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Abstract Marine dissolved organic matter (DOM) is an important, actively cycling carbon reservoir (662 GtC). However, the chemical structure and cycling of DOM within rapidly warming, polar environments remains largely unconstrained. Previous studies have shown rapid surface cycling of carbohydrates as biologically-labile DOM (LDOM). Conversely, carboxyl-rich alicyclic molecules (CRAM) are often used as examples of biologically-recalcitrant DOM (RDOM). Traditional DOM isolation methods (e.g., ultrafiltration (10–30% of DOM) and solid-phase extraction (40–60% of DOM) induce chemical-, size- and compositional-bias – complicating inferences to total DOM cycling. Here, we use a total DOM proton (1H) nuclear magnetic resonance (NMR) spectroscopy method to show carbohydrates and CRAM have high concentrations in the surface ocean and low concentrations at depth in Baffin Bay. Between 21–43% of surface CRAM is removed at depth. These results suggest both CRAM and carbohydrates are major LDOM constituents – contradicting the existing CRAM cycling paradigm and further constraining the long-term persistence of deep ocean DOM.

Abstract Depression questionnaire cutoffs are calibrated for screening accuracy and not to assess prevalence, but the Geriatric Depression Scale (GDS-15) is often used to estimate diagnostic prevalence among older adults, most commonly with scores of ≥ 5. We conducted an individual participant data meta-analysis to compare depression prevalence based on GDS-15 ≥ 5 to Structured Clinical Interview for Diagnostic and Statistical Manual (SCID) diagnoses and assessed whether an alternative cutoff could be more accurate. We used generalized linear mixed models to estimate prevalence. Data from 14 studies (3602 participants, 434 SCID major depression) were included. Pooled GDS-15 ≥ 5 prevalence was 34.2% (95% confidence interval [CI] 27.5–41.6%), and pooled SCID prevalence was 14.8% (95% CI 10.0–21.5%; difference of 17.6%, 95% CI 11.6–23.6%). GDS-15 ≥ 8 provided the closest estimate to SCID with mean difference of − 0.3% (95% prediction interval − 17.0–16.5%). Prevalence estimate differences were not associated with study or participant characteristics. In sum, GDS-15 ≥ 5 substantially overestimated depression prevalence. A cutoff of ≥ 8 was accurate overall, but heterogeneity was too high for implementation in practice. Validated diagnostic interviews should be used to estimate major depression prevalence among older adults.

Abstract Background While pluripotent stem cell (PSC) therapies move toward clinical and commercial applications at a rapid rate, manufacturing reproducibility and robustness are notable bottlenecks in regulatory approval. Therapeutic applications of PSCs require large cell quantities to be generated under highly robust, well-defined, and economically viable conditions. Small-scale and short-term process optimization, however, is often performed in a linear fashion that does not account for time needed to verify the bioprocess protocols and analysis methods used. Design of a reproducible and robust bioprocess should be dynamic and include a continuous effort to understand how the process will respond over time and to different stresses before transitioning into large-scale production where stresses will be amplified. Methods This study utilizes a baseline protocol, developed for the short-term culture of PSC aggregates in Vertical-Wheel® bioreactors, to evaluate key process attributes through long-term (serial passage) suspension culture. This was done to access overall process robustness when performed with various commercially available media and cell lines. Process output variables including growth kinetics, aggregate morphology, harvest efficiency, genomic stability, and functional pluripotency were assessed through short and long-term culture. Results The robust nature of the expansion protocol was demonstrated over a six-day culture period where spherical aggregate formation and expansion were observed with high-fold expansions for all five commercial media tested. Profound differences in cell growth and quality were revealed only through long-term serial expansion and in-vessel dissociation operations. Some commercial media formulations tested demonstrated maintenance of cell growth rates, aggregate morphology, and high harvest recovery efficiencies through three bioreactor serial passages using multiple PSC lines. Exceptional bioprocess robustness was even demonstrated with sustained growth and quality maintenance over 10 serial bioreactor passages. However, some commercial media tested proved less equipped for serial passage cultures in bioreactors as cultures led to cell lysis during dissociation, reduction in growth rates, and a loss of aggregate morphology. Conclusions This study demonstrates the importance of systematic selection and testing of bioprocess input variables, with multiple bioprocess output variables through serial passages to create a truly reproducible and robust protocol for clinical and commercial PSC production using scalable bioreactor systems.

Abstract Depressive symptoms in Schizophrenia Spectrum Disorders (SSDs) negatively impact suicidality, prognosis, and quality of life. Despite this, efficacious treatments are limited, largely because the neural mechanisms underlying depressive symptoms in SSDs remain poorly understood. We conducted a systematic review to provide an overview of studies that investigated the neural correlates of depressive symptoms in SSDs using neuroimaging techniques. We searched MEDLINE, PsycINFO, EMBASE, Web of Science, and Cochrane Library databases from inception through June 19, 2023. Specifically, we focused on structural and functional magnetic resonance imaging (MRI), encompassing: (1) T1-weighted imaging measuring brain morphology; (2) diffusion-weighted imaging assessing white matter integrity; or (3) T2*-weighted imaging measures of brain function. Our search yielded 33 articles; 14 structural MRI studies, 18 functional (f)MRI studies, and 1 multimodal fMRI/MRI study. Reviewed studies indicate potential commonalities in the neurobiology of depressive symptoms between SSDs and major depressive disorders, particularly in subcortical and frontal brain regions, though confidence in this interpretation is limited. The review underscores a notable knowledge gap in our understanding of the neurobiology of depression in SSDs, marked by inconsistent approaches and few studies examining imaging metrics of depressive symptoms. Inconsistencies across studies’ findings emphasize the necessity for more direct and comprehensive research focusing on the neurobiology of depression in SSDs. Future studies should go beyond “total score” depression metrics and adopt more nuanced assessment approaches considering distinct subdomains. This could reveal unique neurobiological profiles and inform investigations of targeted treatments for depression in SSDs.

Abstract Introduction Systemic sclerosis (SSc) is a rare, complex autoimmune rheumatic disease with multiple factors that contribute to pain. People with SSc emphasize the effect pain has on their quality of life, but no studies have systematically examined the frequency and relative importance of different SSc pain sources, patterns of pain from different sources, and pain management experiences. Our objectives are to (1) develop a tool, jointly with researchers, health care providers, and patients, to map sources of pain in SSc, determine patterns of pain from different sources, and understand pain management experiences; and (2) administer the final tool version to participants in the large multinational Scleroderma Patient-centered Intervention Network (SPIN) Cohort. Methods First, we will use validated pain assessment tools as templates to develop an initial version of our pain assessment tool, and we will obtain input from patient advisors to adapt it for SSc. The tool will include questions on pain sources, pain patterns, pain intensity, pain management techniques, and barriers to pain management in SSc. Second, we will conduct nominal group technique sessions with people living with SSc and health care providers who care for people with SSc to further refine the tool. Third, we will conduct individual usability testing sessions with SPIN Cohort participants. Once the tool has been finalized, we will administer it to individuals in the multinational SPIN Cohort, which currently includes over 1,300 active participants from 54 sites in 7 countries. We will perform unsupervised clustering using the KAy-Means for MIxed LArge data (KAMILA) method to identify participant subgroups with similar profiles of pain sources (present or absent) and to evaluate predictors of subgroup membership. We will use latent profile analysis to identify subgroups of participants with similar profiles based on pain intensity scores for each pain source and evaluate predictors. Discussion Once completed, our pain assessment tool will allow our team and other researchers to map sources of pain in SSc and to understand pain management experiences of people living with SSc. This knowledge will provide avenues for studies on the pathophysiology of pain in SSc and studies of interventions to improve pain management.

Background Data on associations between inflammation and depressive symptoms largely originate from high income population settings, despite the greatest disease burden in major depressive disorder being attributed to populations in lower-middle income countries (LMICs). Aims We assessed the prevalence of low-grade inflammation in adults with treatment-resistant depression (TRD) in Pakistan, an LMIC, and investigated associations between peripheral C-reactive protein (CRP) levels and depressive symptoms. Method This is a secondary analysis of two randomised controlled trials investigating adjunctive immunomodulatory agents (minocycline and simvastatin) for Pakistani adults with TRD (n = 191). Logistic regression models were built to assess the relationship between pre-treatment CRP (≥ or

Introduction:. International medical graduates (IMGs) continue to play an important role in the US health care system, but little is known about their trends of matching into highly competitive residencies such as orthopedic surgery. The purpose of this study was to analyze temporal trends of IMG applicants matching into US orthopedic residency programs between 2008 and 2024 and compare them with US allopathic (MD) and osteopathic (DO) graduates. Methods:. Orthopedic residency specific data for years 2008 to 2024 was obtained from the National Resident Match Program and Electronic Residency Application Service. Variables collected included total number of programs, total positions offered, number of applicants (MD, DO, and IMG), positions filled, and fill rate for each group. Trends were examined using simple linear regression modeling. Results:. The number of orthopedic residency programs increased from 160 (2008) to 218 (2024), with total positions increasing from 636 (2008) to 916 (2024). The IMG fill rate decreased from 2.99% in 2008 to 0.87% in 2024 (p < 0.01 for linear trend; β −0.069). This corresponds to an absolute number decrease of 19 IMGs in 2008 to 8 in 2024. More specifically, the proportion of US IMGs decreased from 0.94% to 0.66%, and the proportion of non-US IMGs decreased from 2.04% to 0.21%. Over the 17-year study period, a total of 105 US IMGs and 110 non-US IMGs matched into orthopedic surgery. The US MD applicant fill rate decreased significantly from 96.5% to 85.0% (p < 0.001; β −0.944). The DO applicant fill rate increased significantly from 0.31% to 13.97% (p < 0.0001; β 0.990). Conclusion:. The declining rate of IMGs matching into orthopedic residency programs in the United States underscores the growing challenges faced by IMGs in accessing training in this competitive specialty. The notable increase in DO graduates securing orthopedic residency positions likely reflects the integration of a unified accreditation system for MD and DO residency programs established in 2020. Level of Evidence:. Retrospective Cohort Study; IV

Gastrointestinal mucosal surface is frequently under challenge due to it’s the large surface area and most common entry of microbes. IL-37, an anti-inflammatory cytokine, regulates local and systemic host immunity. H. pylori infection leads to the inhibition of IL-37 in the gastric mucosa, contributing to heightened mucosal inflammation and destruction, thereby facilitating increased proliferation of H. pylori. Food allergy, due to immune dysregulation, also contribute to GI injury. On the other hand, elevated levels of IL-37 observed in gastric cancer patients align with reduced host immunity at the cellular and humoral levels, indicating that IL-37 may contribute to the development of gastric cancer via suppressing pro-inflammatory responses. While IL-37 provides protection in an IBD animal model, the detection of highly produced IL-37 in IBD patients suggests a stage-dependent role, being protective in acute inflammation but potentially exacerbates the development of IBD in chronic conditions. Moreover, elevated colonic IL-37 in CRC correlates with overall survival time and disease time, indicating a protective role for IL-37 in CRC. The differential regulation and expression of IL-37 between upper- and lower-GI organs may be attributed to variations in the microbial flora. This information suggests that IL-37 could be a potential therapeutic agent, depending on the stage and location.

