MSLN induced EMT, cancer stem cell traits and chemotherapy resistance of pancreatic cancer cells.

Chemoresistance is one of the main reasons for poor prognosis of pancreatic cancer. The effects of mesothelin (MSLN) on chemoresistance in pancreatic cancer are still unclear. We aim to investigate potential roles of MSLN in chemoresistance and its relationship with proliferation, epithelial-mesenchymal transition (EMT) and cancer stemness of pancreatic cancer cells. Human pancreatic cancer cell lines ASPC-1 and Mia PaCa-2 with high and low expression of MSLN, respectively, were selected. The ASPC-1 with MSLN knockout (KO) and Mia PaCa-2 of MSLN overexpression (OE) were generated. The effects of MSLN on cell phenotypes, expression of EMT-related markers, clone formation, tumor sphere formation, and pathologic role of MSLN in tumorigenesis were detected. Sensitivity of tumor cells to gemcitabine was evaluated. The results showed that adhesion, proliferation, migration and invasion were decreased significantly in ASPC-1 with MSLN KO, whereas increased significantly in Mia PaCa-2 with MSLN OE. The size and the number of clones and tumor spheres were decreased in ASPC-1 with MSLN KO, and increased in Mia PaCa-2 with MSLN OE. In xenograft model, tumor volume was decreased (tumor grew slower) in MSLN KO group compared to control group, while increased in MSLN OE group. Mia PaCa-2 with MSLN OE had a higher IC50 of gemcitabine, while ASPC-1 with MSLN KO had a lower IC50. We concluded that MSLN could induce chemoresistance by enhancing migration, invasion, EMT and cancer stem cell traits of pancreatic cancer cells. Targeting MSLN could represent a promising therapeutic strategy for reversing EMT and chemoresistance in pancreatic cancer cells.

The cGAS-STING pathway in viral infections: a promising link between inflammation, oxidative stress and autophagy.

The host defence responses play vital roles in viral infection and are regulated by complex interactive networks. The host immune system recognizes viral pathogens through the interaction of pattern-recognition receptors (PRRs) with pathogen-associated molecular patterns (PAMPs). As a PRR mainly in the cytoplasm, cyclic GMP-AMP synthase (cGAS) senses and binds virus DNA and subsequently activates stimulator of interferon genes (STING) to trigger a series of intracellular signalling cascades to defend against invading pathogenic microorganisms. Integrated omic and functional analyses identify the cGAS-STING pathway regulating various host cellular responses and controlling viral infections. Aside from its most common function in regulating inflammation and type I interferon, a growing body of evidence suggests that the cGAS-STING signalling axis is closely associated with a series of cellular responses, such as oxidative stress, autophagy, and endoplasmic reticulum stress, which have major impacts on physiological homeostasis. Interestingly, these host cellular responses play dual roles in the regulation of the cGAS-STING signalling axis and the clearance of viruses. Here, we outline recent insights into cGAS-STING in regulating type I interferon, inflammation, oxidative stress, autophagy and endoplasmic reticulum stress and discuss their interactions with viral infections. A detailed understanding of the cGAS-STING-mediated potential antiviral effects contributes to revealing the pathogenesis of certain viruses and sheds light on effective solutions for antiviral therapy.

Quantifying the Impact of Motions on Human Aiming Performance: Evidence from Eye Tracking and Bio-Signals.

Working on a moving platform can significantly impede human performance. Previous studies on moving vehicles have often focused on the overall impact on general task performance, whereas our study's emphasis is on precise hand movements, exploring the interaction between body motion and the escalation of task difficulty. We recruited 28 participants to engage in reciprocal aiming tasks, following Paul Fitts's setting, under both in-motion and stationary conditions. The task index of difficulty (ID) was manipulated by varying the width of the targets and the distance between the targets. We measured participants' movement time (MT), performance errors, and monitored their eye movements using an eye-tracking device, heart rate (HR), and respiration rate (RR) during the tasks. The measured parameters were compared across two experimental conditions and three ID levels. Compared to the stationary conditions, the in-motion conditions degraded human aiming performance, resulting in significantly prolonged MT, increased errors, and longer durations of eye fixations and saccades. Furthermore, HR and RR increased under the in-motion conditions. Linear relationships between MT and ID exhibited steeper slopes under the in-motion conditions compared to the stationary conditions. This study builds a foundation for us to explore the control mechanisms of individuals working in dynamic and demanding environments, such as pilots in airplanes and paramedics in ambulances.

