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Background: Cutaneous squamous cell carcinoma (cSCC) is one of the most frequent types of cutaneous cancer. The composition and heterogeneity of the tumor microenvironment significantly impact patient prognosis and the ability to practice precision therapy. However, no research has been conducted to examine the design of the tumor microenvironment and its interactions with cSCC. Material and Methods: We retrieved the datasets GSE42677 and GSE45164 from the GEO public database, integrated them, and analyzed them using the SVA method. We then screened the core genes using the WGCNA network and LASSO regression and checked the model's stability using the ROC curve. Finally, we performed enrichment and correlation analyses on the core genes. Results: We identified four genes as core cSCC genes: DTYMK, CDCA8, PTTG1 and MAD2L1, and discovered that RORA, RORB and RORC were the primary regulators in the gene set. The GO semantic similarity analysis results indicated that CDCA8 and PTTG1 were the two most essential genes among the four core genes. The results of correlation analysis demonstrated that PTTG1 and HLA-DMA, CDCA8 and HLA-DQB2 were significantly correlated. Conclusions: Examining the expression levels of four primary genes in cSCC aids in our understanding of the disease's pathophysiology. Additionally, the core genes were found to be highly related with immune regulatory genes, suggesting novel avenues for cSCC prevention and treatment.

Image inpainting aims to synthesize missing regions in images that are coherent with the existing visual content. Generative adversarial networks have made significant strides in the development of image inpainting. However, existing approaches heavily rely on the surrounding pixels while ignoring that the boundaries might be uninformative or noisy, leading to blurred images. As complementary, global visual features from the remote image contexts depict the overall structure and texture of the vanilla images, contributing to generating pixels that blend seamlessly with the existing visual elements. In this paper, we propose a novel model, PA-DeepFill, to repair high-resolution images. The generator network follows a novel progressive learning paradigm, starting with low-resolution images and gradually improving the resolutions by stacking more layers. A novel attention-based module, the gathered attention block, is further integrated into the generator to learn the importance of different distant visual components adaptively. In addition, we have designed a local discriminator that is more suitable for image inpainting tasks, multi-task guided mask-level local discriminator based PatchGAN, which can guide the model to distinguish between regions from the original image and regions completed by the model at a finer granularity. This local discriminator can capture more detailed local information, thereby enhancing the model’s discriminative ability and resulting in more realistic and natural inpainted images. Our proposal is extensively evaluated over popular datasets, and the experimental results demonstrate the superiority of our proposal.

Aiming at the problems of subjective enhancement caused by the discretization of credit data and the lack of a multi-dimensional portrait of credit users in the current credit data research, this paper proposes an improved Fuzzy MLKNN multi-label learning algorithm based on MLKNN. On the one hand, the subjectivity of credit data after discretization is weakened by introducing intuitionistic fuzzy numbers. On the other hand, the algorithm is improved by using the corresponding fuzzy Euclidean distance to realize the multi-label portrait of credit users. The experimental results show that Fuzzy MLKNN performs significantly better than MLKNN on credit data and has the most significant improvement on One Error.

The correlation-based network is a powerful tool to reveal the influential mechanisms and relations in stock markets. However, current methods for developing network models are dominantly based on the pairwise relationship of positive correlations. This work proposes a new approach for developing stock relationship networks by using the linear relationship model with LASSO to explore negative correlations under a systemic framework. The developed model not only preserves positive links with statistical significance but also includes link directions and negative correlations. We also introduce blends cliques with the balance theory to investigate the consistency properties of the developed networks. The ASX 200 stock data with 194 stocks are applied to evaluate the effectiveness of our proposed method. Results suggest that the developed networks not only are highly consistent with the correlation coefficient in terms of positive or negative correlations but also provide influence directions in stock markets.

The interactive effect is significant in the Chinese stock market, exacerbating the abnormal market volatilities and risk contagion. Based on daily stock returns in the Shanghai Stock Exchange (SSE) A-shares, this paper divides the period between 2005 and 2018 into eight bull and bear market stages to investigate interactive patterns in the Chinese financial market. We employ the Least Absolute Shrinkage and Selection Operator (LASSO) method to construct the stock network, compare the heterogeneity of bull and bear markets, and further use the Map Equation method to analyse the evolution of modules in the SSE A-shares market. Empirical results show that (1) the connected effect is more significant in bear markets than bull markets and gives rise to abnormal volatilities in the stock market; (2) a system module can be found in the network during the first four stages, and the industry aggregation effect leads to module differentiation in the last four stages; (3) some stocks have leading effects on others throughout eight periods, and medium- and small-cap stocks with poor financial conditions are more likely to become risk sources, especially in bear markets. Our conclusions are beneficial to improving investment strategies and making regulatory policies.

