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Skeletal muscles of the head and trunk originate in distinct lineages with divergent regulatory programmes converging on activation of myogenic determination factors. Branchiomeric head and neck muscles share a common origin with cardiac progenitor cells in cardiopharyngeal mesoderm (CPM). The retinoic acid (RA) signalling pathway is required during a defined early time window for normal deployment of cells from posterior CPM to the heart. Here, we show that blocking RA signalling in the early mouse embryo also results in selective loss of the trapezius neck muscle, without affecting other skeletal muscles. RA signalling is required for robust expression of myogenic determination factors in posterior CPM and subsequent expansion of the trapezius primordium. Lineage-specific activation of a dominant-negative RA receptor reveals that trapezius development is not regulated by direct RA signalling to myogenic progenitor cells in CPM, or through neural crest cells, but indirectly through the somitic lineage, closely apposed with posterior CPM in the early embryo. These findings suggest that trapezius development is dependent on precise spatiotemporal interactions between cranial and somitic mesoderm at the head/trunk interface., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Pulmonary sarcoidosis is a multisystem granulomatous interstitial lung disease (ILD) with a variable presentation and prognosis. The early accurate detection of pulmonary sarcoidosis may prevent progression to pulmonary fibrosis, a serious and potentially life-threatening form of the disease. However, the lack of a gold-standard diagnostic test and specific radiographic findings poses challenges in diagnosing pulmonary sarcoidosis. Chest computed tomography (CT) imaging is commonly used but requires expert, chest-trained radiologists to differentiate pulmonary sarcoidosis from lung malignancies, infections, and other ILDs. In this work, we develop a multichannel, CT and radiomics-guided ensemble network (RadCT-CNNViT) with visual explainability for pulmonary sarcoidosis vs. lung cancer (LCa) classification using chest CT images. We leverage CT and hand-crafted radiomics features as input channels, and a 3D convolutional neural network (CNN) and vision transformer (ViT) ensemble network for feature extraction and fusion before a classification head. The 3D CNN sub-network captures the localized spatial information of lesions, while the ViT sub-network captures long-range, global dependencies between features. Through multichannel input and feature fusion, our model achieves the highest performance with accuracy, sensitivity, specificity, precision, F1-score, and combined AUC of 0.93 ± 0.04, 0.94 ± 0.04, 0.93 ± 0.08, 0.95 ± 0.05, 0.94 ± 0.04, and 0.97, respectively, in a five-fold cross-validation study with pulmonary sarcoidosis (n = 126) and LCa (n = 93) cases. A detailed ablation study showing the impact of CNN + ViT compared to CNN or ViT alone, and CT + radiomics input, compared to CT or radiomics alone, is also presented in this work. Overall, the AI model developed in this work offers promising potential for triaging the pulmonary sarcoidosis patients for timely diagnosis and treatment from chest CT.

Purpose: To determine the reliability of an artificial intelligence, deep learning (AI/DL)-based method of chest computer tomography (CT) scan analysis to distinguish pulmonary sarcoidosis from negative lung cancer screening chest CT scans (Lung Imaging Reporting and Data System score 1, Lung-RADS score 1)., Methods: Chest CT scans of pulmonary sarcoidosis were evaluated by a clinician experienced with sarcoidosis and a chest radiologist for clinical and radiologic evidence of sarcoidosis and exclusion of alternative or concomitant pulmonary diseases. The AI/DL based method used an ensemble network architecture combining Convolutional Neural Networks (CNNs) and Vision Transformers (ViTs). The method was applied to 126 pulmonary sarcoidosis and 96 Lung-RADS score 1 CT scans. The analytic approach of training and validation of the AI/DL method used a fivefold cross-validation technique, where 4/5th of the available data set was used to train a diagnostic model and tested on the remaining 1/5th of the data set, and repeated 4 more times with non-overlapping validation/test data. The probability values were used to generate Receiver Operating Characteristic (ROC) curves to assess the model's discriminatory power., Results: The sensitivity, specificity, positive and negative predictive value of the AI/DL method for the 5 folds of the training/validation sets and the entire set of CT scans were all over 94% to distinguish pulmonary sarcoidosis from LUNG-RADS score 1 chest CT scans. The area under the curve for the corresponding ROC curves were all over 97%., Conclusion: This AL/DL model shows promise to distinguish sarcoidosis from alternative pulmonary conditions using minimal radiologic data., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

