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Simple Summary: The incidence of endometrial cancer is increasing, creating a need for fast and efficient diagnostic methods. This study explores a new, non-invasive approach using urinary fluorescence spectroscopy to detect endometrial cancer. By analyzing morning urine samples and utilizing advanced machine learning techniques, we identified prospective spectral markers that differentiate between control, benign, and malignant gynecological patients. Our findings indicate good sensitivity and specificity, with high AUC from machine learning models, suggesting this method could significantly improve early cancer detection. This approach is easier and more affordable, especially in resource-limited settings. It has the potential to change the way endometrial cancer is diagnosed, offering a simpler and more accessible option for patients. Endometrial cancer is becoming increasingly common, highlighting the need for improved diagnostic methods that are both effective and non-invasive. This study investigates the use of urinary fluorescence spectroscopy as a potential diagnostic tool for endometrial cancer. Urine samples were collected from endometrial cancer patients (n = 77), patients with benign uterine tumors (n = 23), and control gynecological patients attending regular checkups or follow-ups (n = 96). These samples were analyzed using synchronous fluorescence spectroscopy to measure the total fluorescent metabolome profile, and specific fluorescence ratios were created to differentiate between control, benign, and malignant samples. These spectral markers demonstrated potential clinical applicability with AUC as high as 80%. Partial Least Squares Discriminant Analysis (PLS-DA) was employed to reduce data dimensionality and enhance class separation. Additionally, machine learning models, including Random Forest (RF), Logistic Regression (LR), Support Vector Machine (SVM), and Stochastic Gradient Descent (SGD), were utilized to distinguish between controls and endometrial cancer patients. PLS-DA achieved an overall accuracy of 79% and an AUC of 90%. These promising results indicate that urinary fluorescence spectroscopy, combined with advanced machine learning models, has the potential to revolutionize endometrial cancer diagnostics, offering a rapid, accurate, and non-invasive alternative to current methods. [ABSTRACT FROM AUTHOR]

Endometrial cancer is the most common gynecological malignancy in high-income countries and the sixth most common cancer in women. Overall incidence has risen in the last few decades as a consequence of the increase in the prevalence of its risk factors, mainly obesity and the aging of the population, and although diagnoses have increased across all age groups, the incidence rates have doubled in women under the age of 40 years. The survival rates of endometrial cancer are highly dependent on its stage at diagnosis, bringing to the fore the importance of early diagnosis. The aim of a screening strategy in this type of tumor should be to detect the disease in the pre-invasive or early stage (before developing myometrial invasion), which would improve cure rates, reduce the morbidity associated with aggressive treatment and offer uterus-sparing management options for younger women. The ideal screening tool in this scenario would be a minimally invasive, inexpensive and easy-to-perform test or auto-test, which could be implemented in a routine gynecologic checkup of patients at-risk or in the general adult population. In this comprehensive review, we aim to define the populations at higher risk of developing endometrial cancer, to assess the performance of current diagnostic tools when used in a screening setting and to discuss the accuracy of new molecular screening strategies. [ABSTRACT FROM AUTHOR]

Endogenous retroviruses (ERVs), once thought to be mere remnants of ancient viral integrations in the mammalian genome, are now recognized for their critical roles in various physiological processes, including embryonic development, innate immunity, and tumorigenesis. Their impact on host organisms is significant driver of evolutionary changes, offering insight into evolutionary mechanisms. In our study, we explored the functionality of ERVs by examining single-cell transcriptomic profiles from human embryonic stem cells and urine cells. This led to the discovery of a unique ERVH48-1 expression pattern between these cell types. Additionally, somatic cell reprogramming efficacy was enhanced when ERVH48-1 was overexpressed in a urine cell-reprogramming system. Induced pluripotent stem cells (iPSCs) generated with ERVH48-1 overexpression recapitulated the traits of those produced by traditional reprogramming approaches, and the resulting iPSCs demonstrated the capability to differentiate into all three germ layers in vitro. Our research elucidated the role of ERVs in somatic cell reprogramming. [ABSTRACT FROM AUTHOR]

Gastropoda assemblages were investigated for four seasons in 2016–2017 (autumn, winter, spring, and summer) near Umm Al-Namil Island in Kuwait in rocky and sandy habitats to study the effect of season and habitat type on species richness, abundance, evenness, and diversity. A total of 28 gastropod species belonging to 14 families were identified (26 in sandy, 20 in rocky, 18 in common between both habitats). Clypeomorus bifasciata (31.07%) and Trochus erithreus (21.43%) were the most abundant species in the rocky habitat. Pirenella arabica (27.51%), C. bifasciata (26.15%) and Mitrella blanda (15.66%) dominated the sandy habitat. At the rocky habitat, total abundance ranged from 6.5 ± 4.71 to 40 ± 45.17 ind m−2 in autumn and summer, respectively. As for the sandy habitat, total abundance varied from 53.0 ± 22.60 to 294.0 ± 316.67 ind m−2 in summer and winter, respectively. The results of the rocky habitat showed that diversity and evenness were strongly affected by season more than habitat type. Species richness and abundance were strongly influenced by habitat type rather than the season. However, the sandy habitat had a higher value of abundance, diversity, species richness, and evenness throughout the sampling period than the rocky habitat. There was almost a distinction between the species resident in both habitats throughout the study. These findings could be attributed mainly to the feeding habits of these gastropods and their burrowing nature. [ABSTRACT FROM AUTHOR]

