin (150 mg/kg/day) was fed by gastric gavage during Ang II infusion. Compared to the animals with Ang II infusion, curcumin significantly decreased the mean arterial blood pressure during the course of the observation. The protein level of the Ang II type 1 (AT1) receptor was reduced, and the Ang II type 2 (AT2) receptor was up-regulated, evidenced by an increased ratio of the AT2 receptor over the AT1 receptor in the curcumin group (1.2±0.02%) vs in the Ang II group (0.7±0.03%, P

A late post-traumatic seizure (LPTS), a consequence of traumatic brain injury (TBI), can potentially evolve into a lifelong condition known as post-traumatic epilepsy (PTE). Presently, the mechanism that triggers epileptogenesis in TBI patients remains elusive, inspiring the epilepsy community to devise ways to predict which TBI patients will develop PTE and to identify potential biomarkers. In response to this need, our study collected comprehensive, longitudinal multimodal data from 48 TBI patients across multiple participating institutions. A supervised binary classification task was created, contrasting data from LPTS patients with those without LPTS. To accommodate missing modalities in some subjects, we took a two-pronged approach. Firstly, we extended a graphical model-based Bayesian estimator to directly classify subjects with incomplete modality. Secondly, we explored conventional imputation techniques. The imputed multimodal information was then combined, following several fusion and dimensionality reduction techniques found in the literature, and subsequently fitted to a kernel- or a tree-based classifier. For this fusion, we proposed two new algorithms: recursive elimination of correlated components (RECC) that filters information based on the correlation between the already selected features, and information decomposition and selective fusion (IDSF), which effectively recombines information from decomposed multimodal features. Our cross-validation findings showed that the proposed IDSF algorithm delivers superior performance based on the area under the curve (AUC) score. Ultimately, after rigorous statistical comparisons and interpretable machine learning examination using Shapley values of the most frequently selected features, we recommend the two following magnetic resonance imaging (MRI) abnormalities as potential biomarkers: the left anterior limb of internal capsule in diffusion MRI (dMRI), and the right middle temporal gyrus in functional MRI (fMRI)., 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 Ltd. All rights reserved.)

Study Design: Retrospective cohort., Objective: To compare the rates of all-cause surgical complications of synthetic interbody devices versus allograft or autograft in patients undergoing 1-2 levels anterior cervical discectomy and fusion (ACDF) procedures., Summary of Background Data: Cervical degenerative disorders affect up to 60% of older adults in the United States. Both traditional allograft or autograft and synthetic interbody devices (polyetheretherketone or titanium) are used for decompression and arthrodesis, with increasing utilization of the latter. However, the differences in their postsurgical complication profiles are not well-characterized., Patients and Methods: Patients who underwent 1-2 level ACDFs for cervical radiculopathy or myelopathy between 2010 and 2022 were identified using the PearlDiver Mariner all-claims insurance database. Patients undergoing surgery for nondegenerative pathologies, such as tumors, trauma, or infection, were excluded. 1:1 exact matching was performed based on factors that were significant predictors of all-cause surgical complications in a linear regression model. The primary outcome measure was the development of all-cause surgical complications after 1-2 level ACDFs. The secondary outcome was all-cause medical complications., Results: 1:1 exact matching resulted in two equal groups of 11,430 patients who received treatment with synthetic interbody devices or allograft/autograft. No statistically significant difference in all-cause surgical complications was found between the synthetic cohort and the allograft or autograft cohort after 1-2 level ACDFs (Relative Risk: 0.86, 95% confidence interval: 0.730-1.014, P = 0.079). No significant differences were observed regarding any specific surgical complications except for pseudoarthrosis (Relative Risk: 0.73, 95% confidence interval: 0.554-0.974, P = 0.037), which was higher in the allograft/autograft cohort., Conclusion: After 1:1 exact matching to control for confounding variables, the findings of this study suggest that all-cause surgical complications are similar in patients undergoing ACDFs with synthetic interbody devices or allograft/autographs. However, the rate of pseudarthrosis appears to be higher in patients with allograft/autographs. Future prospective studies are needed to corroborate these findings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: This was a retrospective cohort study., Objective: To compare the rates of pseudarthrosis in patients undergoing 1 to 3 level transforaminal lumbar interbody fusion (TLIF) procedures between cannabis users and noncannabis users., Summary of Background Data: Recreational use of cannabis is common, though it remains poorly studied and legally ambiguous in the United States. Patients with back pain may turn to adjunctive use of cannabis to manage their pain. However, the implications of cannabis use on the achievement of bony fusion are not well-characterized., Methods: Patients who underwent 1 to 3 level TLIF for degenerative disc disease or degenerative spondylolisthesis between 2010 and 2022 were identified using the PearlDiver Mariner all-claims insurance database. Cannabis users were identified with ICD 10 code F12.90. Patients undergoing surgery for nondegenerative pathologies such as tumors, trauma, or infection were excluded. 