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Abstract Spatial omics technologies decipher functional components of complex organs at cellular and subcellular resolutions. We introduce Spatial Graph Fourier Transform (SpaGFT) and apply graph signal processing to a wide range of spatial omics profiling platforms to generate their interpretable representations. This representation supports spatially variable gene identification and improves gene expression imputation, outperforming existing tools in analyzing human and mouse spatial transcriptomics data. SpaGFT can identify immunological regions for B cell maturation in human lymph nodes Visium data and characterize variations in secondary follicles using in-house human tonsil CODEX data. Furthermore, it can be integrated seamlessly into other machine learning frameworks, enhancing accuracy in spatial domain identification, cell type annotation, and subcellular feature inference by up to 40%. Notably, SpaGFT detects rare subcellular organelles, such as Cajal bodies and Set1/COMPASS complexes, in high-resolution spatial proteomics data. This approach provides an explainable graph representation method for exploring tissue biology and function.

Abstract Global atmospheric concentrations of nitrous oxide have been increasing over previous decades with emerging research suggesting the Arctic as a notable contributor. Thermokarst processes, increasing temperature, and changes in drainage can cause degradation of polygonal tundra landscape features resulting in elevated, well-drained, unvegetated soil surfaces that exhibit large nitrous oxide emissions. Here, we outline the magnitude and some of the dominant factors controlling variability in emissions for these thermokarst landscape features in the North Slope of Alaska. We measured strong nitrous oxide emissions during the growing season from unvegetated high centered polygons (median (mean) = 104.7 (187.7) µg N2O-N m−2 h−1), substantially higher than mean rates associated with Arctic tundra wetlands and of similar magnitude to unvegetated hotspots in peat plateaus and palsa mires. In the absence of vegetation, isotopic enrichment of 15N in these thermokarst features indicates a greater influence of microbial processes, (denitrification and nitrification) from barren soil. Findings reveal that the thermokarst features discussed here (~1.5% of the study area) are likely a notable source of nitrous oxide emissions, as inferred from chamber-based estimates. Growing season emissions, estimated at 16 (28) mg N2O-N ha−1 h−1, may be large enough to affect landscape-level greenhouse gas budgets.

Abstract Large-extent maps of three-dimensional vegetation structure are important for understanding the hydrologic cycle, climate, carbon fluxes, and habitat. We aggregated over 7 billion lidar shots from the Global Ecosystem Dynamics Investigation (GEDI) to produce analysis-ready, gridded rasters of 36 vegetation structure metrics at three spatial resolutions (1, 6, and 12 km). We used 8 statistics to grid shots in every pixel, specifically the mean, bootstrapped standard error of the mean, median, standard deviation, interquartile range, Shannon’s Diversity Index, and shot count. We quantified uncertainty of the mean by randomly selecting 100 subsets of shots (i.e. bootstrapping) within each pixel. We also assessed the accuracy of several gridded metrics using fine spatial resolution airborne laser scanning data. The gridded metrics are generally more accurate at mid latitudes due to higher shot density and lower density of vegetation. Statistics associated with the central or maximum tendency of a metric are more accurate than statistics related to variability of metric values within the pixel.

Abstract While the simultaneous degradation of muscle composition and postural stability in aging are independently highly investigated due to their association with fall risk, the interplay between the two has received little attention. Thus, the purpose of this study is to explore how age-related changes in muscle composition relate to postural stability. To that aim, we collected posturography measures and ultrasound images of the dominant Vastus Lateralis and Biceps Brachii from 32 young (18–35 year old) and 34 older (65–85 year old) participants. Muscle properties were quantified with echo-intensity and texture-based metrics derived from gray-level co-occurrence matrix analysis, and postural stability with the variability of the center of pressure during bipedal stance tasks. Ultrasound parameters revealed that young muscle possessed lower echo-intensity and higher homogeneity compared to the elderly. Echo-intensity and muscle thickness, and several texture-based parameters possessed outstanding young versus older classification performance. A canonical correlation analysis demonstrated a significant relationship between ultrasound and postural measures only within the young group (r = 0.53, p

Abstract Test subjects were assessed in a partial gravity environment during parabolic flight while they performed mission-critical activities that challenged their balance and locomotion. These functional activities included rising from a seated position and walking, jumping down, recovering from falls, and maintaining an upright stance. Twelve volunteers were tested during 10 parabolas that produced 0.25×g, 0.5×g, or 0.75×g, and at 1×g during level flight intervals between parabolas. Additionally, 14 other subjects were tested using identical procedures in a 1×g laboratory setting. Partial gravity altered the performance of settling after standing and navigating around obstacles. As gravity levels decreased, the time required to stand up, settle, walk, and negotiate obstacles, and the number of falls increased. Information obtained from these tests will allow space agencies to assess the vestibular, sensorimotor, and cardiovascular risks associated with different levels of partial gravity.

Abstract Booster vaccinations are recommended to improve protection against severe disease from SARS-CoV-2 infection. With primary vaccinations involving various adenoviral vector and mRNA-based formulations, it remains unclear if these differentially affect the immune response to booster doses. We examined the effects of homologous (mRNA/mRNA) and heterologous (adenoviral vector/mRNA) vaccination on antibody and memory B cell (Bmem) responses against ancestral and Omicron subvariants. Healthy adults who received primary BNT162b2 (mRNA) or ChAdOx1 (vector) vaccination were sampled 1-month and 6-months after their 2nd and 3rd dose (homologous or heterologous) vaccination. Recombinant spike receptor-binding domain (RBD) proteins from ancestral, Omicron BA.2 and BA.5 variants were produced for ELISA-based serology, and tetramerized for immunophenotyping of RBD-specific Bmem. Dose 3 boosters significantly increased ancestral RBD-specific plasma IgG and Bmem in both cohorts. Up to 80% of ancestral RBD-specific Bmem expressed IgG1+. IgG4+ Bmem were detectable after primary mRNA vaccination, and expanded significantly to 5–20% after dose 3, whereas heterologous boosting did not elicit IgG4+ Bmem. Recognition of Omicron BA.2 and BA.5 by ancestral RBD-specific plasma IgG increased from 20% to 60% after the 3rd dose in both cohorts. Reactivity of ancestral RBD-specific Bmem to Omicron BA.2 and BA.5 increased following a homologous booster from 40% to 60%, but not after a heterologous booster. A 3rd mRNA dose generates similarly robust serological and Bmem responses in homologous and heterologous vaccination groups. The expansion of IgG4+ Bmem after mRNA priming might result from the unique vaccine formulation or dosing schedule affecting the Bmem response duration and antibody maturation.