IntroductionPhysical activity is known to enhance cognitive functioning across the lifespan, yet the effects of sedentary behaviors on cognitive functioning remain unclear. The purpose of this study was to determine how an acute daily bout of prolonged sitting influenced working memory, inhibitory control, and cerebral oxygenation (HbO2) in a sample of healthy young adults.MethodsForty-one young adults (aged between 18–30 years of age) participated in an exploratory design intended to establish a control standard for determining how an acute 2-h bout of prolonged sitting influenced working memory, inhibitory control, and HbO2. The Flanker task, Simon task, and Delayed Match to Sample were utilized to assess inhibitory control and working memory, respectively, while functional near-infrared spectroscopy assessed HbO2. Participants were further subdivided into a physically active (Active) group and a physically inactive group (Inactive) based on self-reported physical activity participation. Paired sample t-tests were used to determine any changes in working memory, inhibitory control, and HbO2 from pre-to-post and between groups.ResultsThere were no differences in working memory or inhibitory control reaction time following prolonged sitting for the entire sample (p > 0.05) or between activity groups (p > 0.05). There was a significant reduction in Flanker accuracy post-prolonged sitting for both the congruent (p < 0.05) and incongruent (p < 0.05) conditions. For those in the Inactive group, there was no difference in HbO2 concentrations post-prolonged sitting. Those in the Active group exhibited a significant reduction in HbO2 during the Flanker Task following prolonged sitting (p < 0.05).ConclusionsAn acute bout of daily prolonged sitting significantly reduced HbO2 in physically active young adults but not in inactive young adults. We recommend that future studies examining the effects of sedentary behaviors on microvasculature include an objective assessment of physical fitness and a direct measure of physical activity patterns and consider these values when assigning participants to the intervention condition.

Poly- and per-fluoroalkyl substances (PFAS) are synthetic environmentally persistent chemicals. Despite the phaseout of specific PFAS, their inherent stability has resulted in ubiquitous and enduring environmental contamination. PFAS bioaccumulation has been reported globally with omnipresence in most populations wherein they have been associated with a range of negative health effects, including strong associations with increased instances of testicular cancer and reductions in overall semen quality. To elucidate the biological basis of such effects, we employed an acute in vitro exposure model in which the spermatozoa of adult male mice were exposed to a cocktail of PFAS chemicals at environmentally relevant concentrations. We hypothesized that direct PFAS treatment of spermatozoa would induce reactive oxygen species generation and compromise the functional profile and DNA integrity of exposed cells. Despite this, post-exposure functional testing revealed that short-term PFAS exposure (3 h) did not elicit a cytotoxic effect, nor did it overtly influence the functional profile, capacitation rate, or the in vitro fertilization ability of spermatozoa. PFAS treatment of spermatozoa did, however, result in a significant delay in the developmental progression of the day 4 pre-implantation embryos produced in vitro. This developmental delay could not be attributed to a loss of sperm DNA integrity, DNA damage, or elevated levels of intracellular reactive oxygen species. When considered together, the results presented here raise the intriguing prospect that spermatozoa exposed to a short-term PFAS exposure period potentially harbor an alternate stress signal that is delivered to the embryo upon fertilization.

Background: This study aims to determine the effect of time and imaging modality (three-dimensional (3D) CT vs. 3D magnetic resonance imaging (MRI)) on the surgical procedure indicated for shoulder instability. The hypothesis is there will be no clinical difference in procedure selection between time and imaging modality. Methods: Eleven shoulder surgeons were surveyed with the same ten shoulder instability clinical scenarios at three time points. All time points included history of present illness, musculoskeletal exam, radiographs, and standard two-dimensional MRI. To assess the effect of imaging modality, survey 1 included 3D MRI while survey 2 included a two-dimensional and 3D CT scan. To assess the effect of time, a retest was performed with survey 3 which was identical to survey 2. The outcome measured was whether surgeons made a “major” or “minor” surgical change between surveys. Results: The average major change rate was 14.1% (standard deviation: 7.6%). The average minor change rate was 12.6% (standard deviation: 7.5%). Between survey 1 to the survey 2, the major change rate was 15.2%, compared to 13.1% when going from the second to the third survey (P = .68). The minior change rate between the first and second surveys was 12.1% and between the second to third interview was 13.1% (P = .8). Discussion: The findings suggest that the major factor related to procedural changes was time between reviewing patient information. Furthermore, this study demonstrates that there remains significant intrasurgeon variability in selecting surgical procedures for shoulder instability. Lastly, the findings in this study suggest that 3D MRI is clinically equivalent to 3D CT in guiding shoulder instability surgical management. Conclusion: This study demonstrates that there is significant variability in surgical procedure selection driven by time alone in shoulder instability. Surgical decision making with 3D MRI was similar to 3D CT scans and may be used by surgeons for preoperative planning.

Abstract Background Selective reporting of results from only well-performing cut-offs leads to biased estimates of accuracy in primary studies of questionnaire-based screening tools and in meta-analyses that synthesize results. Individual participant data meta-analysis (IPDMA) of sensitivity and specificity at each cut-off via bivariate random-effects models (BREMs) can overcome this problem. However, IPDMA is laborious and depends on the ability to successfully obtain primary datasets, and BREMs ignore the correlation between cut-offs within primary studies. Methods We compared the performance of three recent multiple cut-off models developed by Steinhauser et al., Jones et al., and Hoyer and Kuss, that account for missing cut-offs when meta-analyzing diagnostic accuracy studies with multiple cut-offs, to BREMs fitted at each cut-off. We used data from 22 studies of the accuracy of the Edinburgh Postnatal Depression Scale (EPDS; 4475 participants, 758 major depression cases). We fitted each of the three multiple cut-off models and BREMs to a dataset with results from only published cut-offs from each study (published data) and an IPD dataset with results for all cut-offs (full IPD data). We estimated pooled sensitivity and specificity with 95% confidence intervals (CIs) for each cut-off and the area under the curve. Results Compared to the BREMs fitted to the full IPD data, the Steinhauser et al., Jones et al., and Hoyer and Kuss models fitted to the published data produced similar receiver operating characteristic curves; though, the Hoyer and Kuss model had lower area under the curve, mainly due to estimating slightly lower sensitivity at lower cut-offs. When fitting the three multiple cut-off models to the full IPD data, a similar pattern of results was observed. Importantly, all models had similar 95% CIs for sensitivity and specificity, and the CI width increased with cut-off levels for sensitivity and decreased with an increasing cut-off for specificity, even the BREMs which treat each cut-off separately. Conclusions Multiple cut-off models appear to be the favorable methods when only published data are available. While collecting IPD is expensive and time consuming, IPD can facilitate subgroup analyses that cannot be conducted with published data only.

Traditional transvenous pacemakers consist of a pacemaker generator usually positioned surgically in the upper left chest on the pectoral muscle fascia and one or more leads positioned through the veins to the right atrium and across the tricuspid valve to the right ventricular apex. While these devices reduce symptoms and improve survival among patients with symptomatic bradycardia, they are associated with an increased risk of infection, venous occlusion, heart failure, and tricuspid valve regurgitation. Although new pacemaker designs minimize these risks, none of the current-generation pacemaker designs effectively eliminate all of them. A personalized approach to selecting the appropriate pacemaker for each patient is needed to optimize outcomes.

Abstract Dissolved organic matter (DOM) is a key component of the global carbon cycle, with rivers delivering significant amounts of DOM to oceans. Urbanization and agricultural land‐use alter the age and chemical composition of riverine DOM, which likely impact the downstream bioavailability of riverine DOM. Here, we use bioreactor incubations of a marine bacterium (Pseudoalteromonas sp. 3D05) to investigate DOM bioavailability from two distinct rivers: the Suwannee River (natural, non‐urbanized), and the Upper Mississippi River Basin (anthropogenically influenced). We measured rates of microbial CO2 production and radiocarbon ages (as Δ14C) to assess DOM remineralization. We observed nearly identical cell densities and degradation patterns for both riverine DOM incubations. Respired DOM Δ14C values were also similar and decreased over time indicative of preferential utilization of recently synthesized “modern” substrates. These findings reveal unexpected similarities in riverine DOM bioavailability, indicating similar short term biological reactivity despite large DOM compositional differences.