Background: This study investigates the intricate role of Heme Oxygenase 1 (HMOX1) in ovarian cancer, emphasizing its prognostic significance, influence on immune cell infiltration, and impact on the malignant characteristics of primary ovarian cancer cells. Materials and methods: Our research began with an analysis of HMOX1 expression and its prognostic implications using data from The Cancer Genome Atlas (TCGA) dataset, supported by immunohistochemical staining. Further analyses encompassed co-expression studies, Gene Ontology (GO) annotations, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. We utilized the TIMER and TISIDB platforms to evaluate the immunotherapeutic potential of HMOX1. Additionally, in vitro studies that involved modulating HMOX1 levels in primary ovarian cancer cells were conducted to confirm its biological functions. Results: Our findings indicate a significant overexpression of HMOX1 in ovarian cancer, which correlates with increased tumor malignancy and poorer prognosis. HMOX1 was shown to significantly modulate the infiltration of immune cells, particularly neutrophils and macrophages. Single-cell RNA sequencing (scRNA-seq) analysis revealed that HMOX1 is predominantly expressed in tumor-associated macrophages (TAMs), with a positive correlation to chemokines and their receptors. An increase in HMOX1 levels was associated with heightened levels of immunoinhibitors, immunostimulators, and MHC molecules. Functional assays demonstrated that HMOX1 knockdown promotes apoptosis, attenuating cell proliferation and invasion, while its overexpression yields opposing effects. Conclusion: HMOX1 emerges as a critical therapeutic target, intricately involved in immunomodulation, prognosis, and the malignant behavior of ovarian cancer. This highlights HMOX1 as a potential biomarker and therapeutic target in the fight against ovarian cancer. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the most dangerous malignancies in women. Prolonged survival times are made possible by breakthroughs in early recognition and efficient treatment of a disease.The existing methods are lagging on finding the important attributes to predict the survival outcome. The main objective of this study is to find individuals with cervical cancer who are at greater risk of death from recurrence by predicting the survival.A novel approach in a proposed technique is Triangulating feature importance to find the important risk factors through which the treatment may vary to improve the survival outcome.Five algorithms Support vector machine, Naive Bayes, supervised logistic regression, decision tree algorithm, Gradient boosting, and random forest are used to build the concept. Conventional attribute selection methods like information gain (IG), FCBF, and ReliefFare employed. The recommended classifier is evaluated for Precision, Recall, F1, Mathews Correlation Coefficient (MCC), Classification Accuracy (CA), and Area under curve (AUC) using various methods. Gradient boosting algorithm (CAT BOOST) attains the highest accuracy value of 0.99 to predict survival outcome of recurrence cervical cancer patients. The proposed outcome of the research is to identify the important risk factors through which the survival outcome of the patients improved. [ABSTRACT FROM AUTHOR]

Unlike metals where dislocations carry strain singularity but no charge, dislocations in oxide ceramics are characterized by both a strain field and a local charge with a compensating charge envelope. Oxide ceramics with their deliberate engineering and manipulation are pivotal in numerous modern technologies such as semiconductors, superconductors, solar cells, and ferroics. Dislocations facilitate plastic deformation in metals and lead to a monotonous increase in the strength of metallic materials in accordance with the widely recognized Taylor hardening law. However, achieving the objective of tailoring the functionality of oxide ceramics by dislocation density still remains elusive. Here a strategy to imprint dislocations with {100}<100> slip systems and a tenfold change in dislocation density of BaTiO3 single crystals using high‐temperature uniaxial compression are reported. Through a dislocation density‐based approach, dielectric permittivity, converse piezoelectric coefficient, and alternating current conductivity are tailored, exhibiting a peak at medium dislocation density. Combined with phase‐field simulations and domain wall potential energy analyses, the dislocation‐density‐based design in bulk ferroelectrics is mechanistically rationalized. These findings may provide a new dimension for employing plastic strain engineering to tune the electrical properties of ferroics, potentially paving the way for advancing dislocation technology in functional ceramics. [ABSTRACT FROM AUTHOR]

Lipid bi‐layered particles known as membrane vesicles (MVs), produced by Gram‐positive bacteria are a communication tool throughout the entire bacterial growth. However, the MVs characteristics may vary across all stages of maternal culture growth, leading to inconsistencies in MVs research. This, in turn, hinders their employment as nanocarriers, vaccines and other medical applications. In this study, we aimed to comprehensively characterize MVs derived from Lacticaseibacillus rhamnosus CCM7091 isolated at different growth stages: early exponential (6 h, MV6), late exponential (12 h, MV12) and late stationary phase (48 h, MV48). We observed significant differences in protein content between MV6 and MV48 (data are available via ProteomeXchange with identifier PXD041580), likely contributing to their different immunomodulatory capacities. In vitro analysis demonstrated that MV48 uptake rate by epithelial Caco‐2 cells is significantly higher and they stimulate an immune response in murine macrophages RAW 264.7 (elevated production of TNFα, IL‐6, IL‐10, NO). This correlated with increased expression of lipoteichoic acid (LTA) and enhanced TLR2 signalling in MV48, suggesting that LTA contributes to the immunomodulation. In conclusion, we showed that Lacticaseibacillus rhamnosus CCM7091‐derived MVs from the late stationary phase boost the immune response the most effectively, which pre‐destines them for therapeutical application as nanocarriers. [ABSTRACT FROM AUTHOR]

Simple Summary: Secondary cytoreductive surgery is a treatment option for patients with relapsed platinum-sensitive epithelial ovarian cancer, yet the precise indications and criteria for patient selection remain to be outlined. Furthermore, the impact on progression-free and overall survival remains unclear. The objective of this systematic review was to determine the precise indications for secondary cytoreductive surgery and to elucidate the factors contributing to favorable outcomes associated with the intervention compared to conventional treatment modalities like standard-of-care chemotherapy. Our review confirmed that secondary cytoreductive surgery maintains morbidity, mortality, and quality of life standards for patients. While the trials included utilized different selection criteria for the procedure, our findings underscore the importance of careful patient selection to improve survival in conjunction with conventional chemotherapy. Secondary cytoreductive surgery is a treatment option for relapsed platinum-sensitive epithelial ovarian cancer, but no clear indications are defined for the procedure. This systematic review aims to establish clear indications and compare outcomes versus standard-of-care chemotherapy. We conducted an electronic literature search across three databases and identified 2033 articles, including three phase 3 randomized controlled trials (RCT). The review adhered to PRISMA 2020 guidelines and was registered in PROSPERO (no. CRD42022379817). Despite varying patient selection methods, surgery plus chemotherapy demonstrated significantly prolonged progression-free survival compared to chemotherapy alone. However, overall survival outcomes were inconsistent: while GOG-0213 did not show extended overall survival, recent studies with stricter defined criteria for surgery (SOC-1 and DESKTOP-III) reported improved overall survival with the addition of surgery. Morbidity and mortality rates were low, with no difference in quality of life between the surgery and no-surgery groups. In conclusion, cytoreductive surgery presents a promising option for recurrent epithelial ovarian cancer treatment. Nonetheless, well-defined selection criteria appear crucial for achieving increased overall survival compared to conventional treatment. [ABSTRACT FROM AUTHOR]