Abstract Background Partner support is associated with better weight loss outcomes in observational studies, but randomized trials show mixed results for including partners. Unclear is whether teaching communication skills to couples will improve weight loss in a person attempting weight loss (index participant). Purpose To compare the efficacy of a partner-assisted intervention versus participant-only weight management program on 24-month weight loss. Methods This community-based study took place in Madison, WI. Index participants were eligible if they met obesity guideline criteria to receive weight loss counseling, were aged 18–74 years, lived with a partner, and had no medical contraindications to weight loss; partners were aged 18–74 years and not underweight. Couples were randomized 1:1 to a partner-assisted or participant-only intervention. Index participants in both arms received an evidence-based weight management program. In the partner-assisted arm, partners attended half of the intervention sessions, and couples were trained in communication skills. The primary outcome was index participant weight at 24 months, assessed by masked personnel; secondary outcomes were 24-month self-reported caloric intake and average daily steps assessed by an activity tracker. General linear mixed models were used to compare group differences in these outcomes following intent-to-treat principles. Results Among couples assigned to partner-assisted (n = 115) or participant-only intervention (n = 116), most index participants identified as female (67%) and non-Hispanic White (87%). Average baseline age was 47.27 years (SD 11.51 years) and weight was 106.55 kg (SD 19.41 kg). The estimated mean 24-month weight loss was similar in the partner-assisted (2.66 kg) and participant-only arms (2.89 kg) (estimated mean difference, 0.23 kg [95% CI, -1.58, 2.04 kg], p=0.80). There were no differences in 24-month average daily caloric intake (estimated mean difference 50 cal [95% CI: -233, 132 cal], p=0.59) or steps (estimated mean difference 806 steps [95% CI: -1675, 64 steps], p=0.07). The percentage of participants reporting an adverse event with at least possible attribution to the intervention did not differ by arm (partner-assisted: 9%, participant-only, 3%, p = 0.11). Conclusions Partner-assisted and individual weight management interventions led to similar outcomes in index participants. Trial registration Clinicaltrials.gov NCT03801174, January 11, 2019.

Abstract Background Hepatitis C virus (HCV) continues to cause significant morbidity and mortality within the US, and disproportionately impacts those involved with the criminal justice system. Despite this, knowledge and attitudes regarding HCV treatment among adults on probation have not been well studied. We conducted a cross-sectional survey of adults on probation accessing on-site HCV testing and linkage services at the adult probation department in Denver, Colorado. The survey assessed general knowledge of HCV and HCV treatment, as well as attitudes surrounding HCV treatment that might reflect medical mistrust. We used bivariate and multivariable logistic regression to identify factors associated with previous HCV testing, previous HCV treatment, and HCV antibody positivity at the time the survey was conducted. Results A total of 402 participants completed all or a portion of the survey. 69% of the participants were cis-gender men; 29% were white, 27% were Black, and 30% were Hispanic/Latinx. Fewer than half of participants correctly identified that HCV infection is commonly asymptomatic (46%), that there is currently no vaccine that prevents HCV (19%), and that reinfection after treatment is possible (47%). Very few participants felt that side-effects (9%) or cost of treatment (10%) were barriers to care. Many participants believed that racial disparities exist in the treatment of HCV (59%). The belief that people who use substances are treated inequitably by health care providers was also commonly reported (35% of participants). Self-reported injection drug use and higher HCV-related knowledge were positively associated with previous testing for HCV. Higher HCV-related knowledge was positively associated with HCV antibody positivity at the time of survey completion, though the magnitude of the association was small. Conclusion Interventions are needed to increase knowledge of HCV, to improve access to HCV testing and treatment, and to reduce bias associated with HCV and substance use within the probation population.

Abstract Ionizing radiation has been pivotal in cancer therapy since its discovery. Despite its therapeutic benefits, IR causes significant acute and chronic complications due to DNA damage and the generation of reactive oxygen species, which harm nucleic acids, lipids, and proteins. While cancer cells are more vulnerable to ionizing radiation due to their inefficiency in repairing damage, healthy cells in the irradiated area also suffer. Various types of cell death occur, including apoptosis, necrosis, pyroptosis, autophagy-dependent cell death, immunogenic cell death, and ferroptosis. Ferroptosis, driven by iron-dependent lipid peroxide accumulation, has been recognized as crucial in radiation therapy’s therapeutic effects and complications, with extensive research across various tissues. This review aims to summarize the pathways involved in radiation-related ferroptosis, findings in different organs, and drugs targeting ferroptosis to mitigate its harmful effects.

Total knee arthroplasty (TKA) is one of the most commonly performed orthopedic surgeries, with nearly one million performed in 2020 in the United States alone. Changing patient demographics, predominately indicated by increases in younger, more active, and more obese patients undergoing TKA, poses a challenge to orthopedic surgeons as these factors present a greater risk of long-term complications. Historically, cemented TKA has been the gold standard for fixation, but long-term aseptic loosening continues to be a risk for cemented implants. Cementless TKA, which relies on the surface morphology of a porous coating for biologic fixation of implant to bone, may provide improved long-term survivorship compared with cement. The quality of this bond is dependent on an interference fit and the roughness, or coefficient of friction, between the implant and the bonebone. Stress shielding is a measure of the difference in the stress experienced by implanted bone versus surrounding native bone. A finite element model (FEM) can be used to quantify and better understand stress shielding in order to better evaluate and optimize implant design. In this study, a FEM was constructed to investigate how the surface coating of cementless implants (coefficient of friction) and the location of the coating application affected the stress-shielding response in the tibia. It was determined that the stress distribution in the native tibia surrounding a cementless TKA implant was dependent on the coefficient of friction applied at the tip of the implant’s stem. Materials with lower friction coefficients applied to the stem tip resulted in higher compressive stress experienced by implanted bone, and more favorable overall stress-shielding responses.

Abstract Mood disorders are an enigmatic class of debilitating illnesses that affect millions of individuals worldwide. While chronic stress clearly increases incidence levels of mood disorders, including major depressive disorder (MDD), stress-mediated disruptions in brain function that precipitate these illnesses remain largely elusive. Serotonin-associated antidepressants (ADs) remain the first line of therapy for many with depressive symptoms, yet low remission rates and delays between treatment and symptomatic alleviation have prompted skepticism regarding direct roles for serotonin in the precipitation and treatment of affective disorders. Our group recently demonstrated that serotonin epigenetically modifies histone proteins (H3K4me3Q5ser) to regulate transcriptional permissiveness in brain. However, this non-canonical phenomenon has not yet been explored following stress and/or AD exposures. Here, we employed a combination of genome-wide and biochemical analyses in dorsal raphe nucleus (DRN) of male and female mice exposed to chronic social defeat stress, as well as in DRN of human MDD patients, to examine the impact of stress exposures/MDD diagnosis on H3K4me3Q5ser dynamics, as well as associations between the mark and depression-related gene expression. We additionally assessed stress-induced/MDD-associated regulation of H3K4me3Q5ser following AD exposures, and employed viral-mediated gene therapy in mice to reduce H3K4me3Q5ser levels in DRN and examine its impact on stress-associated gene expression and behavior. We found that H3K4me3Q5ser plays important roles in stress-mediated transcriptional plasticity. Chronically stressed mice displayed dysregulated H3K4me3Q5ser dynamics in DRN, with both AD- and viral-mediated disruption of these dynamics proving sufficient to attenuate stress-mediated gene expression and behavior. Corresponding patterns of H3K4me3Q5ser regulation were observed in MDD subjects on vs. off ADs at their time of death. These findings thus establish a neurotransmission-independent role for serotonin in stress-/AD-associated transcriptional and behavioral plasticity, observations of which may be of clinical relevance to human MDD and its treatment.

