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The endonuclease MCPIP1 protects against liver cancer development in a sex-dependent manner by modulating β-catenin and CREB1
No full textBackground & Aims: Monocyte chemoattractant protein-induced protein 1 (MCPIP1), encoded by ZC3H12A, is a negative regulator of inflammation and tumorigenesis. While its role has been implicated in various cancers, the function of MCPIP1 in hepatocellular carcinoma (HCC) remains poorly understood. This study explored the contribution of hepatocyte-specific MCPIP1 loss to HCC pathogenesis, highlighting its role in overcoming the inherent tumor resistance observed in female mice. Methods: Liver tissues (N≥5 per group) and primary hepatocytes (N≥3 per group) were evaluated using Western blot, immunohistochemistry, immunofluorescence, RNA-seq and pathway enrichment analysis. The expression levels of MCPIP1 in HCC were measured by qRT-PCR. The results are presented as mean ± SD, student's t or Mann-Whitney U tests were used for statistical analysis of two groups. For more than two groups, ordinary two-way ANOVA was used. Results: The hepatocyte-specific loss of MCPIP1 markedly promoted fibrosis and tumorigenesis, particularly in female mice, disrupting the normal sex-related protection observed in the diethylnitrosamine (DEN) model. As determined by next-generation sequencing and bioinformatics analysis, oncogenic and fibrotic programs, including the EMT, Wnt/β-catenin, and JAK/STAT3 pathways, were activated in MCPIP1 knockout livers. These molecular events activated β-catenin, c-Met, and IL-6/STAT3/NFκB signaling, and they enhanced fibrotic remodeling. In MCPIP1-deficient hepatocytes, active β-catenin and CREB1 accumulated in the nucleus, and the expression of protumorigenic targets, such as Spp1, Tgfb2, and Adam17 increased. Moreover, MCPIP1 expression was significantly downregulated in human HCC tissues and correlated with tumor progression. Conclusions: MCPIP1 plays a protective role against inflammation-driven hepatocarcinogenesis, particularly in females, by restraining fibrotic remodeling and oncogenic signaling. The downregulation of MCPIP1 expression promotes a tumor-promoting microenvironment through the coordinated activation of the β-catenin, STAT3, and CREB1 pathways
Evaluation of the CorPath-GRX technIQ automated movements during robotic-PCI (NAVIGATE GRX study)
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No full textThe career of the term resilience has been remarkable in the global political arena of the last two decades. This introductory chapter delves into genealogies of resilience within security studies and crisis research, showing how it assumed different modes and interpretations within academic literature. At the same time, it discusses the main points of criticism, indicating that, without deeper contextual analyses of specific (national) cases, the debate on sources, characteristics, and consequences of resilience is incomplete. The chapter also introduces a comparative and multidisciplinary approach used to examine Polish, German, and Ukrainian national security strategies, policy documents, and case studies to explore the concept’s diverse interpretations and applications within these three countries. Ultimately, it shows the importance of expanding the existing resilience literature by exploring perspectives from a region often overlooked in the debate
Hardware-agnostic framework for general-purpose data acquisition systems
No full textModern data acquisition systems in physics experiments of various scales rely heavily on precise time synchronization of electronic components used for digitizing analog signals generated by detectors. Scientific collaborations often develop custom, in-house solutions designed for particular use cases that form ecosystems of compatible hardware platforms, protocols, and standards. In this work, we present and evaluate a set of gateware and software components that enable the implementation of complete data acquisition systems with synchronization, data transport, and control functionalities over multi-gigabit transceivers. The components can be organized to form a logical system structure, including the master, data concentrators, and endpoint modules, on virtually any hardware platform equipped with a Field-Programmable Gate Array with an exposed transceiver. The system allows for a rapid deployment of complete measurement systems with facilitated integration of new elements on both commercially available and custom-designed platforms
Beyond video-EEG : identifying functional/dissociative seizures through clinical assessment
No full textPredictive impact of the behavior of the Carhart's notch after stapedotomy on speech audiometry parameters
