Corrigendum: Referent data for investigations of upper limb accelerometry: harmonized data from three cohorts of typically-developing children.

[This corrects the article DOI: 10.3389/fped.2024.1361757.].

Quantifying the effects of sleep on sensor-derived variables from upper limb accelerometry in people with and without upper limb impairment.

BACKGROUND: Despite the promise of wearable sensors for both rehabilitation research and clinical care, these technologies pose significant burden on data collectors and analysts. Investigations of factors that may influence the wearable sensor data processing pipeline are needed to support continued use of these technologies in rehabilitation research and integration into clinical care settings. The purpose of this study was to investigate the effect of one such factor, sleep, on sensor-derived variables from upper limb accelerometry in people with and without upper limb impairment and across a two-day wearing period. METHODS: This was a secondary analysis of data collected during a prospective, longitudinal cohort study (n = 127 individuals, 62 with upper limb impairment and 65 without). Participants wore a wearable sensor on each wrist for 48 h. Five upper limb sensor variables were calculated over the full wear period (sleep included) and with sleep time removed (sleep excluded): preferred time, non-preferred time, use ratio, non-preferred magnitude and its standard deviation. Linear mixed effects regression was used to quantify the effect of sleep on each sensor variable and determine if the effect differed between people with and without upper limb impairment and across a two-day wearing period. RESULTS: There were significant differences between sleep included and excluded for the variables preferred time (p < 0.001), non-preferred time (p < 0.001), and non-preferred magnitude standard deviation (p = 0.001). The effect of sleep was significantly different between people with and without upper limb impairment for one variable, non-preferred magnitude (p = 0.02). The effect of sleep was not substantially different across wearing days for any of the variables. CONCLUSIONS: Overall, the effects of sleep on sensor-derived variables of upper limb accelerometry are small, similar between people with and without upper limb impairment and across a two-day wearing period, and can likely be ignored in most contexts. Ignoring the effect of sleep would simplify the data processing pipeline, facilitating the use of wearable sensors in both research and clinical practice.

Timed up and go demonstrates strong interrater agreement and criterion validity as a functional test in geriatric dogs.

OBJECTIVE: To measure interobserver agreement for 4 functional tasks and their summed geriatric functional score (GFS) and correlate tasks and GFS with client-specific outcome measurements (CSOMs): Canine Brief Pain Inventory (CBPI) pain severity, CBPI pain interference, and Liverpool Osteoarthritis in Dogs. ANIMALS: 89 geriatric dogs were recruited between April and September 2023 from staff, friends, and clients of the Cornell University College of Veterinary Medicine with a median age of 11.0 years and weight of 26.4 kg. METHODS: Dogs underwent 4 sequential functional tests: timed up and go (TUG), cavallettis, figure 8s, and down to stands. Two observers independently scored each dog. The GFS was calculated based on the summed scores of the individual tests. Additional information collected included signalment, weight, measurements reflecting the comorbidities of aging (body condition score and muscle condition score), and CSOMs. RESULTS: Strong interrater agreement was found for all functional tests. The TUG in seconds (sTUG) and figure 8s demonstrated significant (P < .05) moderate to strong correlations to all CSOMs. The GFS showed similar significant correlations with all CSOMs except CBPI pain severity; however, when correlating individual tests to CSOMs, only figure 8s and TUG were significantly contributing to GFS results. Receiver operating characteristic curve analysis defined highly functional dogs as those completing the sTUG in under 3.83 seconds. The sTUG represented the best test for geriatric function given it was objective, reliable, correlated well to CSOMs, and could help identify highly functioning dogs. CLINICAL RELEVANCE: The sTUG appears to be the first practical and reliable functional test of canine geriatric mobility.

Referent data for investigations of upper limb accelerometry: harmonized data from three cohorts of typically-developing children.