The inherent heterogeneity of cancer contributes to highly variable responses to any anticancer treatments. This underscores the need to first identify precise biomarkers through complex multi-omics datasets that are now available. Although much research has focused on this aspect, identifying biomarkers associated with distinct drug responders still remains a major challenge. Here, we develop MOMLIN, a multi-modal and -omics machine learning integration framework, to enhance drug-response prediction. MOMLIN jointly utilizes sparse correlation algorithms and class–specific feature selection algorithms, which identifies multi-modal and -omics–associated interpretable components. MOMLIN was applied to 147 patients' breast cancer datasets (clinical, mutation, gene expression, tumor microenvironment cells and molecular pathways) to analyze drug-response class predictions for non-responders and variable responders. Notably, MOMLIN achieves an average AUC of 0.989, which is at least 10% greater when compared with current state-of-the-art (data integration analysis for biomarker discovery using latent components, multi-omics factor analysis, sparse canonical correlation analysis). Moreover, MOMLIN not only detects known individual biomarkers such as genes at mutation/expression level, most importantly, it correlates multi-modal and -omics network biomarkers for each response class. For example, an interaction between ER-negative-HMCN1-COL5A1 mutations-FBXO2-CSF3R expression-CD8 emerge as a multimodal biomarker for responders, potentially affecting antimicrobial peptides and FLT3 signaling pathways. In contrast, for resistance cases, a distinct combination of lymph node-TP53 mutation-PON3-ENSG00000261116 lncRNA expression-HLA-E-T-cell exclusions emerged as multimodal biomarkers, possibly impacting neurotransmitter release cycle pathway. MOMLIN, therefore, is expected advance precision medicine, such as to detect context–specific multi-omics network biomarkers and better predict drug-response classifications. [ABSTRACT FROM AUTHOR]

Rebuttable presumptions--ones that offer the opportunity to overcome a presumed fact--are a common fixture in U.S. civil law. Some rebuttable presumptions, however, are not in fact rebuttable at all and are instead rebuttable in name only. Nonetheless, courts often take at face value a presumption's claim to be rebuttable when reviewing challenges to such presumptions. This Article contends that such so-called rebuttable presumptions should be recognized as a distinct category of presumptions: effectively irrebuttable presumptions. It argues that effectively irrebuttable presumptions violate constitutional due process norms because, although they offer proceedings, they deprive process. Part I examines a so-called rebuttable presumption in the immigration context, which, once triggered, precludes individuals from applying for persecution-based forms of relief. Part II proffers a four-part framework for defining effectively irrebuttable presumptions, which looks at the structure of the presumption, the ways it has (and has not) been implemented, and the number of cases that have successfully rebutted it. Part III argues that such effectively irrebuttable presumptions offend procedural due process norms. Applying two procedural due process frameworks, it argues that effectively irrebuttable presumptions violate the axiomatic guarantee of a meaningful opportunity to be heard at a full and fair hearing. Part IV then sets forth recommendations for procedural safeguards necessary to identify and bring effectively irrebuttable presumptions in line with due process norms. This Article focuses on the constitutional dilemma effectively irrebuttable presumptions pose in the immigration context, but its implications may reach broadly to other civil contexts. [ABSTRACT FROM AUTHOR]

Simple Summary: Gynecological diseases still make up a large percentage of the overall global disease burden. While oral contraceptives and gonadotropin-releasing hormone drugs for endometriosis and gynecological cancers exist, their known inflammatory side effects can counteract progress in therapy. With this, the present study made use of a systems biology approach to identify correlations between gynecological diseases using gene expression data from DNA microarray samples that contain endometriosis, ovarian cancer, cervical cancer, and endometrial cancer. The highly preserved gene modules and their top interacting hub genes were determined to provide a further understanding of the signaling pathways and biological processes affected. Potential drugs were screened based on the upregulated and downregulated hub genes, which identified drug candidates that have known anti-inflammatory effects, implying the potential of specific inflammatory pathways in estrogen-dependent gynecological diseases as a therapeutic avenue. Gynecological diseases are triggered by aberrant molecular pathways that alter gene expression, hormonal balance, and cellular signaling pathways, which may lead to long-term physiological consequences. This study was able to identify highly preserved modules and key hub genes that are mainly associated with gynecological diseases, represented by endometriosis (EM), ovarian cancer (OC), cervical cancer (CC), and endometrial cancer (EC), through the weighted gene co-expression network analysis (WGCNA) of microarray datasets sourced from the Gene Expression Omnibus (GEO) database. Five highly preserved modules were observed across the EM (GSE51981), OC (GSE63885), CC (GSE63514), and EC (GSE17025) datasets. The functional annotation and pathway enrichment analysis revealed that the highly preserved modules were heavily involved in several inflammatory pathways that are associated with transcription dysregulation, such as NF-kB signaling, JAK-STAT signaling, MAPK-ERK signaling, and mTOR signaling pathways. Furthermore, the results also include pathways that are relevant in gynecological disease prognosis through viral infections. Mutations in the ESR1 gene that encodes for ERα, which were shown to also affect signaling pathways involved in inflammation, further indicate its importance in gynecological disease prognosis. Potential drugs were screened through the Drug Repurposing Encyclopedia (DRE) based on the up-and downregulated hub genes, wherein a bacterial ribosomal subunit inhibitor and a benzodiazepine receptor agonist were the top candidates. Other drug candidates include a dihydrofolate reductase inhibitor, glucocorticoid receptor agonists, cholinergic receptor agonists, selective serotonin reuptake inhibitors, sterol demethylase inhibitors, a bacterial antifolate, and serotonin receptor antagonist drugs which have known anti-inflammatory effects, demonstrating that the gene network highlights specific inflammatory pathways as a therapeutic avenue in designing drug candidates for gynecological diseases. [ABSTRACT FROM AUTHOR]

Ovarian cancer accounts for more deaths than any other female reproductive tract cancer. The major reasons for the high mortality rates include delayed diagnoses and drug resistance. Hence, improved diagnostic and therapeutic options for ovarian cancer are a pressing need. Extracellular vesicles (EVs), that include exosomes provide hope in both diagnostic and therapeutic aspects. They are natural lipid nanovesicles secreted by all cell types and carry molecules that reflect the status of the parent cell. This facilitates their potential use as biomarkers for an early diagnosis. Additionally, EVs can be loaded with exogenous cargo, and have features such as high stability and favorable pharmacokinetic properties. This makes them ideal for tumor-targeted delivery of biological moieties. The International Society of Extracellular Vesicles (ISEV) based on the Minimal Information for Studies on Extracellular Vesicles (MISEV) recommends the usage of the term "small extracellular vesicles (sEVs)" that includes exosomes for particles that are 30–200 nm in size. However, majority of the studies reported in the literature and relevant to this review have used the term "exosomes". Therefore, this review will use the term "exosomes" interchangeably with sEVs for consistency with the literature and avoid confusion to the readers. This review, initially summarizes the different isolation and detection techniques developed to study ovarian cancer-derived exosomes and the potential use of these exosomes as biomarkers for the early diagnosis of this devastating disease. It addresses the role of exosome contents in the pathogenesis of ovarian cancer, discusses strategies to limit exosome-mediated ovarian cancer progression, and provides options to use exosomes for tumor-targeted therapy in ovarian cancer. Finally, it states future research directions and recommends essential research needed to successfully transition exosomes from the laboratory to the gynecologic-oncology clinic. [ABSTRACT FROM AUTHOR]