There is a need for adaptive technology to enhance indoor wayfinding by visually-impaired people. To address this need, we have developed and tested a Digital Sign System. The hardware and software consist of digitally-encoded signs widely distributed throughout a building, a handheld sign-reader based on an infrared camera, image-processing software, and a talking digital map running on a mobile device. Four groups of subjects-blind, low vision, blindfolded sighted, and normally sighted controls-were evaluated on three navigation tasks. The results demonstrate that the technology can be used reliably in retrieving information from the signs during active mobility, in finding nearby points of interest, and following routes in a building from a starting location to a destination. The visually impaired subjects accurately and independently completed the navigation tasks, but took substantially longer than normally sighted controls. This fully functional prototype system demonstrates the feasibility of technology enabling independent indoor navigation by people with visual impairment.

Few data are known regarding the use of interim positron emission tomography (iPET) after the first two cycles (iPET2) of chemotherapy in treatment-naïve classical Hodgkin lymphoma (cHL) in routine clinical practice, and about the real-life adoption of intensification strategies for iPET positive patients. We conducted a multicenter retrospective study on cHL to investigate the use of iPET in the real-life setting, its prognostic role and outcomes of patients early shifted to intensification. Six hundreds and forty-one patients were enrolled (62% had advanced stage). iPET2 was positive in 89 patients (14%) including 8.7% and 17% early and advanced stage patients, respectively (p = 0.003). Among iPET 2 positive cases treatment was immediately modified in 19 cases; in 14 cases treatment was modified after an additional positive iPET4. Overall 56 iPET2 positive patients never received intensified therapies. Most frequently used intensified therapy was autologous stem cell transplantation followed by BEACOPP. After a median follow-up of 72 months, the 5-year progression-free survival (PFS) was 82% with iPET2 positive patients showing a worse PFS compared with iPET2 negative cases: 31% versus 85%. Focusing on advanced stage patients with a positive iPET2, the 5-year PFS was 59% for patients shifted to intensified therapy at any time point versus 61% for patients who never received intensified therapy. Our study confirmed the higher curability of naïve cHL patients in a real-world setting, and the prognostic role of iPET2 in this setting. A poor adherence to response-adapted strategy which however did not translate into a difference in patient outcomes., (© 2024 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

Along with the fact that classical Hodgkin lymphoma (cHL) in older adults is frequently considered biologically different from cHL in younger patients, its most distinctive feature is its dismal clinical outcome due to the decreased effectiveness and greater toxicity of therapies. Although strategies to mitigate specific toxicities (e.g., cardiological and pulmonary) have obtained some results, in general, reduced-intensity schemes, proposed as an alternative to ABVD, have proved to be less effective. The addition of brentuximab vedotin (BV) to AVD, especially in a sequential scheme, has demonstrated good efficacy. However, the problem of toxicity persists even with this new therapeutic combination, with comorbidities remaining an important prognostic factor. The adequate stratification of functional status is necessary to distinguish between those patients who will benefit from full treatment and those who will benefit from alternative strategies. A simplified geriatric assessment based on the determination of ADL (activity of daily living), IADL (instrumental ADL), and CIRS-G (Cumulative Illness Rating Scale-Geriatric) scores is an easy-to-use tool that permits adequate patient stratification. Other factors of considerable impact on functional status such as sarcopenia and immunosenescence are currently being studied. A fitness-based treatment choice would also be very useful for relapsed or refractory patients, a more frequent and challenging situation than that is found in young cHL patients.