Aim: The rise of wearable sensing technology shows promise for addressing the challenges of measuring motor behavior in pediatric populations. The current pediatric wearable sensing literature is highly variable with respect to the number of sensors used, sensor placement, wearing time, and how data extracted from the sensors are analyzed. Many studies derive conceptually similar variables via different calculation methods, making it hard to compare across studies and clinical populations. In hopes of moving the field forward, this report provides referent upper limb wearable sensor data from accelerometers on 25 variables in typically-developing children, ages 3-17 years. Methods: This is a secondary analysis of data from three pediatric cohorts of children 3-17 years of age. Participants (n = 222) in the cohorts wore bilateral wrist accelerometers for 2-4 days for a total of 622 recording days. Accelerometer data were reprocessed to compute 25 variables that quantified upper limb movement duration, intensity, symmetry, and complexity. Analyses examined the influence of hand dominance, age, gender, reliability, day-to-day stability, and the relationships between variables. Results: The majority of variables were similar on the dominant and non-dominant sides, declined slightly with age, and were not different between boys and girls. ICC values were moderate to excellent. Variation within individuals across days generally ranged from 3% to 32%. A web-based R shiny object is available for data viewing. Interpretation: With the use of wearable movement sensors increasing rapidly, these data provide key, referent information for researchers as they design studies, and analyze and interpret data from neurodevelopmental and other pediatric clinical populations. These data may be of particularly high value for pediatric rare diseases.

Literature review details and supports the application of platelet-rich plasma products in canine medicine, particularly as an orthobiologic agent for osteoarthritis.

Platelet-rich plasma (PRP) and other platelet-derived products represent a subset of regenerative medicine and have been researched in the veterinary community for the treatment of osteoarthritis, soft tissue wounds, tendinopathies, periodontitis, and fracture repairs. PRP is simple to produce, relatively affordable, safe, and can be delivered on site, making it an appealing therapeutic agent in veterinary medicine. As an orthobiologic for the treatment of osteoarthritis, it is one of few interventions with clinical study support that possess anabolic potential. Platelet product variability is wide ranging and often described in terms of cellular content or platelet enrichment. Growth factors associated with platelet activation and subsequent degranulation may mediate inflammation, modulate cellular immune response, and promote tissue repair. Product composition, dosage, and application likely influence treatment outcomes depending on the classification of the disease targeted. Sufficient canine data regarding the formulation and clinical application of canine PRP exist to warrant review. The aim of this narrative is to provide scientific background and clinical insight for veterinarians regarding platelet product content/formulation, mechanisms of action, considerations for use, and clinical application in dogs.

Moderate to Vigorous Intensity Locomotor Training After Stroke: A Systematic Review and Meta-analysis of Mean Effects and Response Variability.

BACKGROUND AND PURPOSE: This meta-analysis quantified mean effects of moderate to vigorous intensity locomotor training (LT mv ) on walking outcomes in subacute and chronic stroke, and the magnitude of variability in LT mv response. METHODS: Databases were searched for randomized trials comparing LT mv with no intervention, nongait intervention, or low-intensity gait training. Comfortable gait speed (CGS), fastest gait speed (FGS), 6-minute walk test (6MWT), walking activity (steps per day), and adverse effect/event (AE) data were extracted. Pooled estimates were calculated for mean changes, AE relative risks, and the standard deviation of response (SD response ) to LT mv versus control groups, stratified by study chronicity where possible. RESULTS: There were 19 eligible studies (total N = 1096): 14 in chronic stroke (N = 839) and 5 in subacute stroke (N = 257). Compared with control interventions, LT mv yielded significantly greater increases in CGS (chronic, +0.06 m/s [95% confidence interval (CI), 0.01-0.10]; subacute, +0.16 [0.12-0.19]; subacute vs chronic, P = 0.03), FGS (chronic, +0.07 m/s [0.02-0.13]; subacute, +0.21 [0.01, 0.41]; P = 0.04), and 6MWT (chronic, +33 m [24-42]; subacute, +51 [26-77]; P = 0.054) but not steps/day (+260 [-1159 to 1679]). There were no treatment-related serious AEs among 398 LT mv participants in 14 AE-reporting studies. SD response estimates indicated substantial response variability: CGS, 0.11 m/s [0.00-0.15]; FGS, 0.14 m/s [-0.00 to 0.20]; and 6MWT, 41 m [27-51]. DISCUSSION AND CONCLUSIONS: LT mv improves mean walking capacity outcomes in subacute and chronic stroke and does not appear to have high risk of serious harm. Response magnitude varies within and between chronicity subgroups, and few studies have tested effects on daily walking activity or non-serious AEs.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A452 ).