Introduction: The novel COVID-19 disease detected in 2019 widely affected individuals’ social movements, likely disrupting the ability to participate in leisure-related physical activity. Because of this, participation in sedentary behavior is thought to have increased. The purpose of this study was to determine how the COVID-19 pandemic affected U.S. young adult physical activity and sedentary behavior. Methods: A total of 333 U.S. young adults (aged between 18 and 30 years) completed an online, comprehensive questionnaire during the early parts of COVID-19. Wilcoxon signed-rank tests were used to determine the change in time spent in physical activity and sedentary behavior during COVID-19 compared with that before COVID-19. Results: There was a significant decrease in physical activity minutes (p

Purpose: Individuals who do not complete substance use disorder treatment (SUDT) have similar outcomes to the untreated. Recovery capital (RC) is the collection of one’s resources that contribute to the initiation and maintenance of sobriety. The aim of this paper was to identify individual measures of RC that are associated with SUDT completion. Methods: RC data for 69 residents from a men’s recovery center was obtained from questionnaires administered to residents at intake and after SUDT graduation or dismissal. Participant data was divided into two groups, Graduates (n = 39, age 35.87±10.83) and Non-Graduates (n = 30, age 34.35±14.44), and retrospectively analyzed to compare RC between groups at various points during SUDT and which RC measures are associated with SUDT completion. Results: At baseline all participants reported limited RC and there was no significant difference in RC between groups. At graduation, Graduates reported significantly more RC in all measures when compared to baseline and Non-Graduates at dismissal. Non-Graduates reported a significant increase in Checking and Savings at dismissal but no other measure. Conclusion: Baseline levels of RC in both groups were limited and not significantly different which limited the capacity of the study to identify measures of RC associated with SUDT completion. A lack of RC at onset of SUDT did not preclude SUDT completion and obtaining RC during SUDT was associated with completion as only Graduates reported increases in RC. Future study designs should include participants with variable amounts of RC when entering SUDT.

Abstract Dissolved organic carbon (DOC) in the global oceans is an important long‐term carbon sink. Connections between molecular size, reactivity, and isotopic characteristics show that DOC exists on a continuum from biologically reactive to recalcitrant. The driving mechanisms behind the creation and persistence of recalcitrant DOC remain unknown. We show mean recalcitrant DOC (isolated via solid‐phase extraction; SPE‐DOC) δ13C values are 1.3 ± 0.6‰ lower than mean total DOC δ13C between depth ranges 0–200 m and 2–4 km on three GO‐SHIP Repeat Hydrography cruises. Lowest observed δ13C values correlate with low ∆14C and proximity to deep ocean hydrothermal systems. These data support the hypothesis that reworking of DOC through the microbial carbon pump is a key driver of the ocean's long‐term carbon sink. Mass‐balance modeling shows deep‐ocean DOC not captured by SPE is enriched in 13C, highlighting the need for continued research on non‐retained DOC to predict mechanisms that drive ocean carbon storage.

IntroductionProstate Cancer (PCa) remains a significant concern in male cancer-related mortality. Tumour development is intricately regulated by the complex interactions between tumour cells and their microenvironment, making it essential to determine which is/are key factor(s) that influence the progression of PCa within the tumour microenvironment.Materials and methodsThe current study utilised histopathology and immunohistochemistry to determine the expression of IL-38 in PCa and analysed the correlation between the expression level of IL-38 within PCa and clinical pathological characteristics.ResultsThere was a significant increase in IL-38 expression in PCa tissues compared to adjacent non-PCa tissues (P < 0.0001). In addition, IL-38 expression was significantly higher in tumour cells with a high proliferation index compared to those with a low value-added index. ROC curve analysis demonstrated that IL-38 has high specificity and sensitivity for the diagnosis of PCa (AUC=0.76). Moreover, we Probed the cellular source of IL-38 in prostate cancer tissue by immunofluorescence double staining. Additionally, within PCa, the expression of IL-38 was inversely correlated with the expression levels of CD8 and PD-1. Survival analysis revealed a significantly lower overall survival rate for PCa patients with high IL-38 expression (P=0.0069), and when IL-38 was co-expressed with CD8, the survival rate of the IL-38high/CD8low group was decreased significantly. Multivariate analysis indicated that the expression level of IL-38 and TNM staging were independent predictors of survival in PCa patients.ConclusionThese findings suggest that IL-38 plays a crucial role in the development of PCa, and the exploration of the correlation between IL-38 and various immune factors in the tumour microenvironment further reveals its mechanism of action, making it a potential target for immunotherapy in PCa.

Introduction: Distal radius fractures make up around 20% of adult fractures, varying in type and severity, thus requiring different treatments. Cast immobilization is effective in indicated fractures, but is associated with several disadvantages such that 3D-printed orthoses (3D-Braces) have been introduced as a potentially advantageous alternative. The present study was designed to test the hypothesis that short-arm 3D-printed Polylactic Acid (PLA) orthoses would provide superior biomechanical properties when compared to plaster of Paris short-arm casts for immobilization of distal radial fractures. Methods: Modified mannequin forearms were utilized as human models for the creation of both the circular casts and the 3D Braces. A total of five plaster cast prototypes were produced, based on a standard cylindrical plaster cast application technique used in the treatment of distal radius fractures, and another five samples were 3D printed braces. Each sample was then subjected to a three-point bend load test, using an Instron 68SC2 testing machine, and the data was collected and exported to an Excel spreadsheet and analyzed using SPSS Statistics version 26 (IBM Corp., Armonk, N.Y., USA). Results: The 3D-Braces can withstand significantly higher forces at yield and maximum force, implying they may offer superior mechanical stability. Moreover, our findings indicated a higher strain at yield for the 3D-Braces compared to conventional plaster casts. Conclusions: 3D-printed Polylactic Acid short-arm orthoses demonstrated superior biomechanical properties when compared to plaster of Paris short-arm casts designed for immobilization of distal radial fractures. Taken together with data from previous studies, preclinical evidence suggests that PLA 3D-Braces can effectively maintain distal radius fracture alignment and stability with potential advantages over traditional casts with respect to biomechanical properties as well as post-fabrication adjustment, patient hygiene, comfort, and daily activities.

Abstract Purpose To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening in a primary care setting for hypertension in adults aged 18 years and older. This protocol outlines the scope and methods for a series of systematic reviews and one overview of reviews. Methods To evaluate the benefits and harms of screening for hypertension, the Task Force will rely on the relevant key questions from the 2021 United States Preventive Services Task Force systematic review. In addition, a series of reviews will be conducted to identify, appraise, and synthesize the evidence on (1) the association of blood pressure measurement methods and future cardiovascular (CVD)-related outcomes, (2) thresholds for discussions of treatment initiation, and (3) patient acceptability of hypertension screening methods. For the review of blood pressure measurement methods and future CVD-related outcomes, we will perform a de novo review and search MEDLINE, Embase, CENTRAL, and APA PsycInfo for randomized controlled trials, prospective or retrospective cohort studies, nested case–control studies, and within-arm analyses of intervention studies. For the thresholds for discussions of treatment initiation review, we will perform an overview of reviews and update results from a relevant 2019 UK NICE review. We will search MEDLINE, Embase, APA PsycInfo, and Epistemonikos for systematic reviews. For the acceptability review, we will perform a de novo systematic review and search MEDLINE, Embase, and APA PsycInfo for randomized controlled trials, controlled clinical trials, and observational studies with comparison groups. Websites of relevant organizations, gray literature sources, and the reference lists of included studies and reviews will be hand-searched. Title and abstract screening will be completed by two independent reviewers. Full-text screening, data extraction, risk-of-bias assessment, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will be completed independently by two reviewers. Results from included studies will be synthesized narratively and pooled via meta-analysis when appropriate. The GRADE approach will be used to assess the certainty of evidence for outcomes. Discussion The results of the evidence reviews will be used to inform Canadian recommendations on screening for hypertension in adults aged 18 years and older. Systematic review registration This protocol is registered on PROSPERO and is available on the Open Science Framework (osf.io/8w4tz).

Abstract Background Patient engagement in research is important to ensure research questions address problems important to patients, that research is designed in a way that can effectively answer those questions, and that findings are applicable, relevant, and credible. Yet, patients are rarely involved in the dissemination stage of research. This study explored one way to engage patients in dissemination, through co-presenting research. Methods Semi-structured, one-on-one, audio-recorded interviews were conducted with researchers and patients who co-presented research at one patient conference (the 2022 Canadian National Scleroderma Conference) in Canada. A pragmatic orientation was adopted, and following verbatim transcription, data were analyzed using conventional content analysis. Results Of 8 researchers who were paired with 7 patients, 5 researchers (mean age = 28 years, SD = 3.6 years) and 5 patients (mean age = 45 years, SD = 14.2 years) participated. Researcher and patient perspectives about their experiences co-presenting and how to improve the experience were captured across 4 main categories: (1) Reasons for accepting the invitation to co-present; (2) Degree that co-presenting expectations were met; (3) The process of co-presenting; and (4) Lessons learned: recommendations for co-presenting. Conclusions Findings from this study suggest that the co-presenting experience was a rewarding and enjoyable way to tailor research dissemination to patients. We identified a patient-centred approach and meaningful and prolonged patient engagement as essential elements underlying co-presenting success.