Cohen syndrome combined with psychiatric symptoms: a case report.

BACKGROUND: Cohen syndrome (CS) is a rare autosomal recessive inherited condition characterized by pathological changes affecting multiple systems. The extensive clinical variability associated with CS poses a significant diagnostic challenge. Additionally, there is limited documentation on the co-occurrence of CS with psychiatric symptoms. CASE REPORT: We report a case of a 30-year-old patient exhibiting characteristic physical features and psychiatric symptoms. Whole exome sequencing identified two heterozygous variants, a nonsense variation c.4336 C > T and a missense mutation c.4729G > A. Integrating clinical manifestations with genetic test results, we established the diagnosis of CS combined with psychiatric symptoms. CONCLUSIONS: This case introduces a novel missense variant as a candidate in the expanding array of VPS13B pathogenic variants. Its clinical significance remains unknown, and further investigation may broaden the spectrum of pathogenic variants associated with the VPS13B gene. Early diagnosis of CS is crucial for the prognosis of young children and holds significant importance for their families.

Enhancing Semi-Supervised Semantic Segmentation of Remote Sensing Images via Feature Perturbation-Based Consistency Regularization Methods.

In the field of remote sensing technology, the semantic segmentation of remote sensing images carries substantial importance. The creation of high-quality models for this task calls for an extensive collection of image data. However, the manual annotation of these images can be both time-consuming and labor-intensive. This has catalyzed the advent of semi-supervised semantic segmentation methodologies. Yet, the complexities inherent within the foreground categories of these remote sensing images present challenges in preserving prediction consistency. Moreover, remote sensing images possess more complex features, and different categories are confused within the feature space, making optimization based on the feature space challenging. To enhance model consistency and to optimize feature-based class categorization, this paper introduces a novel semi-supervised semantic segmentation framework based on Mean Teacher (MT). Unlike the conventional Mean Teacher that only introduces perturbations at the image level, we incorporate perturbations at the feature level. Simultaneously, to maintain consistency after feature perturbation, we employ contrastive learning for feature-level learning. In response to the complex feature space of remote sensing images, we utilize entropy threshold to assist contrastive learning, selecting feature key-values more precisely, thereby enhancing the accuracy of segmentation. Extensive experimental results on the ISPRS Potsdam dataset and the challenging iSAID dataset substantiate the superior performance of our proposed methodology.

A novel stratification scheme combined with internal arteries in CT imaging for guiding postoperative adjuvant transarterial chemoembolization in hepatocellular carcinoma: a retrospective cohort study.

BACKGROUND: Although postoperative adjuvant transarterial chemoembolization (PA-TACE) improves survival outcomes in a subset of patients with resected hepatocellular carcinoma (HCC), the lack of reliable biomarkers for patient selection remains a significant challenge. The present study aimed to evaluate whether computed tomography (CT) imaging can provide more value for predicting benefits from PA-TACE and to establish a new scheme for guiding PA-TACE benefits. METHODS: In this retrospective study, patients with HCC who had undergone preoperative contrast-enhanced CT and curative hepatectomy were evaluated. Inverse probability of treatment weight was performed to balance the difference of baseline characteristics. Cox models were used to test the interaction among PA-TACE, imaging features and pathological indicators. An HCC imaging and pathological classification (HIPC) scheme incorporating these imaging and pathological indicators was established. RESULTS: This study included 1,488 patients (median age, 52 y [IQR, 45-61 y]; 1,309 male). Microvascular invasion (MVI) positive, and diameter>5 cm tumors achieved a higher recurrence-free survival (RFS), and overall survival (OS) benefit, respectively, from PA-TACE than MVI negative, and diameter ≤5 cm tumors. Patients with internal arteries (IA) positive benefited more than those with IA negative in terms of RFS (P=0.016) and OS (P=0.018). PA-TACE achieved significant RFS and OS improvements in HIPC3 (IA present and diameter, or two or three tumors) patients but not in HIPC1 (diameter ≤5 cm, MVI negative) and HIPC2 (other single tumor) patients. Our scheme may decrease the number of patients receiving PA-TACE by approximately 36.5% compared to the previous suggestion. CONCLUSIONS: IA can provide more value for predicting the benefit of PA-TACE treatment. The proposed HIPC scheme can be used to stratify patients with and without survival benefits from PA-TACE.

