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Background: The efficacy of prophylactic cranial irradiation (PCI) is still controversial in small cell lung cancer (SCLC) patients with pT1-2N0M0 disease after complete resection. The majority of previous studies haven't discerned the potential benefit of PCI in this subgroup of patients, probably due to the paucity of these patients and distinct treating modalities. The aim of this study is to demonstrate the potential medical benefit of PCI in these patients. Methods: A retrospective study was conducted to evaluate the potential benefit of PCI in pT1-2N0M0 SCLC patients after complete resection. We retrospectively reviewed 112 pT1-2N0M0 SCLCs after complete resection and adjuvant chemotherapy between January 2013 and January 2022. Survival and Cox regression analysis were conducted to elucidate the potential medical benefit of PCI in these patients. Results: The median overall survival (OS) has not been reached. The 2-year, 5-year, 8-year OS rate was 93.7%, 73.2%, and 65.7%, respectively. Brain metastasis (BM) was observed in 17.0% (19/112) patients during the process of follow-up. PCI significantly decreased the BM actuarial risk from 23.9 to 4.9% (log-rank p = 0.0097, HR = 0.180, 95% CI: 0.041–0.778). The brain metastasis free survival (BMFS, log-rank p = 0.02) and OS (log-rank p = 0.05) in PCI cohort were also significantly longer than that of non_PCI group. Cox analysis demonstrated that PCI was an independent prognostic factor in both BM actuarial risk (HR = 0.198, 95% CI: 0.046–0.859, p = 0.031) and BMFS (HR = 0.387, 95% CI: 0.169–0.890, p = 0.025). Moreover, T2 patients showed a significant superior prognosis in terms of BM actuarial risk with comparison to those with T1 disease in non_PCI cohort (log-rank p = 0.016, HR = 3.345, 95% CI: 1.177–9.511), whereas the difference could not be observed in PCI cohort. Conclusions: PCI was significantly associated with a better clinical outcome in pT1-2N0M0 SCLC patients who received complete resection and adjuvant chemotherapy, especially in T2 patients. [ABSTRACT FROM AUTHOR]

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion: USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients. [ABSTRACT FROM AUTHOR]

Haired skin is a defining characteristic of mammals. However, some specialized skin regions, such as human palms, soles and ventral wrist, and mouse plantar foot, are entirely hairless. Using mouse plantar skin as a model system, we show that the endogenous secreted Wnt inhibitor DKK2 suppresses plantar hair follicle development and permits the formation of hairless skin. Plantar skin retains all of the mechanistic components needed for hair follicle development, as genetic deletion of Dkk2 permits formation of fully functional plantar hair follicles that give rise to external hair, contain sebaceous glands and a stem cell compartment, and undergo regenerative growth. In the absence of Dkk2, Wnt/β-catenin signaling activity is initially broadly elevated in embryonic plantar skin and gradually becomes patterned, mimicking follicular development in normally haired areas. These data provide a paradigm in which regionally restricted expression of a Wnt inhibitor underlies specification of hairless versus hairy skin.

Mesenchymal stem cells (MSCs) have been proved to exert considerable therapeutic effects on ischemia‐reperfusion (I/R)‐induced injury, but the underlying mechanism remains unknown. In this study, we aimed to explore the potential molecular mechanism underlying the therapeutic effect of MSCs‐derived exosome reinforced with miR‐20a in reversing liver I/R injury. Quantitative real‐time polymerase chain reaction, Western blot, and IHC were carried out to compare the differential expressions of miR‐20a, Beclin‐I, FAS, Caspase‐3, mTOR and P62 in IR rats and normal rats. TUNEL was performed to assess IR‐induced apoptosis in IR rats, and luciferase assay was used to confirm the inhibitory effect of miR‐20a on Beclin‐I and FAS expression. Among the 12 candidate microRNAs (miRNAs), miR‐486, miR‐25, miR‐24, miR‐20a,miR‐466 and miR‐433‐3p were significantly downregulated in I/R. In particular, miR‐20a, a miRNA highly expressed in umbilical cord‐derived mesenchymal stem cells, was proved to bind to the 3ʹ UTR of Beclin‐I and FAS to exert an inhibitory effect on their expressions. Since Beclin‐I and FAS were aberrantly upregulated in IR, exosomes separated from UC‐MSCs showed therapeutic efficacy in reversing I/R induced apoptosis. In addition, exosomes reinforced with miR‐20a and separated from UC‐MSCs almost fully alleviated I/R injury. Furthermore, our results showed that miR‐20a could alleviate the abnormal expression of genes related to apoptosis and autophagy, such as active Caspase‐3, mTOR, P62, and LC3II. This study presented detailed evidence to clarify the mechanism underlying the therapeutic efficacy of UC‐MSCs in the treatment of I/R injury. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: To develop and validate a radiomics signature, utilizing baseline and restaging CT, for preoperatively predicting progression-free survival (PFS) after neoadjuvant chemotherapy (NAC) in locally advanced gastric cancer (LAGC)., Methods: A total of 316 patients with LAGC who received NAC followed by gastrectomy were retrospectively included in this single-center study; these patients were split into two cohorts, one for training (n = 243) and the other for validation (n = 73), based on the different districts of our hospital. A total of 1316 radiomics features were extracted from the volume of interest of the gastric-cancer lesion on venous phase CT images. Four radiomics signatures were built for predicting PFS based on baseline CT (Pre-Rad), restaging CT (Post-Rad), delta radiomics (Delta-Rad) and multi-time radiomics (PrePost-Rad), respectively. Then the PrePost-Rad was combined with clinical factors to establish a nomogram (Rad-clinical model). Kaplan-Meier survival curves with log-rank tests were used to assess the prognostic usefulness of the Rad-clinical model., Results: All baseline characteristics were not statistically different between the two cohorts. The PrePost-Rad achieved improved predictive value by a C-index of 0.724 (95% CI: 0.639-0.809) in the validation cohort [Pre-Rad: 0.715 (0.632-0.798); Post-Rad: 0.632 (0.538-0.725), Delta-Rad: 0.549 (0.447-0.651)]. In terms of clinical benefit, calibration capability, and prediction efficacy, the Rad-clinical model performed well for PFS prediction, with a C-index of 0.754 (95% CI: 0.707-0.800) and 0.719 (95% CI: 0.639-0.800) in the training and validation cohorts, respectively, superior to the clinical model (cN stage and CA199) but comparable to the PrePost-Rad. Moreover, the Rad-clinical model could accurately classify gastric-cancer patients after NAC into three PFS risk groups in both training and validation cohorts. The risk stratification also performed well in most subgroups (good responders, poor responders, ypTNM Ⅱ, and ypTNM Ⅲ/Ⅳ)., Conclusions: The Rad-clinical model integrating longitudinal radiomics score and clinical factors performed well in preoperatively predicting PFS of LAGC patients after NAC and surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)