Abstract Some of the most metabolically diverse species of bacteria (e.g., Actinobacteria) have higher GC content in their DNA, differ substantially in codon usage, and have distinct protein folding environments compared to tractable expression hosts like Escherichia coli. Consequentially, expressing biosynthetic gene clusters (BGCs) from these bacteria in E. coli often results in a myriad of unpredictable issues with regard to protein expression and folding, delaying the biochemical characterization of new natural products. Current strategies to achieve soluble, active expression of these enzymes in tractable hosts can be a lengthy trial-and-error process. Cell-free expression (CFE) has emerged as a valuable expression platform as a testbed for rapid prototyping expression parameters. Here, we use a type III polyketide synthase from Streptomyces griseus, RppA, which catalyzes the formation of the red pigment flaviolin, as a reporter to investigate BGC refactoring techniques. We applied a library of constructs with different combinations of promoters and rppA coding sequences to investigate the synergies between promoter and codon usage. Subsequently, we assess the utility of cell-free systems for prototyping these refactoring tactics prior to their implementation in cells. Overall, codon harmonization improves natural product synthesis more than traditional codon optimization across cell-free and cellular environments. More importantly, the choice of coding sequences and promoters impact protein expression synergistically, which should be considered for future efforts to use CFE for high-yield protein expression. The promoter strategy when applied to RppA was not completely correlated with that observed with GFP, indicating that different promoter strategies should be applied for different proteins. In vivo experiments suggest that there is correlation, but not complete alignment between expressing in cell free and in vivo. Refactoring promoters and/or coding sequences via CFE can be a valuable strategy to rapidly screen for catalytically functional production of enzymes from BCGs, which advances CFE as a tool for natural product research.

Abstract Bacterial contamination is the most prevalent infectious complication of blood transfusion in the developed world. To mitigate this, several ultraviolet light-based pathogen reduction technologies (PRTs), some of which require photo-chemicals, have been developed to minimize infection transmission. Relative to UV light, visible 405-nm light is safer and has shown potential to be developed as a PRT for the in situ treatment of ex vivo human plasma and platelet concentrates, without the need for photo-chemicals. This study investigates the effect of 405-nm light on human plasma, with focus on the compatibility of antimicrobial light doses with essential plasma clotting factors. To determine an effective antimicrobial dose that is compatible with plasma, prebagged human plasma (up to 300 mL) was seeded with common microbial contaminants and treated with increasing doses of 405-nm light (16 mW cm−2; ≤ 403 J cm−2). Post-exposure plasma protein integrity was investigated using an AOPP assay, in vitro coagulation tests, and ELISA-based measurement of fibrinogen and Protein S. Microbial contamination in 300 mL prebagged human plasma was significantly reduced (P ≤ 0.05) after exposure to ≤ 288 J cm−2, with microbial loads reduced by > 96.2%. This dose did not significantly affect the plasma protein quality parameters tested (P > 0.05). Increased doses (≥ 345 J cm−2) resulted in a 4.3% increase in clot times with no statistically significant change in protein activity or levels. Overall, this study has demonstrated that the effective microbicidal 405 light dose shows little to no negative effect on plasma quality.

Abstract Advanced epithelial ovarian cancer (EOC) survival rates are dishearteningly low, with ~25% surviving beyond 5 years. Evidence suggests that cancer stem cells contribute to acquired chemoresistance and tumor recurrence. Here, we show that IRAK1 is upregulated in EOC tissues, and enhanced expression correlates with poorer overall survival. Moreover, low molecular weight hyaluronic acid, which is abundant in malignant ascites from patients with advanced EOC, induced IRAK1 phosphorylation leading to STAT3 activation and enhanced spheroid formation. Knockdown of IRAK1 impaired tumor growth in peritoneal disease models, and impaired HA-induced spheroid growth and STAT3 phosphorylation. Finally, we determined that TCS2210, a known inducer of neuronal differentiation in mesenchymal stem cells, is a selective inhibitor of IRAK1. TCS2210 significantly inhibited EOC growth in vitro and in vivo both as monotherapy, and in combination with cisplatin. Collectively, these data demonstrate IRAK1 as a druggable target for EOC.

Abstract Background It is unknown if serum concentrations of cobalamin, folate, canine pancreatic lipase immunoreactivity (cPLI), and canine trypsin‐like immunoreactivity (cTLI) obtained postprandially are equivalent to measurements obtained after withholding food in dogs with suspected gastrointestinal disease. Hypothesis/Objectives Measurements of serum concentrations of cobalamin, folate, cPLI, and cTLI postprandially will be equivalent to measurements after 12 hours of withholding food in dogs with signs of chronic gastrointestinal disease. Changes observed will not alter clinical interpretation. Animals 51 client‐owned dogs with signs of gastrointestinal disease. Methods Prospective single arm clinical trial. Serum concentrations of cobalamin, folate, cPLI and cTLI 2, 4, and 8 hours postprandially were compared by equivalence testing to values after withholding food for 12 hours (baseline). Results Mean serum cobalamin concentrations 2 hours (498.1 ± 213.1 ng/L; P = 0.024) and 4 hours (501.9 ± 207.4 ng/L; P = 0.008) postprandial were equivalent to baseline (517.3 ± 211.5 ng/L). Mean serum cTLI 2 hours (31.3 ± 14 μg/L; P

Background: Both an open cheilectomy with a Moberg osteotomy and percutaneous cheilectomy have been successfully used to treat hallux rigidus and preserve motion. However, there have been no studies that have compared these 2 procedures using validated patient-reported outcomes such as the Patient Reported Outcome Measurement Information System. Methods: A retrospective review of hallux rigidus patients between January 2016 and July 2021 collected 48 percutaneous cheilectomy (PC) patients and 71 open cheilectomy with Moberg (OCM) patients. Preoperative and minimum 1-year postoperative PROMIS scores were collected. Results: The OCM and PC cohorts did not have significant differences in their postoperative PROMIS scores. Both cohorts had modest but significant improvements postoperatively in the physical function, pain interference, and pain intensity domains. The OCM group had a larger degree of improvement in physical function, pain interference, and pain intensity ( P = .015, .011, .001, respectively). No significant difference was identified in the reoperation rate. Conclusion: Patients undergoing an OCM had worse preoperative PROMIS scores and a modestly greater change in patient-reported outcomes than patients undergoing a PC. Level of Evidence: Level III, retrospective review.

IntroductionBed rest can be used as a ground-based analog of the body unloading associated with spaceflight. In this study, we determined how strict head-down tilt bed rest affects subjects’ performance of functional tests (sit-to-stand, tandem walk, walk-and-turn, dynamic posturography) that challenge astronauts’ balance control systems immediately after they return from space.MethodsForty-seven participants were assessed before and a few hours after 30 days of 6° head down tilt bed rest at the DLR:envihab facility. During this bed rest study, called SANS-CM, the participants were divided into 4 groups that either a) were positioned in head-down tilt continuously throughout the 30 days; b) sat upright for 6 h a day; c) were exposed to lower body negative pressure (LBNP) for 6 h a day; or d) exercised for 60 min and then wore venous-occlusive cuffs for 6 h a day.ResultsResults showed that strict head-down tilt bed rest caused deficits in performance of functional tasks that were similar to those observed in astronauts after spaceflight. Seated upright posture mitigated these deficits, whereas exercise or LBNP and cuffs partly mitigated them.DiscussionThese data suggest that more direct, active sensorimotor-based countermeasures may be necessary to maintain preflight levels of functional performance after a long period of body unloading.

Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark of ferroptosis is uncontrolled and overwhelming peroxidation of polyunsaturated fatty acids contained in membrane phospholipids, which eventually leads to rupture of the plasma membrane. Ferroptosis is unique in that it is essentially a spontaneous, uncatalyzed chemical process based on perturbed iron and redox homeostasis contributing to the cell death process, but that it is nonetheless modulated by many metabolic nodes that impinge on the cells’ susceptibility to ferroptosis. Among the various nodes affecting ferroptosis sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets for the treatment of numerous currently incurable diseases. Herein, the current members of a Germany-wide research consortium focusing on ferroptosis research, as well as key external experts in ferroptosis who have made seminal contributions to this rapidly growing and exciting field of research, have gathered to provide a comprehensive, state-of-the-art review on ferroptosis. Specific topics include: basic mechanisms, in vivo relevance, specialized methodologies, chemical and pharmacological tools, and the potential contribution of ferroptosis to disease etiopathology and progression. We hope that this article will not only provide established scientists and newcomers to the field with an overview of the multiple facets of ferroptosis, but also encourage additional efforts to characterize further molecular pathways modulating ferroptosis, with the ultimate goal to develop novel pharmacotherapies to tackle the various diseases associated with – or caused by – ferroptosis.

Abstract Objective Existing behavioral weight management interventions produce clinically meaningful weight loss. The onset of the COVID‐19 pandemic led to the quick transition of such interventions from in‐person to virtual platforms. This provided a unique opportunity to compare engagement and outcomes for an in‐person versus virtually delivered weight management intervention. Methods A non‐randomized comparison of engagement and weight outcomes was performed between two cohorts who participated in a weight management intervention in person (N = 97) versus three who participated virtually via videoconference (N = 134). Various metrics of engagement were examined, including group class and individual phone call attendance and duration, and retention for weight assessments. Behavioral targets of daily caloric intake and step‐counts and the clinical weight outcome were explored. Results Cohorts (mean [standard deviation] age 47.3 (11.5), 67.1% women: 86.8% White) that participated virtually attended more group sessions (p

Introduction A minority of geriatric hip fracture patients pursue non-operative treatment. Compared with surgical patients, non-operative patients have higher mortality rates. However, patient satisfaction following non-operative vs operative treatment has not been investigated extensively. The purpose of this study was to compare satisfaction among non-operatively vs operatively treated hip fracture patients. Methods We identified patients aged 60+ years with proximal femur fractures treated over a 10-year period. Excluded were patients with isolated greater/lesser trochanteric fractures. Patients or relatives were asked to complete a 6-question survey about their treatment satisfaction. Results Survey responses from 56 operative and 28 non-operative patients were recorded. Overall, 91.1% of operative and 82.1% of non-operative patients were satisfied with their treatment course ( P = 0.260). However, only 71.4% of non-operative patients were satisfied with treatment option explanations vs 83.9% of operative patients ( P = 0.014). While only 64.3% of non-operative respondents were satisfied with the ultimate treatment outcome (vs 85.7% of operative patients, P = 0.025), 89.3% of patients in each cohort would choose the same treatment plan again. Discussion Our findings highlight the complexity of defining patient satisfaction, particularly in a geriatric hip fracture population. Unlike previous studies, we chose a direct approach to quantifying patient satisfaction by asking participants specifically about satisfaction with treatment outcome and the overall treatment course. Additional survey questions were then included to assess factors considered important in treatment satisfaction, such as health care provider treatment explanations, post-treatment mobility, and palliative care service involvement. Conclusions We identified significant differences between non-operatively and operatively treated geriatric hip fracture patients regarding satisfaction with the explanation of treatment options, and ultimate treatment outcomes. There was no significant difference in overall satisfaction with the treatment course or likelihood of choosing the same treatment again. Further research investigating patient satisfaction following geriatric hip fracture treatment is warranted.

Background: Hallux valgus deformity affects more than 35% of people aged ≥65 years. Surgical correction in this population can be more complicated because of poor bone quality, worse deformity, and postoperative recovery challenges. The purpose of this study was to compare the radiographic and clinical outcomes of patients aged ≥65 years who underwent either open Lapidus or minimally invasive chevron Akin osteotomy for bunion correction. Methods: A retrospective review identified 62 patients aged ≥65 years who were treated surgically for hallux valgus with at least 1-year postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores (physical function and pain interference). Preoperative and at least 6-month postoperative radiographs were measured for the hallux valgus angle and intermetatarsal angle. PROMIS scores were obtained preoperatively and at 1 and/or 2 years postoperatively. Differences in demographic, clinical, and radiographic outcomes were assessed using the Mann Whitney U test and P values were adjusted for a false discovery rate of 5%. Results: There was no difference between the MIS and open cohorts in pre- or postoperative radiographic measurements or clinical outcomes at any time point. At 1 year postoperatively, both groups had statistically significant improvements in the PROMIS pain interference domain but only the MIS group had a statistically significant improvement in the PROMIS physical function domain. Clinical significance was equivocal. At 2 years postoperatively, there were clinically and statistically significant improvements in the PROMIS pain interference and physical function domains for the open and MIS groups. Conclusion: Patients in both surgical groups had improvement in radiographic measurements and 2-year PROMIS scores, although there was no clinical or statistical difference found between groups. MIS and open surgical techniques appear to be safe and effective in correcting hallux valgus in older patients; however, patients may need to be counseled that maximum improvement after surgery may take more than 1 year. Level of Evidence: Level III, retrospective cohort study.

Interaction of the lanthanide nitrates M(NO3)3 (M = Gd, Eu) with methylcucurbit[5]uril (Me10Q[5]) in the presence of transition metal chlorides (ZnCl2 and FeCl3) in acidic media resulted in the isolation of the complexes [Me10Q[5]Gd(H2O)2Cl Gd(H2O)6](ZnCl4)2∙Cl∙8.9H2O (1) and [Me10Q[5]Eu(H2O)3Cl(H3O)](FeCl4)3 (2). The molecular structures of 1 and 2 have been determined by single crystal X-ray crystallography, and reveal discrete complexes which are involved in dense stacking with adjacent Me10Q[5]s linked via H-bonding and/or metal anions resulting in a supramolecular assembly.

Nonparametric combinations of permutation tests for pairwise comparison of scale parameters, based on deviances, are examined. Permutation tests for comparing two or more groups based on the ratio of deviances have been investigated, and a procedure based on Higgins’ RMD statistic was found to perform well, but two other tests were sometimes more powerful. Thus, combinations of these tests are investigated. A simulation study shows a combined test can be more powerful than any single test.

Abstract Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat partly due to development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, here we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition in the catheterized bladder, are predisposed to severe CAUTI and septicemia by diverse uropathogens in mono- and poly-microbial infections. Furthermore, here we found that Enterococcus faecalis, a prevalent CAUTI pathogen, uses the secreted protease, SprE, to induce fibrin accumulation and create a niche ideal for growth, biofilm formation, and persistence during CAUTI.