Characterizing the impact of multiple chronic conditions on return to participation in chronic stroke survivors.

BACKGROUND: Each year, 795,000 Americans experience a stroke. As stroke mortality declines, more individuals are in the chronic phase of recovery (>6 months post-stroke). Over 80% of stroke survivors have multiple, chronic health conditions (MCC). While the relationship between MCC and mortality and function during acute recovery has been explored, less is known about how MCC burden affects participation in chronic stroke survivors. OBJECTIVE: This study investigated whether MCC burden is related to participation in those with chronic stroke. METHODS: Two hundred and sixty-six participants with chronic (≥6 months) stroke were included in this cross-sectional and retrospective analysis. Participants had a mean age of 62.2 ± 12.8 years, and time since stroke (TSS) of 36.0 ± 44.6 months (114F/152 M). Participants completed the 6-minute Walk Test (6MWT), Activities-Specific Balance Confidence Scale (ABC), Modified Cumulative Illness Rating Scale (MCIR) to quantify the presence and severity of chronic illness across 14 body systems, and the Stroke Impact Scale - Participation subscale (SIS-P). Participation (SIS-P) was the dependent variable. Independent variables were entered into a sequential regression model in three blocks: demographic variables, physical capacity (6MWT distance) and balance self-efficacy (ABC), and MCC burden (MCIR). RESULTS: After adjusting for age, sex, and time since stroke, physical capacity and balance self-efficacy explained 31.4% (p < 0.001), and the MCC burden explained 2.0% (p = 0.004). Higher participation was related to lower MCC burden. CONCLUSIONS: MCC burden is a significant contributor to variance in participation in chronic stroke survivors, above and beyond demographics, physical capacity, and self-efficacy, and therefore should be considered when creating rehabilitation programs to improve participation.

Increasing Activity After Stroke: A Randomized Controlled Trial of High-Intensity Walking and Step Activity Intervention.

BACKGROUND: Physical inactivity in people with chronic stroke profoundly affects daily function and increases recurrent stroke risk and mortality, making physical activity improvements an important target of intervention. We compared the effects of a high-intensity walking intervention (FAST), a step activity monitoring behavioral intervention (SAM), or a combined intervention (FAST+SAM) on physical activity (ie, steps/day). We hypothesized the combined intervention would yield the greatest increase in steps/day. METHODS: This assessor-blinded multisite randomized controlled trial was conducted at 4 university/hospital-based laboratories. Participants were 21 to 85 years old, walking without physical assistance following a single, unilateral noncerebellar stroke of ≥6 months duration, and randomly assigned to FAST, SAM, or FAST+SAM for 12 weeks (2-3 sessions/week). FAST training consisted of walking-related activities at 70% to 80% heart rate reserve, while SAM received daily feedback and goal setting of walking activity (steps/day). Assessors and study statistician were masked to group assignment. The a priori-determined primary outcome and end point was a comparison of the change in steps/day between the 3 intervention groups from pre- to post-intervention. Adverse events were tracked after randomization. All randomized participants were included in the intent-to-treat analysis. RESULTS: Participants were enrolled from July 18, 2016, to November 16, 2021. Of 2385 participants initially screened, 250 participants were randomized (mean [SE] age, 63 [0.80] years; 116 females/134 males), with 89 assigned to FAST, 81 to SAM, and 80 to FAST+SAM. Steps/day significantly increased in both the SAM (mean [SE], 1542 [267; 95% CI, 1014-2069] P<0.001) and FAST+SAM group (1307 [280; 95% CI, 752-1861] P<0.001) but not in the FAST group (406 [238; 95% CI, -63 to 876] P=0.09). There were no deaths or serious study-related adverse events. CONCLUSIONS: Only individuals with chronic stroke who completed a step activity monitoring behavioral intervention with skilled coaching and goal progression demonstrated improvements in physical activity (steps/day). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02835313.

Non-invasive real-time genomic monitoring of the critically endangered kakapo.