Central nervous system (CNS) relapse of mantle cell lymphoma (MCL) is a rare phenomenon with dismal prognosis, where no standard therapy exists. Since the covalent Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in relapsed/refractory MCL and penetrates the blood-brain barrier (BBB), on behalf of Fondazione Italiana Linfomi and European Mantle Cell Lymphoma Network we performed a multicenter retrospective international study to investigate the outcomes of patients treated with ibrutinib or chemoimmunotherapy. In this observational study, we recruited patients with MCL with CNS involvement at relapse who received CNS-directed therapy between 2000 and 2019. The primary objective was to compare the overall survival (OS) of patients treated with ibrutinib or BBB crossing chemotherapy. A propensity score based on a multivariable binary regression model was applied to balance treatment cohorts. Eighty-eight patients were included. The median age at study entry was 65 years (range, 39-87), 76% were males, and the median time from lymphoma diagnosis to CNS relapse was 16 months (range, 1-122). Patients were treated with ibrutinib (n = 29, ibrutinib cohort), BBB crossing chemotherapy (ie, high-dose methotrexate ± cytarabine; n = 29, BBB cohort), or miscellaneous treatments (n = 30, other therapy cohort). Both median OS (16.8 vs 4.4 months; P = .007) and median progression-free survival (PFS) (13.1 vs 3.0 months; P = .009) were superior in the ibrutinib cohort compared with the BBB cohort. Multivariable Cox regression model revealed that ibrutinib therapeutic choice was the strongest independent favorable predictive factor for both OS (hazard ratio [HR], 6.8; 95% confidence interval [CI], 2.2-21.3; P < .001) and PFS (HR, 4.6; 95% CI, 1.7-12.5; P = .002), followed by CNS progression of disease (POD) >24 months from first MCL diagnosis (HR for death, 2.4; 95% CI, 1.1-5.3; P = .026; HR for death or progression, 2.3; 95% CI, 1.1-4.6; P = .023). The addition of intrathecal (IT) chemotherapy to systemic CNS-directed therapy was not associated with superior OS (P = .502) as the morphological variant (classical vs others, P = .118). Ibrutinib was associated with superior survival compared with BBB-penetrating chemotherapy in patients with CNS relapse of MCL and should be considered as a therapeutic option., (© 2022 by The American Society of Hematology.)

In recent years, the clinical use of extracellular miRNAs as potential biomarkers of disease has increasingly emerged as a new and powerful tool. Serum, urine, saliva and stool contain miRNAs that can exert regulatory effects not only in surrounding epithelial cells but can also modulate bacterial gene expression, thus acting as a "master regulator" of many biological processes. We think that in order to have a holistic picture of the health status of an individual, we have to consider comprehensively many "omics" data, such as miRNAs profiling form different parts of the body and their interactions with cells and bacteria. Moreover, Artificial Intelligence (AI) and Machine Learning (ML) algorithms coupled to other multiomics data (i.e., big data) could help researchers to classify better the patient's molecular characteristics and drive clinicians to identify personalized therapeutic strategies. Here, we highlight how the integration of "multiomic" data (i.e., miRNAs profiling and microbiota signature) with other omics (i.e., metabolomics, exposomics) analyzed by AI algorithms could improve the diagnostic and prognostic potential of specific biomarkers of disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Paolini, Baldassarre, Bruno, Felli, Muzi, Ahmadi Badi, Siadat, Sarshar and Masotti.)

