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Timely diagnosis of dysphagia is important for people with an intellectual disability. Periodic screening of each individual by speech-language therapists is barely feasible with respect to limited resources. Therefore, preselection of individuals with an increased dysphagia risk through screening by caregivers is crucial. This study aimed to develop the novel "Screening instrument for Dysphagia for people with an Intellectual Disability" (SD-ID).The SD-ID was developed, validated and optimised in two rounds. Version 3, consisting of nine risk factors and 20 items concerning eating/drinking behaviour, was thoroughly studied for feasibility, concurrent validity and reliability, and then optimised. The SD-ID (version 3) was filled out in an average of four minutes (feasibility). A strong positive association was found between scores on SD-ID and Dysphagia Disorder Survey (concurrent validity). Test-retest and interrater reliability were very good. Two additional risk factors were added and two items removed to yield the final version 4. The most optimal cut-off score appeared to be either 4 or 5.The SD-ID is a reliable instrument to screen for an increased risk of dysphagia in people with an intellectual disability. Ideally it is part of a cyclic work process: Screening with SD-ID (step 1), diagnostic work-up if necessary (step 2), recommendations (step 3), and evaluation (step 4).

Background: Standardized consensus-based radiological reports for shoulder instability may improve clinical quality, reduce heterogeneity, and reduce workload. Therefore, the aim of this study was to determine important elements for the x-ray, magnetic resonance imaging (MRI) arthrography (MRA), and computed tomography (CT) report, the extent of variability, and important MRI views and settings. Methods: An expert panel of musculoskeletal radiologists and orthopedic surgeons was recruited in a three-round Delphi design. Important elements were identified for the x-ray, MRA, and CT report and important MRI views and setting. These were rated on a 0-9 Likert scale. High variability was defined as at least one score between 1-3 and 7-9. Consensus was reached when ≥80% scored an element 1-3 or 7-9. Results: The expert panel consisted of 21 musculoskeletal radiologists and 15 orthopedic surgeons. The number of elements identified in the first round was seventeen for the x-ray report, 52 for MRA, 21 for CT, and 23 for the MRI protocol. The number of elements that reached consensus was five for x-ray, twenty for MRA, nine for CT, and two for the MRI protocol. High variability was observed in 76.5% (n = 13) x-ray elements, 85.0% (n = 45) MRA, 76.2% (n = 16) CT, and 85.7% (n = 18) MRI protocol. Conclusion: Substantial variability was observed in the scoring of important elements in the radiological for the evaluation of anterior shoulder instability, regardless of modality. Consensus was reached for five elements in the x-ray report, twenty in the MRA report, and nine in the CT report. Finally, consensus was reached on two elements regarding MRA views and settings.

Abstract Background Many individuals with neurodegenerative (NDD) and immune-mediated inflammatory disorders (IMID) experience debilitating fatigue. Currently, assessments of fatigue rely on patient reported outcomes (PROs), which are subjective and prone to recall biases. Wearable devices, however, provide objective and reliable estimates of gait, an essential component of health, and may present objective evidence of fatigue. This study explored the relationships between gait characteristics derived from an inertial measurement unit (IMU) and patient-reported fatigue in the IDEA-FAST feasibility study. Methods Participants with IMIDs and NDDs (Parkinson's disease (PD), Huntington's disease (HD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjogren’s syndrome (PSS), and inflammatory bowel disease (IBD)) wore a lower-back IMU continuously for up to 10 days at home. Concurrently, participants completed PROs (physical fatigue (PF) and mental fatigue (MF)) up to four times a day. Macro (volume, variability, pattern, and acceleration vector magnitude) and micro (pace, rhythm, variability, asymmetry, and postural control) gait characteristics were extracted from the accelerometer data. The associations of these measures with the PROs were evaluated using a generalised linear mixed-effects model (GLMM) and binary classification with machine learning. Results Data were recorded from 72 participants: PD = 13, HD = 9, RA = 12, SLE = 9, PSS = 14, IBD = 15. For the GLMM, the variability of the non-walking bouts length (in seconds) with PF returned the highest conditional R2, 0.165, and with MF the highest marginal R2, 0.0018. For the machine learning classifiers, the highest accuracy of the current analysis was returned by the micro gait characteristics with an intrasubject cross validation method and MF as 56.90% (precision = 43.9%, recall = 51.4%). Overall, the acceleration vector magnitude, bout length variation, postural control, and gait rhythm were the most interesting characteristics for future analysis. Conclusions Counterintuitively, the outcomes indicate that there is a weak relationship between typical gait measures and abnormal fatigue. However, factors such as the COVID-19 pandemic may have impacted gait behaviours. Therefore, further investigations with a larger cohort are required to fully understand the relationship between gait and abnormal fatigue.

