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Adrenomedullin has emerged as a promising biomarker in the field of viral diseases. Numerous studies have demonstrated its potential in assessing disease severity, predicting clinical outcomes, and monitoring treatment response. Adrenomedullin (AM) is a multifaceted peptide implicated in vasodilation, hormone secretion, antimicrobial defense, cellular growth, angiogenesis, and, importantly, chronic pain. AM and related peptides interface with cytoskeletal proteins within neuronal contexts, influencing microtubule dynamics. AM has primarily been utilized in diagnosing diseases of bacterial origin, including sepsis. Nevertheless, there are reports suggesting its utility in diseases of viral origin, and this is the focus of the present study. Furthermore, adrenomedullin has been shown to be elevated in various viral infections, suggesting its role in immune response modulation. Furthermore, AM may contribute to neuronal dysfunction through mechanisms involving immune and inflammatory responses, apoptosis, and disruptions in calcium homeostasis. This review aims to consolidate current knowledge regarding AM and its potential implications in viral diseases, elucidating its diverse roles in neurological pathophysiology. This review highlights the growing importance of adrenomedullin as a biomarker in viral diseases and the need for further functional studies to understand the underlying mechanisms involved. [ABSTRACT FROM AUTHOR]

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Background: Algorithmic decision-making (ADM) utilises algorithms to collect and process data and develop models to make or support decisions. Advances in artificial intelligence (AI) have led to the development of support systems that can be superior to medical professionals without AI support in certain tasks. However, whether patients can benefit from this remains unclear. The aim of this systematic review is to assess the current evidence on patient-relevant benefits and harms, such as improved survival rates and reduced treatment-related complications, when healthcare professionals use ADM systems (developed using or working with AI) compared to healthcare professionals without AI-related ADM (standard care)—regardless of the clinical issues. Methods: Following the PRISMA statement, MEDLINE and PubMed (via PubMed), Embase (via Elsevier) and IEEE Xplore will be searched using English free text terms in title/abstract, Medical Subject Headings (MeSH) terms and Embase Subject Headings (Emtree fields). Additional studies will be identified by contacting authors of included studies and through reference lists of included studies. Grey literature searches will be conducted in Google Scholar. Risk of bias will be assessed by using Cochrane's RoB 2 for randomised trials and ROBINS-I for non-randomised trials. Transparent reporting of the included studies will be assessed using the CONSORT-AI extension statement. Two researchers will screen, assess and extract from the studies independently, with a third in case of conflicts that cannot be resolved by discussion. Discussion: It is expected that there will be a substantial shortage of suitable studies that compare healthcare professionals with and without ADM systems concerning patient-relevant endpoints. This can be attributed to the prioritisation of technical quality criteria and, in some cases, clinical parameters over patient-relevant endpoints in the development of study designs. Furthermore, it is anticipated that a significant portion of the identified studies will exhibit relatively poor methodological quality and provide only limited generalisable results. Systematic review registration: This study is registered within PROSPERO (CRD42023412156). [ABSTRACT FROM AUTHOR]

Abstract Background Algorithmic decision-making (ADM) utilises algorithms to collect and process data and develop models to make or support decisions. Advances in artificial intelligence (AI) have led to the development of support systems that can be superior to medical professionals without AI support in certain tasks. However, whether patients can benefit from this remains unclear. The aim of this systematic review is to assess the current evidence on patient-relevant benefits and harms, such as improved survival rates and reduced treatment-related complications, when healthcare professionals use ADM systems (developed using or working with AI) compared to healthcare professionals without AI-related ADM (standard care)—regardless of the clinical issues. Methods Following the PRISMA statement, MEDLINE and PubMed (via PubMed), Embase (via Elsevier) and IEEE Xplore will be searched using English free text terms in title/abstract, Medical Subject Headings (MeSH) terms and Embase Subject Headings (Emtree fields). Additional studies will be identified by contacting authors of included studies and through reference lists of included studies. Grey literature searches will be conducted in Google Scholar. Risk of bias will be assessed by using Cochrane’s RoB 2 for randomised trials and ROBINS-I for non-randomised trials. Transparent reporting of the included studies will be assessed using the CONSORT-AI extension statement. Two researchers will screen, assess and extract from the studies independently, with a third in case of conflicts that cannot be resolved by discussion. Discussion It is expected that there will be a substantial shortage of suitable studies that compare healthcare professionals with and without ADM systems concerning patient-relevant endpoints. This can be attributed to the prioritisation of technical quality criteria and, in some cases, clinical parameters over patient-relevant endpoints in the development of study designs. Furthermore, it is anticipated that a significant portion of the identified studies will exhibit relatively poor methodological quality and provide only limited generalisable results. Systematic review registration This study is registered within PROSPERO (CRD42023412156).

This paper investigates the squeezing action of hybridized nanofluid flow that takes place in the mechanism of truck brakes, dampers, polymer manufacturing, power transportation, oiling structure, and food production. The modeling technique relied on a set of partial differential equations to direct the fluid, taking into consideration external factors like the magnetized force and the time-dependent source of heat and thermal radiation. The hybridized nanofluid consists of copper and aluminum oxide nanoparticles that are dispersed in the machine oil. Entropic thermodynamic analysis is also examined to evaluate its role in the thermal examination of the system. The optimal homotopy asymptotic and Adomian decomposition methods were used to solve the problem. The study examined the changes in the rate of entropy formation and the characteristics of fluid velocities, heat transference rate, and performance based on the kind and concentration of nanoparticles and external thermal impacts. The results are presented in many key components, including a notable 30% increase in heat conductivity when using a combination of nanoparticles. The use of hybridized nanofluids manages to reduce surface frictional force, whereas the employment of a combination of particles results in an increase in friction owing to the heightened viscosity of the mixture. [ABSTRACT FROM AUTHOR]