Perfusion of hepatocellular carcinomas measured by diffusion-derived vessel density biomarker: Higher hepatocellular carcinoma perfusion than earlier intravoxel incoherent motion reports.

Diffusion-derived vessel density (DVDD) is a physiological surrogate of the area of microvessels per unit tissue area. DDVD is calculated according to DDVD(b0b2) = Sb0/ROIarea0 - Sb2/ROIarea2, where Sb0 and Sb2 refer to the liver signal when b is 0 or 2 s/mm2 . Pathohistological studies and contrast-enhanced CT/MRI data showed higher blood volume in hepatocellular carcinoma (HCC) relative to native liver tissue. With intravoxel incoherent motion (IVIM) imaging, most authors paradoxically reported a decreased perfusion fraction of HCC relative to the adjacent liver. This study applied DDVD to assess the perfusion of HCC. MRI was performed with a 3.0-T magnet. Diffusion-weighted images with b-values of 0 and 2 s/mm2 were acquired in 72 HCC patients. Thirty-two patients had microvascular invasion (MVI(+)) and 40 patients did not have microvascular invasion (MVI(-)). Fifty-eight patients had Edmondson-Steiner grade I or II HCC, and 14 patients had Edmondson-Steiner grade III or IV HCC. DDVD measurement was conducted on the axial slice that showed the largest HCC size. DDVD(b0b2) T/L = HCC DDVD(b0b2)/liver DDVD(b0b2). DDVD(b0b2) T/L median (95% confidence interval) of all HCCs was 2.942 (2.419-3.522), of MVI(-) HCCs was 2.699 (2.030-3.522), of MVI(+) HCCs was 2.988 (2.423-3.990), of Edmondson-Steiner grade I/II HCCs was 2.873 (2.277-3.465), and of Edmondson-Steiner grade III/IV HCCs was 3.403 (2.008-4.485). DDVD(b0b2) T/L approximately agrees with contrast agent dynamically enhanced CT/MRI literature data, whereas it differs from earlier IVIM study results, where HCC perfusion fraction was paradoxically lower relative to native liver tissue. A weak trend was noted with MIV(+) HCCs had a higher DDVD(b0b2) T/L than that of MVI(-) HCCs, and a weak trend was noted with the poorly differentiated group of HCCs (Edmondson-Steiner grade III and IV) had a higher DDVD(b0b2) T/L than that of the better differentiated group of HCCs (Edmondson-Steiner grade I and II).

BCLAF1 binds SPOP to stabilize PD-L1 and promotes the development and immune escape of hepatocellular carcinoma.

Interaction between programmed death-1 (PD-1) ligand 1 (PD-L1) on tumor cells and PD-1 on T cells allows tumor cells to evade T cell-mediated immune surveillance. Strategies targeting PD-1/PD-L1 have shown clinical benefits in a variety of cancers. However, limited response rates in hepatocellular carcinoma (HCC) have prompted us to investigate the molecular regulation of PD-L1. Here, we identify B cell lymphoma-2-associated transcription factor 1 (BCLAF1) as a key PD-L1 regulator in HCC. Specifically, BCLAF1 interacts with SPOP, an E3 ligase that mediates the ubiquitination and degradation of PD-L1, thereby competitively inhibiting SPOP-PD-L1 interaction and subsequent ubiquitination and degradation of PD-L1. Furthermore, we determined an SPOP-binding consensus (SBC) motif mediating the BCLAF1-SPOP interaction on BCLAF1 protein and mutation of BCLAF1-SBC motif disrupts the regulation of the SPOP-PD-L1 axis. In addition, BCLAF1 expression was positively correlated with PD-L1 expression and negatively correlated with biomarkers of T cell activation, including CD3 and CD8, as well as with the level of immune cell infiltration in HCC tissues. Besides, BCLAF1 depletion leads to a significant reduction of PD-L1 expression in vitro, and this reduction of PD-L1 promoted T cell-mediated cytotoxicity. Notably, overexpression of BCLAF1 sensitized tumor cells to checkpoint therapy in an in vitro HCC cells-Jurkat cells co-culture model, whereas BCLAF1-SBC mutant decreased tumor cell sensitivity to checkpoint therapy, suggesting that BCLAF1 and its SBC motif serve as a novel therapeutic target for enhancing anti-tumor immunity in HCC.