Objectives Methotrexate (MTX) is one of the most commonly used medications to treat rheumatoid arthritis (RA). However, the effect of MTX treatment on cellular immune responses remains incompletely understood. This raises concerns about the vulnerability of these patients to emerging infections and following vaccination.Methods In the current study, we investigated the impact of MTX treatment in patients with immune-mediated inflammatory disease on B and CD4 T cell SARS-CoV-2 vaccination responses. Eighteen patients with RA and two patients with psoriatic arthritis on MTX monotherapy were included, as well as 10 patients with RA without immunosuppressive treatment, and 29 healthy controls. CD4 T and B cell responses were analysed 7 days and 3–6 months after two SARS-CoV-2 messenger RNA vaccinations. High-dimensional flow cytometry analysis was used to analyse fresh whole blood, an activation-induced marker assay to measure antigen-specific CD4 T cells, and spike probes to study antigen-specific B cells.Results Seven days following two SARS-CoV-2 vaccinations, total B and T cell counts were similar between MTX-treated patients and controls. In addition, spike-specific B cell frequencies were unaffected. Remarkably, the frequency of antigen-specific CD4 T cells was reduced in patients using MTX and correlated strongly with anti-RBD IgG antibodies. These results suggest that decreased CD4 T cell activity may result in slower vaccination antibody responses in MTX-treated patients.Conclusion Taken together, MTX treatment reduces vaccine-induced CD4 T cell activation, which correlates with lower antibody responses.Trial registration number NL8900.

As of March 31, 2023, more than 30,000 monkeypox (mpox) cases had been reported in the United States in an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) and transgender persons (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) was approved by the Food and Drug Administration (FDA) in 2019 for the prevention of smallpox and mpox via subcutaneous injection as a 2-dose series (0.5 mL per dose, administered 4 weeks apart) (2). To expand vaccine access, an Emergency Use Authorization was issued by FDA on August 9, 2022, for dose-sparing intradermal injection of JYNNEOS as a 2-dose series (0.1 mL per dose, administered 4 weeks apart) (3). Vaccination was available to persons with known or presumed exposure to a person with mpox (postexposure prophylaxis [PEP]), as well as persons at increased risk for mpox or who might benefit from vaccination (preexposure mpox prophylaxis [PrEP]) (4). Because information on JYNNEOS vaccine effectiveness (VE) is limited, a matched case-control study was conducted in 12 U.S. jurisdictions,† including nine Emerging Infections Program sites and three Epidemiology and Laboratory Capacity sites,§ to evaluate VE against mpox among MSM and transgender adults aged 18-49 years. During August 19, 2022-March 31, 2023, a total of 309 case-patients were matched to 608 control patients. Adjusted VE was 75.2% (95% CI = 61.2% to 84.2%) for partial vaccination (1 dose) and 85.9% (95% CI = 73.8% to 92.4%) for full vaccination (2 doses). Adjusted VE for full vaccination by subcutaneous, intradermal, and heterologous routes of administration was 88.9% (95% CI = 56.0% to 97.2%), 80.3% (95% CI = 22.9% to 95.0%), and 86.9% (95% CI = 69.1% to 94.5%), respectively. Adjusted VE for full vaccination among immunocompromised participants was 70.2% (95% CI = -37.9% to 93.6%) and among immunocompetent participants was 87.8% (95% CI = 57.5% to 96.5%). JYNNEOS is effective at reducing the risk for mpox. Because duration of protection of 1 versus 2 doses remains unknown, persons at increased risk for mpox exposure should receive the 2-dose series as recommended by the Advisory Committee on Immunization Practices (ACIP),¶ regardless of administration route or immunocompromise status.