1:1 exact matching was performed using demographic factors, medical comorbidities, and surgical factors which were significantly associated with pseudarthrosis in a linear regression model. The primary outcome measure was development of pseudarthrosis within 24 months after 1 to 3 level TLIF. The secondary outcomes were the development of all-cause surgical complications as well as all-cause medical complications., Results: A 1:1 exact matching resulted in two equal groups of 1593 patients who did or did not use cannabis and underwent 1 to 3 level TLIF. Patients who used cannabis were 80% more likely to experience pseudarthrosis compared with patients who do not [relative risk (RR): 1.816, 95% CI: 1.291-2.556, P <0.001]. Similarly, cannabis use was associated with significantly higher rates of all-cause surgical complications (RR: 2.350, 95% CI: 1.399-3.947, P =0.001) and all-cause medical complications (RR: 1.934, 95% CI: 1.516-2.467, P <0.001)., Conclusion: After 1:1 exact matching to control for confounding variables, the findings of this study suggest that cannabis use is associated with higher rates of pseudarthrosis, as well as higher rates of all-cause surgical and all-cause medical complications. Further studies are needed to corroborate our findings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

In the complex tumor microenvironment (TME), mesenchymal cells are key players, yet their specific roles in prostate cancer (PCa) progression remain to be fully deciphered. This study employs single-cell RNA sequencing to delineate molecular changes in tumor stroma that influence PCa progression and metastasis. Analyzing mesenchymal cells from four genetically engineered mouse models (GEMMs) and correlating these findings with human tumors, we identify eight stromal cell populations with distinct transcriptional identities consistent across both species. Notably, stromal signatures in advanced mouse disease reflect those in human bone metastases, highlighting periostin's role in invasion and differentiation. From these insights, we derive a gene signature that predicts metastatic progression in localized disease beyond traditional Gleason scores. Our results illuminate the critical influence of stromal dynamics on PCa progression, suggesting new prognostic tools and therapeutic targets., (© 2024. The Author(s).)

Introduction: There continues to be a growing demand for military-civilian partnerships (MCPs) in research collaborations developing medical trauma care in domestic and international affairs. The objective of this comprehensive review is to investigate the difference in the quantity of MCP trauma and critical care publications before and after the COVID-19 pandemic., Methods: A systematic literature review was performed for the calendar years 2018 and 2021 utilizing MEDLINE, Cochrane, and EMBASE databases. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a three-tiered review of 603 English language articles to identify trauma-related military and/or civilian partners and describe the changes in geographical relationships., Results: A total of 96 (2018) and 119 (2021) articles met screening criteria for trauma and critical care studies and were used for final data extraction. Ultimately, 59 (2018) and 71 (2021) papers met the inclusion criteria of identifying trauma/critical care MCPs and identified both military and civilian partners. There was also an increase from 10 (2018) to 17 (2021) publications that mentioned advocacy for MCP. Using the author affiliations, four regional MCP types were recorded: of 2018 articles, locoregional (3.4%), US-national (47.5%), single international country (42.4%), and between multiple countries (6.8%); of 2021 articles, locoregional (15.5%), US-national (38%), single international country (29.6%), and between multiple countries (16.9%). There has been an increase in the number of locoregional and multinational MCPs and an overall increase in the number of collaborative trauma publications and MCP advocacy papers. A national geographical heat map was developed to illustrate the changes from 2018 to 2021., Conclusions: There has been an increase in the number of recorded trauma and critical care MCP publications post-pandemic. The growth in the number of manuscripts in more regions post-pandemic suggests an increase in the recognition of collaborations that contribute not only to conflict readiness but also advancements in trauma and surgical care., (Published by Elsevier Inc.)