Background: Two-stages pre-pectoral breast reconstruction may confer advantages over direct to implant (DTI) and subpectoral reconstruction in selected patients who have no indication for autologous reconstruction. The primary endpoint of the study was to evaluate and compare the incidence of capsular contracture in the pre-pectoral two-stages technique versus the direct to implant technique. Complications related to the two surgical techniques and patient satisfaction were also evaluated. Methods: A retrospective review of 45 two stages and 45 Direct-to-implant, DTI patients was completed. Acellular dermal matrix was used in all patients. An evaluation of anthropometric and clinical parameters, surgical procedures and complications was conducted. Minimum follow-up was 12 months after placement of the definitive implant. Results: There was no statistically significant difference in the rate of capsular contracture in the two groups. Rippling occurred more in DTI reconstruction. In the two-stages reconstruction, lipofilling was applied more often and there was a higher incidence of seroma. Patient satisfaction extrapolated from the Breast Q questionnaire was better for patients submitted to two-stage implant-based breast reconstruction. Conclusion: Dual-stage pre-pectoral reconstruction with acellular dermal matrix appears to be a good reconstructive solution in patients with relative contraindications for one-stage heterologous reconstruction with definitive prosthesis and no desire for autologous reconstruction. [ABSTRACT FROM AUTHOR]

Breast reconstruction following mastectomy plays a vital role in many individuals’ recovery, symbolizing a shift from loss back to wholeness. Yet, this path can be complex, particularly in instances involving complicating factors such as radiotherapy and significant breast size. In such scenarios, often viewed as suboptimal for implant-based breast reconstruction, prioritizing the patient’s preferences is crucial. This article showcases the experience of a 50-year-old Caucasian woman who came to our department with a breast lump, later diagnosed as invasive mammary carcinoma of no specific type (NST) via percutaneous biopsy. Post a radical mastectomy of the left breast, left axillary lymphadenectomy and the placement of an expander beneath the pectoralis major muscle, she underwent radiotherapy following the tumor board’s advice due to positive lymph nodes. Patient opted not to have autologous breast reconstruction and we proceeded with the second phase, exchanging the expander for a breast implant and adding Acellular Dermal Matrix (ADM) in the infero-lateral pole of the breast for essential support and stability. Despite the challenges faced, our case successfully illustrates that with careful surgical planning and a patient diligently following postoperative care, implant-based breast reconstruction with ADM’s support can be effectively and safely achieved, even in less-than-ideal situations, fulfilling patient expectations. [ABSTRACT FROM AUTHOR]

The present manuscript proposes different modification procedures for the standard Adomian Decomposition Method (ADM). These procedures are based on the application of orthogonal polynomials that play vital parts in approximation theories. Moreover, the study also scrutinizes four nonlinear inhomogeneous initial-value problems, and distinctively examines their respective absolute error differences. Remarkably, different computational benefits of the proposed modification are noted with regard high-level of accuracy and fewer computational steps. [ABSTRACT FROM AUTHOR]

In this paper, the characteristics of absolute value memristors are verified through the circuit implementation and construction of a chaotic system with a conditional symmetric fractional-order memristor. The dynamic behavior of fractional-order memristor systems is explored using fractional-order calculus theory and the Adomian Decomposition Method (ADM). Concurrently, the investigation probes into the existence of coexisting symmetric attractors, multiple coexisting bifurcation diagrams, and Lyapunov exponent spectra (LEs) utilizing system parameters as variables. Additionally, the system demonstrates an intriguing phenomenon known as offset boosting, where the embedding of an offset can adjust the position and size of the system's attractors. To ensure the practical applicability of these findings, a fractional-order sliding mode synchronization control scheme, inspired by integer-order sliding mode theory, is designed. The rationality and feasibility of this scheme are validated through a theoretical analysis and numerical simulation. [ABSTRACT FROM AUTHOR]

The concept of „automated decision making” (ADM) is currently a key vector reshaping industries in the era of technology-based decision making, and the use of artificial intelligence (AI) in this process is a hot topic worldwide with the adoption of generative AI tools like ChatGPT. ADM enables companies to use technology for tasks that were not long ago the domain of human judgment. AI is essential in financial services, such as credit worthiness assessment, automated investment advice (often called robo-advice) or insurance. The regulation of activities related to ADM is contained in various acts and regulations, including the Sale of Goods Directive 2019/771, the Digital Contracts Directives 2019/770 and the EU General Regulation on Data Protection. However, these directives do not contain special rules for new technologies such as Artificial Intelligence (AI). Although recently, the EU has moved forward with regulations on product liability laws affecting digital products and services, with the EU Data Act, the EU Cyber Resilience Act and the highly publicized EU AI Act - regulations with a transition period of two years for compliance, the speed with which in practice the ADM tools are developed and trained make the legislative efforts slow and incomprehensible. In light of this issue, this article explores the relationship between AI, ADM and discusses whether existing EU consumer law is equipped to deal with situations where AI systems are either used for internal purposes by companies or offered to consumers as the main subject of the contract. The paper will reveal a number of gaps in current EU consumer law and briefly discuss future legislation. This article also reviews the efficiency of key EU consumer law directives for the conclusion of contracts with consumers through the use of AI, with recommendations for clarifications and additions to improve the use of ADM.