Abstract Congenital nucleotide excision repair (NER) deficiency gives rise to several cancer-prone and/or progeroid disorders. It is not understood how defects in the same DNA repair pathway cause different disease features and severity. Here, we show that the absence of functional ERCC1-XPF or XPG endonucleases leads to stable and prolonged binding of the transcription/DNA repair factor TFIIH to DNA damage, which correlates with disease severity and induces senescence features in human cells. In vivo, in C. elegans, this prolonged TFIIH binding to non-excised DNA damage causes developmental arrest and neuronal dysfunction, in a manner dependent on transcription-coupled NER. NER factors XPA and TTDA both promote stable TFIIH DNA binding and their depletion therefore suppresses these severe phenotypical consequences. These results identify stalled NER intermediates as pathogenic to cell functionality and organismal development, which can in part explain why mutations in XPF or XPG cause different disease features than mutations in XPA or TTDA.

Abstract Prototypic receptors for human influenza viruses are N-glycans carrying α2,6-linked sialosides. Due to immune pressure, A/H3N2 influenza viruses have emerged with altered receptor specificities that bind α2,6-linked sialosides presented on extended N-acetyl-lactosamine (LacNAc) chains. Here, binding modes of such drifted hemagglutinin’s (HAs) are examined by chemoenzymatic synthesis of N-glycans having 13C-labeled monosaccharides at strategic positions. The labeled glycans are employed in 2D STD-1H by 13C-HSQC NMR experiments to pinpoint which monosaccharides of the extended LacNAc chain engage with evolutionarily distinct HAs. The NMR data in combination with computation and mutagenesis demonstrate that mutations distal to the receptor binding domain of recent HAs create an extended binding site that accommodates with the extended LacNAc chain. A fluorine containing sialoside is used as NMR probe to derive relative binding affinities and confirms the contribution of the extended LacNAc chain for binding.

Abstract Programmed death-ligand 1 (PD-L1) expression is currently used in the clinic to assess eligibility for immune-checkpoint inhibitors via the tumor proportion score (TPS), but its efficacy is limited by high interobserver variability. Multiple papers have presented systems for the automatic quantification of TPS, but none report on the task of determining cell-level PD-L1 expression and often reserve their evaluation to a single PD-L1 monoclonal antibody or clinical center. In this paper, we report on a deep learning algorithm for detecting PD-L1 negative and positive tumor cells at a cellular level and evaluate it on a cell-level reference standard established by six readers on a multi-centric, multi PD-L1 assay dataset. This reference standard also provides for the first time a benchmark for computer vision algorithms. In addition, in line with other papers, we also evaluate our algorithm at slide-level by measuring the agreement between the algorithm and six pathologists on TPS quantification. We find a moderately low interobserver agreement at cell-level level (mean reader-reader F1 score = 0.68) which our algorithm sits slightly under (mean reader-AI F1 score = 0.55), especially for cases from the clinical center not included in the training set. Despite this, we find good AI-pathologist agreement on quantifying TPS compared to the interobserver agreement (mean reader-reader Cohen’s kappa = 0.54, 95% CI 0.26–0.81, mean reader-AI kappa = 0.49, 95% CI 0.27—0.72). In conclusion, our deep learning algorithm demonstrates promise in detecting PD-L1 expression at a cellular level and exhibits favorable agreement with pathologists in quantifying the tumor proportion score (TPS). We publicly release our models for use via the Grand-Challenge platform.