Abstract Background The motivational climate within a course has been shown to be an important predictor of students’ engagement and course ratings. Because little is known about how students’ perceptions of the motivational climate in a computer science (CS) course vary by sex, race/ethnicity, and academic major, we investigated these questions: (1) To what extent do students’ achievement and perceptions of motivational climate, cost, ease, and effort vary by sex, race/ethnicity, or major? and (2) To what extent do the relationships between students’ achievement and perceptions of motivational climate, cost, and effort vary by sex, race/ethnicity, and major? Participants were enrolled in a large CS course at a large public university in the southeastern U.S. A survey was administered to 981 students in the course over three years. Path analyses and one-way MANOVAs and ANOVAs were conducted to examine differences between groups. Results Students’ perceptions of empowerment, usefulness, interest, and caring were similar across sexes and races/ethnicities. However, women and Asian students reported lower success expectancies. Students in the same academic major as the course topic (i.e., CS) generally reported higher perceptions of the motivational climate than students who did not major or minor in the course topic. Final grades in the course did not vary by sex or race/ethnicity, except that the White and Asian students obtained higher grades than the Black students. Across sex, race/ethnicity, and major, students’ perceptions of the motivational climate were positively related to effort, which was positively related to achievement. Conclusions One implication is that females, Asian students, and non-CS students may need more support, or different types of support, to help them believe that they can succeed in computer science courses. On average, these students were less confident in their abilities to succeed in the course and were more likely to report that they did not have the time needed to do well in the course. A second implication for instructors is that it may be possible to increase students’ effort and achievement by increasing students’ perceptions of the five key constructs in the MUSIC Model of Motivation: eMpowerment, Usefulness, Success, Interest, and Caring.

Introduction/Purpose: While hallux valgus (HV) is understood to be a triplanar deformity of the first metatarsal, less is known about the contribution of the sesamoid-metatarsal joint (SMJ) to pain and function. Osteoarthritis of the SMJ is frequently present in HV feet, with an incidence rate ranging from 32% to 81%. Following surgical correction, approximately 10% of HV patients remain dissatisfied, but factors affecting postoperative outcomes are poorly understood. The primary aim of our study was to describe the relationship between degenerative changes at the SMJ as measured on weightbearing CT (WBCT) scans and 1-year patient-reported outcome scores following a modified Lapidus procedure for correction of HV. We hypothesized that decreased joint space at the SMJ would affect postoperative patient-reported outcomes. Methods: This study included 48 consecutive patients who underwent a modified Lapidus procedure for HV, had preoperative and at least 5-month postoperative WBCT scans, and had preoperative PROMIS scores and at least 1-year postoperative PROMIS Physical Function (PF), Pain Interference, and Pain Intensity scores. For each patient, the first metatarsal and sesamoids on pre- and postoperative WBCT scans were segmented using Disior Bonelogic software and uploaded to Geomagic Design X to perform distancing mapping. The minimum and average distances between the first metatarsal head and medial sesamoid (medial-SMJ) for each patient pre- and postoperatively were calculated. Sesamoid subluxation was measured on WBCT scans using the grading system from 0 to 3 (Yildirim et al.). A simple linear regression model was used to investigate the correlations between minimum preoperative and postoperative medial-SMJ distances and 1-year postoperative PROMIS scores in patients with postoperative reduction of the sesamoids (grade 0). Results: Preoperatively, the mean minimum and average medial-SMJ distances were 0.76 ± 0.37 mm and 1.54 ± 0.33 mm, respectively. Postoperatively, the mean minimum and average medial-SMJ distances were 1.08 ± 0.25 mm and 1.73 ± 0.24 mm, respectively. Thirty-five of 48 patients had a complete reduction of the sesamoids. Lower preoperative minimum distances at the medial-SMJ were significantly correlated with worse 1-year PROMIS PF scores (r=0.405, P=0.016) (Figure 1). Similarly, lower preoperative minimum distances at the medial-SMJ were significantly correlated with worse 1-year PROMIS Pain Intensity scores (r=-0.350, P=0.039) but did not reach significance for 1-year PROMIS Pain Interference scores (r=-0.286, P=0.095). The postoperative minimum medial-SMJ distance was not correlated with 1-year PROMIS PF, Pain Interference, and Pain Intensity scores. Conclusion: In HV patients undergoing a modified Lapidus procedure with postoperatively reduced sesamoids, decreased joint space at the medial sesamoid-metatarsal head articulation was associated with worse 1-year postoperative function as measured by PROMIS PF scores and worse 1-year postoperative pain as measured by PROMIS Pain Intensity scores. In contrast, postoperative degenerative changes at the SMJ were not found to be associated with patient-reported outcomes. Our results suggest that pre-existing SMJ arthritic changes may affect postoperative outcomes and may be a source of dissatisfaction following HV surgery despite appropriate correction of the deformity. Figure 1. Preoperative medial sesamoid to the first metatarsal head minimum distance relative to 1-year PROMIS Physical Function, Pain Intensity, and Pain Interference scores. A simple linear regression demonstrates a significant association between preoperative medial sesamoid –metatarsal head minimum joint distance and 1-year PROMIS Physical Function (r=0.405, P=0.016) and Pain Intensity (r=‒0.305, P=0.039) scores.

IntroductionColorectal cancer (CRC) presents a substantial challenge characterized by unacceptably high mortality and morbidity, primarily attributed to delayed diagnosis and reliance on palliative care. The immune response of the host plays a pivotal role in carcinogenesis, with IL-38 emerging as a potential protective factor in CRC. However, the precise involvement of IL-38 among various leucocytes, its interactions with PD-1/PD-L1, and its impact on metastasis require further elucidation.ResultsOur investigation revealed a significant correlation between IL-38 expression and metastasis, particularly concerning survival and interactions among diverse leucocytes within draining lymph nodes. In the mesentery lymph nodes, we observed an inverse correlation between IL-38 expression and stages of lymph node invasions (TNM), invasion depth, distance, and differentiation. This aligns with an overall survival advantage associated with higher IL-38 expression in CRC patients’ nodes compared to lower levels, as well as elevated IL-38 expression on CD4+ or CD8+ cells. Notably, a distinct subset of patients characterized by IL-38high/PD-1low expression exhibited superior survival outcomes compared to other combinations.DiscussionOur findings demonstrate that IL-38 expression in colorectal regional nodes from CRC patients is inversely correlated with PD-1/PD-L1 but positively correlated with infiltrating CD4+ or CD8+ lymphocytes. The combined assessment of IL-38 and PD-1 expression in colorectal regional nodes emerges as a promising biomarker for predicting the prognosis of CRC.

IntroductionWound healing poses a clinical challenge in diabetes mellitus (DM) due to compromised host immunity. CD64, an IgG-binding Fcgr1 receptor, acts as a pro-inflammatory mediator. While its presence has been identified in various inflammatory diseases, its specific role in wound healing, especially in DM, remains unclear.ObjectivesWe aimed to investigate the involvement of CD64 in diabetic wound healing using a DM animal model with CD64 KO mice.MethodsFirst, we compared CD64 expression in chronic skin ulcers from human DM and non-DM skin. Then, we monitored wound healing in a DM mouse model over 10 days, with or without CD64 KO, using macroscopic and microscopic observations, as well as immunohistochemistry.ResultsCD64 expression was significantly upregulated (1.25-fold) in chronic ulcerative skin from DM patients compared to non-DM individuals. Clinical observations were consistent with animal model findings, showing a significant delay in wound healing, particularly by day 7, in CD64 KO mice compared to WT mice. Additionally, infiltrating CD163+ M2 macrophages in the wounds of DM mice decreased significantly compared to non-DM mice over time. Delayed wound healing in DM CD64 KO mice correlated with the presence of inflammatory mediators.ConclusionCD64 seems to play a crucial role in wound healing, especially in DM conditions, where it is associated with CD163+ M2 macrophage infiltration. These data suggest that CD64 relies on host immunity during the wound healing process. Such data may provide useful information for both basic scientists and clinicians to deal with diabetic chronic wound healing.

BACKGROUND: Placenta accreta spectrum disorders are a complex range of placental pathologies that are associated with significant maternal morbidity and mortality. A diagnosis of placenta accreta spectrum relies on ultrasonographic findings with modest positive predictive value. Exosomal microRNAs are small RNA molecules that reflect the cellular processes of the origin tissues. OBJECTIVE: We aimed to explore exosomal microRNA expression to understand placenta accreta spectrum pathology and clinical use for placenta accreta spectrum detection. STUDY DESIGN: This study was a biomarker analysis of prospectively collected samples at 2 academic institutions from 2011 to 2022. Plasma specimens were collected from patients with suspected placenta accreta spectrum, placenta previa, or repeat cesarean deliveries. Exosomes were quantified and characterized by nanoparticle tracking analysis and western blotting. MicroRNA were assessed by polymerase chain reaction array and targeted single quantification. MicroRNA pathway analysis was performed using the Ingenuity Pathway Analyses software. Placental biopsies were taken from all groups and analyzed by polymerase chain reaction and whole cell enzyme-linked immunosorbent assay. Receiver operating characteristic curve univariate analysis was performed for the use of microRNA in the prediction of placenta accreta spectrum. Clinically relevant outcomes were collected from abstracted medical records. RESULTS: Plasma specimens were analyzed from a total of 120 subjects (60 placenta accreta spectrum, 30 placenta previa, and 30 control). Isolated plasma exosomes had a mean size of 71.5 nm and were 10 times greater in placenta accreta spectrum specimens (20 vs 2 particles/frame). Protein expression of exosomes was positive for intracellular adhesion molecule 1, flotilin, annexin, and CD9. MicroRNA analysis showed increased detection of 3 microRNAs (mir-92, -103, and -192) in patients with placenta accreta spectrum. Pathway interaction assessment revealed differential regulation of p53 signaling in placenta accreta spectrum and of erythroblastic oncogene B2 or human epidermal growth factor 2 in control specimens. These findings were subsequently confirmed in placental protein analysis. Placental microRNA paralleled plasma exosomal microRNA expression. Biomarker assessment of placenta accreta spectrum signature microRNA had an area under the receiver operating characteristic curve of 0.81 (P

Abstract Purpose The aim of the study was to examine the validity evidence for the 19-item form of the MUSIC Model of Academic Motivation Inventory (College Student version) within health science schools in three different countries. The MUSIC Inventory includes five scales that assess the motivational climate by measuring students’ perceptions related to five separate constructs: empowerment, usefulness, success, interest, and caring. Background The 26-item form of the MUSIC Inventory has been validated for use with undergraduate students and with students in professional schools, including students at a veterinary medicine school, a pharmacy school, and a medical school. A 19-item form of the MUSIC Inventory has also been validated for use with undergraduate students, but it has not yet been validated for use with medical school students. The purpose of this study was to provide validity evidence for the use of the 19-item form in heath science schools in three different countries to determine if this version is acceptable for use in different cultures. If validated, this shorter form of the MUSIC Inventory would provide more differentiation between the Interest and Usefulness scales and could reduce respondent fatigue. Methodology Cook et al’s [1] practical guidelines were followed to implement Kane’s [2] validity framework as a means to examine the evidence of validity through scoring inferences, generalization inferences, and extrapolation inferences. Students (n = 667) in health science schools within three countries were surveyed. Results The results produced evidence to support all five hypotheses related to scoring, generalization, and extrapolation inferences. Conclusions Scores from the 19-item form of the MUSIC Inventory are valid for use in health science courses within professional schools in different countries. Therefore, the MUSIC Inventory can be used in these schools to assess students’ perceptions of the motivational climate.

