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Background: Macromastia is a well-known issue in breast reconstruction. Skin-reducing mastectomy (SRM) was introduced as a skin-sparing mastectomy that utilizes a skin reduction pattern similar to breast reduction or breast lift surgery, specifically to manage hypertrophic and pendulous breasts. Over time, numerous authors have contributed to refining the SRM technique, leading to the development of various technical variants. However, the diversity of approaches inspired by SRM has created confusion, and clear surgical indications are lacking. Methods: We propose a unifying concept called breast reshaping mastectomy (BRM), which encompasses all techniques based on SRM principles. The BRM aims not only to preserve and reduce the breast skin envelope but also to immediately reshape it for a more aesthetic outcome. This approach is applicable to all mastectomies where skin envelope preservation (with or without the nipple-areola complex) is oncologically safe, a modification of breast skin coverage is needed for better aesthetic results, and an implant-based reconstruction is planned. Results: To define the BRM concept, we reviewed the existing literature on SRM and its related techniques. Our analysis focused on four key elements: skin incision pattern, implant coverage strategy, nipple-areola complex (NAC) management, and the choice between two-stage and direct-to-implant reconstruction. Conclusions: By integrating these four components into a single surgical framework, BRM provides a structured approach to breast reconstruction that enhances both oncologic safety and aesthetic outcomes. Standardizing these techniques could help clarify surgical indications and improve reconstructive planning for patients undergoing skin-sparing mastectomy. [ABSTRACT FROM AUTHOR]

Background: Hypotension is a common side effect of propofol induction, and when severe, it is associated with adverse outcomes. Ultrasonography of the inferior vena cava (IVC) is a reliable indicator of the intravascular volume. This study investigated whether preoperative IVC ultrasound measurements could predict hypotension after propofol induction in patients undergoing colonoscopies. Methods: Sixty-two adult patients with American Society of Anesthesiologists physical status (ASA) I-II scheduled for colonoscopy after propofol induction were recruited. The Ultrasound Maximum IVC diameter (dIVCmax), minimum IVC diameter (dIVCmin), and collapsibility index (IVC-CI) were assessed in all patients before propofol induction. Mean blood pressure (MBP) was recorded before induction. Propofol was injected intravenously after ultrasound measurements. MBP was recorded 1, 3, 5, and 10 min after propofol induction. The receiver operating characteristic (ROC) curve of IVC-CI was compared with that of patients who developed hypotension after propofol induction. Results: Sixty-two patients completed the study, and their data were considered for statistical analysis. After induction,30 patients developed hypotension. The area under the curve (95% confidence interval) was 0.72 (0.595 to 0.849) for IVC-CI. The optimal IVC-CI cutoff value was 38.25%, with a sensitivity of 56.7% and specificity of 71.9%. IVC-CI before induction strongly correlated with the maximum percentage of MBP drop after propofol induction. (regression coefficient = 0.33, P = 0.008), respectively. Conclusion: Pre-induction IVC-CI > 38.25% is a non-invasive predictor of propofol-induced hypotension in patients undergoing colonoscopy and is strongly correlated with MBP drop. Trial registration: This clinical trial was approved by the Ethics Committee of The Affiliated Lianyungang Hospital of Xuzhou Medical University (YJ-20190529001). All the study procedures were performed in accordance with the ethical standards of the Helsinki Declaration of 2013. [ABSTRACT FROM AUTHOR]

The ubiquitous Notch receptor signalling network is essential for tissue growth and maintenance. Operationally, receptor activity is regulated by two principal, counterposed mechanisms: intercellular Notch transactivation triggered by interactions between receptors and ligands expressed in neighbouring cells; intracellular cis inhibition mediated by ligands binding to receptors expressed in the same cell. Moreover, different Notch receptor/ligand combinations are known to elicit distinct molecular and cellular responses, and together, these phenomena determine the strength, the duration and the specificity of Notch receptor signalling. To date, it has been assumed that these processes involve discrete ligand homomers and not heteromeric complexes composed of more than one ligand species. In this study, we explore the molecular basis of the opposing actions of the Notch ligands, DLL4 and JAG1, which control angiogenic sprouting. Through a combination of experimental approaches and mathematical modelling, we provide evidence that two mechanisms could underpin this process: 1) DLL4 rather than JAG1 induces efficient Notch1 receptor transactivation; 2) JAG1 directly blocks DLL4-dependent cis-inhibition of Notch signalling through the formation of a JAG1/DLL4 complex. We propose a new model of Notch signalling that recapitulates the formation of tip and stalk cells, which is necessary for sprouting angiogenesis. Author summary: The ancient Notch signalling pathway is a central regulator of metazoan cell fate, and corruption of it has been implicated in numerous diseases including the majority of solid tumours. Since its discovery in the second decade of the last century one central question to emerge is how such a wide range of different cellular/physiological processes can be governed by such a relatively simple repertoire of Notch receptors and ligands. In this study, using a combination of experimental approaches and mathematical modelling, we provide the first evidence that Notch ligands can directly bind to each other, and that this novel mechanism of ligand heterodimerization could help determine the strength, the duration and the specificity of Notch signalling. Our model faithfully recapitulates both our presented experimental results as well as the recently published work of others, and provides a novel perspective for understanding Notch-regulated biological processes, most notably angiogenesis. [ABSTRACT FROM AUTHOR]