Background: This study aims to develop and validate a pretreatment MRI-based radiomics model to predict lymph node metastasis (LNM) following neoadjuvant chemotherapy (NACT) in patients with locally advanced cervical cancer (LACC). Methods: Patients with LACC who underwent NACT from two centers between 2013 and 2022 were enrolled retrospectively. Based on the lymph node (LN) status determined in the pathology reports after radical hysterectomy, patients were categorized as LN positive or negative. The patients fromcenter 1 were assigned as the training set while those from center 2 formed the validation set. Radiomics features were extracted from pretreatment sagittal T2-weighted imaging (Sag-T2WI), axial diffusion-weighted imaging (Ax-DWI), and the delayed phase of dynamic contrast-enhanced sagittal T1-weighted imaging (Sag-T1C) for each patient. The K-best and least absolute shrinkage and selection operator (LASSO) methods were employed to reduce dimensionality, and the radiomics features strongly associated with LNM were selected and used to construct three singlesequence models. Furthermore, clinical variables were incorporated through multivariate regression analysis and fused with the selected radiomics features to construct the clinical-radiomics combined model. The diagnostic performance of the models was assessed using receiver operating characteristic (ROC) curve analysis. The clinical utility of the models was evaluated by the area under the ROC curve (AUC) and decision curve analysis (DCA). Results: A total of 282 patients were included, comprising 171 patients in the training set, and 111 patients in the validation set. Compared to the Sag-T2WI model (AUC, 95%CI, training set, 0.797, 0.722-0.782; validation set, 0.648, 0.521-0.776) and the Sag-T1C model (AUC, 95%CI, training set, 0.802, 0.723-0.882; validation set, 0.630, 0.505-0.756), the Ax-DWI model exhibited the highest diagnostic performance with AUCs of 0.855 (95%CI, 0.791-0.919) in training set, and 0.753 (95%CI, 0.638-0.867) in validation set, respectively. The combined model, integrating selected features from three sequences and FIGO stage, surpassed predictive ability compared to the single-sequence models, with AUC of 0.889 (95%CI, 0.833-0.945) and 0.859 (95%CI, 0.781-0.936) in the training and validation sets, respectively. Conclusions: The pretreatment MRI-based radiomics model, integrating radiomics features from three sequences and clinical variables, exhibited superior performance in predicting LNM following NACT in patients with LACC. [ABSTRACT FROM AUTHOR]

The excretory–secretory proteome plays a pivotal role in both intercellular communication during disease progression and immune escape mechanisms of various pathogens including cestode parasites like Taenia solium. The cysticerci of T. solium causes infection in the central nervous system known as neurocysticercosis (NCC), which affects a significant population in developing countries. Extracellular vesicles (EVs) are 30–150‐nm‐sized particles and constitute a significant part of the secretome. However, the role of EV in NCC pathogenesis remains undetermined. Here, for the first time, we report that EV from T. solium larvae is abundant in metabolites that can negatively regulate PI3K/AKT pathway, efficiently internalized by macrophages to induce AKT and mTOR degradation through auto‐lysosomal route with a prominent increase in the ubiquitination of both proteins. This results in less ROS production and diminished bacterial killing capability among EV‐treated macrophages. Due to this, both macro‐autophagy and caspase‐linked apoptosis are upregulated, with a reduction of the autophagy substrate sequestome 1. In summary, we report that T. solium EV from viable cysts attenuates the AKT–mTOR pathway thereby promoting apoptosis in macrophages, and this may exert immunosuppression during an early viable stage of the parasite in NCC, which is primarily asymptomatic. Further investigation on EV‐mediated immune suppression revealed that the EV can protect the mice from DSS‐induced colitis and improve colon architecture. These findings shed light on the previously unknown role of T. solium EV and the therapeutic role of their immune suppression potential. [ABSTRACT FROM AUTHOR]

The text provides an overview of the historical context and ongoing challenges surrounding equal citizenship rights in the United States. It discusses the impact of various Supreme Court decisions, including the veto of a Reconstruction-era statute and rulings on discrimination cases. The text emphasizes the importance of social movements and public engagement in shaping constitutional meaning and encourages individuals to uphold the ideal of equal citizenship, despite potential limitations from the current Court majority. [Extracted from the article]

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic β-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis. [ABSTRACT FROM AUTHOR]

Background & Objective: Endometrial Carcinoma (EC) is the most common gynecological cancer with a global incidence of 23.2 per 1 lakh population. Histological subclassification of EC is extremely crucial for the diagnosis, proper management strategies, and prognosis. This study was conducted in a tertiary care institute to analyze the expression pattern of a minimum panel of 4 markers (ER, p53, CEA, Napsin A) with emphasis on their utility in the routine histological subtyping, aberrant expression, and correlation with various clinicopathological parameters. Methods: A time-bound cross-sectional observational and analytical study was conducted, which includes cases diagnosed in our laboratory from January 2016 to April 2021. Results: Sixty cases diagnosed as EC during the study period formed the sample cases. The ER was expressed in 85% (53/60) of cases in the current study. Among them, 94% (50/53) were endometrioid endometrial carcinomas (EECs). A negative correlation was found between ER intensity and age (r= -1.48). Of 60 EC cases, 10 (16%) cases expressed p53. The tumors positive for p53 with higher intensity were negative for ER and vice versa. The expression pattern of ER and p53 was statistically significant (P=-0.021). On IHC, 84.6% (11/13) of CEA-positive cases expressed both ER and CEA, suggesting mucinous differentiation. Napsin A was expressed in two cases of EEC, FIGO grade I, and one case of serous carcinoma. Conclusion: An inverse association was found between ER and p53 expression. The CEA is valuable in identifying EEC with mucinous differentiation. [ABSTRACT FROM AUTHOR]

In 2022 to 2023, the U.S. Court of Appeals for the Federal Circuit (“Federal Circuit”) continued its conversation with the Court of Appeals for Veterans Claims (“Veterans Court”), Department of Veterans Affairs (“VA”), and veterans to help sculpt the jurisprudence coming from the youngest of the federal courts, the Veterans Court. The Federal Circuit’s jurisprudence addressed ten main legal issues: class actions, petitions for writ of mandamus under the All Writs Act, defining standards of proof with the term “results from,” the benefit of the doubt doctrine post-Lynch, education benefits, less than honorable discharges, the rating schedule, implicit denials, equitable tolling and estoppel, and prejudicial error post-Tadlock. [ABSTRACT FROM AUTHOR]