Pancreatic ductal adenocarcinoma (PDAC) can originate from acinar-to-ductal metaplasia (ADM). Pancreatic acini harboring oncogenic Kras mutations are transdifferentiated to a duct-like phenotype that further progresses to become pancreatic intraepithelial neoplasia (PanIN) lesions, giving rise to PDAC. Although ADM formation is frequently observed in KrasG12D transgenic mouse models of PDAC, the exact mechanisms of how oncogenic KrasG12D regulates this process remain an enigma. Herein, we revealed a new downstream target of oncogenic Kras, cytokine CCL9, during ADM formation. Higher levels of CCL9 and its receptors, CCR1 and CCR3, were detected in ADM regions of the pancreas in p48cre:KrasG12D mice and human PDAC patients. Knockdown of CCL9 in KrasG12D-expressed pancreatic acini reduced KrasG12D-induced ADM in a 3D organoid culture system. Moreover, exogenously added recombinant CCL9 and overexpression of CCL9 in primary pancreatic acini induced pancreatic ADM. We also showed that, functioning as a downstream target of KrasG12D, CCL9 promoted pancreatic ADM through upregulation of the intracellular levels of reactive oxygen species (ROS) and metalloproteinases (MMPs), including MMP14, MMP3 and MMP2. Blockade of MMPs via its generic inhibitor GM6001 or knockdown of specific MMP such as MMP14 and MMP3 decreased CCL9-induced pancreatic ADM. In p48cre:KrasG12D transgenic mice, blockade of CCL9 through its specific neutralizing antibody attenuated pancreatic ADM structures and PanIN lesion formation. Furthermore, it also diminished infiltrating macrophages and expression of MMP14, MMP3 and MMP2 in the ADM areas. Altogether, our results provide novel mechanistic insight into how oncogenic Kras enhances pancreatic ADM through its new downstream target molecule, CCL9, to initiate PDAC. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is an incurable malignant plasma cell disorder characterized by the infiltration of clonal plasma cells in the bone marrow compartment. Gene Expression Profiling (GEP) has emerged as a powerful investigation tool in modern myeloma research enabling the dissection of the molecular background of MM and allowing the identification of gene products that could potentially serve as targets for therapeutic intervention. In this study we investigated shared transcriptomic abnormalities across newly diagnosed multiple myeloma (NDMM) patient cohorts. In total, publicly available transcriptomic data of 7 studies from CD138+ cells from 281 NDMM patients and 44 healthy individuals were integrated and analyzed. Overall, we identified 28 genes that were consistently differentially expressed (DE) between NDMM patients and healthy donors (HD) across various studies. Of those, 9 genes were over/under-expressed in more than 75% of NDMM patients. In addition, we identified 4 genes (MT1F, PURPL, LINC01239 and LINC01480) that were not previously considered to participate in MM pathogenesis. Meanwhile, by mining three drug databases (ChEMBL, IUPHAR/BPS and DrugBank) we identified 31 FDA-approved and 144 experimental drugs that target 8 of these 28 over/underexpressed MM genes. Taken together, our study offers new insights in MM pathogenesis and importantly, it reveals potential new treatment options that need to be further investigated in future studies. [ABSTRACT FROM AUTHOR]

Ternary hybrid nanoparticles require infected blood cell base fluid flow. Blood vessels feature ciliated walls and peristaltic waves. Anemia comes from cancer treatment-induced red blood cell destruction. This study reproduces Jeffrey model blood flow through a ciliary peristaltic artery using ternary hybrid nanoparticles of gold, iron oxide, and copper. This work examines ternary hybrid nanofluid MHD ciliary peristaltic motion using Jeffrey curves. A nonlinear PDE system has heat and induced magnetic force equations. The Adomian Decomposition Method solved this system without long-wavelength approximation. Visualize how essential biological and physical elements affect velocity, temperature, trapping, magnetic force contours, induced magnetic field components, axial pressure, and normal pressure. Flow, temperature, magnetic features, and other important properties are plotted and discussed against biological and biomedical parameters. We discovered full consistency with modest scenario efforts. The increase in nanoparticles gives ternary hybrid nanofluid a larger friction force than hybrid, so its axial pressure gradient at the wall is stronger, decays at hybrid, decays further from nanofluid to base fluid, and reverses at the intermediate area. Peristaltic ciliary activity alters magnetic force contours, shrinks loops, and forms four contour groups with different implications. [ABSTRACT FROM AUTHOR]

The present manuscript proposes a computational approach to efficiently tackle a class of two-point boundary value problems that features third-order nonlinear ordinary differential equations. Specifically, this approach is based upon a combination of the shooting method with a modification of the renowned Adomian decomposition method. The approach starts by transforming the governing BVP into two appropriate initial-value problems, and thereafter, solves the resulting IVPs recurrently. In addition, the application of this method to varied test models remains feasible—of course, this is supported by the competing Runge–Kutta method, among others, and reported through comparison plots and tables. [ABSTRACT FROM AUTHOR]

Research suggests that people prefer human over algorithmic decision-makers at work. Most of these studies, however, use hypothetical scenarios and it is unclear whether such results replicate in more realistic contexts. We conducted two between-subjects studies (N=270; N=183) in which the decision-maker (human vs. algorithmic, Study 1 and 2), explanations regarding the decision- process (yes vs. no, Study 1 and 2), and the type of selection test (requiring human vs. mechanical skills for evaluation, Study 2) were manipulated. While Study 1 was based on a hypothetical scenario, participants in pre-registered Study 2 volunteered to participate in a qualifying session for an attractively remunerated product test, thus competing for real incentives. In both studies, participants in the human condition reported higher levels of trust and acceptance. Providing explanations also positively influenced trust, acceptance, and perceived transparency in Study 1, while it did not exert any effect in Study 2. Type of the selection test affected fairness ratings, with higher ratings for tests requiring human vs. mechanical skills for evaluation. Results show that algorithmic decision-making in personnel selection can negatively impact trust and acceptance both in studies with hypothetical scenarios as well as studies with real incentives. [ABSTRACT FROM AUTHOR]