During development, lymph node (LN) initiation is coordinated by lymphoid tissue organizer (LTo) cells that attract lymphoid tissue inducer (LTi) cells at strategic positions within the embryo. The identity and function of LTo cells during the initial attraction of LTi cells remain poorly understood. Using lineage tracing, we demonstrated that a subset of Osr1-expressing cells was mesenchymal LTo progenitors. By investigating the heterogeneity of Osr1 + cells, we uncovered distinct mesenchymal LTo signatures at diverse anatomical locations, identifying a common progenitor of mesenchymal LTos and LN-associated adipose tissue. Osr1 was essential for LN initiation, driving the commitment of mesenchymal LTo cells independent of neural retinoic acid, and for LN-associated lymphatic vasculature assembly. The combined action of chemokines CXCL13 and CCL21 was required for LN initiation. Our results redefine the role and identity of mesenchymal organizer cells and unify current views by proposing a model of cooperative cell function in LN initiation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To determine whether deterioration of dental condition at the outset of management of head and neck cancer (HNC) is a nutritional risk and whether social deprivation is a cause of the poor dental condition observed in HNC patients., Material and Methods: A nutritional assessment form (NAF) and the Nutrition Risk Index (NRI) were used to standardize the nutritional status of 108 patients at the outset of management of HNC (2017-2019). The NAF includes assessment of weight loss over the past 3 months, the amount and difficulty of food intake, and the presence of digestive disorders. Dental condition was assessed by the decayed, filled, and missing teeth acopre (DFM) index and the masticatory coefficient (MC). Dental status and social deprivation were correlated with the EPICES score., Results: A correlation was found between the extent of weight loss and dental condition. The MC was higher in absence of weight loss (46% vs. 27%, p = 0.03) and the DMF lower when weight loss was less than 5% (22.3 vs. 26.9 if > 5% loss of weight, p = 0.005). No correlation was found between dental status and nutritional status. Social deprivation was associated with a lower MC (26% vs. 50%, p < 0.001)., Conclusion: Dental condition is a risk factor for weight loss at the outset of management of HNC but is not a determinant of nutritional status. Clinical relevance Dental condition is no longer considered simply as a source of potential complications after radiotherapy but also as an important factor for nutritional status., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Branchiomeric muscles of the head and neck originate in a population of cranial mesoderm termed cardiopharyngeal mesoderm that also contains progenitor cells contributing to growth of the embryonic heart. Retrospective lineage analysis has shown that branchiomeric muscles share a clonal origin with parts of the heart, indicating the presence of common heart and head muscle progenitor cells in the early embryo. Genetic lineage tracing and functional studies in the mouse, as well as in Ciona and zebrafish, together with recent experiments using single cell transcriptomics and multipotent stem cells, have provided further support for the existence of bipotent head and heart muscle progenitor cells. Current challenges concern defining where and when such common progenitor cells exist in mammalian embryos and how alternative myogenic derivatives emerge in cardiopharyngeal mesoderm. Addressing these questions will provide insights into mechanisms of cell fate acquisition and the evolution of vertebrate musculature, as well as clinical insights into the origins of muscle restricted myopathies and congenital defects affecting craniofacial and cardiac development., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Reduced body weight at the time of intensive care unit (ICU) admission is associated with worse survival, and a paradoxical benefit of obesity has been suggested in critical illness. However, no research has addressed the survival effects of disaggregated body constituents of dry weight such as skeletal muscle, fat, and bone density., Methods: Single-center, prospective observational cohort study of medical ICU (MICU) patients from an academic institution in the USA. Five hundred and seven patients requiring CT scanning of chest or abdomen within the first 24 h of ICU admission were evaluated with erector spinae muscle (ESM) and subcutaneous adipose tissue (SAT) areas and with bone density determinations at the time of ICU admission, which were correlated with clinical outcomes accounting for potential confounders., Results: Larger admission ESM area was associated with decreased odds of 6-month mortality (OR per cm 2 , 0.96; 95% CI, 0.94-0.97; p < 0.001) and disability at discharge (OR per cm 2 , 0.98; 95% CI, 0.96-0.99; p = 0.012). Higher bone density was similarly associated with lower odds of mortality (OR per 100 HU, 0.69; 95% CI, 0.49-0.96; p = 0.027) and disability at discharge (OR per 100 HU, 0.52; 95% CI, 0.37-0.74; p < 0.001). SAT area was not significantly associated with these outcomes' measures. Multivariable modeling indicated that ESM area remained significantly associated with 6-month mortality and survival after adjusting for other covariates including preadmission comorbidities, albumin, functional independence before admission, severity scores, age, and exercise capacity., Conclusion: In our cohort, ICU admission skeletal muscle mass measured with ESM area and bone density were associated with survival and disability at discharge, although muscle area was the only component that remained significantly associated with survival after multivariable adjustments. SAT had no association with the analyzed outcome measures.

Background: Skeletal muscle dysfunction occurring as a result of ICU admission associates with higher mortality. Although preadmission higher BMI correlates with better outcomes, the impact of baseline muscle and fat mass has not been defined. We therefore investigated the association of skeletal muscle and fat mass at ICU admission with survival and disability at hospital discharge., Methods: This single-center, prospective, observational cohort study included medical ICU (MICU) patients from an academic institution in the Unites States. A total of 401 patients were evaluated with pectoralis muscle area (PMA) and subcutaneous adipose tissue (SAT) determinations conducted by CT scanning at the time of ICU admission, which were later correlated with clinical outcomes accounting for potential confounders., Results: Larger admission PMA was associated with better outcomes, including higher 6-month survival (OR, 1.03; 95% CI, 1.01-1.04; P < .001), lower hospital mortality (OR, 0.96; 95% CI, 0.93-0.98; P < .001), and more ICU-free days (slope, 0.044 ± 0.019; P = .021). SAT was not significantly associated with any of the measured outcomes. In multivariable analyses, PMA association persisted with 6 months and hospital survival and ICU-free days, whereas SAT remained unassociated with survival or other outcomes. PMA was not associated with regaining of independence at the time of hospital discharge (OR, 0.99; 95% CI, 0.98-1.01; P = .56)., Conclusions: In this study cohort, ICU admission PMA was associated with survival during and following critical illness; it was unable to predict regaining an independent lifestyle following discharge. ICU admission SAT mass was not associated with survival or other measured outcomes., (Published by Elsevier Inc.)