Brain macrophages encompass two major populations: microglia in the parenchyma and border-associated macrophages (BAMs) in the extra-parenchymal compartments. These cells play crucial roles in maintaining brain homeostasis and immune surveillance. Microglia and BAMs are phenotypically and epigenetically distinct and exhibit highly specialized functions tailored to their environmental niches. Intriguingly, recent studies have shown that both microglia and BAMs originate from the same myeloid progenitor during yolk sac hematopoiesis, but their developmental fates diverge within the brain. Several works have partially unveiled the mechanisms orchestrating the development of microglia and BAMs in both mice and humans; however, many questions remain unanswered. Defining the molecular underpinnings controlling the transcriptional and epigenetic programs of microglia and BAMs is one of the upcoming challenges for the field. In this review, we outline current knowledge on ontogeny, phenotypic diversity, and the factors shaping the ecosystem of brain macrophages. We discuss insights garnered from human studies, highlighting similarities and differences compared to mice. Lastly, we address current research gaps and potential future directions in the field. Understanding how brain macrophages communicate with their local environment and how the tissue instructs their developmental trajectories and functional features is essential to fully comprehend brain physiology in homeostasis and disease. [ABSTRACT FROM AUTHOR]

Background: Methotrexate (MTX) is a cytotoxic drug that can trigger neurotoxicity via enhancing oxidative stress, apoptosis, and inflammation. On the other hand, erythropoietin (EPO) functions as an antioxidant, anti-apoptotic, and anti-inflammatory agent, in addition to its hematopoietic effects. Aim: The present study was developed to examine the neuroprotective impact of EPO against MTX-provoked neurotoxicity in rats. Methods: Chemo fog was elicited in Wistar rats via injection of one dosage of MTX (20 mg/kg, i.p) on the sixth day of the study. EPO was injected at 500 IU/kg/day, i.p for 10 successive days. Results: MTX triggered memory and learning impairment as evidenced by Morris water maze, passive avoidance, and Y-maze cognitive tests. In addition, MTX induced oxidative stress as evident from the decline in hippocampal Nrf2 and HO-1 levels. MTX brought about apoptosis, as demonstrated by the elevation in p53, caspase-3, and Bax levels, as well as the decrease in Bcl2 levels. MTX also decreased Beclin-1, an autophagy-related marker, and increased P62 expression. In addition, MTX downregulated Sirt-1/AKT/FoxO3a pathway and increased miRNA-34a gene expression. Moreover, MTX increased acetylcholinesterase activity and reduced neurogenesis. EPO administration remarkably counteracted MTX-induced molecular and behavioral disorders in rat hippocampi. Conclusion: Our findings impart preclinical indication for repurposing of EPO as a promising neuroprotective agent through modulating miRNA-34a, autophagy, and the Sirt-1/FoxO3a signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Myelin-laden foamy macrophages accumulate extensively in the lesion epicenter, exhibiting characteristics of autophagolysosomal dysfunction, which leads to prolonged inflammatory responses after spinal cord injury (SCI). Trehalose, known for its neuroprotective properties as an autophagy inducer, has yet to be fully explored for its potential to mitigate foamy macrophage formation and exert therapeutic effects in the context of SCI. Results: We observed that trehalose significantly enhances macrophage phagocytosis and clearance of myelin in a dose-dependent manner in vitro. In vivo, trehalose administration markedly reduced myelin debris accumulation, inhibited foamy macrophage formation, suppressed inflammatory responses, decreased fibrotic scarring, and promoted axonal growth and motor function recovery after SCI. These beneficial effects of trehalose may be related to the overexpression of transcription factor EB (TFEB), a key regulator of the autophagy-lysosomal system, which can rescue autophagic dysfunction in foamy macrophages and inhibit inflammatory responses. Additionally, the effects of trehalose on macrophages were abolished by chloroquine, an autophagy inhibitor, suggesting trehalose's potential as a therapeutic candidate for enhancing myelin debris clearance post-SCI. Conclusions: Our findings underscore the pivotal role of trehalose in modulating myelin debris clearance within macrophages, providing new perspectives for the treatment of spinal cord injury. [ABSTRACT FROM AUTHOR]