We used non-invasive real-time genomic approaches to monitor one of the last surviving populations of the critically endangered kakapo (Strigops habroptilus). We first established an environmental DNA metabarcoding protocol to identify the distribution of kakapo and other vertebrate species in a highly localized manner using soil samples. Harnessing real-time nanopore sequencing and the high-quality kakapo reference genome, we then extracted species-specific DNA from soil. We combined long read-based haplotype phasing with known individual genomic variation in the kakapo population to identify the presence of individuals, and confirmed these genomically informed predictions through detailed metadata on kakapo distributions. This study shows that individual identification is feasible through nanopore sequencing of environmental DNA, with important implications for future efforts in the application of genomics to the conservation of rare species, potentially expanding the application of real-time environmental DNA research from monitoring species distribution to inferring fitness parameters such as genomic diversity and inbreeding.

Grapevine bacterial communities display compartment-specific dynamics over space and time within the Central Valley of California.

BACKGROUND: Plant organs (compartments) host distinct microbiota which shift in response to variation in both development and climate. Grapevines are woody perennial crops that are clonally propagated and cultivated across vast geographic areas, and as such, their microbial communities may also reflect site-specific influences. These site-specific influences along with microbial differences across sites compose 'terroir', the environmental influence on wine produced in a given region. Commercial grapevines are typically composed of a genetically distinct root (rootstock) grafted to a shoot system (scion) which adds an additional layer of complexity via genome-to-genome interactions. RESULTS: To understand spatial and temporal patterns of bacterial diversity in grafted grapevines, we used 16S rRNA amplicon sequencing to quantify soil and compartment microbiota (berries, leaves, and roots) for grafted grapevines in commercial vineyards across three counties in the Central Valley of California over two successive growing seasons. Community composition revealed compartment-specific dynamics. Roots assembled site-specific bacterial communities that reflected rootstock genotype and environment influences, whereas bacterial communities of leaves and berries displayed associations with time. CONCLUSIONS: These results provide further evidence of a microbial terroir within the grapevine root systems but also reveal that the microbiota of above-ground compartments are only weakly associated with the local soil microbiome in the Central Valley of California.

How do threatened plant species with low genetic diversity respond to environmental stress? Insights from comparative conservation epigenomics and phenotypic plasticity.

Many threatened plants have low genetic diversity, which may reduce their capacity for genetically based adaptation, increasing their extinction risk. Non-genetic variation (e.g. epigenomic modifications such as DNA methylation) and plasticity may facilitate the persistence of threatened plants, yet are rarely incorporated into conservation assessments. We present a case study investigating variation and plasticity in DNA methylation and phenotypic traits in four genetically depauperate species of Leavenworthia (Brassicaceae), including one widespread species and one asexual, threatened species. We grew individuals from several maternal lines and populations per species in contrasting watering treatments, measured phenotypic traits and analysed DNA methylation using whole-genome bisulphite sequencing. We addressed four questions: (1) How do patterns of DNA methylation differ within and among species? (2) Within species, how do phenotypic traits and patterns of DNA methylation vary in response to drought? (3) Does variation in DNA methylation correspond to phenotypic variation? (4) What are the implications for conservation? We found that taxa were epigenomically distinct and that each species exhibited variation in DNA methylation among populations that could be relevant for conservation. Within species, the DNA methylation response to environmental stress corresponded to its phenotypic response. Species differed in their DNA methylation and phenotypic responses to environmental stress, with the extent of plasticity possibly related to species geographic range size. We also found phenotypic and DNA methylation variation in the asexual, threatened species that may be relevant for conservation. Our results suggest that variation in DNA methylation may promote the persistence of genetically depauperate threatened plants, highlighting its potential as a novel conservation target to reduce extinction risk.

Childhood maltreatment history and trauma-specific predictors of parenting stress in new fathers.

For new fathers, parenting stress is a risk factor for impaired early parenting and child maltreatment perpetration. Predictors of parenting stress, including fathers' own experiences of trauma, could be useful intervention targets to support new fathers. We aim to examine associations between new fathers' own histories of child maltreatment, and their perinatal mental health, relationships, and parenting stress. We recruited 298 first-time fathers for a survey that measured child maltreatment history, trauma sequelae including posttraumatic stress disorder (PTSD), major depressive disorder (MDD), interpersonal reactivity, substance use, anger expression, coparenting quality, and parenting stress. On the Parenting Stress Index (PSI) (from 36 to 180), bivariate analysis demonstrated that new fathers who experienced child maltreatment (n = 94) had significantly higher parenting stress (x̅ = 85.3, σ = 18.7) than those who did not (n = 204; x̅ = 76.0, σ = 16.6; P < .000). Hierarchical linear regression modeling indicated that a child maltreatment history, PTSD, and MDD were significantly associated with parenting stress. The strongest predictors of parenting stress were coparenting quality and complex trauma sequelae-interpersonal reactivity and anger expression. Interventions to reduce fathers' parenting stress by targeting known mental health and relationship sequelae of maltreatment are promising avenues to breaking intergenerational transmission of child maltreatment and psychiatric vulnerability.