Background: Emergency departments (EDs) manage many patients with suicide risk, but effective interventions for suicidality are challenging to implement in this setting. ReachCare is a technology-facilitated version of an evidence-based intervention for suicidal ED patients. Here, we present findings on the acceptability and quality of ReachCare in the ED, as well as a comparison of these measures across 3 potential delivery modalities., Objective: Our aim was to test the feasibility of the ReachCare intervention in its entirety through conducting a pilot study with patients presenting with suicidality to the ED. We tested three different ways of receiving the ED-based components of ReachCare: (1) self-administered on the tablet app using a chatbot interface, (2) administered by an in-person clinician, or (3) administered by a telehealth clinician., Methods: In total, 47 ED patients who screened positive for suicide risk were randomly allocated to receive one of three delivery modalities of ReachCare in the ED: (1) self-administered on the patient-facing tablet app with a chatbot interface, (2) delivered by an in-person clinician, or (3) delivered by a telehealth clinician, with the latter two using a clinician-facing web app. We measured demographic and clinical characteristics, acceptability and appropriateness of the intervention, and quality and completeness of the resulting safety plans., Results: Patients assigned high ratings for the acceptability (median 4.00/5, IQR 4.00-4.50) and appropriateness (median 4.00/5, IQR 4.00-4.25) of ReachCare's ED components, and there were no substantial differences across the 3 delivery modalities [H(acceptability)=3.90, P=.14; H(appropriateness)=1.05, P=.59]. The self-administered modality took significantly less time than the 2 clinician modalities (H=27.91, P<.001), and the usability of the self-administered version was in the "very high" range (median 93.75/100, IQR 80.00-97.50). The safety plans created across all 3 modalities were high-quality (H=0.60, P=.74)., Conclusions: Patients rated ReachCare in the ED as highly acceptable and appropriate regardless of modality. Self-administration may be a feasible way to ensure patients with suicide risk receive an intervention in resource constrained EDs. Limitations include small sample size and demographic differences between those enrolled versus not enrolled. Further research will examine the clinical outcomes of patients receiving both the in-ED and post-ED components of ReachCare., Trial Registration: ClinicalTrials.gov NCT04720911; https://clinicaltrials.gov/ct2/show/NCT04720911., (©Celine Larkin, Bengisu Tulu, Soussan Djamasbi, Roscoe Garner, Fatima Varzgani, Mariam Siddique, John Pietro, Edwin D Boudreaux. Originally published in JMIR Mental Health (https://mental.jmir.org), 24.10.2023.)

As data sharing has become more prevalent, three pillars - archives, standards, and analysis tools - have emerged as critical components in facilitating effective data sharing and collaboration. This paper compares four freely available intracranial neuroelectrophysiology data repositories: Data Archive for the BRAIN Initiative (DABI), Distributed Archives for Neurophysiology Data Integration (DANDI), OpenNeuro, and Brain-CODE. The aim of this review is to describe archives that provide researchers with tools to store, share, and reanalyze both human and non-human neurophysiology data based on criteria that are of interest to the neuroscientific community. The Brain Imaging Data Structure (BIDS) and Neurodata Without Borders (NWB) are utilized by these archives to make data more accessible to researchers by implementing a common standard. As the necessity for integrating large-scale analysis into data repository platforms continues to grow within the neuroscientific community, this article will highlight the various analytical and customizable tools developed within the chosen archives that may advance the field of neuroinformatics., (© 2023. Springer Nature Limited.)