Background: Recently there has been an increasing number of studies have explored apoptosis mechanisms in lung cancer (LC). However, no researchers have conducted a bibliometric analysis of the most cited articles in this field. Objective: To examine the top 100 most influential and cited publications on apoptosis in non-small cell lung cancer (NSCLC) from 2004 to 2023, summarizing research trends and key focus areas. Methods: This study utilized the Web of Science Core Database (WOSCC) to research NSCLC apoptosis from 2004 to 2023, using keyword selection and manual screening for article searches. Bibliometrix package of R software 4.3.1 was used to generate distribution statistics for the top ten institutions, journals and authors. Citespace6.2. R6 was used to create the visualization maps for keyword co-occurrence and clustering. VOSviewer1.6.19 was used to conduct cluster analysis of publishing countries (regions), with data exported to SCImago Graphica for geographic visualization and cooperation analysis. VOSviewer1.6.19 was used to produced co-citation maps of institutions, journals, authors, and references. Results: From 2004 to 2023, 13316 articles were retrieved, and the top 100 most cited were chosen. These were authored by 934 individuals from 269 institutions across 18 countries and appeared in 45 journals. Citations ranged from 150 to 1,389, with a median of 209.5. The most influential articles appeared in 2005 and 2007 (n=13). The leading countries (regions), institutions, journals and authors were identified as the United States (n=60), Harvard University (n=64), CANCER RESEARCH (n=15), SUN M and YANG JS (n=6). The top five keywords were "expression", "activation", "apoptosis", "pathway" and "gefitinib". This study indicates that enhancing apoptosis through circular RNA regulation and targeting the Nrf2 signaling pathway could become a key research focus in recent years. Conclusion: Apoptosis has been the subject of extensive research over many years, particularly in relation to its role in the pathogenesis, diagnosis, and treatment of NSCLC. This study aims to identify highly influential articles and forecast emerging research trends, thereby offering insights into novel therapeutic targets and strategies to overcome drug resistance. The findings are intended to serve as a valuable reference for scholars engaged in this field of study. [ABSTRACT FROM AUTHOR]

TREM2 is a signaling receptor expressed on microglia that has emerged as an important drug target for Alzheimer's disease and other neurodegenerative diseases. While a number of TREM2 ligands have been identified, little is known regarding the structural details of how they engage. To better understand this, we created a protein library of 28 different TREM2 variants that could be used to map interactions with various ligands using biolayer interferometry. The variants are located in previously identified putative binding surfaces on TREM2 called the hydrophobic site, basic site, and site 2. We found that mutations to the hydrophobic site ablated binding to apoE4 and TDP-43. Competition binding experiments indicated that apoE4 and oAβ42 share overlapping binding sites on TREM2. In contrast, binding to C1q was disrupted most strongly by mutations to the basic site, including R46, with some mutations to the hydrophobic site also attenuating binding, thus suggesting a broader mediation of binding across the two sites. Supporting this, competition experiments indicated that C1q binding could be blocked by both apoE and oAβ42. TREM2 binding to IL-34 was mediated by the basic site at a surface centering on R76. Competition binding experiments validated the unique site for IL-34, showing little to no competition with either oAβ42 or apoE4. However, competition experiments between C1q and IL34 suggest that the ligands compete for binding at the basic site. Altogether, our results suggest that TREM2 utilizes the hydrophobic site (consisting of CDR1, CDR2, and CDR3) as a common site to engage multiple ligands, and uses distinct basic sites to engage others. Our findings imply that pharmaceutical strategies targeting these surfaces might be effective to modulate TREM2 functions. [ABSTRACT FROM AUTHOR]

As research progresses, our understanding of the tumor microenvironment (TME) has undergone profound changes. The TME evolves with the developmental stages of cancer and the implementation of therapeutic interventions, transitioning from an immune-promoting to an immunosuppressive microenvironment. Consequently, we focus intently on the significant role of the TME in tumor proliferation, metastasis, and the development of drug resistance. AXL is highly associated with tumor progression; however, previous studies on AXL have been limited to its impact on the biological behavior of cancer cells. An increasing body of research now demonstrates that AXL can influence the function and differentiation of immune cells, mediating immune suppression and thereby fostering tumor growth. A comprehensive analysis to identify and overcome the causes of immunosuppressive microenvironments represents a novel approach to conquering cancer. In this review, we focus on elucidating the role of AXL within the immunosuppressive microenvironments, discussing and analyzing the effects of AXL on tumor cells, T cells, macrophages, natural killer (NK) cells, fibroblasts, and other immune-stromal cells. We aim to clarify the contributions of AXL to the progression and drug resistance of cancer from its functional role in the immune microenvironment. [ABSTRACT FROM AUTHOR]