Para nuevos papás, el estrés de crianza es un factor de riesgo para la deficiente crianza temprana y para cometer maltrato infantil. Los factores de predicción del estrés de crianza, incluyendo las propias experiencias de trauma de los papás, pueden ser útiles metas de intervención para apoyar a los nuevos papás. Nos propusimos examinar las asociaciones entre las propias historias de maltrato de los nuevos papás, y su salud mental perinatal, relaciones y estrés de crianza. Reclutamos 298 papás primerizos para una encuesta que medía la historia de maltrato infantil, la secuela de trauma incluyendo el trastorno de estrés postraumático (PTSD), el trastorno depresivo serio (MDD), la reactividad interpersonal, el uso de sustancias, la expresión de ira, la calidad de la crianza compartida, así como el estrés de crianza. En el Índice de Estrés de Crianza (de 36-180), los análisis bivariantes demostraron que los nuevos papás que habían experimentado maltrato infantil (N = 94) tenían significativamente un mayor estrés de crianza (x̅ = 85.3, σ = 18.7) que aquellos que no habían tenido tal experiencia (N = 204; x̅ = 76.0, σ = 16.6; P<.000). El modelo de regresión lineal jerárquica indicó que una historia de maltrato infantil, PTSD y MDD estaban significativamente asociados con el estrés de crianza. Los más fuertes factores de predicción del estrés de crianza fueron la calidad de la crianza compartida y la compleja secuela de trauma-la reactividad interpersonal y la expresión de la ira. Las intervenciones para reducir el estrés de crianza de los papás por medio del enfoque en la salud mental conocida y las secuelas en la relación del maltrato son una vía prometedora para romper la transmisión intergeneracional del maltrato infantil y la vulnerabilidad siquiátrica.

Pour les nouveaux pères le stress de parentage est un facteur de risque pour le parentage précoce compromis et la perpétration de maltraitance de l'enfant. Les prédicteurs de stress de parentage, y compris les propres expériences de trauma des pères, pourraient être des cicles d'intervention utiles afin de soutenir les nouveaux pères. Nous nous sommes donné pour but d'examiner les liens entre le propre passé de maltraitance de l'enfant des nouveaux pères et leur santé mentale périnatale, leurs relations et le stress de parentage. Nous avons recruté 298 nouveaux pères (pères pour la première fois) pour un sondage mesurant l'histoire de la maltraitance de l'enfant, les séquelles de trauma y compris les troubles de stress post-traumatique (TSPT), les troubles dépressifs majeurs (MDD en anglais), la réactivité interpersonnelle, la toxicomanie, l'expression de colère et la qualité du co-parentage ainsi que le stress parental. Pour l'Index de Stress de Parentage (de 36-180), une analyse bivariée a montré que les nouveaux pères qui avaient fait l'expérience de maltraitance de l'enfance (N = 94) avaient un stress de parentage bien plus élevé (x̅ = 85,3, σ = 18,7) que ceux n'en ayant pas fait l'expérience (N = 204; x̅ = 76,0, σ = 16,6; P<,000). Un modèle de régression linéaire hiérarchique a indiqué qu'un passé de maltraitance de l'enfant, le TSPT et le MDD étaient fortement liés au stress de parentage. Les facteurs de prédiction les plus forts de stress de parentage étaient la qualité du co-parentage et les séquelles de trauma complexes - réactivité interpersonnelle et l'expression de la colère. Les interventions pour réduire le stress de parentage des pères en ciblant la santé mentale connue et les séquelles de maltraitance sont un chemin prometteur pour casser la transmission intergénérationnelle de la maltraitance de l'enfant et la vulnérabilité psychiatrique.