A corporation controlled by a majority shareholder may engage in selfdealings that harm the interests of the minority shareholders. If a minority shareholder challenges the decision in court, what should be the appropriate methods for judicial decision-making? Theoretically, courts can choose between balancing or structured decision-making. Existing studies show that balancing has signifcant advantages over structured decision procedures in antitrust, discrimination law, and constitutional law. This article develops an economic theory to illustrate the advantages of structured decision-making in the context of corporate law. In Delaware, courts have adopted the structured decision-making method in the protection of minority shareholders. The underlying rationale for Delaware courts’ approach can be illustrated using the law and economics theory of property rule and liability rule protection for minority rights. Delaware courts have essentially applied a combination of property rules and liability rules, an approach that this article refers to as “structured pliability rules,” to protect minority shareholders. Courts can incorporate the consent of minority shareholders into their judicial rulings through the implementation of structured decision-making approaches, thereby altering the probabilities of success for various parties depending on whether the decision has received approval from a majority of minority shareholders. The theory of structured pliability rules presented in this article has significant explanatory and normative implications. It explains the underlying rationale of Delaware law regarding self-dealings, offers normative guidance for the design of judicial decision-making methods in appraisal actions, and provides insights on enhancing corporate law in other jurisdictions. Furthermore, this article contends that structured pliability rules should extend beyond corporate self-dealings and be applied in other scenarios involving majority-minority conficts. It further explores the potential application of structured pliability rules in the judicial review of constitutional law pertaining to takings. In cases where a government intends to expropriate private lands, courts should employ distinct decision-making rules based on the level of approval among the affected landowners. [ABSTRACT FROM AUTHOR]

The central purpose of corporate law is to facilitate the relationship between the shareholders who provide the corporation’s equity capital and the managers who make the bulk of corporate decisions. Although select aspects of corporate law consider the economic merits of those decisions (“substance”), the bulk of corporate law regulates the procedures by which a corporation’s managers reached those decisions (“process”). Moreover, recent judicial decisions have tended to push corporate law even further toward process-centered considerations. Courts have defended such tendencies on the basis that the courts charged with reviewing disputed corporate decisions are often better at evaluating process than engaging in financial analysis, an argument with which this Article largely agrees. [ABSTRACT FROM AUTHOR]

This Article describes the emergence of corporate law federalism across a long twentieth century. The period begins with New Jersey’s successful initiation of charter competition in 1888 and ends with the enactment of the Sarbanes-Oxley Act in 2002. The federalism in question describes the interrelation of state and federal regulation of corporate internal affairs. This Article takes a positive approach, pursuing no normative bottom line. It makes six observations: (1) the federalism describes a division of subject matter, with internal affairs regulated by the states and securities issuance and trading regulated by the federal government; (2) the federalism is an artifact of history rather than an instantiation or reflection of a theory of government; (3) competition for charters at the state level resulted in a stable, as opposed to a volatile legal regime; (4) just as economic contractions lead to new regulatory constraints on the conduct of business, so do economic expansions lead to increased regulatory slack; (5) even though regulation on the ground never fully adhered to the subject matter division, the division became increasingly salient over time, taking on positive normative implications; and (6) federal lawmakers came to adhere to a norm of noninterference in state regulation of internal affairs. [ABSTRACT FROM AUTHOR]

The article analyzes and refutes the expressio unius, diversion of funds, and unconstitutional conditions objections that school voucher opponents raise against the programs. Topics include why expressio unius should not apply to state education articles and how the Florida court erroneously reached the opposite conclusion, argument on the lack of jurisdiction of the courts to mandate how states remedy funding deficiencies in public schools, and the unconstitutional conditions doctrine.

Objective: Benign Brenner tumor (BBT) is a rare ovarian tumor, and there are few discrete reports about its manifestation in an ultrasound. This study sought to investigate the two-dimensional (2D) and contrast-enhanced ultrasound (CEUS) features of this entity. Methods: This is a retrospective single-center study. The clinical manifestations, laboratory examination, and ultrasound data of 25 female patients with BBT were confirmed by pathology when they underwent 2D and/or CEUS examination at Ningbo First Hospital from January 2012 to June 2023. The ultrasound findings of the patients were analyzed using the terminology of the International Organization for the Analysis of Ovarian Tumor and were read by two senior sonographers who reached an agreement. Results: Among the all 25 patients, most of them were unilateral, and only one patient was bilateral. Thus, 26 lesions were found: 44.0% (11/25) were in the left and 52.0% (13/25) were in the right. Moreover, 53.84% (14/26) were solid lesions, 15.38% (4/26) were mixed lesions, and 26.92% (7/26) were cystic lesions. Among the solid-type patients, 42.85% (6/14) of the cases were with calcification. Upon laboratory examination, 12.0% (3/25) of the patients had high carbohydrate antigen 125 (CA-125) level, and 19.04% (4/21) of the patients had an elevated carbohydrate antigen724 (CA-724) level in the serum tumor markers. In the hormone test, 14.28% (3/21) were found to have a high postmenopausal estrogen level and 14.28%(3/21) were found to have a high level of follicle-stimulating hormone (FSH). One patient with complex manifestations and three with solid manifestations were examined by CEUS to observe the microcirculation perfusion of the tumor. One with solid and cystic separation was rapidly hyperenhanced and cleared, and the filling subsided faster than the uterus. The postoperative pathological diagnosis was benign Brenner tumor with mucinous cystadenoma. The other three cases were solid adnexal lesions, which showed isoenhancement on CEUS and disappeared slowly, synchronizing with the uterus. The CEUS results were considered as benign tumors and confirmed by pathology. Conclusions: BBT can show ovarian cystic, mixed cystic and solid type, and solid echo in 2D ultrasound. Unilateral ovarian fibrosis with punctate calcification is an important feature of BBT in 2D ultrasound. However, for solid adnexal masses and mixed cystic and solid masses with unclear diagnosis, if CEUS shows isoenhancement or hyperenhancement, the possibility of BBT cannot be excluded. [ABSTRACT FROM AUTHOR]