Study Design: Retrospective cohort., Objective: To compare the rate of adjacent segment disease (ASD) in patients undergoing anterior lumbar interbody fusion (ALIF) versus transforaminal lumbar interbody fusion (TLIF) for the treatment of degenerative stenosis and spondylolisthesis., Summary of Background Data: ALIF and TLIF are frequently used to treat Lumbar stenosis and spondylolisthesis. While both approaches have distinct advantages, it is unclear whether there are any differences in rates of ASD and postoperative complications., Methods: A retrospective cohort study of patients who underwent index 1-3 levels ALIF or TLIF between 2010 and 2022, using the PearlDiver Mariner Database, an all-claims insurance database (120 million patients). Patients with a history of prior lumbar surgery and those undergoing surgery for cancer, trauma, or infection were excluded. Exact 1:1 matching was performed using demographic factors, medical comorbidities, and surgical factors found to be significantly associated with ASD in a linear regression model. The primary outcome was a new diagnosis of ASD within 36 months of index surgery, and secondary outcomes were all-cause medical and surgical complications., Results: Exact 1:1 matching resulted in 2 equal groups of 106,451 patients undergoing TLIF and ALIF. The TLIF approach was associated with a lower risk of ASD (RR 0.58, 95% CI 0.56-0.59, P < 0.001) and all-cause medical complications (RR 0.94, 95% CI 0.91-0.98, P =0.002). All-cause surgical complications were not significantly different between both groups., Conclusion: After 1:1 exact matching to control for confounding variables, this study suggests that for patients with symptomatic degenerative stenosis and spondylolisthesis, a TLIF procedure (compared to ALIF) is associated with a decreased risk of developing ASD within 36 months of index surgery. Future prospective studies are needed to corroborate these findings., Level of Evidence: Level-3., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A gap exists between scientific discovery and implementation and adoption of research findings in healthcare and public health practice. This gap is due to the fact that research on treatment efficacy and safety in clinical trials ends prematurely with the publication of results, leaving a lack of knowledge of treatment effectiveness in real-world clinical and community settings. Comparative effectiveness research (CER) can facilitate the translation of research findings, reducing the gap between discovery and adoption into practice. Getting CER findings to patients and healthcare providers requires efforts to disseminate and train providers to successfully implement and sustain change in the healthcare setting. Advanced practice registered nurses (APRNs) are instrumental in the implementation of evidence-based research in primary care settings and an important group to target for the dissemination of research findings. There are numerous implementation training programs, but none focus specifically on APRNs., Objective: The objective of this article is to describe the infrastructure established to develop a 3-day implementation training program for APRNs and an implementation support system., Method: A description of the processes and strategies is provided, including stakeholder engagement through focus groups and the formation of a multistakeholder program planning advisory team, which includes APRNs, organization leaders, and patients. The program also includes curriculum development and program planning as well as the development of an implementation toolkit., Results: Stakeholders were instrumental in shaping the implementation training program, including the content of the curriculum and the program agenda. In addition, the unique perspective of each stakeholder group contributed to the selection of the CER findings disseminated through the intensive training program., Conclusion: It is important that strategies to address the lack of implementation training opportunities for APRNs be discussed and disseminated within the healthcare community. This article discusses the plan to address implementation training for APRNs through the development of an implementation curriculum and toolkit for APRNs., (Copyright © 2023 JBI. Unauthorized reproduction of this article is prohibited.)