Background: Fatigue is a prominent symptom in many diseases and is strongly associated with impaired daily function. The measurement of daily function is currently almost always done with questionnaires, which are subjective and imprecise. With the recent advances of digital wearable technologies, novel approaches to evaluate daily function quantitatively and objectively in real-life conditions are increasingly possible. This also creates new possibilities to measure fatigue-related changes of daily function using such technologies. Summary: This review examines which digitally assessable parameters in immune-mediated inflammatory and neurodegenerative diseases may have the greatest potential to reflect fatigue-related changes of daily function. Key Messages: Results of a standardized analysis of the literature reporting about perception-, capacity-, and performance-evaluating assessment tools indicate that changes of the following parameters: physical activity, independence of daily living, social participation, working life, mental status, cognitive and aerobic capacity, and supervised and unsupervised mobility performance have the highest potential to reflect fatigue-related changes of daily function. These parameters thus hold the greatest potential for quantitatively measuring fatigue in representative diseases in real-life conditions, e.g., with digital wearable technologies. Furthermore, to the best of our knowledge, this is a new approach to analysing evidence for the design of performance-based digital assessment protocols in human research, which may stimulate further systematic research in this area.

IntroductionExtra-uterine life support technology could provide a more physiologic alternative for the treatment of extremely premature infants, as it allows further fetal growth and development ex utero. Animal studies have been carried out which involved placing fetuses in a liquid-filled incubator, with oxygen supplied through an oxygenator connected to the umbilical vessels. Hence, by delaying lung exposure to air, further lung development and maturation can take place. This medical intervention requires adjustments to current obstetric procedures to maintain liquid-filled lungs through a so-called transfer procedure.MethodsOur objective was to develop obstetric device prototypes that allow clinicians to simulate this birth procedure to safely transfer the infant from the mother's uterus to an extra-uterine life support system. To facilitate a user-centered design, implementation of medical simulation during early phase design of the prototype development was used. First, the requirements for the procedure and devices were established, by reviewing the literature and through interviewing direct stakeholders. The initial transfer device prototypes were tested on maternal and fetal manikins in participatory simulations with clinicians.Results & discussionThrough analysis of recordings of the simulations, the prototypes were evaluated on effectiveness, safety and usability with latent conditions being identified and improved. This medical simulation-based design process resulted in the development of a set of surgical prototypes and allowed for knowledge building on obstetric care in an extra-uterine life support context.

Precise and prompt information on forest disturbances in the tropics is critical to support law enforcement and protect tropical forests. In 2023, medium resolution ALOS-2 ScanSAR data (∼100 m spatial resolution) was made available for Southeast Asia, marking the first freely accessible large-area L-Band dataset. We assessed its potential for large-area forest disturbance mapping and its combination with high-resolution C-band Sentinel-1 data (∼20 m spatial resolution). We mapped forest disturbances in Sumatra, Indonesia for the year 2021 based on ALOS-2 ScanSAR data and Sentinel-1 data separately, and subsequently combined the mapped disturbances. Forest disturbances detected by both C-band and L-band SAR using a probabilistic change algorithm were combined at the product level by merging both sets of detections. The added benefit of combining both sensors was particularly evident in higher detection rates, as indicated by an improved producer accuracy (78.9 ± 11.9 %) compared to detections based on single sensor ALOS-2 ScanSAR (40.8 ± 6.3 %) and Sentinel-1 data (63.3 ± 9.6 %). Both combined and single sensor detections showed negligible false detections. ALOS-2 ScanSAR showed advantages for overcoming limited capability of Sentinel-1 to detect large-sized disturbance events characterized by post-disturbance tree remnants, occurring at locations with large-scale agricultural clearings. The medium resolution of approximately 100 m restricts the detection capability of ALOS-2 ScanSAR data for small-scale disturbances, resulting in missed detections. ALOS-2 ScanSAR detections showed a delay of up to 17.8 days compared to detections based solely on Sentinel-1 data. Combining ALOS-2 ScanSAR and Sentinel-1-based disturbances resulted in improved detection timeliness, with an average improvement of up to 16.5 days compared to Sentinel-1-based detections. Furthermore, we observed improved detection rates for our ALOS-2 ScanSAR-based detections compared to those of the ALOS-2 ScanSAR-based JICA-JAXA Forest Early Warning System in the Tropics (JJ-FAST) forest disturbance alerting product. This suggests that the potential of ALOS-2 ScanSAR data in operational forest monitoring systems is not currently fully realized. Comparing the SAR-based disturbance detections from this study with existing optical-based forest disturbance products (GFC and GLAD-L) suggested improved detection accuracies by overcoming sensor-specific omission errors when using combined SAR and optical data. The demonstrated potential of L-Band ALOS-2 ScanSAR data for improving operational forest monitoring efforts using C-band radar and optical satellites is expected to be amplified by upcoming L-Band satellite missions like NiSAR (2024) and ROSE-L (2028), which will provide freely accessible L-Band data with higher spatial resolution.