Background: Distal lower extremity reconstruction is challenging. This study aims to propose a protocol for the treatment of traumatic soft tissue defects. The key concept is to combine the surgical armamentarium of the reconstructive surgeon with the advantages provided by hyperbaric oxygen therapy. Methods: This retrospective study analyzed data of 57 patients affected with unilateral or bilateral lower extremity trauma distal to the knee and involving soft tissues with no indication of immediate reconstruction between 2010 and 2021. Before the reconstructive procedure, all the patients underwent a stick swab procedure for the collection of microbiological samples and debridement. Patients were divided into two treatment groups and only one group underwent a combined therapeutic procedure with hyperbaric oxygen therapy. Negative pressure wound therapy (NPWT) was employed only if deemed necessary according to the defect's depth and wound exudate. Surgical techniques, outcomes, and complications were discussed. Results: All patients achieved a complete recovery with no major complications and only minor complications observed. The study group treated with HBOT had a lower complication rate and lower percentages of minimal and partial graft loss compared with the same complications observed in the control group. No patients experienced HBOT-related complications. Significant reductions in the time to complete healing and the time from reconstruction to healing were found (p = 0.002 and p < 0.00001, respectively). Conclusions: A lower complication rate was observed in the group treated with HBOT. The administration of HBOT prior to soft tissue reconstruction significantly reduced the time to complete healing and the time interval from skin grafting to healing. However, prospective studies and randomized trials with larger cohorts should be designed to investigate the efficacy of HBOT for the treatment of lower extremity injuries with extensive soft tissue defects. [ABSTRACT FROM AUTHOR]

The investigation detailed in this paper explores the behavior of a slippery nanofluid flowing over a permeable stretched sheet under the influence of magnetohydrodynamic forces, considering factors like thermal radiation, viscous dissipation, and convective boundary conditions. The analysis systematically establishes principles for conserving mass, heat, momentum, and nanoparticle concentration, deriving a set of nonlinear ordinary differential equations from the governing partial differential equations. To tackle these challenges, the Adomian decomposition approach is utilized as a central element of the solution methodology. Graphical representations are employed to depict the solutions across various physical parameters. Despite the significance of nanofluids in both industrial and scientific contexts, there exists a noticeable research gap concerning the combined impacts of thermal radiation, viscous dissipation, and convective boundary conditions on heat and mass transfer, especially when coupled with a permeable linear rough stretched sheet. This study aims to fill this void by offering quantitative insights into these intricate phenomena, thereby enhancing our understanding of nanofluid dynamics and their practical implications. The findings indicate that increasing slip velocity and magnetic parameters reduce the boundary layer thickness of the velocity profile but increase it for the temperature profile, suggesting a nuanced interplay between slip velocity and magnetic effects on velocity boundary layers, while the temperature boundary layer exhibits distinct thermal dynamics within the system.

Human skin-derived ECM aids cell functions but can trigger immune reactions; therefore it is addressed through decellularization. Acellular dermal matrices (ADMs), known for their regenerative properties, are used in tissue and organ regeneration. ADMs now play a key role in plastic and reconstructive surgery, enhancing aesthetics and reducing capsular contracture risk. Innovative decellularization with supercritical carbon dioxide preserves ECM quality for clinical use. The study investigated the cytotoxicity, biocompatibility, and anti-inflammatory properties of supercritical CO2 acellular dermal matrix (scADM) in vivo based on Sprague Dawley rat models. Initial experiments in vitro with fibroblast cells confirmed the non-toxic nature of scADM and demonstrated cell infiltration into scADMs after incubation. Subsequent tests in vitro revealed the ability of scADM to suppress inflammation induced by lipopolysaccharides (LPS) presenting by the reduction of pro-inflammatory cytokines TNF-α, IL-6, IL-1β, and MCP-1. In the in vivo model, histological assessment of implanted scADMs in 6 months revealed a decrease in inflammatory cells, confirmed further by the biomarkers of inflammation in immunofluorescence staining. Besides, an increase in fibroblast infiltration and collagen formation was observed in histological staining, which was supported by various biomarkers of fibroblasts. Moreover, the study demonstrated vascularization and macrophage polarization, depicting increased endothelial cell formation. Alteration of matrix metalloproteinases (MMPs) was analyzed by RT-PCR, indicating the reduction of MMP2, MMP3, and MMP9 levels over time. Simultaneously, an increase in collagen deposition of collagen I and collagen III was observed, verified in immunofluorescent staining, RT-PCR, and western blotting. Overall, the findings suggested that scADMs offer significant benefits in improving outcomes in implant-based procedures as well as soft tissue substitution.

Background and Aims: The regenerative capacity of the pancreas diminishes with age. Understanding acinar cell responses to injury and the resolution of regenerative processes is crucial for tissue homeostasis. However, knowledge about the impact of aging on these processes remains limited. Methods: To investigate the influence of aging on pancreas regeneration, we established a cohort of young (7–14 weeks) and old (18 months) C57bl/6 mice. Experimental pancreatitis was induced using caerulein, and pancreas samples were collected at various time points after induction, covering acute damage response, inflammation, peak proliferation, and inflammation resolution. Our analysis involved immunohistochemistry, quantitative imaging, and gene expression analyses. Results: Our study revealed a significant decline in the regenerative capacity of the pancreas in old mice. Despite similar morphology and transcriptional profiles between the pancreas of young and old mice under homeostasis, the aged pancreas is primed to generate an exacerbated proinflammatory reaction in response to injury. Specifically, we observed notable upregulation of Junb expression in acinar cells and aberrant myofibroblast activation in the aged pancreas. Conclusion: The response of acinar cells to injury in the pancreas of aged mice is characterized by an increased susceptibility to inflammation and stromal reactions. Our findings uncover a pre-existing proinflammatory state in aged acinar cells, offering insights into potential strategies to prevent the onset of pancreatic insufficiency and the development of inflammatory conditions. These insights hold implications for preventing conditions such as chronic pancreatitis and pancreatic ductal adenocarcinoma.