Clinical study on the necessity and feasibility of routine MRCP in patients with cholecystolithiasis before LC.

BACKGROUND: In the past quite a long time, intraoperative cholangiography(IOC)was necessary during laparoscopic cholecystectomy (LC). Now magnetic resonance cholangiopancreatography (MRCP) is the main method for diagnosing common bile duct stones (CBDS). Whether MRCP can replace IOC as routine examination before LC is still inconclusive. The aim of this study was to analyze the clinical data of patients undergoing LC for cholecystolithiasis, and to explore the necessity and feasibility of preoperative routine MRCP in patients with cholecystolithiasis. METHODS: According to whether MRCP was performed before operation, 184 patients undergoing LC for cholecystolithiasis in the Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University from January 1, 2017 to December 31, 2018 were divided into non-MRCP group and MRCP group for this retrospective study. The results of preoperative laboratory test, abdominal ultrasound and MRCP, biliary related comorbidities, surgical complications, hospital stay and hospitalization expenses were compared between the two groups. RESULTS: Among the 184 patients, there were 83 patients in non-MRCP group and 101 patients in MRCP group. In MRCP group, the detection rates of cholecystolithiasis combined with CBDS and common bile duct dilatation by MRCP were higher than those by abdominal ultrasound (P < 0.05). The incidence of postoperative complications in non-MRCP group (8.43%) was significantly higher (P < 0.05) than that in MRCP group (0%). There was no significant difference in hospital stay (P > 0.05), but there was significant difference in hospitalization expenses (P < 0.05) between the two groups. According to the stratification of gallbladder stone patients with CBDS, hospital stay and hospitalization expenses were compared, and there was no significant difference between the two groups (P > 0.05). CONCLUSIONS: The preoperative MRCP can detect CBDS, cystic duct stones and anatomical variants of biliary tract that cannot be diagnosed by abdominal ultrasound, which is helpful to plan the surgical methods and reduce the surgical complications. From the perspective of health economics, routine MRCP in patients with cholecystolithiasis before LC does not increase hospitalization costs, and is necessary and feasible.

The Study of Endothelial-Mesenchymal Transition in an Atrial Fibrillation Rat Model.

Background: Activated fibroblasts are reported partly of endothelial origin, derived through endothelial-mesenchymal transition (EndMT). Few studies have investigated EndMT in atrial fibrillation (AF), which may have a potential effect on cardiac fibrosis. Objective: To investigate whether EndMT occurs in an animal model of AF. Methods: A total of 80 Sprague‒Dawley rats (8 weeks, male, 200-250 g) were randomly divided into two groups: the control group and the AF group (n = 40 in each group). Rats in the AF group received a daily intravenous injection of acetylcholine-calcium chloride for seven days to establish an AF model, and rats in the control rats were injected with saline in the same way. At different time points (Day 3, Day 5, Day 7, Day 9, Day 11, Day 13, Day 15, and Day 17), we observed changes in EndMT-related indexes (CD31, VE-cadherin, FSP-1, TGF-ß1 and collagen) and HIF-1α in the rat atria of two groups, as well as immunofluorescence co-expression of CD31/FSP-1 and VE-cadherin/FSP-1 in the endocardial endocardium of the atria. Results: In the AF group, atrial EndMT was observed and enhanced with time. Compared with the control group, the levels of CD31 and VE-cadherin in the AF group decreased, while mesenchymal marker (FSP-1) and EndMT inducer (TGF-ß1) were dynamically increased after Day 3. The co-expression of CD31/FSP-1 and VE-cadherin/FSP-1 was observed from Day 3 to the end of observation time Day 17 by immunofluorescence in AF rat hearts, indicating the existence of EndMT. In addition, the level of HIF-1α in the hearts of AF rats was increased. Conclusion: As far as we know, this is the first study to explore the dynamic process of EndMT in an AF rat model. The presence of EndMT was verified in the atria of the AF rat model, and Day 7-Day 17 was the best observation time point for the model. This may lead to a better understanding of the pathological changes and mechanisms in AF with a short modeling cycle.