Challenges associated with cubozoan jellyfish detection and the limitations of current detection techniques limit the ability of scientists to fill critical knowledge gaps surrounding their ecology. Environmental DNA (eDNA), however, has proven useful as an ecological survey tool to detect and study these deadly jellyfish. This study aimed to leverage the power of eDNA to detect and explore the distribution of the Australian box jellyfish (Chironex fleckeri), encompassing both its medusae and polyp life history stages, within an open coastal bay (Horseshoe Bay) of Magnetic Island, Queensland, Australia. Our investigation focused on a hypothesis concerning the source locations of the jellyfish within Horseshoe Bay and, through a comparison of both life history stage distributions, aimed to determine potential population stock boundaries. eDNA results aligned with the predicted nearshore distribution of medusae. Further, the elusive benthic polyp stage was also detected. These findings confirmed Horseshoe Bay as a source location of the jellyfish. Moreover, our evidence supported a model that the area likely represents a population stock of the species. This adds to growing evidence suggesting some cubozoan jellyfish have population stocks of small spatial scales in both open and relatively closed ecosystems such as estuaries. In conclusion, this study serves as a notable example of eDNA’s ability to resolve critical knowledge gaps surrounding cubozoan ecology and to enhance the management ability of these deadly jellyfish to reduce envenomations.

Abstract Plant biomass is a fundamental ecosystem attribute that is sensitive to rapid climatic changes occurring in the Arctic. Nevertheless, measuring plant biomass in the Arctic is logistically challenging and resource intensive. Lack of accessible field data hinders efforts to understand the amount, composition, distribution, and changes in plant biomass in these northern ecosystems. Here, we present The Arctic plant aboveground biomass synthesis dataset, which includes field measurements of lichen, bryophyte, herb, shrub, and/or tree aboveground biomass (g m−2) on 2,327 sample plots from 636 field sites in seven countries. We created the synthesis dataset by assembling and harmonizing 32 individual datasets. Aboveground biomass was primarily quantified by harvesting sample plots during mid- to late-summer, though tree and often tall shrub biomass were quantified using surveys and allometric models. Each biomass measurement is associated with metadata including sample date, location, method, data source, and other information. This unique dataset can be leveraged to monitor, map, and model plant biomass across the rapidly warming Arctic.

Abstract Subgenome dominance has been reported in diverse allopolyploid species, where genes from one subgenome are preferentially retained and are more highly expressed than those from other subgenome(s). However, the molecular mechanisms responsible for subgenome dominance remain poorly understood. Here, we develop genome-wide map of accessible chromatin regions (ACRs) in cultivated strawberry (2n = 8x = 56, with A, B, C, D subgenomes). Each ACR is identified as an MNase hypersensitive site (MHS). We discover that the dominant subgenome A contains a greater number of total MHSs and MHS per gene than the submissive B/C/D subgenomes. Subgenome A suffers fewer losses of MHS-related DNA sequences and fewer MHS fragmentations caused by insertions of transposable elements. We also discover that genes and MHSs related to stress response have been preferentially retained in subgenome A. We conclude that preservation of genes and their cognate ACRs, especially those related to stress responses, play a major role in the establishment of subgenome dominance in octoploid strawberry.

Abstract During long-duration spaceflight, astronauts experience headward fluid shifts and expansion of the cerebral perivascular spaces (PVS). A major limitation to our understanding of the changes in brain structure and physiology induced by spaceflight stems from the logistical difficulties of studying astronauts. The current study aimed to determine whether PVS changes also occur on Earth with the spaceflight analog head-down tilt bed rest (HDBR). We examined how the number and morphology of magnetic resonance imaging-visible PVS (MV-PVS) are affected by HDBR with and without elevated carbon dioxide (CO2). These environments mimic the headward fluid shifts, body unloading, and elevated CO2 observed aboard the International Space Station. Additionally, we sought to understand how changes in MV-PVS are associated with signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), ocular structural alterations that can occur with spaceflight. Participants were separated into two bed rest campaigns: HDBR (60 days) and HDBR + CO2 (30 days with elevated ambient CO2). Both groups completed multiple magnetic resonance image acquisitions before, during, and post-bed rest. We found that at the group level, neither spaceflight analog affected MV-PVS quantity or morphology. However, when taking into account SANS status, persons exhibiting signs of SANS showed little or no MV-PVS changes, whereas their No-SANS counterparts showed MV-PVS morphological changes during the HDBR + CO2 campaign. These findings highlight spaceflight analogs as models for inducing changes in MV-PVS and implicate MV-PVS dynamic compliance as a mechanism underlying SANS. These findings may lead to countermeasures to mitigate health risks associated with human spaceflight.

Background: Blue light therapy (BLT) is a Food and Drug Administration cleared modality used in dermatology as an effective treatment of acne. The primary purpose of this study is to determine if there are dose-dependent antimicrobial effects of BLT against Cutibacterium acnes (C. acnes). Methods: A known strain of C. acnes was grown on chocolate agar in a controlled laboratory environment under anaerobic conditions for 1 week. After 1 week, 2-3 colonies of C. acnes were isolated and transferred to broth medium to incubate for 2 or 7 days. Broth vials (treatment arm) then underwent 1 of 6 different blue light dosing treatment regimens and a duplicate broth vial served as a control left open to the same environment. The BLT regimens were a single treatment of 25 J/cm2, 50 J/cm2, 75 J/cm2, 100 J/cm2, 2 serial treatments of 50 J/cm2 separated by 24 hours, or 2 serial treatments of 75 J/cm2 separated by 24 hours. The Omnilux Blue device (415 nm wavelength) was used for all BLT treatments and delivered, on average, 1.68 ± 0.004 J/min. Following treatment, the control and treatment broth samples were plated on chocolate agar and allowed to grow for 7 days. After 7 days, plates were counted and colony forming units (CFUs) were calculated. Six trials were completed for each BLT dosing regimen based on an a priori power analysis of 6 individual 2-sided t-tests. Comparisons in the primary outcome were made via mixed-effects analysis of variance with replicate as a random effect. Results: All BLT treatment regimens resulted in significantly fewer CFUs than their aggregate control plate CFUs (P

Abstract A precise, scalable, and computationally efficient mathematical framework is proposed for region-wide autonomous electric vehicle (AEV) fleet management, sizing and infrastructure planning for urban ride-hailing services. A comprehensive techno-economic analysis in New York City is conducted not only to calculate the societal costs but also to quantify the environmental and health benefits resulting from reduced emissions. The results reveal that strategic fleet management can reduce fleet size and unnecessary cruising mileage by up to 40% and 70%, respectively. This alleviates traffic congestion, saves travel time, and further reduces fleet sizes. Besides, neither large-battery-size AEVs nor high-power charging infrastructure is necessary to achieve efficient service. This effectively alleviates financial and operational burdens on fleet operators and power systems. Moreover, the reduced travel time and emissions resulting from efficient fleet autonomy create an economic value that exceeds the total capital investment and operational costs of fleet services.

Abstract European starlings are one of the most abundant and problematic avian invaders in the world. From their native range across Eurasia and North Africa, they have been introduced to every continent except Antarctica. In 160 years, starlings have expanded into different environments throughout the world, making them a powerful model for understanding rapid evolutionary change and adaptive plasticity. Here, we investigate their spatiotemporal morphological variation in North America and the native range. Our dataset includes 1217 specimens; a combination of historical museum skins and modern birds. Beak length in the native range has remained unchanged during the past 206 years, but we find beak length in North American birds is now 8% longer than birds from the native range. We discuss potential drivers of this pattern including dietary adaptation or climatic pressures. Additionally, body size in North American starlings is smaller than those from the native range, which suggests a role for selection or founder effect. Taken together, our results indicate rapid recent evolutionary change in starling morphology coincident with invasion into novel environments.