This study introduces a greedy algorithm for deriving decision rules from decision tree ensembles, targeting enhanced interpretability and generalization in distributed data environments. Decision rules, known for their transparency, provide an accessible method for knowledge extraction from data, facilitating decision-making processes across diverse fields. Traditional decision tree algorithms, such as CART and ID3, are employed to induce decision trees from bootstrapped datasets, which represent distributed data sources. Subsequently, a greedy algorithm is applied to derive decision rules that are true across multiple decision trees. Experiments are performed, taking into account knowledge representation and discovery perspectives. They show that, as the value of α , 0 ≤ α < 1 , increases, shorter rules are obtained, and also it is possible to improve the classification accuracy of rule-based models. [ABSTRACT FROM AUTHOR]

Multiple studies and review papers have concluded that early warning systems have a positive effect on clinical outcomes, patient safety and clinical performances. Despite the substantial evidence affirming the efficacy of EWS applications, persistent barriers hinder their seamless integration into clinical practice. Notably, EWS, such as the National Early Warning Score, simplify multifaceted clinical conditions into singular numerical indices, thereby risking the oversight of critical clinical indicators and nuanced fluctuations in patients' health status. Furthermore, the optimal deployment of EWS within clinical contexts remains elusive. Manual assessment of EWS parameters exacts a significant temporal toll on healthcare personnel. Addressing these impediments necessitates innovative approaches. In this regard, wearable medical technologies emerge as promising solutions capable of continual monitoring of hospitalized patients' vital signs. To overcome the barriers of the use of early warning scores, wearable medical technology has the potential to continuously monitor vital signs of hospitalised patients. However, a fundamental inquiry arises regarding the comparability of their reliability to the current used golden standards. This inquiry underscores the imperative for rigorous evaluation and validation of wearable medical technologies to ascertain their efficacy in augmenting extant clinical practices. This prospective, single-center study aimed to evaluate the accuracy of heart rate and respiratory rate measurements obtained from the Vivalink Cardiac patch in comparison to the ECG-based monitoring system utilized at AZ Maria Middelares Hospital in Ghent. Specifically, the study focused on assessing the concordance between the data obtained from the Vivalink Cardiac patch and the established ECG-based monitoring system among a cohort of ten post-surgical intensive care unit (ICU) patients. Of these patients, five were undergoing mechanical ventilation post-surgery, while the remaining five were not. The study proceeded by initially comparing the data recorded by the Vivalink Cardiac patch with that of the ECG-based monitoring system. Subsequently, the data obtained from both the Vivalink Cardiac patch and the ECG-based monitoring system were juxtaposed with the information derived from the ventilation machine, thereby providing a comprehensive analysis of the patch's performance in monitoring vital signs within the ICU setting. For heart rate, the Vivalink Cardiac patch was on average within a 5% error range of the ECG-based monitoring system during 85.11±10.81% of the measured time. For respiratory rate this was during 40.55±17.28% of the measured time. Spearman's correlation coefficient showed a very high correlation of ρ = 0.9 8 for heart rate and a moderate correlation of ρ = 0.66 for respiratory rate. In comparison with the ventilated respiratory rate (ventilation machine) the Vivalink and ECG-based monitoring system both had a moderate correlation of ρ = 0.68 . A very high correlation was found between the heart rate measured by the Vivalink Cardiac patch and that of the ECG-based monitoring system of the hospital. Concerning respiratory rate the correlation between the data from the Vivalink Cardiac patch, the ECG-based monitoring system and the ventilation machine was found to be moderate., Competing Interests: Declarations. Conflict of interest: The authors have not disclosed any competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Oncogenic programs regulate the proliferation and maintenance of cancer stem cells, and can define pharmacologic dependencies. In acute myeloid leukemia (AML) with the chromosome inversion 16 (inv(16)), the fusion oncoprotein CBFβ::MYH11 regulates pathways associated with leukemia stem cell activity. Here we demonstrate that expression of Neuropilin-1 (NRP1) is regulated by the fusion oncoprotein, and promotes AML expansion. Mechanistically, we show that the NRP1 locus has open chromatin in inv(16) AML, and that CBFβ::MYH11 modulates the local function of the transcription factors ERG, GATA2 and RUNX1 to sustain NRP1 levels. We found that ERG activates NRP1 expression, and that CBFβ::MYH11 knockdown represses ERG expression, thereby allowing the repressive activity of GATA2/RUNX1 at three NRP1 enhancers. Functionally, we demonstrate that NRP1 enhances the expansion of leukemic cells in vitro and in mice, and that this activity is dependent on its VEGFR-associated FV/FVIII domain. Finally, we show that treatment with VEGF inhibitor axitinib reduces AML cell growth and delays median leukemia latency in vivo. Our findings reveal that the NRP1/VEGF axis mediates proliferation in inv(16) AML blasts, and suggest that targeting NRP1 function could be promising in combination AML therapy., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)