Repeatability and reproducibility comparisons of liver IVIM imaging with free-breathing or respiratory-triggered sequences.

For liver intravoxel incoherent motion (IVIM) data acquisition, respiratory-triggering (RT) MRI is commonly used, and there are strong motivations to shorten the scan duration. For the same scan duration, more b values or higher numbers of excitations can be allowed for free-breathing (FB) imaging than for RT. We studied whether FB can be used to replace RT when careful IVIM image acquisition and image processing are conducted. MRI data of 22 healthy participants were acquired using a 3.0 T scanner. Diffusion imaging was based on a single-shot spin-echo-type echo-planar sequence and 16 b values of 0, 2, 4, 7, 10, 15, 20, 30, 46, 60, 72, 100, 150, 200, 400, and 600 s/mm2 . Each subject attended two scan sessions with an interval of 10-20 days. For each scan session, a subject was scanned twice, first with RT and then with FB. The mean image acquisition time was 5.4 min for FB and 10.8 min for RT. IVIM parameters were calculated with bi-exponential model segmented fitting with a threshold b value of 60 s/mm2 , and fitting started from b = 2 s/mm2 . There was no statistically significant difference between IVIM parameters measured with FB imaging or RT imaging. Perfusion fraction ICC (intraclass correlation coefficient) for FB imaging and RT imaging in the same scan session was 0.824. For perfusion fraction, wSD (within-subject standard deviation), BA (Bland-Altman) difference, BA 95% limit, and ICC were 0.022, 0.0001, -0.0635~0.0637, and 0.687 for FB and 0.031, 0.0122, -0.0723~0.0967, and 0.611 for RT. For Dslow (×10-3  s/mm2 ), wSD, BA difference, BA 95% limit, and ICC were 0.057, 0.0268, -0.1258~0.1793, and 0.471 for FB and 0.073, -0.0078, -0.2170-0.2014, and <0.4 for RT. The Dfast coefficient of variation was 0.20 for FB imaging and 0.28 for RT imaging. All reproducibility indicators slightly favored FB imaging.

Glutathione-triggered prodrugs: Design strategies, potential applications, and perspectives.

The burgeoning prodrug strategy offers a promising avenue toward improving the efficacy and specificity of cytotoxic drugs. Elevated intracellular levels of glutathione (GSH) have been regarded as a hallmark of tumor cells and characteristic feature of the tumor microenvironment. Considering the pivotal involvement of elevated GSH in the tumorigenic process, a diverse repertoire of GSH-triggered prodrugs has been developed for cancer therapy, facilitating the attenuation of deleterious side effects associated with conventional chemotherapeutic agents and/or the attainment of more efficacious therapeutic outcomes. These prodrug formulations encompass a spectrum of architectures, spanning from small molecules to polymer-based and organic-inorganic nanomaterial constructs. Although the GSH-triggered prodrugs have been gaining increasing interests, a comprehensive review of the advancements made in the field is still lacking. To fill the existing lacuna, this review undertakes a retrospective analysis of noteworthy research endeavors, based on a categorization of these molecules by their diverse recognition units (i.e., disulfides, diselenides, Michael acceptors, and sulfonamides/sulfonates). This review also focuses on explaining the distinct benefits of employing various chemical architecture strategies in the design of these prodrug agents. Furthermore, we highlight the potential for synergistic functionality by incorporating multiple-targeting conjugates, theranostic entities, and combinational treatment modalities, all of which rely on the GSH-triggering. Overall, an extensive overview of the emerging field is presented in this review, highlighting the obstacles and opportunities that lie ahead. Our overarching goal is to furnish methodological guidance for the development of more efficacious GSH-triggered prodrugs in the future. By assessing the pros and cons of current GSH-triggered prodrugs, we expect that this review will be a handful reference for prodrug design, and would provide a guidance for improving the properties of prodrugs and discovering novel trigger scaffolds for constructing GSH-triggered prodrugs.