No full text<b>Introduction:</b> Stapedotomy improves air conduction thresholds and restores one of the components of bone conduction (BC): sound transmission to the inner ear via vibrations of the ossicular chain. This results in a measurable improvement in BC thresholds. Audiometric confirmation of pseudoperceptual hearing loss is the loss of the Carhart's notch (CN) observed after surgery. Sensorineural hearing loss is characterized by varying degrees of speech incomprehension impairment, particularly clinically apparent when the impairment affects frequencies essential for communication. <br><br><b>Aim:</b> The aim of the study was to analyze the influence of the occurrence and behavior of the CN on selected speech audiometry parameters after stapedotomy in patients with otosclerosis. <br><br><b>Materials and methods:</b> A retrospective analysis of 116 patients undergoing otosclerosis surgery between 2016 and 2019 was conducted. Patients were divided into groups based on the presence of a CN in the operated ear, based on pure-tone audiometry (PTA) performed preoperatively and during postoperative follow-up after 2–3 years of stapedotomy. Speech audiometry analysis considered changes in speech detection threshold (SDT), speech reception threshold (SRT), and speech discrimination threshold. <br><br><b>Results:</b> In the group of patients who did not have a CN on PTA preoperatively, improving mean BC threshold values after stapedotomy had a beneficial effect on SDT improvement. This association was not confirmed when assessing the effect of mean BC values on SRT. More profound sensorineural hearing loss in the preoperative assessment was associated with poorer SDT, SRT, and speech discrimination threshold in the absence of a CN on PTA. In the group of patients who had a CN on PTA preoperatively, a strong correlation was found between CN disappearance and improvement in SDT and SRT after surgery. A persistent CN after surgery proved to be an unfavorable prognostic factor for improvement in speech audiometry parameters. <br><br><b>Conclusions:</b> 1. The disappearance of the preoperatively observed CN after stapedotomy is a significant prognostic factor for improving the SDT and speech reception threshold; 2. A CN persisting after surgical treatment is an unfavorable factor in improving speech audiometry parameters; 3. Profound sensorineural hearing loss in the absence of the CN in the preoperative assessment is an unfavorable factor in improving the SRT, SDT and speech discrimination threshold; 4. Improvement of mean BC threshold values after stapedotomy, regardless of the preservation of the CN, has a beneficial effect on the improvement of SDT but not on SRT (the study showed that the improvement of SRT correlates with CN disappearing).</ns3:p
A dyadic perspective on ADHD : adolescent–parent reports of behavioural problems and family functioning
No full textDiagnosing behavioural problems in adolescents often relies on subjective reports from parents or caregivers. Systemic theory emphasizes the need for multiple perspectives, including those of the adolescent. This study examined the alignment between adolescents' and parents' perceptions of behavioural problems in ADHD and non‐ADHD groups and explored how family cohesion and flexibility explain the severity of externalizing and internalizing behaviours from both perspectives. Participants included 214 adolescents diagnosed with ADHD and their parents (adolescents: Mage = 11.24, SD = 0.91, 75.23% boys; parents: Mage = 41.92, SD = 6.43, 84.11% mothers) and 514 adolescents without ADHD and their parents (adolescents: Mage = 11.34, SD = 0.75, 51.56% boys; parents: Mage = 42.29, SD = 5.58, 87.55% mothers), from 18 cities in southern Poland. The variables were measured using the ASEBA instruments (Child Behaviour Checklist, Youth Self Report) and the Family Adaptation and Cohesion Evaluation Scales. Data were analysed using Actor–Partner Interdependence Models to examine actor and partner associations within adolescent–parent dyads. More boys were diagnosed with ADHD, showing slightly more externalizing problems than girls. Lower family flexibility predicted externalizing behaviours, with parent‐rated flexibility linked to parent‐rated behaviours, and adolescent‐rated flexibility linked to adolescent‐rated behaviours. Adolescent‐rated family cohesion rated by adolescents predicted fewer externalizing behaviours as reported by parents in the ADHD group and by adolescents in the non‐ADHD group. Internalizing behaviours were linked to family flexibility and cohesion, regardless of the actor (adolescent or parent). The predominance of actor effects indicates that each informant's perception of family functioning is uniquely linked to their own reports of symptoms; given only moderate parent‐adolescent agreement, these perspectives appear complementary rather than redundant. Assessing behavioural problems requires data from both parents and adolescents, as family cohesion and flexibility significantly impact adolescent functioning