Preclinical MRI studies have been utilized for the discovery of biomarkers that predict post-traumatic epilepsy (PTE). However, these single site studies often lack statistical power due to limited and homogeneous datasets. Therefore, multisite studies, such as the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx), are developed to create large, heterogeneous datasets that can lead to more statistically significant results. EpiBioS4Rx collects preclinical data internationally across sites, including the United States, Finland, and Australia. However, in doing so, there are robust normalization and harmonization processes that are required to obtain statistically significant and generalizable results. This work describes the tools and procedures used to harmonize multisite, multimodal preclinical imaging data acquired by EpiBioS4Rx. There were four main harmonization processes that were utilized, including file format harmonization, naming convention harmonization, image coordinate system harmonization, and diffusion tensor imaging (DTI) metrics harmonization. By using Python tools and bash scripts, the file formats, file names, and image coordinate systems are harmonized across all the sites. To harmonize DTI metrics, values are estimated for each voxel in an image to generate a histogram representing the whole image. Then, the Quantitative Imaging Toolkit (QIT) modules are utilized to scale the mode to a value of one and depict the subsequent harmonized histogram. The standardization of file formats, naming conventions, coordinate systems, and DTI metrics are qualitatively assessed. The histograms of the DTI metrics were generated for all the individual rodents per site. For inter-site analysis, an average of the individual scans was calculated to create a histogram that represents each site. In order to ensure the analysis can be run at the level of individual animals, the sham and TBI cohort were analyzed separately, which depicted the same harmonization factor. The results demonstrate that these processes qualitatively standardize the file formats, naming conventions, coordinate systems, and DTI metrics of the data. This assists in the ability to share data across the study, as well as disseminate tools that can help other researchers to strengthen the statistical power of their studies and analyze data more cohesively., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Mental health and neurocognitive conditions are important causes of hospitalization among immigrants, though patterns may vary by immigrant category, world region of origin, and time since arrival in Canada. This study uses linked administrative data to explore differences in mental health hospitalization rates between immigrants and individuals born in Canada., Methods: Hospital records from the Discharge Abstract Database and the Ontario Mental Health Reporting System for 2011 to 2017 were linked to the 2016 Longitudinal Immigrant Database and to Statistics Canada's 2011 Canadian Census Health and Environment Cohort. Age-standardized hospitalization rates for mental health-related conditions (ASHR-MHs) were derived for immigrants and the Canadian-born population. ASHR-MHs overall and for leading mental health conditions were compared between immigrants and the Canadian-born population, stratified by sex and selected immigration characteristics. Quebec hospitalization data were not available., Results: Overall, immigrants had lower ASHR-MHs compared to the Canadian-born population. Mood disorders were leading causes of mental health hospitalization for both cohorts. Psychotic, substance-related, and neurocognitive disorders were also leading causes of mental health hospitalization, although there was variation in their relative importance between subgroups. Among immigrants, ASHR-MHs were higher among refugees and lower among economic immigrants, those from East Asia, and those who arrived in Canada most recently., Conclusion: Differences in hospitalization rates among immigrants from various immigration streams and world regions, particularly for specific types of mental health conditions, highlight the importance of future research that incorporates both inpatient and outpatient mental health services to further understand these relationships., (© 2023. Crown.)

Tardigrades are remarkable in their ability to survive extreme environments. The damage suppressor (Dsup) protein is thought responsible for their extreme resistance to reactive oxygen species (ROS) generated by irradiation. Here we show that expression of Ramazzottius varieornatus Dsup in Saccharomyces cerevisiae reduces oxidative DNA damage and extends the lifespan of budding yeast exposed to chronic oxidative genotoxicity. This protection from ROS requires either the Dsup HMGN-like domain or sequences C-terminal to same. Dsup associates with no apparent bias across the yeast genome, using multiple modes of nucleosome binding; the HMGN-like region interacts with both the H2A/H2B acidic patch and H3/H4 histone tails, while the C-terminal region binds DNA. These findings give precedent for engineering an organism by physically shielding its genome to promote survival and longevity in the face of oxidative damage., Competing Interests: COMPETING INTERESTS EpiCypher is a commercial developer and supplier of reagents (e.g., fully PTM-defined nucleosomes (dNucs) and SNAP-CUTANA® K-MetStat nucleosomes) and platforms (e.g., dCypher and CUTANA CUT&RUN) used in this study. LK, ARH, RW, MWC, MRM and MCK are currently employed by (and own shares in) EpiCypher. RJE and HEW were previously employed by (and own shares in) EpiCypher. MRM and MCK are board members of EpiCypher.

