A Multimodal Knowledge-Based Deep Learning Approach for MGMT Promoter Methylation Identification

Glioblastoma Multiforme (GBM) is considered one of the most aggressive malignant tumors, characterized by a tremendously low survival rate. Despite alkylating chemotherapy being typically adopted to fight this tumor, it is known that O(6)-methylguanine-DNA methyltransferase (MGMT) enzyme repair abilities can antagonize the cytotoxic effects of alkylating agents, strongly limiting tumor cell destruction. However, it has been observed that MGMT promoter regions may be subject to methylation, a biological process preventing MGMT enzymes from removing the alkyl agents. As a consequence, the presence of the methylation process in GBM patients can be considered a predictive biomarker of response to therapy and a prognosis factor. Unfortunately, identifying signs of methylation is a non-trivial matter, often requiring expensive, time-consuming, and invasive procedures. In this work, we propose to face MGMT promoter methylation identification analyzing Magnetic Resonance Imaging (MRI) data using a Deep Learning (DL) based approach. In particular, we propose a Convolutional Neural Network (CNN) operating on suspicious regions on the FLAIR series, pre-selected through an unsupervised Knowledge-Based filter leveraging both FLAIR and T1-weighted series. The experiments, run on two different publicly available datasets, show that the proposed approach can obtain results comparable to (and in some cases better than) the considered competitor approach while consisting of less than 0.29% of its parameters. Finally, we perform an eXplainable AI (XAI) analysis to take a little step further toward the clinical usability of a DL-based approach for MGMT promoter detection in brain MRI

An Edge-Based Architecture to Support Efficient Applications for Healthcare Industry 4.0

Edge computing paradigm has attracted many interests in the last few years as a valid alternative to the standard cloud-based approaches to reduce the interaction timing and the huge amount of data coming from Internet of Things (IoT) devices toward the Internet. In the next future, Edge-based approaches will be essential to support time-dependent applications in the Industry 4.0 context; thus, the paper proposes BodyEdge, a novel architecture well suited for human-centric applications, in the context of the emerging healthcare industry. It consists of a tiny mobile client module and a performing edge gateway supporting multiradio and multitechnology communication to collect and locally process data coming from different scenarios; moreover, it also exploits the facilities made available from both private and public cloud platforms to guarantee a high flexibility, robustness, and adaptive service level. The advantages of the designed software platform have been evaluated in terms of reduced transmitted data and processing time through a real implementation on different hardware platforms. The conducted study also highlighted the network conditions (data load and processing delay) in which BodyEdge is a valid and inexpensive solution for healthcare application scenarios

Influence of diabetes mellitus on inflammatory bowel disease course and treatment outcomes. A systematic review with meta-analysis

Diabetes Mellitus (DM) may occur in IBD and influence the disease progression

Role of Diacylglycerol Kinases in Acute Myeloid Leukemia

: Diacylglycerol kinases (DGKs) play dual roles in cell transformation and immunosurveillance. According to cancer expression databases, acute myeloid leukemia (AML) exhibits significant overexpression of multiple DGK isoforms, including DGKA, DGKD and DGKG, without a precise correlation with specific AML subtypes. In the TGCA database, high DGKA expression negatively correlates with survival, while high DGKG expression is associated with a more favorable prognosis. DGKA and DGKG also feature different patterns of co-expressed genes. Conversely, the BeatAML and TARGET databases show that high DGKH expression is correlated with shorter survival. To assess the suitability of DGKs as therapeutic targets, we treated HL-60 and HEL cells with DGK inhibitors and compared cell growth and survival with those of untransformed lymphocytes. We observed a specific sensitivity to R59022 and R59949, two poorly selective inhibitors, which promoted cytotoxicity and cell accumulation in the S phase in both cell lines. Conversely, the DGKA-specific inhibitors CU-3 and AMB639752 showed poor efficacy. These findings underscore the pivotal and isoform-specific involvement of DGKs in AML, offering a promising pathway for the identification of potential therapeutic targets. Notably, the DGKA and DGKH isoforms emerge as relevant players in AML pathogenesis, albeit DGKA inhibition alone seems insufficient to impair AML cell viability