Synthetic nicotinamide biomimetics (NCBs) have emerged as alternatives to the use of natural cofactors. The relatively low cost and ease of manufacture of NCBs may enable the scaling of biocatalytic reactions to produce bulk chemicals (e.g., biofuels and plastics). NCBs are also recognized by only a subset of NAD(P)/NAD(P)H-dependent enzymes, which potentially allows access to orthogonal redox cascades that can be run simultaneously within a single reactor. In the work presented here, a series of NCBs was prepared and tested for activity with alcohol dehydrogenases and ene-reductases. While the NCBs did not support enzymatic activity with the alcohol dehydrogenases, the observed rate of the ene-reductases with NCBs was greater than when incubated with the natural cofactor (consistent with previous observations). We obtained the structures of an ene-reductase and an alcohol dehydrogenase with an NCB bound in their active sites. While the NCB bound to the ene-reductases in a productive position and orientation for hydride transfer to the isoalloxazine ring of the flavin cofactor, the NCB failed to adopt a catalytically competent binding mode in the alcohol dehydrogenase.

Chondrocyte-based cell therapy has been used for more than 30 years and is still considered to be a promising method of cartilage repair despite some limitations. This review introduces the latest developments of four generations of autologous chondrocyte implantation and current autologous chondrocyte products. The regeneration of cartilage from adult chondrocytes is limited by culture-induced dedifferentiation and patient age. Cartibeads is an innovative three-step method to produce high-quality hyaline cartilage microtissues, and it is developed from adult dedifferentiated chondrocytes with a high number of cell passages. In addition, allogeneic chondrocyte therapies using the Quantum hollow-fiber bioreactor and several signaling pathways involved in chondrocyte-based cartilage repair are mentioned, such as WNT signaling, the BMP-2/WISP1 pathway, and the FGF19 pathway.

Category: Ankle Arthritis; Ankle Introduction/Purpose: Surgical treatment options for symptomatic, full-thickness articular cartilage loss in the ankle are not consistently effective in restoring ankle function. Osteochondral allograft transplantation provides a standard-of-care alternative for patients, however, outcomes reported to date have been only fair, with a high incidence of reoperation and revision. However, recent cartilage storage and preservation techniques have significantly improved the percent viable chondrocytes at the time of implantation in OCAs. These high-chondrocyte-viability allografts should lead to improved survivability of OCAs and improved outcome measures. This study aimed to document the initial outcomes for patients undergoing bipolar OCA transplantation in the ankle after advances in tissue preservation, transplantation techniques, and patient management strategies. Methods: Patients with symptomatic tibiotalar arthritis were prospectively enrolled into a registry designed to follow outcomes after OCA surgeries in the ankle. All patients underwent complete OCA replacement of their tibial plafond and talar dome, with most undergoing fibular articular resurfacing. All OCA were size and side matched and preserved in Missouri Osteochondral Allograft Preservation System (MOPS). Patients followed a standardized, procedure-specific rehabilitation protocol after surgery, including remaining non-weight bearing for 8 weeks, weekly therapy visits, limited step count during recovery, and avoidance of high impact activities until 1 year after surgery. Patients followed-up with their physician at regular post-operative timepoints. Radiographs and patient reported outcome measures (VAS, AAOS Foot and Ankle, PROMIS PF, PROMIS Mobility) were obtained at each follow-up visit. Demographic and operative data were collected from the electronic medical record. All reported complications, reoperations, revisions, and failures were recorded in the EMR. Results: 14 patients were included for analyses with 12 undergoing primary OCA transplantation, and 2 undergoing revision OCA transplantation. Mean age and follow up was 36 and 44.1 months, respectively. All patients underwent tibia and talus OCA transplantation, with 10/14 including a fibula OCA transplantation. Initial success was 92.9% with one documented failure (tibial OCA collapse). Radiographic assessments indicated OCA integration and maintenance of joint space in 12 patients (85.7%). AAOS and VAS pain scores improved significantly from preoperative measures at each timepoint (p=.002, p=.03), while postoperative improvements in PROMIS Mobility and PROMIS Physical Function scores did not reach significance (p>0.15) (Table 1). Patients that were non-adherent to postoperative restriction and rehabilitation protocols, all 1-year postoperative PROs were significantly lower than for patients who were adherent. Conclusion: Ankle osteoarthritis in young patients continues to present a challenging dilemma. Previous attempts at large bipolar OCAs in the ankle have yielded fair, to poor, results. However, recent advances in bulk osteochondral allograft preservation has improved chondrocyte viability. Based on the results of our study, the use of high-chondrocyte-viability allografts for OCA transplantation is a viable option for the treatment of symptomatic bipolar osteochondral defects in the ankle joint. However, post operative rehab protocols are equally important in determining outcomes, and patient selection and education is key to ensuring successful outcomes. Longer term follow up is ongoing.

Category: Midfoot/Forefoot; Hindfoot Introduction/Purpose: Although operative treatment of the flexible progressive collapsing foot deformity (PCFD) remains controversial, correction of residual forefoot varus and stabilization of the medial column are important components of reconstruction. An opening wedge medial cuneiform osteotomy or first tarsometatarsal fusion is traditionally performed to plantarflex the first metatarsal. More recently, tendon transfers such as a peroneus brevis (PB) to peroneus longus (PL) have been proposed. However, there is little data to support their use. The aim of our study was to determine the effect of an isolated PB- to-PL transfer (PBT) on medial column and hindfoot joint kinematics in a simulated PCFD (sPCFD) cadaveric model using a robotic gait simulator. We hypothesized that a PBT in a sPCFD model would partially restore kinematics to the intact state. Methods: A validated six-degree of freedom robot (Baxter et al., 2016) was used to simulate the stance phase of level walking for 6 mid-tibia cadaveric specimens (3 male; age: 72 ± 8 years). An eight-camera motion capture system was used to track reflective markers fixed to bones of the foot and ankle. Three conditions were tested for each specimen: intact, sPCFD (Henry et al., 2022), and after PBT. The PBT was performed by transecting the PB and advancing the proximal stump 1 cm into the PL (Sanhudo, 2019). Outcome measures included kinematics of the talonavicular, subtalar, and first tarsometatarsal joints. Maximum differences between the PBT and sPCFD conditions and 95% confidence intervals (95%CIs) were calculated. The percent deformity correction was determined by dividing the difference between the PB and sPCFD states by the difference between the intact and sPCFD states at the site of maximum deformity correction. Results: Relative to the sPCFD condition, the PBT resulted in a maximum increase in talonavicular plantarflexion of 1.8° (95%CI 0.9°-2.7°) with 159% correction during midstance, decrease in talonavicular abduction of 1.5° (95%CI 0.3°-2.8°) with 65% correction during midstance, and decrease in talonavicular eversion of 2.4° (95%CI 1.2°-3.8°) with 90% correction during mid-to- late stance. All deformities had consistent correction at the talonavicular joint during stance (Figure 1). Additionally, the PBT resulted in a maximum increase in subtalar plantarflexion by 0.8° (95%CI 0.3°-1.8°) with 155% correction in early stance, decrease in subtalar abduction by 0.8° (95%CI 0.5°-1.2°) with 191% correction during early stance, and decrease in subtalar eversion by 1.5° (95%CI 0.5°-2.2°) with 178% correction during mid-stance. There was no effect on first tarsometatarsal joint kinematics. Conclusion: A PB-to-PL transfer in a sPCFD model resulted in the correction of multiple deformities including increased plantarflexion and decreased abduction at the talonavicular joint compared to the sPCFD without the transfer, most notably during PB activation in stance. The PBT also decreased eversion at the talonavicular and subtalar joints. Our results suggest that the addition of a PBT as part of the surgical management of the flexible PCFD contributes to correction of the residual forefoot varus, midfoot abduction, and hindfoot valgus deformities by plantarflexing through the medial column and removing a deforming force on the foot by the PB.