Abstract Objectives To assess the occurrence of cardiotoxicity in patients with tumors receiving anthracycline‐based chemotherapy, especially for sarcomas. Methods This study summarized the types and frequency of adverse events (AEs) for three anthracyclines from the FDA adverse event reporting system (FAERS) database. FAERS data from January 2004 to June 2022 were collected and analyzed. Disproportionality analyses, logistic regression, and descriptive analysis were used to compare the differences in cardiac disorders. A retrospective cohort study was conducted in a single center between December 2008 and May 2022. Our hospital‐treated patients with bone and soft tissue sarcomas (BSTSs) with anthracycline‐containing chemotherapy were analyzed. Serum markers, echocardiography, and electrocardiography have been used to evaluate cardiotoxic events. Results One hundred thousand and seventy‐five AE reports were obtained for doxorubicin (ADM), epirubicin (EPI), and liposome doxorubicin (L‐ADM) from the FAERS database. ADM (OR = 3.1, p

Abstract Background Pyroptosis plays an important role in the pathological process of ischemic stroke (IS). However, the exact mechanism of pyroptosis remains unclear. This paper aims to reveal the key molecular markers associated with pyroptosis in IS. Methods We used random forest learning, gene set variation analysis, and Pearson correlation analysis to screen for biomarkers associated with pyroptosis in IS. Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen and glucose deprivation/reoxygenation (OGD/R) models were constructed in vitro and in vivo. Cells were transfected with an Annexin A3 silencing (si-ANXA3) plasmid to observe the effects of ANXA3 on OGD/R + lipopolysaccharides (LPS)-induced pyroptosis. qRT‒PCR and western blotting were used to detect the expression of potential biomarkers and pyroptotic pathways. Results Samples from a total of 170 IS patients and 109 healthy individuals were obtained from 5 gene expression omnibus databases. Thirty important genes were analyzed by random forest learning from the differentially expressed genes. Then, we investigated the relationship between the above genes and the pyroptosis score, obtaining three potential biomarkers (ANXA3, ANKRD22, ADM). ANXA3 and ADM were upregulated in the MCAO/R model, and the fold difference in ANXA3 expression was greater. Pyroptosis-related factors (NLRP3, NLRC4, AIM2, GSDMD-N, caspase-8, pro-caspase-1, cleaved caspase-1, IL-1β, and IL-18) were upregulated in the MCAO/R model. Silencing ANXA3 alleviated the expression of pyroptosis-related factors (NLRC4, AIM2, GSDMD-N, caspase-8, pro-caspase-1, cleaved caspase-1, and IL-18) induced by OGD/R + LPS or MCAO/R. Conclusion This study identified ANXA3 as a possible pyroptosis-related gene marker in IS through bioinformatics and experiments. ANXA3 could inhibit pyroptosis through the NLRC4/AIM2 axis.

Background: Reprogramming of glucose metabolism is a prominent abnormal energy metabolism in glioma. However, the efficacy of treatments targeting glycolysis varies among patients. The present study aimed to classify distinct glycolysis subtypes (GS) of glioma, which may help to improve the therapy response. Methods: The expression profiles of glioma were downloaded from public datasets to perform an enhanced clustering analysis to determine the GS. A total of 101 combinations based on 10 machine learning algorithms were performed to screen out the most valuable glycolysis‐related glioma signature (GGS). Through RSF and plsRcox algorithms, adrenomedullin (ADM) was eventually obtained as the most significant glycolysis‐related gene for prognostic prediction in glioma. Furthermore, drug sensitivity analysis, molecular docking, and in vitro experiments were utilized to verify the efficacy of ADM and ingenol mebutate (IM). Results: Glioma patients were classified into five distinct GS (GS1‐GS5), characterized by varying glycolytic metabolism levels, molecular expression, immune cell infiltration, immunogenic modulators, and clinical features. Anti‐CTLA4 and anti‐PD‐L1 antibodies significantly improved the prognosis for GS2 and GS5, respectively. ADM has been identified as a potential biomarker for targeted glycolytic therapy in glioma patients. In vitro experiments demonstrated that IM inhibited glioma cell progression by inhibiting ADM. Conclusion: This study elucidates that evaluating GS is essential for comprehending the heterogeneity of glioma, which is pivotal for predicting immune cell infiltration (ICI) characterization, prognosis, and personalized immunotherapy regimens. We also explored the glycolysis‐related genes ADM and IM to develop a theoretical framework for anti‐tumor strategies targeting glycolysis. [ABSTRACT FROM AUTHOR]

The progression and metastasis of oral squamous cell carcinoma (OSCC) are highly influenced by cancer stem cells (CSCs) due to their unique self-renewal and plasticity. In this study, data were obtained from a single-cell RNA-sequencing dataset (GSE172577) in the GEO database, and LASSO-Cox regression analysis was performed on 1344 CSCs-related genes to establish a six-gene prognostic signature (6-GPS) consisting of ADM, POLR1D, PTGR1, RPL35A, PGK1, and P4HA1. High-risk scores were significantly associated with unfavorable survival outcomes, and these features were thoroughly validated in the ICGC. The results of nomograms, calibration plots, and ROC curves confirmed the good prognostic accuracy of 6-GPS for OSCC. Additionally, the knockdown of ADM or POLR1D genes may significantly inhibit the proliferation, migration, and invasion of OSCC cells through the JAK/HIF-1 pathway. Furthermore, cell-cycle arrest occurred in the G1 phase by suppressing Cyclin D1. In summary, 6-GPS may play a crucial role in the occurrence and development of OSCC and has the potential to be developed further as a diagnostic, therapeutic, and prognostic tool for OSCC. [ABSTRACT FROM AUTHOR]