Background: Elderly classical Hodgkin lymphoma (cHL) (ecHL) is a rare disease with dismal prognosis and no standard treatment. Fitness-based approaches may help design appropriate treatments. Sarcopenia has been associated with an increased risk of treatment-related toxicities and worse survival in various solid tumours, but its impact in ecHL is unknown. The aim of this retrospective multicentre study was to investigate the prognostic role of sarcopenia in ecHL., Methods: We included newly diagnosed >64 years old cHL patients who performed a baseline comprehensive geriatric assessment and high-dose computed tomography (CT) or 18fluorine-fluorodeoxyglucose positron emission tomography/CT before any treatment. Sarcopenia was measured as skeletal muscle index (SMI, cm 2 /m 2 ) by the analysis of high-dose CT or low-dose positron emission tomography/CT images at the L3 level. The specific cut-offs for the SMI were determined by receiver operator curve analysis and compared with those proposed in literature and studied in diffuse large B-cell lymphoma. Survival functions [progression-free survival [PFS] and overall survival (OS)] were calculated for the whole population and for different subgroups defined as per different sarcopenia cut-off levels., Results: We included 154 patients (median age 71 years old, 76 female). The median L3-SMI was 42 cm 2 /m 2 . The specific cut-off derived in our male population was 45 cm 2 /m 2 ; using this cut-off, 27 male patients (35%) were defined as sarcopenic. After a median follow-up of 5.9 years, the overall 5-year PFS and OS rates were 53% and 65%, respectively, and were significantly shorter in sarcopenic male patients compared with non-sarcopenic (PFS 31% vs. 61%, P = 0.008; OS 51% vs. 74%, P = 0.042). Applying diffuse large B-cell lymphoma-derived sarcopenic thresholds, there were no significant differences between sarcopenic and non-sarcopenic patients for both PFS and OS, with a sole exception of a significant reduced PFS in sarcopenic male patients using Namakura cut-off. The comprehensive geriatric assessment-determined frail functional status was an independent adverse prognostic factor for both female and male patients., Conclusions: Baseline evaluation of sarcopenia through radiological examinations performed for ecHL staging may help define a proportion of male patients with unfavourable outcome with current treatment strategies. Also the functional status evaluation could allow to identify a frail subgroup of patients with worse outcome., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Objectives: High-dose CT (HDCT) is considered the gold-standard imaging for the measurements of skeletal muscle area (SMA), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and intramuscular adipose tissue (IMAT) areas in the abdomen. These parameters may reflect sarcopenia, which can have a prognostic impact in several oncological diseases. The aim of this study was to compare the agreement of measurements of SMA, VAT, SAT and IMAT areas between HDCT and low-dose CT (LDCT) of 18-fludeoxyglucose positron emission tomography ( 18 F-FDG PET)/CT in elderly patients affected by Hodgkin lymphoma (HL)., Methods: We retrospectively included 90 patients affected by HL who underwent baseline 18 F-FDG-PET/CT and HDCT within a mean interval of 7 days. HDCT and LDCT images were analysed by two blinded observers using segmentation software (Slice-O-Matic, Tomovision) to quantify the areas. HDCT and LDCT measurements were compared using Bland-Altman plots and Passing-Bablock regression analyses. Pearson correlation coefficient (r) was used to correlate measurements from the two imaging modalities., Results: Comparison of HDCT and LDCT data demonstrated a strong correlation for measurement of VAT( r = 0.942, p < 0.0001), SAT ( r = 0.894, p < 0.0001) and SMA ( r = 0.934, p < 0.0001). Instead considering IMAT, correlation was good but less significant ( r = 0.742). The mean difference between the two methods was found to be very small, with a difference of 1% for SAT,+6.1% for VAT,+2.5% for SMA and -1.9% for IMAT., Conclusion: LDCT of PET/CT is a safe, accurate and precise method for the measurements of skeletal muscle area, visceral and subcutaneous adipose tissue. Their measurements are reproducible and correlate closely with HDCT., Advances in Knowledge: LLDCT of PET/CT is a safe and accurate method for the measurements of SMA, VAT and SAT; their measurements are closely correlated with HDCT. LDCT can be considered an accurate alternative tool for measuring abdominal fat and muscles in the clinical practice.

Hodgkin lymphoma (HL) has a bimodal age distribution curve, with a second peak in people aged more than 60 years. Interim PET/CT (iPET/CT) is highly predictive for PFS and OS in young HL, but it has not been sufficiently studied in the elderly. In this retrospective dual-center study, 82 patients with HL and aged 65 or more who performed iPET/CT were included. At iPET/CT, 60 patients had a complete metabolic response, 18 partial responses, and 4 progressions of disease. Baseline PET/CT metabolic features were not significantly correlated with the metabolic response at interim. In patients with interim complete metabolic response, PFS and OS were significantly longer than in patients without complete response( p  < 0.001 and p  = 0.004). Patients with negative iPET had 2-year PFS and OS rates of 57 and 88% compared with 24 and 58% in patients with positive iPET ( p  < 0.001). iPET/CT results demonstrated to be independent prognostic factors for PFS and OS.

Elderly Hodgkin lymphoma (HL) is an aggressive lymphoma subgroup with high 18F-FDG avidity at 18F-FDG-PET/CT but no shared criteria for PET/CT in treatment evaluation and prediction of outcome are available. The aim of our bicentric study was to investigate whether the metabolic baseline PET/CT parameters can predict treatment response and prognosis in elderly HL. We retrospectively included 123 patients who underwent baseline 18F-FDG-PET/CT and end of treatment PET/CT scans. The PET images were analyzed visually and semi-quantitatively by measuring the lesion to liver SUVmax ratio (L-L SUV R), lesion to blood-pool SUVmax ratio (L-BP SUV R), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Survival curves were plotted according to the Kaplan-Meier method. At a median follow-up of 40 months, the median PFS and OS were 29 and 37 months. L-BP SUV R, L-L SUV R, MTV, and TLG were significantly higher in patients with no complete response compared with complete response group at end of treatment. Moreover, these parameters were demonstrated to be independent prognostic factors for PFS together with tumor stage, while only L-L SUV R and L-BP SUV R for OS. End of treatment PET/CT results using Deauville criteria were significantly correlated with outcome survival. End of treatment PET/CT results (using Deauville criteria) and semiquantitative baseline PET/CT parameters were significantly correlated with response to treatment and long-term outcome.