Abstract Highly multiplexed protein imaging is emerging as a potent technique for analyzing protein distribution within cells and tissues in their native context. However, existing cell annotation methods utilizing high-plex spatial proteomics data are resource intensive and necessitate iterative expert input, thereby constraining their scalability and practicality for extensive datasets. We introduce MAPS (Machine learning for Analysis of Proteomics in Spatial biology), a machine learning approach facilitating rapid and precise cell type identification with human-level accuracy from spatial proteomics data. Validated on multiple in-house and publicly available MIBI and CODEX datasets, MAPS outperforms current annotation techniques in terms of speed and accuracy, achieving pathologist-level precision even for typically challenging cell types, including tumor cells of immune origin. By democratizing rapidly deployable and scalable machine learning annotation, MAPS holds significant potential to expedite advances in tissue biology and disease comprehension.

Abstract Catheter-associated urinary tract infections (CAUTIs), a common cause of healthcare-associated infections, are caused by a diverse array of pathogens that are increasingly becoming antibiotic resistant. We analyze the microbial occurrences in catheter and urine samples from 55 human long-term catheterized patients collected over one year. Although most of these patients were prescribed antibiotics over several collection periods, their catheter samples remain colonized by one or more bacterial species. Examination of a total of 366 catheter and urine samples identify 13 positive and 13 negative genus co-occurrences over 12 collection periods, representing associations that occur more or less frequently than expected by chance. We find that for many patients, the microbial species composition between collection periods is similar. In a subset of patients, we find that the most frequently sampled bacteria, Escherichia coli and Enterococcus faecalis, co-localize on catheter samples. Further, co-culture of paired isolates recovered from the same patients reveals that E. coli significantly augments E. faecalis growth in an artificial urine medium, where E. faecalis monoculture grows poorly. These findings suggest novel strategies to collapse polymicrobial CAUTI in long-term catheterized patients by targeting mechanisms that promote positive co-associations.

In the field of tissue engineering, 3D printed shape memory polymers (SMPs) are drawing increased interest. Understanding how these 3D printed SMPs degrade is critical for their use in the clinic, as small changes in material properties can significantly change how they behave after in vivo implantation. Degradation of 3D printed acrylated poly(glycerol-dodecanedioate) (APGD) was examined via in vitro hydrolytic, enzymatic, and in vivo subcutaneous implantation assays. Three APGD manufacturing modalities were assessed to determine differences in degradation. Material extrusion samples showed significantly larger mass and volume loss at 2 months, compared to lasercut and vat photopolymerization samples, under both enzymatic and in vivo degradation. Critically, melt transition temperatures of degraded PGD increased over time in vitro, but not in vivo. Histology of tissue surrounding APGD implants showed no significant signs of inflammation compared to controls, providing a promising outlook for use of 3D printed APGD devices in the clinic.

AbstractPlatelets are central to thrombosis. Research at the intersection of biological and physical sciences provides proof-of-concept for shear rate-dependent platelet slip at vascular stenosis and near device surfaces. Platelet slip extends the observed biological “slip-bonds” to the boundary of functional gliding without contact. As a result, there is diminished engagement of the coagulation cascade by platelets at these surfaces. Comprehending platelet slip would more precisely direct antithrombotic regimens for different shear environments, including for percutaneous coronary intervention (PCI). In this brief report we promote translation of the proof-of-concept for platelet slip into improved antithrombotic regimens by: (1) reviewing new supporting basic biological science and clinical research for platelet slip; (2) hypothesizing the principal variables that affect platelet slip; (3) applying the consequent construct model in support of-and in some cases to challenge-relevant contemporary guidelines and their foundations (including for urgent, higher-risk PCI); and (4) suggesting future research pathways (both basic and clinical). Should future research demonstrate, explain and control platelet slip, then a paradigm shift for choosing and recommending antithrombotic regimens based on predicted shear rate should follow. Improved clinical outcomes with decreased complications accompanying this paradigm shift for higher-risk PCI would also result in substantive cost savings.

Recent studies indicate that treatment of chronic hepatitis D virus (HDV) with either pegylated interferon (IFN)λ or pegylated IFNα monotherapy leads to a dramatic decline in HDV RNA. Herein, we investigated the innate antiviral efficacy of IFNλ and IFNα in humanized mice that lack an adaptive immune response. Humanized mice were either co-infected with hepatitis B virus (HBV) and HDV simultaneously, or HDV infection was performed subsequent to HBV infection (i.e., superinfected). After steady viral replication was achieved, mice received either IFNλ (n = 6) or IFNα (n = 7) for 12 (or 13) weeks. Pretreatment median levels of serum HBV DNA (8.8 [IQR:0.2] log IU/ml), HDV RNA (9.8 [0.5] log IU/ml), HBsAg (4.0 [0.4] log IU/ml) and human albumin, hAlb (6.9 [0.1] log ng/mL) were similar between mice treated with IFNα or IFNλ and between those coinfected versus superinfected. Compared to mice treated with IFNλ, mice treated with IFNα had a significantly greater decline in HBV, HDV, and HBsAg levels. In conclusion, IFNα induces stronger inhibition of HBV and HDV than IFNλ in humanized mice that lack an adaptive immune response. Further studies are needed to assess the respective role of the combined innate-and adaptive-immune systems in the treatment of HBV and HDV with IFNα and IFNλ.

Campylobacter jejuni (C. jejuni), a foodborne pathogen, poses notable hazards to human health and has significant economic implications for poultry production. This study aimed to assess C. jejuni contamination levels in chicken carcasses from both backyard and commercial slaughterhouses in Chiang Mai province, Thailand. It also sought to examine the effects of different slaughtering practices on contamination levels and to offer evidence-based recommendations for reducing C. jejuni contamination. Through the sampling of 105 chicken carcasses and subsequent enumeration of C. jejuni, the study captured the impact of various slaughtering practices. Utilizing k-modes clustering on the observational and bacterial count data, the research identified distinct patterns of contamination, revealing higher levels in backyard operations compared to commercial ones. The application of k-modes clustering highlighted the impact of critical slaughtering practices, particularly chilling, on contamination levels. Notably, samples with the lowest bacterial counts were typically from the chilling step, a practice predominantly found in commercial facilities. This observation underpins the recommendation for backyard slaughterhouses to incorporate ice in their post-evisceration soaking process. Mimicking commercial practices, this chilling method aims to inhibit C. jejuni growth by reducing carcass temperature, thereby enhancing food safety. Furthermore, the study suggests backyard operations adopt additional measures observed in commercial settings, like segregating equipment for each slaughtering step and implementing regular cleaning protocols. These strategic interventions are pivotal in reducing contamination risks, advancing microbiological safety in poultry processing, and aligning with global food safety enhancement efforts.

Prior research documented disproportional representation across racial, ethnic, and socioeconomic lines within the population of students identified as gifted and talented (GT). Less research has focused on what predicts improved representation for English learners (ELs) or students with disabilities (SwDs), or how state GT policies facilitate such representation. This paper attempted to fill that void by analyzing data from the Civil Rights Data Collection and Stanford Education Data Archive along with original coding of state GT policies. We found that while ELs and SwDs are disproportionately underrepresented within the population of students identified as gifted, state mandates for schools to offer GT, requirements for formal gifted education plans, and regular audits for compliance were correlated with higher rates of GT service availability and greater representation among ELs and SwDs. We further describe the characteristics of the top 5% of schools with the highest GT representation for ELs and SwDs.