Simple Summary: In situ/microinvasive adenocarcinoma of the uterine cervix represents the majority of cervical glandular lesions and can be treated conservatively. In contrast to squamous lesions, approximately 15–20% of glandular disease may be HPV-negative and therefore associated with a worse prognosis. Furthermore, up to 4% of cases may show recurrence after three years of follow-up. Given the abovementioned risk, knowing the predictive factors of disease recurrence becomes crucial for post-treatment management. In the present study, HPV testing in follow-up was the best predictor for recurrences in women with in situ/microinvasive AC undergoing conservative treatment. So, its use in clinical practice is of pivotal importance. However, attention should be paid to non-high-risk HPV women in follow-up with non-usual-type histopathology, given that it seems to represent a sub-population at increased risk of recurrences. Objective: The present study aimed to assess long-term follow-up outcomes in women with in situ/microinvasive adenocarcinoma (AC) of the uterine cervix treated conservatively. Methods: Retrospective multi-institutional study including women with early glandular lesions and 5-year follow-up undergoing fertility-sparing treatment. Independent variables associated with recurrence were evaluated. Logistic regression analysis and Kaplan–Meier survival analysis with Logrank test were performed. Results: Of 269 women diagnosed with in situ/microinvasive AC, 127 participants underwent conservative treatment. During follow-up, recurrences were found in nine women (7.1%). The only factor associated with recurrence during follow-up was positive high-risk Human Papillomavirus (hr-HPV) testing (odds ratio 6.21, confidence interval 1.47–26.08, p = 0.012). HPV positivity in follow-up showed a recurrence rate of 21.7% against 3.8% in patients who were HPV-negative (p = 0.002, Logrank test). Among women with negative high-risk HPV tests in follow-up, recurrences occurred in 20.0% of non-usual-type histology vs. 2.1% of usual-type cases (p = 0.005). Conclusion: HPV testing in follow-up is of pivotal importance in women with early glandular lesions undergoing conservative treatment, given its recurrence predictive value. However, women who are high-risk HPV-negative in follow-up with non-usual-type histopathology may represent a sub-population at increased risk of recurrences. Further studies should confirm these findings. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis mutilans (PAM) is the rarest and most severe form of psoriatic arthritis, characterized by erosions of the small joints and osteolysis leading to joint disruption. Despite its severity, the underlying mechanisms are unknown, and no susceptibility genes have hitherto been identified. We aimed to investigate the genetic basis of PAM by performing massive parallel sequencing in sixty-one patients from the PAM Nordic cohort. We found rare variants in the NADPH oxidase 4 (NOX4) in four patients. In silico predictions show that the identified variants are potentially damaging. NOXs are the only enzymes producing reactive oxygen species (ROS). NOX4 is specifically involved in the differentiation of osteoclasts, the cells implicated in bone resorption. Functional follow-up studies using cell culture, zebrafish models, and measurement of ROS in patients uncovered that these NOX4 variants increase ROS levels both in vitro and in vivo. We propose NOX4 as the first candidate susceptibility gene for PAM. Our study links high levels of ROS caused by NOX4 variants to the development of PAM, offering a potential therapeutic target. Synopsis: Genomic analysis of Psoriatic Arthritis Mutilans (PAM) patients from the Nordic PAM cohort uncovered potentially damaging rare variants in the NOX4 gene. NOX4 belongs to a family of enzymes generating reactive oxygen species (ROS); NOX4 generates mainly hydrogen peroxide (H2O2). Three NOX4 rare variants (p.V369F, p.Y512IfsX20, and p.Y512C) affecting NOX4 functional domains were identified in four PAM patients. Enhanced differentiation and higher generation of ROS activity are observed in patient-derived osteoclasts, the cells responsible for bone resorption. NOX4 rare variants show increased generation of ROS in both zebrafish model and HEK293 cells. Increased levels of ROS, particularly H2O2, present promising therapeutic opportunities for addressing PAM. Genomic analysis of Psoriatic Arthritis Mutilans (PAM) patients from the Nordic PAM cohort uncovered potentially damaging rare variants in the NOX4 gene. NOX4 belongs to a family of enzymes generating reactive oxygen species (ROS); NOX4 generates mainly hydrogen peroxide (H2O2). [ABSTRACT FROM AUTHOR]

High‐grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of ovarian cancer, ranks among the deadliest malignancies. Many HGSC patients have excess fluid in the peritoneum called ascites. Ascites is a tumour microenvironment (TME) containing various cells, proteins and extracellular vesicles (EVs). We isolated EVs from patients' ascites by orthogonal methods and analyzed them by mass spectrometry. We identified not only a set of 'core ascitic EV‐associated proteins' but also defined their subset unique to HGSC ascites. Using single‐cell RNA sequencing data, we mapped the origin of HGSC‐specific EVs to different types of cells present in ascites. Surprisingly, EVs did not come predominantly from tumour cells but from non‐malignant cell types such as macrophages and fibroblasts. Flow cytometry of ascitic cells in combination with analysis of EV protein composition in matched samples showed that analysis of cell type‐specific EV markers in HGSC has more substantial prognostic potential than analysis of ascitic cells. To conclude, we provide evidence that proteomic analysis of EVs can define the cellular composition of HGSC TME. This finding opens numerous avenues both for a better understanding of EV's role in tumour promotion/prevention and for improved HGSC diagnostics. [ABSTRACT FROM AUTHOR]

The recent release of Justice John Paul Stevens's papers for the Supreme Court's 1995 term reveals the existence of a previously unknown proposed concurring opinion in the seminal 1996 case Romer v. Evans. That proposed concurrence, co-authored by Justices O'Connor and Breyer, would have emphasized the failure of the challenged law, Colorado's Amendment 2, to satisfy traditional rational basis equal protection review, rather than the law's grounding in anti-LGB animus. Had the concurrence been published, it might have blunted the renewal of animus doctrine, with fascinating implications for subsequent constitutional doctrine involving issues as disparate as LGBT rights, immigration, and religious freedom. This Article is the first work of scholarship to identify this opinion and examine its implications. Of course, that concurrence was never published. Nevertheless, the Justices' negotiations over how much of that concurrence's content should be incorporated into Justice Kennedy's majority opinion, as recounted in correspondence in Justice Stevens's papers, teaches important lessons about the evolution of constitutional doctrine. In particular, the process by which Romer took its final form reminds us that the creation of judicial doctrine is rife with contingencies that belie any view of such creation as a straight-line process free of extraneous and distracting elements. Those lessons are important for us today, despite the fact that the proposed concurrence this Article reveals was never published. [ABSTRACT FROM AUTHOR]

Pelvic lymphoceles are collections of leaked lymphatic fluid which can be postsurgical complications. These are most prevalent following a radical prostatectomy with simultaneous pelvic node dissection to address prostate cancer. Although a common occurrence after this type of procedure, a small percentage may cause significant complications, including deep vein thrombosis. This case study demonstrated an obstructive pelvic lymphocele that was incidentally detected with sonography, during a lower extremity venous Doppler examination. [ABSTRACT FROM AUTHOR]

The board's fiduciary duties are the bedrock of corporate law. Bankruptcy trustees also owe fiduciary duties to the "bankruptcy estate." But corporations in bankruptcy rarely worry about fiduciary duties, even those corporations in chapter 11 reorganization cases, when the company is supposed to act as if it were the bankruptcy trustee. At the same time, modern chapter 11 is increasingly seen as "problematic." Opportunism runs unchecked. This Article argues that these two points are directly connected: the underdevelopment of a corporate debtor's fiduciary duties enables the abuses seen in modern chapter 11. I thus use this Article to frame bankruptcy-specific corporate fiduciary duties and then identify several common instances in which the debtor-corporation's board must act to meet those duties. This Article is the first to analyze the debtor's fiduciary duties from a perspective that integrates the literature on chapter 11 corporate governance and broader corporate bankruptcy policy considerations. While the articles identifying problems with modern chapter 11 are legion, those offering solutions are rare. [ABSTRACT FROM AUTHOR]