Study Design: Retrospective Cohort Study., Objective: The objective of this study was to compare the rate of adjacent segment disease (ASD) between lumbar disk arthroplasty (LDA) and anterior lumbar interbody fusion (ALIF)., Summary of Background Data: LDA and ALIF are alternative surgical approaches used to treat lumbar degenerative disk disease. However, there is a paucity of studies comparing the risk of ASD after these procedures., Methods: Patients who underwent 1- to 2-level LDA or ALIF between 2010 and 2022 were identified in the PearlDiver Mariner insurance all-claims database. Exclusion criteria included the history of prior lumbar spine surgery or surgery for tumors, trauma, or infection. 1:1 propensity matching was performed using demographic factors, medical comorbidities, and surgical factors, which were significantly associated with ASD., Results: 1:1 propensity matching created two equal groups of 1625 patients without baseline differences who underwent LDA or ALIF. LDA was significantly associated with a lower risk of ASD (relative risk: 0.932, 95% CI, 0.899-0.967, P <0.001) and need for revision within 30 days (relative risk: 0.235, 95% CI, 0.079-0.698, P =0.007). There were no differences in all-cause surgical and medical complications between both groups., Conclusions: After risk adjustment for demographic and clinical characteristics, the results suggest that LDA is associated with a lower risk of ASD compared with ALIF. LDA was also associated with lower hospital cost and shorter length of stay., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

PTE is a neurological disorder characterized by recurrent and spontaneous epileptic seizures. PTE is a major public health problem occurring in 2-50% of TBI patients. Identifying PTE biomarkers is crucial for the development of effective treatments. Functional neuroimaging studies in patients with epilepsy and in epileptic rodents have observed that abnormal functional brain activity plays a role in the development of epilepsy. Network representations of complex systems ease quantitative analysis of heterogeneous interactions within a unified mathematical framework. In this work, graph theory was used to study resting state functional magnetic resonance imaging (rs-fMRI) and reveal functional connectivity abnormalities that are associated with seizure development in traumatic brain injury (TBI) patients. We examined rs-fMRI of 75 TBI patients from Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) which aims to identify validated Post-traumatic epilepsy (PTE) biomarkers and antiepileptogenic therapies using multimodal and longitudinal data acquired from 14 international sites. The dataset includes 28 subjects who had at least one late seizure after TBI and 47 subjects who had no seizures within 2 years post-injury. Each subject's neural functional network was investigated by computing the correlation between the low frequency time series of 116 regions of interest (ROIs). Each subject's functional organization was represented as a network consisting of nodes, brain regions, and edges that show the relationship between the nodes. Then, several graph measures concerning the integration and the segregation of the functional brain networks were extracted in order to highlight changes in functional connectivity between the two TBI groups. Results showed that the late seizure-affected group had a compromised balance between integration and segregation and presents functional networks that are hyperconnected, hyperintegrated but at the same time hyposegregated compared with seizure-free patients. Moreover, TBI subjects who developed late seizures had more low betweenness hubs., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) often results in heterogenous lesions that can be visualized through various neuroimaging techniques, such as magnetic resonance imaging (MRI). However, injury burden varies greatly between patients and structural deformations often impact usability of available analytic algorithms. Therefore, it is difficult to segment lesions automatically and accurately in TBI cohorts. Mislabeled lesions will ultimately lead to inaccurate findings regarding imaging biomarkers. Therefore, manual segmentation is currently considered the gold standard as this produces more accurate masks than existing automated algorithms. These masks can provide important lesion phenotype data including location, volume, and intensity, among others. There has been a recent push to investigate the correlation between these characteristics and the onset of post traumatic epilepsy (PTE), a disabling consequence of TBI. One motivation of the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) is to identify reliable imaging biomarkers of PTE. Here, we report the protocol and importance of our manual segmentation process in patients with moderate-severe TBI enrolled in EpiBioS4Rx. Through these methods, we have generated a dataset of 127 validated lesion segmentation masks for TBI patients. These ground-truths can be used for robust PTE biomarker analyses, including optimization of multimodal MRI analysis via inclusion of lesioned tissue labels. Moreover, our protocol allows for analysis of the refinement process. Though tedious, the methods reported in this work are necessary to create reliable data for effective training of future machine-learning based lesion segmentation methods in TBI patients and subsequent PTE analyses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bennett, Garner, Morris, La Rocca, Barisano, Cua, Loon, Alba, Carbone, Gao, Pantoja, Khan, Nouaili, Vespa, Toga and Duncan.)