Background: Degenerative changes at the sesamoid-metatarsal joints (SMJs) may be a source of pain following hallux valgus surgery. The aims of this study were to describe degenerative changes at the SMJs on weightbearing computed tomography (WBCT) scans and, secondarily, investigate their association with 1-year patient-reported outcome scores following a modified Lapidus procedure for hallux valgus. We hypothesized that reduced joint space in the SMJs would correlate with worse patient-reported outcomes. Methods: Fifty-seven hallux valgus patients who underwent a modified Lapidus procedure had preoperative and minimum 5-month postoperative WBCT scans, and preoperative and at least 1-year postoperative PROMIS physical function (PF), pain interference, and pain intensity scores were included. Degenerative changes at the SMJs were measured using distance mapping between the sesamoids and first metatarsal head on preoperative and postoperative WBCT scans. The minimum and average distances between the first metatarsal head and tibial sesamoid (tibial-SMJ) for each patient preoperatively and postoperatively were measured. Sesamoid station was measured on WBCT scans using a 0 to 3 grading system. Linear regression was used to investigate the correlations between minimum preoperative and postoperative tibial-SMJ distances and 1-year postoperative PROMIS scores. Results: The median minimum and average tibial-SMJ distances increased from 0.82 mm (interquartile range [IQR] 0.40-1.03 mm) and 1.62 mm (IQR 1.37-1.75 mm) preoperative to 1.09 mm (IQR 0.96-1.23 mm) and 1.73 mm (IQR 1.60-1.91 mm) postoperative (P

Introduction The Look AHEAD randomized clinical trial reported that an 8-year intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) in adults aged 45–76 years with type 2 diabetes and overweight/obesity delayed kidney disease progression. Here, we report long-term post-intervention follow-up for the trial’s secondary outcome of kidney disease.Research design and methods We examined effects of ILI (n=2570) versus DSE (n=2575) on decline in estimated glomerular filtration rate (eGFR) to 60 years at baseline had benefit in both kidney outcomes during intervention and overall (HR=0.75, 0.62 to 0.90 for eGFR

The Microphthalmia-associated Transcription Factor (MITF) governs numerous cellular and developmental processes. In mice, it promotes specification and differentiation of the retinal pigmented epithelium (RPE), and in humans, some mutations in MITF induce congenital eye malformations. Herein, we explore the function and regulation of Mitf in Drosophila eye development and uncover two roles. We find that knockdown of Mitf results in retinal displacement (RDis), a phenotype associated with abnormal eye formation. Mitf functions in the peripodial epithelium (PE), a retinal support tissue akin to the RPE, to suppress RDis, via the Hippo pathway effector Yorkie (Yki). Yki physically interacts with Mitf and can modify its transcriptional activity in vitro. Severe loss of Mitf, instead, results in the de-repression of retinogenesis in the PE, precluding its development. This activity of Mitf requires the protein phosphatase 2 A holoenzyme STRIPAK-PP2A, but not Yki; Mitf transcriptional activity is potentiated by STRIPAK-PP2A in vitro and in vivo. Knockdown of STRIPAK-PP2A results in cytoplasmic retention of Mitf in vivo and in its decreased stability in vitro, highlighting two potential mechanisms for the control of Mitf function by STRIPAK-PP2A. Thus, Mitf functions in a context-dependent manner as a key determinant of form and fate in the Drosophila eye progenitor epithelium.

BackgroundIn the era of immune checkpoint blockade, the role of cancer vaccines in immune priming has provided additional potential for therapeutic improvements. Prior studies have demonstrated delayed type hypersensitivity and anti-tumor immunity with vaccines engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF). The safety, efficacy and anti-tumor immunity of GM-CSF secreting vaccine in patients with previously treated stage III or IV melanoma needs further investigation.MethodsIn this phase II trial, excised lymph node metastases were processed to single cells, transduced with an adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of 1x106, 4x106, or 1x107 tumor cells, and were injected intradermally and subcutaneously at weekly and biweekly intervals. The primary endpoints were feasibility of producing vaccine in stage III patients and determining the proportion of patients alive at two years in stage IV patients.ResultsGM-CSF vaccine was successfully developed and administered in all 61 patients. Toxicities were restricted to grade 1-2 local skin reactions. The median OS for stage III patients (n = 20) was 71.1 (95% CI, 43.7 to NR) months and 14.9 (95%CI, 12.1 to 39.7) months for stage IV patients. The median PFS in stage III patients was 50.7 (95%CI, 36.3 to NR) months and 4.1 (95% CI, 3.0-6.3) months in stage IV patients. In the overall population, the disease control rate was 39.3% (95%CI, 27.1 to 52.7%). In stage III patients, higher pre-treatment plasma cytokine levels of MMP-1, TRAIL, CXCL-11, CXCL-13 were associated with improved PFS (p

Abstract Peat‐forming wet woodlands (forested wetlands) are naturally occurring carbon‐dense ecosystems that have considerable potential to form an important part of net zero woodland establishment and peatland strategies, as well as provide crucial co‐benefits to restore biodiversity and regulate hydrological systems. Despite their potential, temperate peat‐forming wet woodlands have been widely lost, are critically understudied and are being overlooked in land‐use strategies. Unlike temperate ‘dry’ woodlands, some wet woodlands are peat forming and can store large amounts of carbon below‐ground in peat in addition to the carbon in the tree biomass. The complex structure of these peat‐forming wet woodlands creates high abiotic heterogeneity, resulting in a wide variety of microhabitats to support high levels of biodiversity, and this structural complexity can also increase water storage in the landscape and slow flood flows, providing natural flood protection. Co‐written by experts in academia and UK Government, we highlight critical knowledge gaps in our understanding of peat‐forming wet woodlands that, once addressed, could form the basis for radical changes to their inclusion in net zero and land‐use policies. Policy and practice implications: The significant role that peatland restoration has to play in reaching net zero presents an immediate policy opportunity to consider the full range of ecosystems to achieve net zero targets, while protecting and enhancing socio‐ecological sustainability. In co‐writing this paper, our aim is to stimulate discussion and sharing of knowledge between those involved in research, policy and practice in order to strengthen the evidence base for peat‐forming wet woodland re‐establishment and future management. We call on researchers, policymakers and land managers to take temperate wet woodlands from understudied and overlooked, to integrated ecosystems that hold great promise in the contributions they can make as nature‐based solutions.

The perceptual and motor coordination problems experienced following return from spaceflight reflect the sensory adaptation to altered gravity. The purpose of this study was to develop a ground-based analog that replicates similar sensorimotor impairment using a standard measures test battery and subjective feedback from experienced crewmembers. This Sensorimotor Disorientation Analog (SDA) included varying levels of sensorimotor disorientation through combined vestibular, visual, and proprioceptive disruptions. The SDA was evaluated on five previously flown astronauts to compare with their postflight experience and functional motor performance immediately (Return (R)+0 days) and +24 h (R+1) after landing. The SDA consisted of galvanic vestibular stimulation (GVS), visual disruption goggles, and a weighted suit to alter proprioceptive feedback and replicate perceived heaviness postflight. Astronauts reported that GVS alone replicated ∼50–90% of their postflight performance with the weighted suit fine-tuning the experience to replicate an additional 10%–40% of their experience. Astronauts did not report feeling that the disruption goggles represented either the visual disruptions or illusory sensations that they experienced, nor did they impact motor performance in postflight tasks similarly. Based on these results, we recommend an SDA including the GVS and the weighted suit. These results provide a more realistic and portable SDA framework to provide transient spaceflight-relevant sensorimotor disruptions for use in countermeasure testing and as a pre-flight training tool.