Category: Ankle; Basic Sciences/Biologics Introduction/Purpose: Although double hindfoot arthrodesis (subtalar and talonavicular) provides pain relief and deformity correction for patients with end-stage arthritis, altered ankle biomechanics may occur following these procedures. Furthermore, it has been reported that hindfoot fusions may lead to progressive ankle degenerative changes and a higher failure rate in patients undergoing total ankle arthroplasty. Previous biomechanical studies demonstrated that hindfoot fusion altered ankle joint kinematics and contact mechanics during simplified loading scenarios, but the effect during dynamic activity is unknown. Therefore, this study sought to quantify the changes in ankle kinematics after a double hindfoot arthrodesis during the stance phase of simulated gait. In addition, we sought to assess whether the sequence in which joints are fused plays a role in altering ankle kinematics. Methods: Fourteen mid-tibia specimens underwent stance phase simulations of level walking using a validated six-degree of freedom robot. All specimens had neutral hindfoot alignment. An eight-camera motion system tracked reflective markers in the tibia, talus, calcaneus, and navicular bones. Simulated arthrodeses of the subtalar and talonavicular joints were performed using two 7.0mm and two 5.5mm crossing screws, respectively. The subtalar alignment was set at 5º valgus, and the talonavicular at neutral abduction/adduction. Fluoroscopic images confirmed proper screw position and hindfoot alignment. Each specimen was tested in three conditions: pre-arthrodesis(intact), isolated arthrodesis(subtalar or talonavicular joint), and double arthrodesis(double). Specimens were further divided into two groups depending on whether the subtalar(STDouble) or talonavicular(TNDouble) joint was fused first. Ankle kinematics were calculated for each condition for the entire cohort of specimens and each of the two groups. Bias-corrected 95% confidence intervals of the difference in ankle kinematics relative to the intact condition were constructed. Results: Double hindfoot arthrodesis significantly altered ankle kinematics(Figure1A). Ankle plantarflexion decreased during heel strike by up to 2.0° on average and increased during toe-off by 6.5° compared to the intact condition. Ankle eversion increased by 1.5º and 2.5º on average during mid- and late stance, respectively. Internal rotation decreased during midstance by 1.1º on average and increased in late stance by 4.5°. The order in which hindfoot joints were fused significantly influenced ankle kinematics(Figure1B). On average, the TNDouble condition produced 2.3º and 3.5º more ankle eversion during the mid- and late stance, respectively, and 2.10° more ankle internal rotation during the early stance compared to the STDouble condition (not shown). Significant changes were also present after isolated hindfoot arthrodeses and remained consistent after the double arthrodesis. Conclusion: Double hindfoot arthrodesis significantly altered ankle kinematics throughout stance. Ankle kinematics also differed depending on which joint was fused first. Notably, the TNDouble condition produced more ankle internal rotation during early stance and more ankle eversion during mid- and late stance compared to the STDouble condition. This finding suggests that the sequence in which joints are fused affects the resultant ankle kinematics. Finally, the kinematic changes after isolated hindfoot arthrodesis remained consistent after incorporating the second joint into the fusion. It appears that once one joint needs to be fused, avoiding the double arthrodesis may not necessarily protect the ankle.

Category: Sports; Ankle Introduction/Purpose: Vega et al. describe two components of the anterior talofibular ligament(ATFL), including the intracapsular superior fascicle(sATFL) and the extracapsular inferior fascicle(iATFL). Based on this anatomic distinction, ankle “microinstability” describes instability arising from injury to the sATFL alone. Because the sATFL resides within the ankle joint, synovial fluid limits its healing, potentially leading to pain and subjective ankle instability without a positive anterior drawer exam. Since physical examination is unreliable for microinstability, arthroscopic examination is considered the gold standard for diagnosing sATFL injury. A noninvasive approach for diagnosis would be ideal; however, the efficacy of MRI in detecting injury to the sATFL is not understood. Therefore, we aimed to assess whether MRI could identify the sATFL as an independent structure and diagnose an isolated sATFL tear. Methods: Fourteen mid-tibia cadaveric specimens (7 males, age: 33-78 years) with neutral alignment and no history of trauma or previous surgery were included in the study. A board-certified foot and ankle orthopedic surgeon dissected the lateral ankle ligament complex to confirm the independent presence of the sATFL and the iATFL. After initial dissection, all specimens underwent a clinical MRI scan sequence, and two musculoskeletal radiologists with > 15 years of experience read the images in consensus to identify the sATFL. Half of the specimens were randomly assigned to undergo bisection of the sATFL. All 14 specimens underwent a second MRI scan, and the same radiologists assessed the images while blinded to the sATFL condition. The percentage of specimens with identifiable sATFL during the initial MRI scan and identifiable injury of the sATFL during the second scan were calculated. Results: A total of 14 specimens were dissected down to the lateral ligament complex. The ATFL was observed as a two- fascicle(sATFL and iATFL) ligament in all 14 specimens. A gap between both fascicles was observed. The fibular insertion of the sATFL was located just distal to the fibular insertion of the anterior tibiofibular ligament. In contrast, the fibular insertion of the iATFL was located between the insertion of the sATFL and the fibular tip. In the initial MRI scans, radiologists identified both the sATFL and the iATFL in 10/14(71.4%) specimens. The distinction between the two fascicles was not possible in the other four specimens. In the second set of MRI scans, radiologists correctly identified 6/7(85.7%) specimens that underwent sATFL bibisection and 7/7(100%) specimens with intact sATFL. Conclusion: Our cadaveric dissection confirmed the presence of two distinct fascicles of the ATFL in all specimens. While the radiologists could only identify the discrete bundles of the sATFL and iAFTL in 71.4% of intact specimens, they distinguished the bisected sATFL in 6 out of 7 specimens. These findings suggest that MRI can be a potential tool for diagnosing microinstability. Since microinstability frequently involves intraarticular pathology, performing MRI can be considered if patients experience subjective ankle instability and pain but without signs of ankle laxity on clinical examination.

Category: Ankle; Trauma Introduction/Purpose: Existing literature has established that obese patients have nearly double the risk of sustaining an ankle fracture when compared to a non-obese population. However, few studies have investigated obesity’s effect on fracture complications and patient reported outcomes (PROs) when patients are stratified by fracture type. Furthermore, as the average body mass index (BMI) of our population steadily rises, it becomes prudent to investigate variations in complications rates and patient reported outcomes in various stages of obesity. The aim of this study is to identify trends in complication rates and patient reported outcome scores among patients of different BMI before and after dividing by fracture complexity. Methods: We retrospectively assessed clinical and surgical data from 595 patients who underwent ankle fracture surgery at a single institution between 2017 and 2021 for surgical related complications. All patients had a minimum of 18 months follow up (mean-42.2 [18.2-71.4] months). PROMIS Physical Health and Visual Analog Scale pain scores surveys were available only for patients receiving surgery after November 2019. We aggregated survey data for timepoints between three months and two years post-operatively to assess only patients with meaningful clinical data in regard to their recovery. Patients were divided based on BMI and fracture type. BMI subgroups were classified as: Non-obese (18.5-24.9 kg/m 2 , n=88), Overweight/Obese I (25-34.9 kg/m 2 , n=314), Obese II/III (≥35 kg/m 2 , n=192). Fracture subgroups were divided into two groups: Simple (Unimalleolar types) and complex (Bimalleolar and Trimalleolar variants). Data analysis was performed using Chi-Square and T-Tests with statistical significance set at an alpha (α) of ≤ 0.05. Results: We observed a whole cohort complication rate of (15.3%, n=91/594). Complication rates when stratified by BMI were: Non-obese (12.3%, n=9), Overweight/Obese class I (19.4%, n=61), Obese class II/III (10.3%, n=20). Complication rates for Overweight/Obese I patients were significantly higher when compared to Non-obese patients (p=0.044, OR=2.11). However, there was no significant difference when comparing Non-obese to Class II/III (p=0.972). We observed no significant differences in complications when performing a sub analysis on specific fracture types, regardless of BMI group. Pain scores were significantly higher in both Overweight/Obese I and Obese II/III groups when compared to Non-Obese patients (p= < 0.001, p=0.015). Physical health scores were significantly lower only in the Obese II/III group when compared to Non-Obese patients (p=0.011). Conclusion: Our results indicate that patients who are Overweight/Obese I have a significantly higher risk of complication when compared to patients of normal BMI. Surprisingly, our cohort demonstrated nearly equivalent risk between Obese II/III and Non- obese patient groups. Patient reported outcome data shows different trends with worse pain scores and lower physical health outcomes in the Obese II/III group. These findings add to the growing debate surrounding obesity’s effect on ankle fracture complication rates as well as patient reported outcomes and suggest that increased BMI cannot be viewed purely as a one-to-one relationship with negative outcomes.

Category: Hindfoot; Midfoot/Forefoot Introduction/Purpose: Medial longitudinal arch collapse is one of the key clinical and radiographic features of progressive collapsing foot deformity (PCFD) and can occur anywhere within its three constituents: first tarsometatarsal (TMT1), naviculo- cuneiform (NC), and talonavicular (TN) joints. Medial column osteotomy or fusion has typically been utilized to address this instability. A new procedure involving transferring the flexor hallucis longus (FHL) tendon to the 1st metatarsal base has shown promising results in restoring radiographic alignment of the entire medial column in conjunction with a hindfoot procedure. However, the mechanism of correction in a dynamic environment is unclear. Thus, this study examined the effect of medial column stabilization using FHL transfer on the foot and ankle kinematics during stance phase. Methods: Twelve mid-tibia cadaveric specimen (6 male; Age 48 ± 16 years) underwent stance phase simulations using a validated six-degree of freedom robotic gait simulator. Three conditions were tested each cadaveric specimen: pre-deformity (Intact), after creating a simulated progressive collapsing foot deformity (sPCFD), and after an FHL transfer (FHL). Motion capture cameras tracked the motion of retroreflective markers inserted into bones of the foot and ankle. The FHL transfer was performed on each specimen by harvesting the FHL tendon at its distal insertion and fixing it in the 1st metatarsal with a biotenodesis screw (Figure 1A). Outcome measures include joint rotations of the TMT1, NC, TN, subtalar, and ankle joint. Significant differences (p < 0.05) in joint kinematics were statistically analyzed by constructing 95% confidence intervals of the repeated measures difference between both the sPCFD and FHL conditions and the intact condition. Results: The FHL condition demonstrated significant differences in the kinematics of the medial column compared to the sPCFD condition (Figure 1B). The TMT1 joint showed increased plantarflexion in early and late stance, as well as increased eversion during early and mid-stance. The NC joint demonstrated increased plantarflexion, eversion, and abduction during early stance. At the TN joint, there was increased inversion during early and late stance, as well as increased adduction during mid-stance. At the subtalar joint, subtalar eversion was decreased during early stance, and no significant differences were observed from the intact condition throughout stance. No differences were found in the ankle joint kinematics across all conditions. Conclusion: The results of our study demonstrate that the medial column stabilization procedure with FHL transfer can improve the kinematics of the medial column in sPCFD. Additionally, the correction at the TN and subtalar joint demonstrates the potential efficacy of this procedure for hindfoot correction. The correction occurred during the earlier stance phase as well when the FHL is not active, suggesting that this procedure provides correction in both a dynamic and static manner. This procedure can be used in conjunction with hindfoot corrective procedures in PCFD, particularly when preoperative imaging suggests multiple levels of instability within the medial column.