This Article breaks new ground with its proposal that litigators should consider the First Amendment to combat the avalanche of state legislation stripping transgender, gender nonconforming, intersex, and queer ("TGNCI") people of their rights. In the last year, opinions from the U.S. Federal Courts of Appeals for the Sixth and Eleventh Circuits have used lawsuits challenging anti-TGNCI legislation to roll back decades of progress made under the Equal Protection Clause for transgender people. This Article answers the question of where litigators should turn next and suggests that anti-TGNCI legislation is a form of First Amendment viewpoint discrimination. Specifi- cally, anti-TGNCI legislation erases protected expression while compelling people to abandon sincerely held beliefs about gender and sexuality in favor of the state's immutable perspective. This Article provides guidance to those interested in TGNCI justice by analyzing the use of this theory in the context of anti-TGNCI bathroom legislation. In particular, it focuses on Women in Struggle v. Bain, a recent as-applied challenge to Florida Statute Section 553.865, which criminalizes the use of affirming restrooms by TGNCI people. Finally, this Article identifies potential counterarguments that litigators must grapple with in order to advance the long battle for TGNCI liberation using the First Amendment as a tool. [ABSTRACT FROM AUTHOR]

The article titled "ONE-OFFS" by William D. Araiza explores the concept of court opinions known as "one-offs." These are opinions that are rarely cited by the court that issued them and do not generate further doctrinal development. The article examines three cases that are considered one-offs and analyzes their role in legal and doctrinal development. It concludes that while one-offs can play a useful role in the work of an apex court, they also stand in an uneasy relationship with cases that may be overruled or neglected. The article provides insights into the creation and evolution of judicial doctrine and highlights the relevance of the one-off idea in recent Supreme Court cases. [Extracted from the article]

Background and Objectives: An extracellular vesicle is part of a class of submicron particles derived from cells, mediating cellular crosstalk through microRNA (miRNA). MiRNA is a group of RNA molecules, each of which consists of 15–22 nucleotides and post-transcriptionally modulates gene expression. The complementary mRNAs—onto which the miRNAs hybridize—are involved in processes such as implantation, tumor suppression, proliferation, angiogenesis, and metastasis that define the entire tumor microenvironment. The endometrial biopsy is a standard technique used to recognize cellular atypia, but other non-invasive markers may reduce patient discomfort during the use of invasive methods. The present study aims to examine the distribution and the regulation of the differentially expressed miRNAs (DEMs) and EV-derived substances in women with endometrial cancer. Materials and Methods: We systematically searched the PubMed, EMBASE, Scopus, Cochrane Library, and ScienceDirect databases in April 2023, adopted the string "Endometrial Neoplasms AND Exosomes", and followed the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We selected all the studies that included patients with endometrial cancer and that described the regulation of miRNA molecules in that context. The differences in molecule expression between patients and controls were evaluated as significant when the proteins had a fold change of ±1.5. Results: Seventeen records fulfilled the inclusion criteria: a total of 371 patients and 273 controls were analyzed. The upregulated molecules that had the widest delta between endometrial cancer patients and controls—relative expression ≥ 1 > 3 log2(ratio)—were miR-20b-5p, miR-204-5p, miR-15a-5p, and miR-320a. In particular, miR-20b-5p and miR-204-5p were extracted from both serum and endometrial specimens, whereas miR-15a-5p was only isolated from plasma, and miR-320a was only extracted from the endometrial specimens. In parallel, the most downregulated miRNA in the endometrial cancer patients compared to the healthy subjects was miR-320a, which was found in the endometrial specimens. Conclusions: Although their epigenetic regulation remains unknown, these upregulated molecules derived from EVs are feasible markers for the early detection of endometrial cancer. The modulation of these miRNA molecules should be assessed during different treatments or if recurrence develops in response to a targeted treatment modality. [ABSTRACT FROM AUTHOR]

States are modernizing the use of equitable remedies for state law. Their authority to do so is widely accepted. But one thing stands in the way--the federal courts. Bound by "traditional equitable principles," federal courts dismiss state law claims seeking equitable remedies, even when state law makes the litigant's desired remedy available. Problematically, it is not clear where those traditional equitable principles come from, nor why or how they supplant state law--the very inquiries that the renowned Erie case requires. This Article examines what happens when traditional equitable principles face off against contemporary state law remedies. The resolution offered here preserves state law's remedial design while also accounting for traditional understandings of the federal judicial role in awarding equitable remedies. This Article argues that the traditional principles of equity should be understood as limitations on federal court subject matter jurisdiction. In fact, these principles historically served a jurisdictional function and continue to operate precisely like jurisdictional limits in operation and purpose but lack the formal classification. While federal courts frequently reference their "equitable jurisdiction," there has been no attempt to doctrinally justify traditional equitable principles as jurisdictional and entitled to the treatment that comes with the label. This Article provides that justification. To the extent that state remedial law exceeds the bounds of federal court jurisdiction, therefore, such cases should be adjudicated by state courts with the authority to act beyond equity's traditional limitations. [ABSTRACT FROM AUTHOR]

Financial investigations in the realm of fraud detection demand rigorous data analysis to identify anomalies and inform decision-making. This paper demonstrates the importance of data visualization as a means of conducting initial assessments of testable datasets to validate their suitability and promptly detect unexpected patterns before delving deeper into investigations. Using the publicly available PAYSIM dataset as a case study, we analyzed 6,362,620 records, of which 8213 were fraudulent and the remainder were legitimate. The dataset comprised 9 features and a single target class. Our analysis reveals the powerful role of visualization in identifying early indications of incompatibility with the dataset and guiding analysts to question its fitness for the context at hand. In particular, we show how visualization can highlight key findings and provide an added emphasis to the results. Through visual and numerical analysis, we demonstrate the importance of identifying potential outliers and other anomalies before proceeding with data preprocessing and modeling. Our results suggest that visual analysis of data is an essential step in detecting fraudulent activities in mobile money transactions. This approach can help to improve the accuracy and efficiency of fraud detection systems, thereby protecting users from financial losses. We conclude that data visualization should be an integral part of any data analysis project, especially in the field of fraud detection, to ensure the validity and suitability of the data before proceeding with further investigations. [ABSTRACT FROM AUTHOR]

The article analyzes whether the resurrection of the irreparable harm presumption in false advertising cases under the U.S. Trademark Modernization Act of 2020 is a beneficial policy choice. Topics include a background information on the history and principles surrounding injunctions, the Supreme Court's rulings in the case eBay v. MercExchange related to presumption of irreparable harm, and anti-presumption advocates' arguments against the presumption due to longstanding equitable concerns.