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.

Introduction/Purpose: Physical activity and returning to sports are vital for athletes after foot and ankle surgery. While joint preservation is preferred, joint arthrodesis becomes necessary in certain injuries or deformities. Common procedures include Lisfranc arthrodesis, modified Lapidus for hallux valgus (HV), and first metatarsophalangeal (MTP) arthrodesis for hallux rigidus (HR), addressing pain and deformities. Prior studies show promising outcomes individually, yet lack comparisons, impeding understanding of postoperative differences in function. Comparative insights can guide patient expectations and shared decisions pre-surgery. Thus, this retrospective study aims to compare clinical outcomes and return to sports in the three procedure groups. Methods: Between 2006 and 2014, a study assessed 48 modified Lapidus procedures for HV (average age 37.3 years, average follow-up 2.8 years, 95.8% female), 38 Lisfranc injuries (average age 31.8 years, average follow-up 5.2 years, 47.4% female), and 50 MTP fusion for HR cases (average age 54.9 years, average follow-up 5.1 years, 66% female). The assessment focused on physical activity and return to sport, utilizing sports-specific, patient-administered questionnaires. Clinical outcomes were evaluated through the Foot and Ankle Outcome Score (FAOS), encompassing pain, symptoms, stiffness, daily function, sports function, and quality of life. Comparison among the surgical groups included return-to-activity difficulty, participation levels, postoperative FAOS scores, and patient satisfaction. ANOVA analysis gauged significance in FAOS subscale differences among procedures, followed by the Tukey HSD test to pinpoint specific procedure variations if significant differences arose. Results: Regarding FAOS scores, the procedures yielded similar outcomes in the pain subscale. No differences between Lapidus- Lisfranc in the symptom subscale (P=0.6). However, MTP fusion displayed poorer scores than Lapidus (P=0.04) and Lisfranc (P=0.005). No differences between Lapidus-Lisfranc (P=0.64) and Lapidus-MTP Fusion in Activities of Daily Living (P=0.18). Yet, MTP fusion exhibited notably worse outcomes than Lisfranc (P=0.03). For Sports, no differences between Lapidus-Lisfranc (P=0.94), while MTP fusion showed inferior outcomes to Lapidus (P=0.002) and Lisfranc (P=0.001). Although means varied, no differences were observed for Lapidus vs. Lisfranc (P=0.95), Lapidus vs. MTP Fusion (P=0.09), or Lisfranc vs. MTP fusion (P=0.06) in Quality of Life [Table 1]. Collectively, patients engaged in 40 activities. Return to sport post-surgery percentage, compared among procedure groups, yielded similar outcomes [Table 2]. Conclusion: Although all procedure groups had similar overall return to sports and physical activities patient satisfaction rates, there were significant differences in regard to FAOS scores. Lapidus and Lisfranc procedures displayed similar postoperative outcomes in all FAOS domains. MTP Fusion showed similar postoperative outcomes to both Lapidus and Lisfranc procedures in the FAOS pain and quality of life domains, however displayed significantly worse outcomes in symptoms, activities of daily living, and sports domains. Therefore, it appears that an MTP fusion results in more functional limitations when compared to Lapidus and Lisfranc procedures. Table 1: Comparison of FAOS Scores in Patients who Underwent Lapidus, Lisfranc, and MTP Fusion Procedures; Table 2: Postoperative Changes in Activity Difficulty and Participation Levels

Introduction/Purpose: With the last decade’s surge in total ankle replacement (TAR), there is an anticipated commensurate increase in the number of revisions that orthopaedic foot and ankle surgeons will encounter. The salvage and implant options to deal with a failed primary TAR are expanding. However, the literature on survivorship and outcomes after revision TAR in the modern era is relatively limited. What’s more, little is known about the risk factors for further revision or failure of revision TAR. This study aimed to describe the timing to and survivorship after revision TAR. We hypothesized that tibial-sided failures would occur earlier after the index surgery, and secondary revisions after failure of revision TAR would occur more due to talar-sided failures than tibial-sided failures. Methods: This is a single-institution retrospective cohort study of TAR patients (2012-2022) with minimum 2-year follow-up. Revision TARs (defined as exchange of tibial and/or talar components) with any implant (Cadence, Inbone, Invision, Infinity, Salto, STAR, Vantage, Zimmer; or custom total talus replacement [TTR]) were included. Five surgeons contributed patients. Demographics, primary and revision surgical data, and postoperative complications were recorded. Etiology of failure necessitating revision (tibial failure, talus failure, combined failure) and ultimate outcomes after revision (revision TAR survived, additional revisions, conversion to fusion, below-knee-amputation [BKA]) were recorded. Revisions for periprosthetic joint infection (PJI) and conversions to fusion were excluded. There were 59 ankles that underwent revision for any cause. Excluding 9 2-stage revisions for PJI and 3 conversions to ankle or tibiotalocalcaneal fusion, there were 47 ankles that underwent revision TAR that were included for analysis. Chi-square and ANOVA tests were used to compare risk factors and timing for failure. Results: There were 47 revision TARs, with mean age 60.6 (range: 31-77) years, mean BMI 29.5 kg/m 2 , 19 (40.4%) females, and mean 3.5 years follow-up. Revisions for tibial failure (n=22) occurred significantly earlier (1.3 ± 0.5 years) than those for talus failure (n=19, 2.3 ± 1.7 years) or combined tibial/talus failure (n=6, 2.9 ± 3.3 years) (P=0.048). Revisions for tibial-only failure had significantly better survivorship (95.5%) than revisions for talus or combined tibia/talus failures: 26% of talus failures and 33% of combined tibia/talus failures underwent at least one more revision (P=0.033). Of the 7 failures after revision talus, 2 ultimately underwent BKA, 2 were converted to TTR, 2 were revised to modular stemmed talus implants, and 1 was treated with explant and cement spacer for PJI. Conclusion: This study demonstrates that TAR tibial failures occur earlier than talus failures or combined tibial/talus failures. When patients with isolated tibial failure undergo revision of both tibial and talar components, they usually do well with good survivorship post-revision. However, revisions for talar failures and combined tibial/talar failures occur later but are more devastating: nearly 1/3 go on to a second revision. This is important given the consequences of talar implant subsidence, bone necrosis, loss of bone stock, and limited salvage options. As TAR utilization expands, it is imperative to develop implants and surgical strategies to maximize success for revision surgery. Flowchart of failures after revision TAR. PJI = periprosthetic joint infection. TTC = tibiotalocalcaneal. BKA = below-knee amputation. Tibial implant geometry included: Low-pro = lowprofile tibial implant. Stem = stemmed tibial implant. Keel = keeled tibial implant. Talus implant geometry included: chamfer/round and flat-cuttalus.