The rapid advancement of modern technology has significantly driven progress in various IT-related activities, resulting in a substantial increase in internet penetration rates, particularly among college students. The utilization of the internet has become one of the most essential tools in our modern society. However, internet addiction (IA) has emerged as a serious concern, particularly among college students, adversely affecting academic performance and having significant psychological and psychiatric implications. The aim of the current study was to determine the impact of physical exercise, gender and academic year on IA among college students. In the present study, we investigated internet usage, engagement in sports activities, and academic performance among college students from Western, Middle, and Eastern regions of Chinese universities. It’s noteworthy that most of the respondents were freshmen. Our findings indicate that freshmen students were more susceptible to experiencing IA. Approximately 75% of students engaged in leisure sports activities, revealing an inverse correlation between sports activity and IA. This correlation aligns with the level of sports involvement, emphasizing the potential benefits of physical activity in mitigating IA. However, our study did not uncover any correlation between geographic location and the occurrence of IA, nor did it find differences between medical and non-medical students. Furthermore, our study revealed no significant variations in IA among students from different ethnic backgrounds. The underlying mechanism of IA is being currently determined. Our data suggest that physical exercise, gender, and academic year have a significant impact on IA among college students.

Background Studies about brain structure in bipolar disorder have reported conflicting findings. These findings may be explained by the high degree of heterogeneity within bipolar disorder, especially if structural differences are mapped to single brain regions rather than networks. Aims We aim to complete a systematic review and meta-analysis to identify brain networks underlying structural abnormalities observed on T1-weighted magnetic resonance imaging scans in bipolar disorder across the lifespan. We also aim to explore how these brain networks are affected by sociodemographic and clinical heterogeneity in bipolar disorder. Method We will include case–control studies that focus on whole-brain analyses of structural differences between participants of any age with a standardised diagnosis of bipolar disorder and controls. The electronic databases Medline, PsycINFO and Web of Science will be searched. We will complete an activation likelihood estimation analysis and a novel coordinate-based network mapping approach to identify specific brain regions and brain circuits affected in bipolar disorder or relevant subgroups. Meta-regressions will examine the effect of sociodemographic and clinical variables on identified brain circuits. Conclusions Findings from this systematic review and meta-analysis will enhance understanding of the pathophysiology of bipolar disorder. The results will identify brain circuitry implicated in bipolar disorder, and how they may relate to relevant sociodemographic and clinical variables across the lifespan.

Abstract We aimed to synthesize evidence on (1) the prevalence of mood and anxiety disorders and (2) factors associated with symptoms in systemic sclerosis (SSc). We searched MEDLINE, CINAHL, EMBASE, Cochrane CENTRAL, and PsycINFO via an ongoing living systematic review with automated monthly searches. We identified 6 eligible studies through March 1, 2023. Based on 3 studies (N = 93 to 345), current or 30-day major depressive disorder prevalence was 4% (95% confidence interval [CI] 2%, 6%) in a sample of Canadian outpatients (N = 345), 18% (95% CI 12%, 27%) in a study of Indian outpatients (N = 93), 10% (95% CI 4%, 21%) for French patient conference attendees (N = 51), and 29% (95% CI 18%, 42%) for French inpatients (N = 49). Current or 30-day prevalence of any anxiety disorder was 49% (95% CI 36%, 62%) for French conference attendees and 51% (95% CI 38%, 64%) for French inpatients; current or 30-day prevalence of generalized anxiety disorder was 3% for Indian outpatients (95% CI 1%, 9%; N = 93). In 3 studies (N = 114 to 376) that examined factors associated with depressive symptoms, higher education and being married or living as married were associated with lower symptoms and pulmonary involvement, breathing problems, and tender joint counts with higher symptoms; age and disease severity markers were not associated. Only 1 study (N = 114) assessed factors associated with anxiety symptoms and found no statistically significant associations. Limitations included heterogeneous populations and assessment methods, small samples, and substantial risk of bias concerns. Mood and anxiety disorder prevalence appear high in SSc, but estimates vary, and existing studies have important limitations. Future research should assess mood and anxiety prevalence and factors associated with symptoms using large representative samples and validated classification and assessment methods. Review registration: PROSPERO (CRD 42021251339).

Ginger (Zingiber officinale, Roscoe) is a tropical rhizome crop typically grown from rhizome pieces, but can also be produced from seedlings. No information is available on how the seedling method compares with the rhizome piece method in organic ginger culture. In addition, information on the growing of organic ginger in the mid-Atlantic region is lacking. Some of the challenges include limited knowledge of rhizome storage, types of propagation materials for planting in the field or high tunnel, and acceptable organic fertilizers that will not increase the excess P currently polluting the Chesapeake Bay watershed. The objective of this study was to assess plant development, soil nutrients, and economic feasibility of organic ginger derived from different storage conditions and planting materials when grown in different nutrient sources in a high tunnel. Three types of plant material (single-shoot transplant seedlings derived from 36.5–40.0 g/rhizome, multishoot transplant seedlings derived from 60–120 g/rhizome, and rhizome seeds of 60–120 g) and three fertilizers types [cotton seed meal, 6N–0.9P–0.8K (0.18 kg⋅m–2), plus AZOMITE (1 kg⋅m–2); Nature Safe, 13N–0P–0K (0.07 kg⋅m–2); and Phytamin All Purpose Liquid fertilizer, 4N–1.3P–3.3K (0.26 L⋅m–2)] were used in 2018. In 2019 and 2020, three types of plant material and two fertilizer types at modified rates from the 2018 study, plus two storage containers (pans and flats), were tested. In general, the rhizome storage container did not affect plant height, leaf soil plant analysis development (SPAD) index, and rhizome yield, and its effect on tillers was none or mixed. Fertilizer type had mixed effects on plant height and tiller number, and no effect on the leaf SPAD index. Rhizome yields in 2019 and 2020 were unaffected by fertilizer, but Nature Safe produced a greater benefit-to-cost ratio (BCR) and profitability index (PI) than Phytamin. Soil P was generally less in Nature Safe–fertilized soil than in Phytamin-fertilized soil. Multishoot seedlings produced the greatest rhizome yield, BCR, PI, and tallest plants, and had some of the highest tiller numbers. These findings show that it would be more profitable to use multishoot seedlings as planting material in high tunnels compared with single-shoot seedlings and rhizome seeds. Furthermore, the lower P levels in the Nature Safe–fertilized soils compared with the Phytamin soils, and greater PI suggest that using Nature Safe will be a better choice than Phytamin for growing organic ginger.

Abstract Item 10 of the Edinburgh Postnatal Depression Scale (EPDS) is intended to assess thoughts of intentional self-harm but may also elicit concerns about accidental self-harm. It does not specifically address suicide ideation but, nonetheless, is sometimes used as an indicator of suicidality. The 9-item version of the EPDS (EPDS-9), which omits item 10, is sometimes used in research due to concern about positive endorsements of item 10 and necessary follow-up. We assessed the equivalence of total score correlations and screening accuracy to detect major depression using the EPDS-9 versus full EPDS among pregnant and postpartum women. We searched Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, and Web of Science from database inception to October 3, 2018 for studies that administered the EPDS and conducted diagnostic classification for major depression based on a validated semi-structured or fully structured interview among women aged 18 or older during pregnancy or within 12 months of giving birth. We conducted an individual participant data meta-analysis. We calculated Pearson correlations with 95% prediction interval (PI) between EPDS-9 and full EPDS total scores using a random effects model. Bivariate random-effects models were fitted to assess screening accuracy. Equivalence tests were done by comparing the confidence intervals (CIs) around the pooled sensitivity and specificity differences to the equivalence margin of δ = 0.05. Individual participant data were obtained from 41 eligible studies (10,906 participants, 1407 major depression cases). The correlation between EPDS-9 and full EPDS scores was 0.998 (95% PI 0.991, 0.999). For sensitivity, the EPDS-9 and full EPDS were equivalent for cut-offs 7–12 (difference range − 0.02, 0.01) and the equivalence was indeterminate for cut-offs 13–15 (all differences − 0.04). For specificity, the EPDS-9 and full EPDS were equivalent for all cut-offs (difference range 0.00, 0.01). The EPDS-9 performs similarly to the full EPDS and can be used when there are concerns about the implications of administering EPDS item 10. Trial registration: The original IPDMA was registered in PROSPERO (CRD42015024785).

Network analysis of 16S rRNA-sequencing data collected over six months in the Sannich Inlet on Vancouver Island, Canada, suggests keystone microbial taxa that might contribute to water column N2O production and accumulation.

Abstract Background Evidence-based psychotherapies available to treat patients with bipolar disorders (BD) are limited. Dialectical behavior therapy (DBT) may target several common symptoms of BD. We conducted a systematic review on the efficacy of DBT for mood symptoms in patients with BD. The systematic search used key words related to DBT and BD in Medline, Embase, PsycInfo, CINAHL, and Cochrane Library databases from 1980 to April 1st, 2022. We included studies that enrolled patients with a BD I or II diagnosis (DSM or ICD), age 12 and older who received a DBT-based intervention. Studies reviewed were clinical trials including observational studies that reported at least one outcome related to BD mood symptoms or severity. We did not exclude based upon psychiatric or physical co-morbidity. Results We screened 848 abstracts and reviewed 28 full texts; 10 publications with 11 studies met our pre-determined eligibility criteria. All but one were feasibility pilot studies and most included participants in all mood states except for mania. The studies provided preliminary evidence suggesting these interventions may be effective for improving several core symptoms of BD. Overall, all the studies consistently supported that DBT-based interventions are feasible and acceptable for patients with BD. Conclusion DBT may be an effective treatment for BD; however, the confidence in this conclusion is limited by the small sample sizes, heterogeneity, and high risk of bias in all published trials. Larger well-designed RCTs are now required to establish the effectiveness of DBT in BD.