Multisystem Inflammatory Syndrome in Children Among Persons Who Completed a Two-dose COVID-19 Vaccine Primary Series Compared With Those Reporting No COVID-19 Vaccination, US National MIS-C Surveillance.

We analyzed multisystem inflammatory syndrome in children cases by reported COVID-19 vaccination status (2-dose primary series vs. no vaccination). A total of 46% vaccinated versus 58% unvaccinated persons received intensive care unit-level care ( P = 0.02); the risk of intensive care unit admission was 23% higher (adjusted relative risk: 1.23; 95% confidence interval: 1.03-1.48) among unvaccinated patients; 21 unvaccinated persons died. Multisystem inflammatory syndrome in children occurs after SARS-CoV-2 infection in vaccinated persons, but may be less severe.

Increasing activity after stroke: a randomized controlled trial of highintensity walking and step activity intervention.

Background: Physical inactivity in people with chronic stroke profoundly affects daily function and increases recurrent stroke risk and mortality, making physical activity improvements an important target of intervention. We compared the effects of a highintensity walking intervention (FAST), a step activity monitoring behavioral intervention (SAM), or a combined intervention (FAST+SAM) on physical activity (i.e., steps per day). We hypothesized the combined intervention would yield the greatest increase in steps per day. Methods: This assessor-blinded multi-site randomized controlled trial was conducted at four university/hospital-based laboratories. Participants were 21-85 years old, walking without physical assistance following a single, unilateral non-cerebellar stroke of ≥6 months duration, and randomly assigned to FAST, SAM, or FAST+SAM for 12 weeks (2-3 sessions/week). FAST training consisted of walking-related activities for 40 minutes/session at 70-80% heart rate reserve, while SAM received daily feedback and goal-setting of walking activity (steps per day). Assessors and study statistician were masked to group assignment.The a priori-determined primary outcome and primary endpoint was change in steps per day from pre- to post-intervention. Adverse events (AEs) were tracked after randomization. All randomized participants were included in the intent-to-treat analysis.This study is registered at ClinicalTrials.gov, NCT02835313. Findings: Participants were enrolled from July 18, 2016-November 16, 2021. Of 250 randomized participants (mean[SE] age 63[0.80], 116F/134M), 89 were assigned to FAST, 81 to SAM, and 80 to FAST+SAM. Steps per day significantly increased in both the SAM (mean[SE] 1542[267], 95%CI:1014-2069, p<0.001) and FAST+SAM groups (1307[280], 752-1861, p<0.001), but not in the FAST group (406[238], 63-876, p=0.09). There were no deaths or serious study-related AEs and all other minor AEs were similar between groups. Interpretation: Only individuals with chronic stroke who completed a step activity monitoring behavioral intervention with skilled coaching and goal progression demonstrated improvements in physical activity (steps per day).

COVID-19 associated severe mucocutaneous blistering eruptions: A case series.

Mucocutaneous eruptions are associated with numerous infectious processes and can present as erythema multiforme (EM), reactive infectious mucocutaneous eruption (RIME), Stevens Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN). Limited reports have detailed the association of these eruptions with SARS-CoV-2 infection. We present a series of eight cases of severe mucocutaneous blistering eruptions associated with SARS-CoV-2 infection. A retrospective case series was performed at six tertiary medical centers from March 1, 2020 to August 1, 2022. Inclusion criteria were met with a clinical diagnosis of EM, RIME, SJS, or TEN and a positive SARS-CoV-2 test (rapid antigen or polymerase chain reaction) less than 4 weeks prior to onset of dermatologic manifestation. Data was collected at time of each patient encounter. Eight patients met criteria with six pediatric patients (<18 years of age) having a median age of 15 years and two adult patients (>18 years of age) having a median age of 36 years. Patients were found to have a clinical diagnosis of RIME in 85.7% of cases. Oral mucosal involvement was the most common clinical finding (100%), followed by ocular (50.0%), urogenital (50.0%), and skin (37.5%) involvement. Evaluation did not reveal any additional infectious triggers in four patients. Evidence of possible concurrent or previous infectious triggers were identified in four patients. This case series highlights the development of severe mucocutaneous eruptions in association with COVID-19 infection, as well as the potential contributing role of concurrent or prior infections.