Background: As Canada continues to experience an opioid crisis, it is important to understand the intersection between the demographic, socioeconomic and service use characteristics of those experiencing opioid overdoses to better inform prevention and treatment programs., Data and Methods: The Statistics Canada British Columbia Opioid Overdose Analytical File (BCOOAF) represents people's opioid overdoses between January 2014 and December 2016 (n = 13,318). The BCOOAF contains administrative health data from British Columbia linked to Statistics Canada data, including on health, employment, social assistance and police contacts. Cluster analysis was conducted using the k-prototypes algorithm., Results: The results revealed a six-cluster solution, composed of three groups (A, B and C), each with two distinct clusters (1 and 2). Individuals in Group A were predominantly male, used non-opioid prescription medications and had varying levels of employment. Individuals in Cluster A1 were employed, worked mostly in construction, had high incomes and had a high rate of fatal overdoses, while individuals in Cluster A2 were precariously employed and had varying levels of income. Individuals in Group B were predominantly female; were mostly taking prescription opioids, with about one quarter or less receiving opioid agonist treatment (OAT); mostly had precarious to no employment; and had low to no income. People in Cluster B1 were primarily middle-aged (45 to 65 years) and on social assistance, while people in Cluster B2 were older, more frequently used health services and had no social assistance income. Individuals in Group C were primarily younger males aged 24 to 44 years, with higher prevalence of having experienced multiple overdoses, were medium to high users of health care services, were mostly unemployed and were recipients of social assistance. Most had multiple contacts with police. Those in Cluster C1 predominantly had no documented use of prescription opioid medications, and all had no documented OAT, while all individuals in Cluster C2 were on OAT., Interpretation: The application of machine learning techniques to a multidimensional database enables an intersectional approach to study those experiencing opioid overdoses. The results revealed distinct patient profiles that can be used to better target interventions and treatment.