Two separate feeding trials were undertaken to benchmark a series of commercial diets and determine the nutrient and energy apparent digestibility coefficients of a variety of protein-based feed ingredients when fed to sobaity seabream, Sparidentex hasta. In Experiment 1, triplicate groups of fish (initial body weight: 330.5 ± 2.6 g) were fed with one of three locally available diets containing crude protein (CP) levels ranging from 44 to 46% of dry matter (DM), each with ~12% crude fat. Fish grew at around 3.2 g day−1 with a specific growth rate (SGR) of 0.7% day−1. Both the feed conversion ratio (FCR) and protein efficiency ratio (PER) were significantly better in fish fed diets, which contained the highest (46.4%) crude protein level. Overall, the data from these preliminary studies suggest that the best performance by sobaity seabream was obtained with a diet containing 46% crude protein, 20 MJ/kg, and a protein-to-energy ratio of 23 mg/kJ. In Experiment 2, fish with an initial body weight of 319 ± 7 g were held in 11 tanks and fed reference (D1) and test diets (D2–D11) for 7 days before fecal collection. This process was repeated twice in a blocking arrangement to generate three replicates. Each of the ten test diets contained 30% of a test ingredient, with the remaining 70% proportionally identical to the D1 diet. Diet apparent digestibility coefficients (ADCs) were measured, and the diet ADCs were then used to derive the protein and energy ADCs for the individual test ingredients. Ingredient protein ADC ranged between 75.5 and 93.9%, while ingredient energy ADC ranged between 66.8 and 81.2%.

Seasonal infection rates of individual viruses are influenced by synergistic or inhibitory interactions between coincident viruses. Endemic patterns of SARS-CoV-2 and influenza infection overlap seasonally in the Northern hemisphere and may be similarly influenced. We explored the immunopathologic basis of SARS-CoV-2 and influenza A (H1N1pdm09) interactions in Syrian hamsters. H1N1 given 48 h prior to SARS-CoV-2 profoundly mitigated weight loss and lung pathology compared to SARS-CoV-2 infection alone. This was accompanied by the normalization of granulocyte dynamics and accelerated antigen-presenting populations in bronchoalveolar lavage and blood. Using nasal transcriptomics, we identified a rapid upregulation of innate and antiviral pathways induced by H1N1 by the time of SARS-CoV-2 inoculation in 48 h dual-infected animals. The animals that were infected with both viruses also showed a notable and temporary downregulation of mitochondrial and viral replication pathways. Quantitative RT-PCR confirmed a decrease in the SARS-CoV-2 viral load and lower cytokine levels in the lungs of animals infected with both viruses throughout the course of the disease. Our data confirm that H1N1 infection induces rapid and transient gene expression that is associated with the mitigation of SARS-CoV-2 pulmonary disease. These protective responses are likely to begin in the upper respiratory tract shortly after infection. On a population level, interaction between these two viruses may influence their relative seasonal infection rates.

Abstract We report marine dissolved organic carbon (DOC) concentrations, and DOC Δ14C and δ13C in seawater collected from the West Indian Ocean during the GO‐SHIP I07N cruise in 2018. We find bomb 14C in DOC from the upper 1,000 m of the water column. There is no significant change in ∆14C of DOC in deep water northward, unlike that of dissolved inorganic carbon (DIC), suggesting that transport of deep water northward is not controlling the 14C age of DOC. Variability of DOC ∆14C, including high values in the deep waters, is more pronounced than in other oceans, suggesting that dissolution of surface derived particulate organic carbon is a source of modern carbon to deep DOC in the West Indian Ocean. Low δ13C are present at two of the five stations studied, suggesting a source of low δ13C DOC, or additional microbial utilization of deep DOC.

Abstract Objectives Optimal cutoff thresholds are selected to separate ‘positive’ from ‘negative’ screening results. We evaluated how depression screening tool studies select optimal cutoffs. Methods We included studies from previously conducted meta‐analyses of Patient Health Questionnaire‐9, Edinburgh Postnatal Depression Scale, or Hospital Anxiety and Depression Scale—Depression accuracy. Outcomes included whether an optimal cutoff was selected, method used, recommendations made, and reporting guideline and protocol citation. Results Of 212 included studies, 172 (81%) attempted to identify an optimal cutoff, and 147 of these 172 (85%) reported one or more methods. Methods were heterogeneous with Youden's J (N = 35, 23%) most common. Only 23 of 147 (16%) studies described a rationale for their method. Rationales focused on balancing sensitivity and specificity without describing why desirable. 131 of 172 studies (76%) identified an optimal cutoff other than the standard; most did not make use recommendations (N = 56; 43%) or recommended using a non‐standard cutoff (N = 53; 40%). Only 4 studies cited a reporting guideline, and 4 described a protocol with optimal cutoff selection methods, but none used the protocol method in the published study. Conclusions Research is needed to guide how selection of cutoffs for depression screening tools can be standardized and reflect clinical considerations.

Summary: Background: Systemic sclerosis is a heterogenous disease in which little is known about patterns of patient-reported symptom clusters. We aimed to identify classes of individuals with similar anxiety, depression, fatigue, sleep disturbance, and pain symptoms and to evaluate associated sociodemographic and disease-related characteristics. Methods: This multi-centre cross-sectional study used baseline data from Scleroderma Patient-centered Intervention Network Cohort participants enrolled from 2014 to 2020. Eligible participants completed the PROMIS-29 v2.0 measure. Latent profile analysis was used to identify homogeneous classes of participants based on patterns of anxiety, depression, fatigue, sleep disturbance, and pain scores. Sociodemographic and disease-related characteristics were compared across classes. Findings: Among 2212 participants, we identified five classes, including four classes with “Low” (565 participants, 26%), “Normal” (651 participants, 29%), “High” (569 participants, 26%), or “Very High” (193 participants, 9%) symptom levels across all symptoms. Participants in a fifth class, “High Fatigue/Sleep/Pain and Low Anxiety/Depression” (234 participants, 11%) had similar levels of fatigue, sleep disturbance, and pain as in the “High” class but low anxiety and depression symptoms. There were significant and substantive trends in sociodemographic characteristics (age, education, race or ethnicity, marital or partner status) and increasing disease severity (diffuse disease, tendon friction rubs, joint contractures, gastrointestinal symptoms) across severity-based classes. Disease severity and sociodemographic characteristics of “High Fatigue/Sleep/Pain and Low Anxiety/Depression” class participants were similar to the “High” severity class. Interpretation: Most people with systemic sclerosis can be classified by levels of patient-reported symptoms, which are consistent across symptoms and highly associated with sociodemographic and disease-related variables, except for one group which reports low mental health symptoms despite high levels of other symptoms and substantial disease burden. Studies are needed to better understand resilience in systemic sclerosis and to identify and facilitate implementation of cognitive and behavioural strategies to improve coping and overall quality of life. Funding: National Institute of Nursing Research (F31NR019007), Canadian Institutes of Health Research, Arthritis Society Canada, the Lady Davis Institute for Medical Research, the Jewish General Hospital Foundation, McGill University, Scleroderma Society of Ontario, Scleroderma Canada, Sclérodermie Québec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, and Scleroderma Queensland.

Abstract Background Systemic sclerosis (scleroderma; SSc) is a rare autoimmune connective tissue disease. Functional impairment of hands is common. The Scleroderma Patient-centered Intervention Network (SPIN)-HAND trial compared effects of offering access to an online self-guided hand exercise program to usual care on hand function (primary) and functional health outcomes (secondary) in people with SSc with at least mild hand function limitations. Methods The pragmatic, two-arm, parallel-group cohort multiple randomized controlled trial was embedded in the SPIN Cohort. Cohort participants with Cochin Hand Function Scale (CHFS) scores ≥ 3 and who indicated interest in using the SPIN-HAND Program were randomized (3:2 ratio) to an offer of program access or to usual care (targeted N = 586). The SPIN-HAND program consists of 4 modules that address (1) thumb flexibility and strength; (2) finger bending; (3) finger extension; and (4) wrist flexibility and strength. The primary outcome analysis compared CHFS scores 3 months post-randomization between participants offered versus not offered the program. Secondary outcomes were CHFS scores 6 months post-randomization and functional health outcomes (Patient-Reported Outcomes Measurement Information System profile version 2.0 domain scores) 3 and 6 months post-randomization. Results In total, 466 participants were randomized to intervention offer (N = 280) or usual care (N = 186). Of 280 participants offered the intervention, 170 (61%) consented to access the program. Of these, 117 (69%) viewed at least one hand exercise instruction video and 77 (45%) logged into the program website at least 3 times. In intent-to-treat analyses, CHFS scores were 1.2 points lower (95% CI − 2.8 to 0.3) for intervention compared to usual care 3 months post-randomization and 0.1 points lower (95% CI − 1.8 to 1.6 points) 6 months post-randomization. There were no statistically significant differences in other outcomes. Conclusion The offer to use the SPIN-HAND Program did not improve hand function. Low offer uptake, program access, and minimal usage among those who accessed the program limited our ability to determine if using the program would improve function. To improve engagement, the program could be tested in a group format or as a resource to support care provided by a physical or occupational therapist. Trial registration NCT03419208 . Registered on February 1, 2018.