Objective Gut-residing bacteria, such as Escherichia coli, can acetylate their proteome under conditions of amine starvation. It is postulated that the (gut) microbiome is involved in the breach of immune tolerance to modified self-proteins leading to the anti-modified protein antibodies (AMPAs), hallmarking seropositive rheumatoid arthritis (RA). Our aim was to determine whether acetylated bacterial proteins can induce AMPA responses cross-reactive to modified self-proteins and be recognised by human AMPA (hAMPA).Methods E. coli bacteria were grown under amine starvation to generate endogenously acetylated bacterial proteins. Furthermore, E. coli proteins were acetylated chemically. Recognition of these proteins by hAMPA was analysed by western blotting and ELISA; recognition by B cells carrying a modified protein-reactive B cell receptor (BCR) was analysed by pSyk (Syk phosphorylation) activation assay. C57BL/6 mice were immunised with (modified) bacterial protein fractions, and sera were analysed by ELISA.Results Chemically modified bacterial protein fractions contained high levels of acetylated proteins and were readily recognised by hAMPA and able to activate B cells carrying modified protein-reactive BCRs. Likely due to substantially lower levels of acetylation, endogenously acetylated protein fractions were not recognised by hAMPA or hAMPA-expressing B cells. Immunising mice with chemically modified protein fractions induced a strong cross-reactive AMPA response, targeting various modified antigens including citrullinated proteins.Conclusions Acetylated bacterial proteins are recognisable by hAMPA and are capable of inducing cross-reactive AMPA in mice. These observations provide the first conceptual evidence for a novel mechanism involving the (endogenous) acetylation of the bacterial proteome, allowing a breach of tolerance to modified proteins and the formation of cross-reactive AMPA.

Introduction Treatment with the immune checkpoint inhibitor anti-programmed cell death protein-1 (PD-1) often causes immune-related adverse events (irAEs). Since irAEs resemble autoimmune diseases, autoantibodies might play a role and could potentially be used to identify patients at risk. Therefore, we investigated the association between autoantibody-positivity and toxicity as well as clinical response in patients with melanoma treated with anti-PD-1.Materials and methods This two-center, retrospective study included 143 patients with melanoma treated with anti-PD-1. Toxicities grade ≥2 and recurrences/responses were captured until 6 months after treatment initiation. Autoantibody measurements were performed at baseline and 3 months after treatment initiation, including IgM-rheumatoid factor (RF), antinuclear antibodies (ANA), extractable nuclear antigen, anti-cyclic citrullinated peptide antibodies (anti-CCP2) and anti-thyroid antibodies.Results 169 irAEs were experienced by 86/143 patients (137 grades 1–2, 32 grades 3–4), the most common being thyroiditis (n=25), dermatitis (n=24), and sicca problems (n=19). Patients with autoantibodies at baseline experienced more irAEs (p=0.001), predominantly associated with anti-thyroid antibodies and thyroid dysfunction. No association was observed between any irAE and anti-CCP2, RF or ANA. In women, baseline and on-treatment anti-thyroid antibody-positivity as well as seroconversion during treatment was associated with thyroid dysfunction. In men, this association was only observed on-treatment. The presence of autoantibodies was not associated with melanoma recurrence (p=0.776) or response (p=0.597).Conclusion The presence of autoantibodies prior to anti-PD-1 therapy is associated with irAEs in patients with melanoma. Both baseline positivity and seroconversion of anti-thyroid antibodies were strongly associated with thyroid dysfunction. This association was stronger in women, with all women who were baseline positive developing thyroid dysfunction.