The association between bullous pemphigoid and cognitive outcomes in middle-aged and older adults: A systematic review and meta-analysis.

BACKGROUND: Bullous pemphigoid (BP) is a rare autoimmune skin condition that causes large fluid-filled blisters on the skin, especially in older adults. BP has been linked to various diseases and medications, but its association with cognitive outcomes is unclear. METHODS: We conducted a systematic review and meta-analysis of studies investigating the association between BP and cognitive outcomes, such as all-cause dementia, Alzheimer's disease, and vascular dementia in middle-aged and older adults. We searched PubMed, Embase, and Web of Science databases for relevant studies published up to March 2023. We included studies that reported odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between BP and cognitive outcomes. We pooled the ORs, or HRs using random-effects models and performed subgroup and sensitivity analyses to explore potential sources of heterogeneity. RESULTS: The study selection process identified 13 studies for inclusion in the analysis, 11 studied arms of which used a case-control design and 7 studied arms of which used a cohort design. The studies were conducted primarily in Europe, with a few from Asia and the United States. The meta-analysis found that BP was associated with higher odds of all-cause dementia in middle-aged and older participants in both cohort studies(HR = 1.41,95% CI: 1.20-1.66, P = 0.000) and case-control (OR = 4.25, 95% CI, 2.73-6.61; P = 0.000). The study found no significant publication bias in the included studies. The meta-regression analyses identified some subgroups associated with significantly reported odds ratios in case-control association analysis, including Europe, BP diagnosed based on clinical, histology, immunofluorescence, and both adjustment status of NO and YES. CONCLUSIONS: Our meta-analysis suggests that BP is associated with an increased risk of all-cause dementia in middle-aged and older adults. Further studies are needed to elucidate the underlying mechanisms and causal relationship between BP and cognitive outcomes.

Long-term outcomes of pulmonary atresia with ventricular septal defect by different initial rehabilitative surgical age.

Background: There is a lack of evidence guiding the surgical timing selection in pulmonary atresia with ventricular septal defect. This study aims to compare the long-term outcomes of different initial rehabilitative surgical ages in patients with pulmonary atresia with ventricular septal defect (PAVSD). Methods: From January 2011 to December 2020, a total of 101 PAVSD patients undergoing the initial rehabilitative surgery at our center were retrospectively reviewed. Receiver-operator characteristics curve analysis was used to identify the cutoff age of 6.4 months and therefore to classify the patients into two groups. Competing risk models were used to identify risk factors associated with complete repair. The probability of survival and complete repair were compared between the two groups using the Kaplan-Meier curve and cumulative incidence curve, respectively. Results: The median duration of follow-up was 72.76 months. There were similar ΔMcGoon ratio and ΔNakata index between the two groups. Multivariate analysis showed that age ≤6.4 months (hazard ratio (HR) = 2.728; 95% confidence interval (CI):1.122-6.637; p = 0.027) and right ventricle-to-pulmonary artery connection (HR = 4.196; 95% CI = 1.782-9.883; p = 0.001) were associated with increased probability of complete repair. The cumulative incidence curve showed that the estimated complete repair rates were 64% ± 8% after 3 years and 69% ± 8%% after 5 years in the younger group, significantly higher than 28% ± 6% after 3 years and 33% ± 6% after 5 years in the elder group (p < 0.001). There was no significant difference regarding the estimated survival rate between the two groups. Conclusion: Compared with those undergoing the initial rehabilitative surgery at the age >6.4 months, PAVSD patients at the age ≤6.4 months had an equal pulmonary vasculature development, a similar probability of survival but an improved probability of complete repair.

Magnetic Resonance Deep Learning Radiomic Model Based on Distinct Metastatic Vascular Patterns for Evaluating Recurrence-Free Survival in Hepatocellular Carcinoma.