Purpose: Vitamin D receptors (VDR) play important roles in cardiovascular, immune, metabolic and other functions. Activation of VDR may help improve endothelial dysfunction, atherosclerosis, vascular calcification, and cardiac hypertrophy. However, the specific target genes and mechanisms of VDR in improving Human Umbilical Vein Endothelial Cell (HUVEC) functions remain unclear. This study aims to investigate the function and mechanism of VDR in HUVECs. Methods: Endothelial dysfunction cell model was constructed by oxidized low‐density lipoprotein (ox‐LDL). An animal model of atherosclerosis was established in male homozygous Apoe−/− mice (6 weeks) on a high fat diet for 6 weeks. The relationship between VDR and adrenomedullin (ADM) was studied by bioinformatics analysis, ChIP, and luciferase reporter gene analysis. Endothelial cell function was evaluated by Transwell migration and Tube Formation tests. Ferroptosis was detected by measuring intracellular iron content, levels of oxidative stress markers, and ferroptosis related proteins. Results: Overexpression of VDR in HUVECs inhibits ox‐LDL‐induced endothelial dysfunction and ferroptosis. VDR binds to the ADM promoter sequence and regulates the transcription of ADM. Inhibition of ADM promotes ox‐LDL‐induced endothelial dysfunction and ferroptosis. ADM regulates ox‐LDL‐induced endothelial dysfunction and ferroptosis through the AMPK signaling pathway. Overexpression of VDR in Apoe−/− mice inhibited lipid deposition and plaque area in atherosclerotic mice. Conclusion: VDR inhibits ox‐LDL‐induced endothelial dysfunction and ferroptosis by regulating ADM transcription and acting on AMPK signaling pathway. Overexpression of VDR in Apoe−/− mice reduced lipid deposition and plaque area in the thoracic aorta of atherosclerotic mice. [ABSTRACT FROM AUTHOR]

Case C-634/21 OQ v Land Hessen (Scoring), Judgment of the Court of Justice of the European Union (First Chamber) of 7 December 2023 Article 22 (1) of Regulation (EU) 2016/679 (General Data Protection Regulation) must be interpreted as meaning that the automated establishment, by a credit information agency, of a probability value based on personal data relating to a person and concerning his or her ability to meet payment commitments in the future constitutes 'automated individual decision-making' within the meaning of that provision, where a third party, to which that probability value is transmitted, draws strongly on that probability value to establish, implement or terminate a contractual relationship with that person. [ABSTRACT FROM AUTHOR]

This study was made to assess the effectiveness of the Modular Approach as an Alternative Delivery Mode (ADM) in Teaching Physical Education. It tried to gain some perspectives to improve the implementation of the new curriculum. The researcher identified the teachers’ and students’ engagement, participation, and experiences of the new learning modality in this time of the Covid-19 pandemic. Also, it dealt with the role of school administrators, parents, and other stakeholders and how they took part in the implementation of the program. In undertaking the study, the quantitative method of research was employed with the questionnaire as the principal instrument. The survey / questionnaire contained the following themes: (1) the level of participation of students in using the modular learning delivery in this new normal context; (2) the challenges both the teachers and the students encountered in teaching the Physical Education subject using the modules; and (3) the suggested responses for solutions to faced problems and issues regarding the implementation and participation in the use of the learning modules. The teacher respondents were randomly selected from the different public Secondary Schools in the District of Magsaysay, Occidental Mindoro composed of forty (40) male and female Physical Education teachers from Grades 7-12 who are taking the modular learning approach. An assessment of problems that were gained in the use of the modules revealed information on the factors affecting its integration that could be used as the basis for a proposed perspective for the development of a curriculum or program related to the use of the modular approach learning approach. [ABSTRACT FROM AUTHOR]

Objectives: To assess the occurrence of cardiotoxicity in patients with tumors receiving anthracycline‐based chemotherapy, especially for sarcomas. Methods: This study summarized the types and frequency of adverse events (AEs) for three anthracyclines from the FDA adverse event reporting system (FAERS) database. FAERS data from January 2004 to June 2022 were collected and analyzed. Disproportionality analyses, logistic regression, and descriptive analysis were used to compare the differences in cardiac disorders. A retrospective cohort study was conducted in a single center between December 2008 and May 2022. Our hospital‐treated patients with bone and soft tissue sarcomas (BSTSs) with anthracycline‐containing chemotherapy were analyzed. Serum markers, echocardiography, and electrocardiography have been used to evaluate cardiotoxic events. Results: One hundred thousand and seventy‐five AE reports were obtained for doxorubicin (ADM), epirubicin (EPI), and liposome doxorubicin (L‐ADM) from the FAERS database. ADM (OR = 3.1, p < 0.001), EPI (OR = 1.5, p < 0.001), and sarcomas (OR = 1.8, p < 0.001) may increase the probability of cardiac disorders. Cardiac failure, cardiotoxicity, and cardiomyopathy were anthracyclines' top 3 frequent AEs. Among patients receiving ADM‐containing therapy, those with ADM applied at doses ≥75 mg/m2/cycle were more likely to develop cardiac disorders than the other subgroups (OR = 3.5, p < 0.001). Patients younger than 18 are more likely to benefit from dexrazoxane prevention of cardiac failure. Six hundred and eighty‐three patients with BSTSs receiving anthracycline‐based chemotherapy were analyzed in our center. Patients receiving ADM‐containing chemotherapy were likelier to experience abnormalities in serum troponin‐T and left ventricular ejection fraction (p < 0.05). 2.0% (6/300) of patients receiving ADM‐containing chemotherapy required adjustment of the chemotherapy regimen because of cardiotoxicity, whereas none were in the EPI or L‐ADM groups. Conclusions and Relevance: Among patients receiving anthracycline‐containing therapy, patients with BSTSs were more likely to develop cardiac disorders than other tumors. In addition, patients with BSTSs receiving ADM chemotherapy had a higher likelihood of cardiotoxic events than those receiving EPI or L‐ADM. [ABSTRACT FROM AUTHOR]