Abstract IgG secreted by B cells carry asparagine N(297)-linked glycans in the fragment crystallizable (Fc) region. Changes in Fc glycosylation are related to health or disease and are functionally relevant, as IgG without Fc glycans cannot bind to Fcɣ receptors or complement factors. However, it is currently unknown whether ɣ-heavy chain (ɣHC) glycans also influence the function of membrane-bound IgG-B-cell receptors (BCR) and thus the outcome of the B-cell immune response. Here, we show in a germinal center (GC)-derived human B-cell line that ɣHC glycans do not affect membrane expression of IgG-BCRs. Furthermore, antigen binding or other BCR-facilitated mechanisms appear unaffected, including BCR downmodulation or BCR-mediated signaling. As expected, secreted IgG lacking Fc glycosylation is unable to carry out effector functions. Together, these observations indicate that IgG-Fc glycosylation serves as a mechanism to control the effector functions of antibodies, but does not regulate the activation of IgG-switched B cells, as its absence had no apparent impact on BCR function.

Abstract Background This study aimed to determine the feasibility of a preoperative and postoperative (in- and outpatient) physical rehabilitation program, the Heart-ROCQ-pilot program. Methods This cohort study included patients undergoing cardiac surgery (including coronary artery bypass graft surgery, valve surgery, aortic surgery, or combinations of these surgeries) and participated in the Heart-ROCQ-pilot program. Feasibility involved compliance and characteristics of bicycle and strength training sessions in the three rehabilitation phases. Results Of the eligible patients, 56% (n = 74) participated in the program (41% of exclusions were due to various health reasons). On average across the rehabilitation phases, the compliance rates of bicycle and strength training were 88% and 83%, respectively. Workload to heart rate (W/HR) ratio and total absolute volume load for bicycle and strength training, respectively, improved in each rehabilitation phase (P

Background: The aim of this study was to identify items that healthcare providers and/or patients consider important to include in a questionnaire for clinical trials and cohort studies in shoulder instability research. This could serve as a basis to develop a core outcome set for shoulder instability research. Methods: Healthcare providers and patients were included in a panel for a modified Delphi consensus study. The study consisted of three rounds, comprising (1) identifying items, (2) rating the importance of the items, and (3) rating the importance again after seeing a summary of the results of round two. Importance was rated on a 9-point Likert scale. Consensus was defined as ≥ 80% of the panel giving a score of 7 or higher. Results: In total, 44 healthcare providers and 30 patients completed all three rounds. Round one identified 54 items. After round three, the panel reached a consensus on 11 items that should be included in a questionnaire, comprising re-dislocation (99%), instable feeling of the shoulder (96%), limitations during sport (93%), patient satisfaction with the shoulder (93%), fear/anxiety for re-dislocation (91%), range of motion (88%), return to old level of functioning (85%), performing daily activities (85%), return to sport (82%), return to work (82%), and trusting the shoulder (81%). Conclusion: Healthcare providers and patients reached a consensus on 11 items that should be included in a questionnaire for shoulder instability research. These items can facilitate design and development of future clinical trials and form the basis for the development of a core outcome set.

Abstract The year 2022 saw record breaking temperatures in Europe during both summer and fall. Similar to the recent 2018 drought, close to 30% (3.0 million km2) of the European continent was under severe summer drought. In 2022, the drought was located in central and southeastern Europe, contrasting the Northern-centered 2018 drought. We show, using multiple sets of observations, a reduction of net biospheric carbon uptake in summer (56-62 TgC) over the drought area. Specific sites in France even showed a widespread summertime carbon release by forests, additional to wildfires. Partial compensation (32%) for the decreased carbon uptake due to drought was offered by a warm autumn with prolonged biospheric carbon uptake. The severity of this second drought event in 5 years suggests drought-induced reduced carbon uptake to no longer be exceptional, and important to factor into Europe’s developing plans for net-zero greenhouse gas emissions that rely on carbon uptake by forests.