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

BNT162b2 mRNA COVID-19 vaccine is safe in a setting of patients on biologic therapy with inflammatory bowel diseases: a monocentric real-life study

Objectives Patients with inflammatory bowel disease were excluded from trials that led to the approval of anti-COVID-19 vaccines and are worthy of real-life studies providing information on the safety of these vaccines in this clinical setting. Methods A prospective observational study was performed to estimate BNT162b2 mRNA COVID-19 Vaccine local and systemic adverse events (AEs) incidence related to administration in patients with inflammatory bowel disease through a questionnaire administered at the first, second, and third doses. Disease activity by Mayo Partial Score and Harvey-Bradshaw Index was also evaluated. Results Eighty patients with a median age of 47.5 years were initially enrolled. The local AEs rate was 26.25%, 58.75%, and 28.37% at the first, second, and third doses of the vaccine, respectively. In contrast, the systemic AEs rate was 52.2%, 48.75%, and 43.24%. Clinic-demographic predictor variables for AEs were not identified. Vaccination did not affect disease activity and no statistically significant difference in disease activity index scores was observed between the three doses. No serious adverse events were observed. Conclusion This vaccine was safe in a population of patients with inflammatory bowel disease and, therefore, could be safely administered in this clinical setting

Correction to: Evaluation of the reliability and validity of the Italian version of the schema mode inventory for eating disorders-short form for adults with dysfunctional eating behaviors

The article Evaluation of the reliability and validity of the Italian version

p53 codon 72 alleles influence the response to anticancer drugs in cells from aged people by regulating the cell cycle inhibitor p21WAF1.

A common polymorphism at codon 72 in p53 gene leads to an arginine to proline aminoacidic substitution which affects in an age-dependent manner the susceptibility of cells to undergo apoptosis after oxidative stress. Here we report that dermal fibroblasts from Proline allele carriers (Pro+) display a higher expression of p21WAF1 gene, in both basal conditions and after treatment with doxorubicin and camptothecin. This phenomenon is accompanied by a lower susceptibility of Pro+ cells to undergo apoptosis, a lower capability to over cross G1-S transition and an increased propensity to express markers of cell senescence, with respect to fibroblasts from Arginine homozygotes (Pro-). All these phenomena are particularly evident in cells from centenarians. We conclude that the functional difference between the two p53 codon 72 alleles exerts a broadimpact on the capability of cell from aged people to respond to stressors such as cytotoxic drugs

Evaluation of the reliability and validity of the Italian version of the schema mode inventory for eating disorders: short form for adult with dysfunctional eating behavior

Purpose: To examine the psychometric properties and the factorial structure of the Italian version of the schema mode inventory for eating disorders\u2014short form (SMI-ED-SF) for adults with dysfunctional eating patterns. Methods: 649 participants (72.1% females) completed the 64-item Italian version of the SMI-ED-SF and the eating disorder examination questionnaire (EDE-Q) for measuring eating disorder symptoms. Psychometric testing included confirmatory factor analysis (CFA) and internal consistency. Multivariate analysis of covariance (MANCOVA) was also run to test statistical differences between the EDE-Q subscales on the SMI-ED-SF modes, while controlling for possible confounding variables. Results: Factorial analysis confirmed the 16-factors structure for the SMI-ED-SF [S\u2013B\u3c7 2 (1832) = 3324.799; p <.001; RMSEA = 0.045; 90% CI 0.043\u20130.048; CFI = 0.880; SRMR = 0.066; \u3c7 2/df = 1.81; < 3]. Internal consistency was acceptable in all scales, with Cronbach\u2019s Alpha coefficients ranging from 0.635 to 0.873. Conclusions: The SMI-ED-SF represents a reliable and valid alternative to the long-form SMI-ED for assessment and conceptualization of schema modes in Italian adults with disordered eating habits. Its use is recommended for clinical and research purposes. Level of evidence: Level V, descriptive study