Background: Pyroptosis plays an important role in the pathological process of ischemic stroke (IS). However, the exact mechanism of pyroptosis remains unclear. This paper aims to reveal the key molecular markers associated with pyroptosis in IS. Methods: We used random forest learning, gene set variation analysis, and Pearson correlation analysis to screen for biomarkers associated with pyroptosis in IS. Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen and glucose deprivation/reoxygenation (OGD/R) models were constructed in vitro and in vivo. Cells were transfected with an Annexin A3 silencing (si-ANXA3) plasmid to observe the effects of ANXA3 on OGD/R + lipopolysaccharides (LPS)-induced pyroptosis. qRT‒PCR and western blotting were used to detect the expression of potential biomarkers and pyroptotic pathways. Results: Samples from a total of 170 IS patients and 109 healthy individuals were obtained from 5 gene expression omnibus databases. Thirty important genes were analyzed by random forest learning from the differentially expressed genes. Then, we investigated the relationship between the above genes and the pyroptosis score, obtaining three potential biomarkers (ANXA3, ANKRD22, ADM). ANXA3 and ADM were upregulated in the MCAO/R model, and the fold difference in ANXA3 expression was greater. Pyroptosis-related factors (NLRP3, NLRC4, AIM2, GSDMD-N, caspase-8, pro-caspase-1, cleaved caspase-1, IL-1β, and IL-18) were upregulated in the MCAO/R model. Silencing ANXA3 alleviated the expression of pyroptosis-related factors (NLRC4, AIM2, GSDMD-N, caspase-8, pro-caspase-1, cleaved caspase-1, and IL-18) induced by OGD/R + LPS or MCAO/R. Conclusion: This study identified ANXA3 as a possible pyroptosis-related gene marker in IS through bioinformatics and experiments. ANXA3 could inhibit pyroptosis through the NLRC4/AIM2 axis. [ABSTRACT FROM AUTHOR]

In this study, authors explore how magnetic fields and the buoyancy force resulting from temperature differences work together. The study is focusing at how an Eyring-Powell nanofluid behaves in a ciliated channel when both natural convection and magnetic effects are at play. A technique called the symplectic metachoronal wave has been used to analyze this analysis. A physical assumption of small Reynolds number is considered to simplify the equations describing the flow rate of the Eyring-Powell nanofluid, making it easier to understand. To get a closed form solution, we have incorporated Adomian decomposition method (ADM). It has been observed that the flow is sped up by 10% with increase in the Eyring-Powell fluid parameter M. The quantity of heat transfer increases with increasing values of the Hartmann, Eyring-Powell fluid parameters, and Brinkmann numbers. This study has implications for bio-inspired engineering, medical applications, and the design of microfluidic devices.

Multiple myeloma (MM) is an incurable malignant plasma cell disorder characterized by the infiltration of clonal plasma cells in the bone marrow compartment. Gene Expression Profiling (GEP) has emerged as a powerful investigation tool in modern myeloma research enabling the dissection of the molecular background of MM and allowing the identification of gene products that could potentially serve as targets for therapeutic intervention. In this study we investigated shared transcriptomic abnormalities across newly diagnosed multiple myeloma (NDMM) patient cohorts. In total, publicly available transcriptomic data of 7 studies from CD138+ cells from 281 NDMM patients and 44 healthy individuals were integrated and analyzed. Overall, we identified 28 genes that were consistently differentially expressed (DE) between NDMM patients and healthy donors (HD) across various studies. Of those, 9 genes were over/under-expressed in more than 75% of NDMM patients. In addition, we identified 4 genes (MT1F, PURPL, LINC01239 and LINC01480) that were not previously considered to participate in MM pathogenesis. Meanwhile, by mining three drug databases (ChEMBL, IUPHAR/BPS and DrugBank) we identified 31 FDA-approved and 144 experimental drugs that target 8 of these 28 over/under-expressed MM genes. Taken together, our study offers new insights in MM pathogenesis and importantly, it reveals potential new treatment options that need to be further investigated in future studies.

Abstract Background To promote wound recovery in the recipient region, we studied the impact of exogenous hyaluronic acid (HA) on acellular dermal matrix (ADM) paired with thin intermediate-thickness skin transplant. Methods This study contains animal and clinical experiments. 50 Japanese big ear rabbits were separated into HA1, HA2, PADM, TS, and NS groups. Clinical part included 50 scar patients dividing into 5 groups (TS + HA + ADM 1, TS + ADM2, TS, TS + ADM and normal skin (NS)). Results In the animal trial, after 56 days, the grafts contracted least in the HA2 group; HA2 had the highest microvascular density (MVD), HA concentration, and collagen I and III expression. In clinical work, ADM > HA + ADM2 > HA + ADM1 > TS > NS; Type I and III collagen: HA + ADM1 and HA + ADM2 were higher than ADM; HA content: TS > HA + ADM1 > HA + ADM 2 > ADM. Conclusions ADM, exogenous hyaluronic acid mixed with thin skin autograft has better biomechanical qualities and therapeutic impact than acellular dermal matrix alone, and the reconstructive result is near to self-thick skin autograft in all indexes.

Background & Aims: The apical-basal polarity of pancreatic acinar cells is essential for maintaining tissue architecture. However, the mechanisms by which polarity proteins regulate acinar pancreas injury and regeneration are poorly understood. Methods: Cerulein-induced pancreatitis was induced in mice with conditional deletion of the polarity protein Par3 in the pancreas. The impact of Par3 loss on pancreas injury and regeneration was assessed by histologic analyses and transcriptional profiling by RNA sequencing. Mice were pretreated with the bromodomain and extraterminal domain (BET) inhibitor JQ1 before cotreatment with cerulein to determine the effect of BET inhibition on pancreas injury and regeneration. Results: Initially, we show that Par3 is increased in acinar-ductal metaplasia (ADM) lesions present in human and mouse chronic pancreatitis specimens. Although Par3 loss disrupts tight junctions, Par3 is dispensable for pancreatogenesis. However, with aging, Par3 loss results in low-grade inflammation, acinar degeneration, and pancreatic lipomatosis. Par3 loss exacerbates acute pancreatitis-induced injury and chronic pancreatitis-induced acinar cell loss, promotes pancreatic lipomatosis, and prevents regeneration. Par3 loss also results in suppression of chronic pancreatitis-induced ADM and primary ciliogenesis. Notably, targeting BET proteins attenuates chronic pancreatitis-induced loss of primary cilia and promotes ADM in mice lacking pancreatic Par3. Targeting BET proteins also attenuates cerulein-induced acinar cell loss and enhances recovery of acinar cell mass and body weight of mice lacking pancreatic Par3. Conclusions: Combined, this study demonstrates how Par3 restrains chronic pancreatitis-induced changes in the pancreas and identifies a potential role for BET inhibitors to attenuate pancreas injury and facilitate regeneration.