The anti-CD40L monoclonal antibody AT-1501 promotes islet and kidney allograft survival and function in nonhuman primates.

Prior studies of anti-CD40 ligand (CD40L)-based immunosuppression demonstrated effective prevention of islet and kidney allograft rejection in nonhuman primate models; however, clinical development was halted because of thromboembolic complications. An anti-CD40L-specific monoclonal antibody, AT-1501 (Tegoprubart), was engineered to minimize risk of thromboembolic complications by reducing binding to Fcγ receptors expressed on platelets while preserving binding to CD40L. AT-1501 was tested in both a cynomolgus macaque model of intrahepatic islet allotransplantation and a rhesus macaque model of kidney allotransplantation. AT-1501 monotherapy led to long-term graft survival in both islet and kidney transplant models, confirming its immunosuppressive potential. Furthermore, AT-1501-based regimens after islet transplant resulted in higher C-peptide, greater appetite leading to weight gain, and reduced occurrence of cytomegalovirus reactivation compared with conventional immunosuppression. These data support AT-1501 as a safe and effective agent to promote both islet and kidney allograft survival and function in nonhuman primate models, warranting further testing in clinical trials.

Confusion will be my epitaph: genome-scale discordance stifles phylogenetic resolution of Holothuroidea.

Sea cucumbers (Holothuroidea) are a diverse clade of echinoderms found from intertidal waters to the bottom of the deepest oceanic trenches. Their reduced skeletons and limited number of phylogenetically informative traits have long obfuscated morphological classifications. Sanger-sequenced molecular datasets have also failed to constrain the position of major lineages. Noteworthy, topological uncertainty has hindered a resolution for Neoholothuriida, a highly diverse clade of Permo-Triassic age. We perform the first phylogenomic analysis of Holothuroidea, combining existing datasets with 13 novel transcriptomes. Using a highly curated dataset of 1100 orthologues, our efforts recapitulate previous results, struggling to resolve interrelationships among neoholothuriid clades. Three approaches to phylogenetic reconstruction (concatenation under both site-homogeneous and site-heterogeneous models, and coalescent-aware inference) result in alternative resolutions, all of which are recovered with strong support and across a range of datasets filtered for phylogenetic usefulness. We explore this intriguing result using gene-wise log-likelihood scores and attempt to correlate these with a large set of gene properties. While presenting novel ways of exploring and visualizing support for alternative trees, we are unable to discover significant predictors of topological preference, and our efforts fail to favour one topology. Neoholothuriid genomes seem to retain an amalgam of signals derived from multiple phylogenetic histories.

Computed tomography of suppurative and neoplastic diseases involving the canine omenta and omental bursa.

The greater and lesser omenta are fused peritoneal folds that largely delimit the omental bursa (lesser peritoneal cavity). The omental bursa is a potential space within the abdominal cavity that communicates with the greater peritoneal cavity via the omental (epiploic) foramen: it is subdivided into the omental vestibule, caudal omental recess, and splenic recess. Aims of this retrospective case series study were to describe the frequencies of CT findings of dogs with confirmed inflammatory or neoplastic disease of the omenta, omental bursa, or both. The sample included seven adult, medium-to-large breed dogs. All had fluid in the greater peritoneal cavity and 5/7 (71%) dogs also had fluid in the omental bursa. Primary suppurative inflammatory disease was present in three dogs, each dog had a large abscess with central gas in either the omental vestibule (two dogs) or caudal omental recess (one dog). Both abscesses in the omental vestibule arose from the papillary process of the caudate liver lobe and were surgically removed without complication. Neoplasia was present in four dogs and either arose from omentum (hemangiosarcoma, carcinoma) or infiltrated the omentum from an adjacent organ (splenic leiomyosarcoma, gastric adenocarcinoma). Neoplasms created mass-like tumors, infiltrative tumors, or both and had variable distribution (focal, multifocal, or locally extensive). All dogs with neoplasia were euthanized. CT signs of inflammatory and neoplastic disease overlapped, but the presence of gas might prioritize abscessation. CT signs helped decide feasibility of surgery based on extent of local invasion, especially involvement of structures passing through the porta hepatis.