BACKGROUND: The metastatic vascular patterns of hepatocellular carcinoma (HCC) are mainly microvascular invasion (MVI) and vessels encapsulating tumor clusters (VETC). However, most existing VETC-related radiological studies still focus on the prediction of VETC status. PURPOSE: This study aimed to build and compare VETC-MVI related models (clinical, radiomics, and deep learning) associated with recurrence-free survival of HCC patients. STUDY TYPE: Retrospective. POPULATION: 398 HCC patients (349 male, 49 female; median age 51.7 years, and age range: 22-80 years) who underwent resection from five hospitals in China. The patients were randomly divided into training cohort (n = 358) and test cohort (n = 40). FIELD STRENGTH/SEQUENCE: 3-T, pre-contrast T1-weighted imaging spoiled gradient recalled echo (T1WI SPGR), T2-weighted imaging fast spin echo (T2WI FSE), and contrast enhanced arterial phase (AP), delay phase (DP). ASSESSMENT: Two radiologists performed the segmentation of HCC on T1WI, T2WI, AP, and DP images, from which radiomic features were extracted. The RFS related clinical characteristics (VETC, MVI, Barcelona stage, tumor maximum diameter, and alpha fetoprotein) and radiomic features were used to build the clinical model, clinical-radiomic (CR) nomogram, deep learning model. The follow-up process was done 1 month after resection, and every 3 months subsequently. The RFS was defined as the date of resection to the date of recurrence confirmed by radiology or the last follow-up. Patients were followed up until December 31, 2022. STATISTICAL TESTS: Univariate COX regression, least absolute shrinkage and selection operator (LASSO), Kaplan-Meier curves, log-rank test, C-index, and area under the curve (AUC). P < 0.05 was considered statistically significant. RESULTS: The C-index of deep learning model achieved 0.830 in test cohort compared with CR nomogram (0.731), radiomic signature (0.707), and clinical model (0.702). The average RFS of the overall patients was 26.77 months (range 1-80 months). DATA CONCLUSION: MR deep learning model based on VETC and MVI provides a potential tool for survival assessment. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

A transformer-based multi-task deep learning model for simultaneous infiltrated brain area identification and segmentation of gliomas.

BACKGROUND: The anatomical infiltrated brain area and the boundaries of gliomas have a significant impact on clinical decision making and available treatment options. Identifying glioma-infiltrated brain areas and delineating the tumor manually is a laborious and time-intensive process. Previous deep learning-based studies have mainly been focused on automatic tumor segmentation or predicting genetic/histological features. However, few studies have specifically addressed the identification of infiltrated brain areas. To bridge this gap, we aim to develop a model that can simultaneously identify infiltrated brain areas and perform accurate segmentation of gliomas. METHODS: We have developed a transformer-based multi-task deep learning model that can perform two tasks simultaneously: identifying infiltrated brain areas segmentation of gliomas. The multi-task model leverages shaped location and boundary information to enhance the performance of both tasks. Our retrospective study involved 354 glioma patients (grades II-IV) with single or multiple brain area infiltrations, which were divided into training (N = 270), validation (N = 30), and independent test (N = 54) sets. We evaluated the predictive performance using the area under the receiver operating characteristic curve (AUC) and Dice scores. RESULTS: Our multi-task model achieved impressive results in the independent test set, with an AUC of 94.95% (95% CI, 91.78-97.58), a sensitivity of 87.67%, a specificity of 87.31%, and accuracy of 87.41%. Specifically, for grade II-IV glioma, the model achieved AUCs of 95.25% (95% CI, 91.09-98.23, 84.38% sensitivity, 89.04% specificity, 87.62% accuracy), 98.26% (95% CI, 95.22-100, 93.75% sensitivity, 98.15% specificity, 97.14% accuracy), and 93.83% (95%CI, 86.57-99.12, 92.00% sensitivity, 85.71% specificity, 87.37% accuracy) respectively for the identification of infiltrated brain areas. Moreover, our model achieved a mean Dice score of 87.60% for the whole tumor segmentation. CONCLUSIONS: Experimental results show that our multi-task model achieved superior performance and outperformed the state-of-the-art methods. The impressive performance demonstrates the potential of our work as an innovative solution for identifying tumor-infiltrated brain areas and suggests that it can be a practical tool for supporting clinical decision making.

Atopic dermatitis and cognitive dysfunction in middle-aged and older adults: A systematic review and meta-analysis.