Background: To promote wound recovery in the recipient region, we studied the impact of exogenous hyaluronic acid (HA) on acellular dermal matrix (ADM) paired with thin intermediate-thickness skin transplant. Methods: This study contains animal and clinical experiments. 50 Japanese big ear rabbits were separated into HA1, HA2, PADM, TS, and NS groups. Clinical part included 50 scar patients dividing into 5 groups (TS + HA + ADM 1, TS + ADM2, TS, TS + ADM and normal skin (NS)). Results: In the animal trial, after 56 days, the grafts contracted least in the HA2 group; HA2 had the highest microvascular density (MVD), HA concentration, and collagen I and III expression. In clinical work, ADM > HA + ADM2 > HA + ADM1 > TS > NS; Type I and III collagen: HA + ADM1 and HA + ADM2 were higher than ADM; HA content: TS > HA + ADM1 > HA + ADM 2 > ADM. Conclusions: ADM, exogenous hyaluronic acid mixed with thin skin autograft has better biomechanical qualities and therapeutic impact than acellular dermal matrix alone, and the reconstructive result is near to self-thick skin autograft in all indexes. [ABSTRACT FROM AUTHOR]

Background: In pursuit of diagnostic tools capable of targeting distinct stages of Alzheimer's disease (AD), this study explores the potential of electroencephalography (EEG) combined with machine learning (ML) algorithms to identify patients with mild or moderate AD (ADM) and advanced AD (ADA). Objective: This study aims to assess the classification accuracy of six classical ML algorithms using a dataset of 668 patients from multiple hospitals. Methods: The dataset comprised measurements obtained from 668 patients, distributed among control, ADM, and ADA groups, collected from five distinct hospitals between 2011 and 2022. For classification purposes, six classical ML algorithms were employed: support vector machine, Bayesian linear discriminant analysis, decision tree, Gaussian Naïve Bayes, K-nearest neighbor and random forest. Results: The RF algorithm exhibited outstanding performance, achieving a remarkable balanced accuracy of 93.55% for ADA classification and 93.25% for ADM classification. The consistent reliability in distinguishing ADA and ADM patients underscores the potential of the EEG-based approach for AD diagnosis. Conclusions: By leveraging a dataset sourced from multiple hospitals and encompassing a substantial patient cohort, coupled with the straightforwardness of the implemented models, it is feasible to attain notably robust results in AD classification. [ABSTRACT FROM AUTHOR]

Among cancer treatments, immunotherapy is considered a promising strategy. Nonetheless, only a small number of individuals with head and neck squamous cell carcinoma exhibit positive responses to immunotherapy. This study aims to discover possible antigens for head and neck squamous cell carcinoma, create an mRNA vaccine for this type of cancer, investigate the connection between head and neck squamous cell carcinoma and periodontal disease, and determine the immune subtype of cells affected by head and neck squamous cell carcinoma. To ascertain gene expression profiles and clinical data corresponding to them, an examination was carried out on the TCGA database. Antigen-presenting cells were detected using TIMER. Targeting six immune-related genes (CXCL5, ADM, FGF9, AIMP1, STC1, and CDKN2A) in individuals diagnosedwith head and neck squamous cell carcinoma has shown promising results in immunotherapy triggered by periodontal disease. These genes have been linked to improved prognosis and increased immune cell infiltration. Additionally, CXCL5, ADM, FGF9, AIMP1, STC1, and CDKN2A exhibited potential as antigens in the creation of an mRNA vaccine. A nomogram model containing ADM expression and tumor stage was constructed for clinical practice. To summarize, ADM shows potential as a candidate biomarker for predicting the prognosis, molecular features, and immune characteristics of head and neck squamous cell carcinoma cells. Our results, obtained through real-time PCR analysis, showed a significant upregulation of ADM in the SCC-25 cell line compared to the NOK-SI cell line. This suggests that ADM might be implicated in the pathogenesis of HNSC, highlighting the potential of ADM as a target in HNSC treatment. However, further research is needed to elucidate the functional role of ADM in HNSC. Our findings provide a basis for the further exploration of the molecular mechanisms underlying HNSC and could help develop novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

In this paper, the characteristics of absolute value memristors are verified through the circuit implementation and construction of a chaotic system with a conditional symmetric fractional-order memristor. The dynamic behavior of fractional-order memristor systems is explored using fractional-order calculus theory and the Adomian Decomposition Method (ADM). Concurrently, the investigation probes into the existence of coexisting symmetric attractors, multiple coexisting bifurcation diagrams, and Lyapunov exponent spectra (LEs) utilizing system parameters as variables. Additionally, the system demonstrates an intriguing phenomenon known as offset boosting, where the embedding of an offset can adjust the position and size of the system’s attractors. To ensure the practical applicability of these findings, a fractional-order sliding mode synchronization control scheme, inspired by integer-order sliding mode theory, is designed. The rationality and feasibility of this scheme are validated through a theoretical analysis and numerical simulation.

The present manuscript proposes a computational approach to efficiently tackle a class of two-point boundary value problems that features third-order nonlinear ordinary differential equations. Specifically, this approach is based upon a combination of the shooting method with a modification of the renowned Adomian decomposition method. The approach starts by transforming the governing BVP into two appropriate initial-value problems, and thereafter, solves the resulting IVPs recurrently. In addition, the application of this method to varied test models remains feasible—of course, this is supported by the competing Runge–Kutta method, among others, and reported through comparison plots and tables.