We analyzed safety of NEPA (netupitant/palonosetron) and dexamethasone (NEPA+DEX) for the management of chemotherapy-induced nausea and vomiting (CINV) in classical Hodgkin's lymphoma patients that experienced CINV with a prophylaxis with palonosetron (PALO + DEX). In a retrospective, monocentric, noncomparative study, we analyzed adverse events and CINV grading in patients who switched from PALO + DEX to NEPA + DEX. Among 32 patients treated with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) during the study period, 47% did not properly control CINV with PALO + DEX and were shifted to NEPA + DEX. Among these, 53.3% properly controlled CINV is for all the remaining chemotherapy cycles. We did not observe an increase of adverse events after switching to NEPA. In our study, NEPA did not show drug-drug interaction with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy agents and NEPA administration was well tolerated with mild and transient adverse events., Competing Interests: Financial & competing interests disclosure VR Zilioli has acted as an advisor for Janssen and MSD, and received honoraria from Italfarmaco SpA and Roche. P Codega is an employee of Italfarmaco SpA. C Rusconi acted as an advisor for Roche, Takeda, Celgene and Italfarmaco SpA and received a research grant from Celgene. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2020 Vittorio Ruggero Zilioli.)

14-3-3 proteins are a family of conserved proteins present in eukaryotes as several isoforms, playing a regulatory role in many cellular and physiological processes. In plants, 14-3-3 proteins have been reported to be involved in the response to stress conditions, such as drought, salt and cold. In the present study, 14-3-3ε and 14-3-3ω isoforms, which were representative of ε and non-ε phylogenetic groups, were overexpressed in Arabidopsis thaliana plants; the effect of their overexpression was investigated on H + -ATPase activation and plant response to cold stress. Results demonstrated that H + -ATPase activity was increased in 14-3-3ω-overexpressing plants, whereas overexpression of both 14-3-3 isoforms brought about cold stress tolerance, which was evaluated through ion leakage, lipid peroxidation, osmolyte synthesis, and ROS production assays. A dedicated tandem mass tag (TMT)-based proteomic analysis demonstrated that different proteins involved in the plant response to cold or oxidative stress were over-represented in 14-3-3ε-overexpressing plants., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the need for information in patients with abdominal neoplasms., Methods: The sample consisted of 100 patients hospitalized in a surgical ward for patients with abdominal neoplasms at the National Institute of Cancer José de Alencar Gomes da Silva / INCA, in the period between June and December 2016. To collect the data, the Brazilian Portuguese version of the European Organization for Research and Treatment of Cancer (EORTC) information module questionnaire (QLQ-INFO25) was used., Results: In general, for most items, the patients showed satisfaction with the amount of information received. The items referring to the disease, examinations, treatment and general information stand out, with an average score of more than 80%. For some items, however, there is dissatisfaction with the amount of information received, especially those related to the cause of the disease, aspects of out-of-hospital and home care, different places of care and aspects of self-help, with a satisfaction level of less than 40., Conclusions: Despite the high level of satisfaction with the information received, it was observed that almost all patients would like more information, which makes us recommend that, as part of the care, the information offered to these patients about the treatment and the evolutionary process of the disease should be enhanced., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Universidad de Antioquia.)

Low temperature is an environmental stress that greatly influences plant performance and distribution. Plants exposed to cold stress exhibit modifications of plasma membrane physical properties that can affect their functionality. Here it is reported the effect of low temperature exposure of Arabidopsis plants on the activity of phospholipase D and H + -ATPase, the master enzyme located at the plasma membrane. The H + -ATPase activity was differently affected, depending on the length of cold stress imposed. In particular, an exposure to 4 °C for 6 h determined the strong inhibition of the H + -ATPase activity, that correlates with a reduced association with the regulatory 14-3-3 proteins. A longer exposure first caused the full recovery of the enzymatic activity followed by a significant activation, in accordance with both the increased association with 14-3-3 proteins and induction of H + -ATPase gene transcription. Different time lengths of cold stress treatment were also shown to strongly stimulate the phospholipase D activity and affect the phosphatidic acid levels of the plasma membranes. Our results suggest a functional correlation between the activity of phospholipase D and H + -ATPase mediated by phosphatidic acid release during the cold stress response., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)