BACKGROUND: Atopic dermatitis (AD) is a common chronic inflammatory skin disease that affects adults worldwide. Recent evidence suggests that AD may be associated with cognitive dysfunction, but the results of individual studies have been inconsistent. This systematic review and meta-analysis aimed to evaluate the association between AD and cognitive dysfunction in middle-aged and older adults. METHODS: To find relevant research, a comprehensive search of electronic databases from the beginning to March 2023 was carried out. Data were taken from studies that were eligible, and a meta-analysis was done to determine the pooled hazard ratio (HR) and 95% confidence interval (CI). RESULTS: We searched three databases and found a total of 15 studied arms included in 5 cohort studies with over 8.5 million participants were included in the analysis. The results showed that individuals with AD had a higher risk of developing dementia of all-cause dementia (pooled hazard ratio (HR) = 1.16; 95% CI, 1.10-1.23,P<0.001) and the Alzheimer type (pooled HR = 1.28; 95% CI, 1.01-1.63,P<0.001) but not vascular dementia (pooled HR = 1.42; 95% CI, 0.99-2.04,P<0.001). Subgroup analyses showed that the association between atopic dermatitis and all-cause dementia was significant in Europe (P = 0.004) but not in Asia (P = 0.173) and was significant in prospective cohort studies (P<0.001) but not in non-prospective cohort studies (P = 0.068). Sensitivity analysis and publication bias detection confirmed the reliability of the overall findings. CONCLUSIONS: In conclusion, this study demonstrated that AD was associated with increased risk of cognitive dysfunction, particularly dementia of the Alzheimer type and all-cause dementia, in middle-aged and older participants. Further research is needed to understand the mechanisms behind this association and its potential implications for clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier (CRD42023411627).

Increased team familiarity for surgical time savings: Effective primarily in complex surgical cases.

BACKGROUND: Cohesion between team members is critical for surgical performance. Our previous study has shown that the experience of working together (measured by Team Familiarity Score, TFS) helps reduce procedure time (PT). However, that conclusion was found in a relatively small sample size. With a large dataset including mixed general surgical procedures, we hypothesize that team familiarity makes a significant contribution to the improvement of team performance in complex cases, rather than in medium or basic surgical cases, measured by the procedure time, length of hospital stays (LOS), and surgical cost (COST). STUDY DESIGN: Patient demographics, operation, and patient outcome data of 922 general surgery cases were included. The cases were divided into three subgroups, including basic, medium, and complex surgical procedures. TFS and an Index of Difficulty of Surgery (IDS) were calculated for each procedure. Simple linear regression and random forest regressions were performed to analyze the association between surgical outcomes and all included independent variables (TFS, IDS, patient age, patient weight, and team size). RESULTS: When applied to complex cases, procedure time (r = -0.21) and cost (r = -0.23) dropped as TFS increases. In basic and medium surgical cases, increasing team familiarity failed to shorten the procedure time on average. CONCLUSION: Team familiarity is more important in complex cases because there is greater potential for improvement through team collaboration compared to basic and medium cases. Caution will be needed when applying team familiarity scores for examining surgical team performance in large databases with skewed to basic surgical cases.

The role of ubiquitination and deubiquitination in PI3K/AKT/mTOR pathway: A potential target for cancer therapy.

The PI3K/AKT/mTOR pathway controls key cellular processes, including proliferation and tumor progression, and abnormally high activation of this pathway is a hallmark in human cancers. The post-translational modification, such as Ubiquitination and deubiquitination, fine-tuning the protein level and the activity of members in this pathway play a pivotal role in maintaining normal physiological process. Emerging evidence show that the unbalanced ubiquitination/deubiquitination modification leads to human diseases via PI3K/AKT/mTOR pathway. Therefore, a comprehensive understanding of the ubiquitination/deubiquitination regulation of PI3K/AKT/mTOR pathway may be helpful to uncover the underlying mechanism and improve the potential treatment of cancer via targeting this pathway. Herein, we summarize the latest research progress of ubiquitination and deubiquitination of PI3K/AKT/mTOR pathway, systematically discuss the associated crosstalk between them, as well as focus the clinical transformation via targeting ubiquitination process.