Using the OncoSim All Cancers Model, we estimated the annual cancer incidence, mortality and cancer management costs in Canada from 2020 to 2040. Incidence for each cancer type was estimated from logistic regression analyses of the Canadian Cancer Registry (1992-2017), with province/territory, sex, five-year age groups and year as covariates. Deaths were estimated by sex and tumour site for cancers diagnosed between 2000 and 2017 (deaths to the end of 2017). The total cost of a cancer type was the sum of costs for individuals across four phases of cancer care. The projections presented in this study were generated based on a simulation of 32 million cases. The OncoSim All Cancers Model projects a 40% increase in the overall number of incident cancer cases from 2020 to 2040. The number of the four most commonly diagnosed cancers in Canada (breast, colorectal, lung, and prostate) are projected to increase annually. The overall number of cancer deaths is projected to increase by 44% from 2020 to 2040. More cancer deaths are projected in males than in females. The age-standardized mortality rate is expected to remain relatively stable over time. Overall cancer management costs are projected to increase from $20.6B in 2020 to $31.4B in 2040. Due mainly to an aging population and population growth in Canada, we estimate that cancer incidence, mortality and cancer management costs will increase considerably between 2020 and 2040. These results highlight the importance of planning for increasing investment and capacity in cancer control., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Data sharing is becoming ubiquitous and can be advantageous for most biomedical research. However, some data are inherently more amenable to sharing than others. For example, human intracranial neurophysiology recordings and associated multimodal data have unique features that warrant special considerations. The associated data are heterogeneous, difficult to compare, highly specific, and collected from small cohorts with treatment resistant conditions, posing additional complications when attempting to perform generalizable analyses across projects. We present the Data Archive for the BRAIN Initiative (DABI) and describe features of the platform that are designed to overcome these and other challenges. DABI is a data repository and portal for BRAIN Initiative projects that collect human and animal intracranial recordings, and it allows users to search, visualize, and analyze multimodal data from these projects. The data providers maintain full control of data sharing privileges and can organize and manage their data with a user-friendly and intuitive interface. We discuss data privacy and security concerns, example analyses from two DABI datasets, and future goals for DABI., (© 2023. The Author(s).)

Background: Many individuals with suicide risk present to acute care settings such as emergency departments (EDs). However, staffing and time constraints mean that many EDs are not well equipped to deliver evidence-based interventions for patients experiencing suicidality. An existing intervention initiated in the ED for patients with suicide risk (Emergency Department Safety Assessment and Follow-up Evaluation [ED-SAFE]) has been found to be effective but faces trenchant barriers for widespread adoption., Objective: On the basis of the ED-SAFE intervention, we aimed to develop 2 apps for patients with suicide risk: a web app guiding patients through safety planning in the ED (ED app) and a smartphone app providing patients components of the ED-SAFE program on their phones after discharge (patient app). We then tested the usability of these apps with patients presenting to the ED with suicide risk., Methods: Using a user-centered design framework, we first developed user personas to explore the needs and characteristics of patients who are at risk for suicide using inputs from clinicians (n=3) and suicidologists (n=4). Next, we validated these personas during interviews with individuals with lived experience of suicidality (n=6) and used them to inform our application designs. We field-tested the apps with ED patients presenting with suicide risk (n=14) in 2 iterative cycles to assess their usability and engagement using a mixed methods approach. We also rated the quality and fidelity of the safety plans created., Results: We developed 2 interoperable and complementary apps. The first is a web app designed for use on a tablet device during ED admission that guides the patient by creating a safety plan using a chatbot-style interface. The second is a smartphone app for use after discharge and allows the patient to view, edit, and share their completed safety plan; access self-care education, helplines, and behavioral health referrals; and track follow-up appointments with the study clinician. The initial prototype usability testing (n=9) demonstrated satisfactory scores (ED app System Usability Scale [SUS], mean 78.6/100, SD 24.1; User Engagement Scale, mean 3.74/5, SD 0.72; patient app SUS, mean 81.7/100, SD 20.1). After refining the apps based on participant feedback, the second cycle testing (n=5) showed improvement (ED app SUS, mean 90.5/100, SD 9.9; User Engagement Scale, mean 4.07/5, SD 0.36; patient app SUS, mean 97.0/100, SD 1.9). The quality ratings for completed safety plans were satisfactory (Safety Planning Intervention Scoring Algorithm-Brief, mean 27.4, SD 3.4)., Conclusions: By adopting a user-centered approach and creating personas to guide development, we were able to create apps for ED patients with suicide risk and obtain satisfactory usability, engagement, and quality scores. Developing digital health tools based on user-centered design principles that deliver evidence-based intervention components may help overcome trenchant implementation barriers in challenging health care settings., (©Celine Larkin, Soussan Djamasbi, Edwin D Boudreaux, Fatima Varzgani, Roscoe Garner, Mariam Siddique, John Pietro, Bengisu Tulu. Originally published in JMIR Formative Research (https://formative.jmir.org), 27.01.2023.)