Abstract Background People with physical disabilities and/or chronic diseases tend to have an inactive lifestyle. Monitoring physical activity levels is important to provide insight on how much and what types of activities people with physical disabilities and/or chronic diseases engage in. This information can be used as input for interventions to promote a physically active lifestyle. Therefore, valid and reliable physical activity measurement instruments are needed. This scoping review aims 1) to provide a critical mapping of the existing literature and 2) directions for future research on measurement properties of device-based instruments assessing physical activity behavior in ambulant adults with physical disabilities and/or chronic diseases. Methods Four databases (MEDLINE, CINAHL, Web of Science, Embase) were systematically searched from 2015 to April 16th 2023 for articles investigating measurement properties of device-based instruments assessing physical activity in ambulatory adults with physical disabilities and/or chronic diseases. For the majority, screening and selection of eligible studies were done in duplicate. Extracted data were publication data, study data, study population, device, studied measurement properties and study outcome. Data were synthesized per device. Results One hundred three of 21566 Studies were included. 55 Consumer-grade and 23 research-grade devices were studied on measurement properties, using 14 different physical activity outcomes, in 23 different physical disabilities and/or chronic diseases. ActiGraph (n = 28) and Fitbit (n = 39) devices were most frequently studied. Steps (n = 68) was the most common used physical activity outcome. 97 studies determined validity, 11 studies reliability and 6 studies responsiveness. Conclusion This scoping review shows a large variability in research on measurement properties of device-based instruments in ambulatory adults with physical disabilities and/or chronic diseases. The variability highlights a need for standardization of and consensus on research in this field. The review provides directions for future research.

ObjectivesTwo-dimensional speckle tracking (2D-STE) strain analysis holds promise for assessing fetal cardiac function. Understand the learning curve before introducing 2D-STE into obstetrics is crucial. This study examined the learning curve for offline analysis of fetal left (LV) and right ventricular (RV) global longitudinal strain (GLS) using 2D-STE.MethodsAfter 2D-STE training, three trainees (Maternal-Fetal Medicine fellow, OBGYN resident and medical student) analyzed 100 fetal heart clips using 2D-STE to calculate LV- and RV-GLS. Intra-class correlation coefficients (ICC) and Bland-Altman plots were compared GLS values across four sets of 25 clips for each trainee against the expert. Repeated measurements analysis compared GLS score differences between expert and trainees over time and among trainees, adjusting p-values with a Bonferroni correction.ResultsLV-GLS consistency evolved from poor-to-moderate during the first 50 measurements to moderate-to-good during the second 50 for all trainees. RV-GLS consistency evolved from poor-to-moderate during the first 75 measurements to moderate-to-good during the final 25 measurements for the fellow and resident. The student's RV-GLS consistency was poor during the first 25 measurements, moderate-to good during the second 25 measurements and again poor-to-moderate during the final 50 measurements. Repeated measurements analysis showed a significant decrease in variability of the LV- and RV-GLS score differences between the expert and trainees over time (padjConclusionsA clear learning effect was observed by the significant decrease in variability of the difference in the score between the expert and trainees over time. The consistency of fetal GLS analysis with 2D-STE was generally found to be moderate to good after 100 measurements in trainees.

Incidence of endometrial cancer (EC) is rising in the developed world. The current standard of care, hysterectomy, is often infeasible for younger patients and those with high body mass index. There are limited non-surgical treatment options and a lack of biologically relevant research models to investigate novel alternatives to surgery for EC. The aim of the present study was to develop a long-term, patient-derived explant (PDE) model of early-stage EC and demonstrate its use for investigating predictive biomarkers for a current non-surgical treatment option, the levonorgestrel intra-uterine system (LNG-IUS). Fresh tumour specimens were obtained from patients with early-stage endometrioid EC. Tumours were cut into explants, cultured on media-soaked gelatin sponges for up to 21 days and treated with LNG. Formalin-fixed, paraffin embedded (FFPE) blocks were generated for each explant after 21 days in culture. Tumour architecture and integrity were assessed by haematoxylin and eosin (H&E) and immunohistochemistry (IHC). IHC was additionally performed for the expression of five candidate biomarkers of LNG resistance. The developed ex vivo PDE model is capable of culturing explants from early-stage EC tumours long-term (21 Days). This model can complement existing models and may serve as a tool to validate results obtained in higher-throughput in vitro studies. Our study provides the foundation to validate the extent to which EC PDEs reflect patient response in future research.