The study aimed at exploring the miR-143-3p expression and the mechanism involved in ovarian cancer development. RT-qPCR (Quantitative Real-time PCR) served for the detection of the miR-143-3p level in different ovarian carcinoma cells. Then miR-143-3p underwent transfection and presented overexpression in ovarian carcinoma cells. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, flat cloning experiment, Transwell invasion assay and scratch test served for the evaluation of the influences of miR-143-3p on ovarian cancer cell biological behavior. The candidate target genes were screened by using bioinformatics method. The double luciferase assay and Western blot together assessed the regulatory effect of miR-143- 3p. Relative to the control group (NC), the overexpressed group presented significantly reduced ovarian cancer cell growth (p < 0.01). The results indicated the inhibitory impact of miR-143-3p overexpression on the invasion and migration of ovarian cancer 3AO and SKOV3 cells. Bioinformatics analysis confirmed FGF-9 (Fibroblast Growth Factor 9) as one of target gene of miR-143-3p. Double luciferase assay also attested the direct negative regulatory impact of miR-143-3p on FGF-9 (p < 0.05). The miR-143- 3p overexpression significantly lowered the protein level of FGF-9 in 3AO and SKOV3 cells (p < 0.001). miR-143-3p overexpression negatively regulated the proliferation, invasion and migration abilities of ovarian carcinoma cells, as well as the FGF-9 protein expression. [ABSTRACT FROM AUTHOR]

Our previous study found that miR‐26a alleviates aldosterone‐induced tubulointerstitial fibrosis (TIF). However, the effect of miR‐26a on TIF in diabetic kidney disease (DKD) remains unclear. This study clarifies the role and possible mechanism of exogenous miR‐26a in controlling the progression of TIF in DKD models. Firstly, we showed that miR‐26a was markedly decreased in type 2 diabetic db/db mice and mouse tubular epithelial cells (mTECs) treated with high glucose (HG, 30 mM) using RT‐qPCR. We then used adeno‐associated virus carrying miR‐26a and adenovirus miR‐26a to enhance the expression of miR‐26a in vivo and in vitro. Overexpressing miR‐26a alleviated the TIF in db/db mice and the extracellular matrix (ECM) deposition in HG‐stimulated mTECs. These protective effects were caused by reducing expression of protease‐activated receptor 4 (PAR4), which involved in multiple pro‐fibrotic pathways. The rescue of PAR4 expression reversed the anti‐fibrosis activity of miR‐26a. We conclude that miR‐26a alleviates TIF in DKD models by directly targeting PAR4, which may provide a novel molecular strategy for DKD therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Sentinel lymph node (SLN) mapping has been introduced to endometrial cancer treatment as an alternative to lymph node dissection for lymph node staging. Lymphovascular space invasion (LVSI) is a known prognostic risk factor in endometrial cancer and is associated with lymph node metastasis and worse outcomes. This study shows that LVSI is an independent predictor of recurrence in node-negative endometrial cancer patients with SLN mapping alone. The negative predictive value of sentinel lymph node mapping is significantly lower in LVSI-positive endometrial cancer patients. Due to these findings, importance should be attached to LVSI in early-stage endometrial cancer patients with negative SLN mapping, and adjuvant therapy should be discussed more thoroughly in these cases. Background: SLN mapping has emerged as a standard of care in endometrial cancer due to its high sensitivity and significant reduction in morbidity. Although lymphovascular space invasion (LVSI) is a known risk factor for lymph node metastasis and recurrence, evidence on the reliability of SLN mapping in LVSI-positive patients is scarce. The aim of this study was to determine the impact of LVSI on the diagnostic performance of SLN mapping. Methods: This retrospective cohort study included patients with endometrial cancer who underwent primary surgical treatment at the Bern University Hospital, Switzerland, between 2012 and 2022. Results: LVSI was present in 22% of patients and was significantly associated with lymph node metastasis (p < 0.001) and recurrence (p < 0.001). In node-negative patients with only SLN mapping performed, LVSI was an independent predictor of recurrence during multivariable Cox regression analysis (p = 0.036). The negative predictive value of SLN mapping was 91.5% and was significantly lower in tumors with LVSI (75.0%) compared to LVSI-negative tumors (95.6%, p = 0.004). Conclusion: The presence of LVSI was significantly associated with worse oncological outcomes. LVSI was an independent predictor of recurrence in node-negative patients with only SLN mapping performed. Furthermore, the negative predictive value of SLN mapping was significantly lower in LVSI-positive tumors. [ABSTRACT FROM AUTHOR]

The article discusses the challenges faced by socially conscious corporations, particularly in cases where they are wholly owned subsidiaries of profit-oriented parent companies. It argues that the current legal system does not adequately address these conflicts and proposes a solution involving a two-tiered governance structure for corporations committed to activism.

Many scholars study Supreme Court decisions, but few are attentive to the rhetoric the Court uses to articulate its holdings. This omission is perplexing: the Court’s rhetoric literally becomes law, but scholars typically fixate on the substance, rather than the rhetoric, of its communications. In this Article, I argue that legal scholars should take more seriously the Court’s role as a rhetorical actor. To illustrate this, I analyze the rhetorical effects of the language the Court uses to describe women and mothers in three contexts: gender discrimination, immigration, and abortion. I begin by describing the “inherited language” of motherhood—that is, the narratives, themes, and connotations that are traditionally associated with the idea of motherhood. I then use close readings and discourse analysis of landmark decisions in each substantive area to consider whether and how the Supreme Court engages with that inherited language. My analysis reveals that the Court’s relationship with the inherited language of motherhood varies across contexts. In cases dealing with gender discrimination, the Court anxiously distances itself from traditional narratives about motherhood. In immigration cases, it both embraces and rejects the inherited language. And in abortion cases, its approach has shifted: initially, the Court strongly disavowed inherited narratives, but in its most recent abortion case, Dobbs v. Jackson Women’s Health Organization, it says very little about mothers at all. My analysis also suggests the Court’s attitude toward the inherited language of motherhood may be correlated with the substantive legal outcome in a case: the Court seems to most emphatically reject the inherited language in decisions that protect and reaffirm women’s rights. These findings illustrate why legal scholars should be more attentive to the Supreme Court’s rhetoric. The correlation between the Court’s language and substantive outcomes suggests that in some cases, the Court’s rhetorical decisions might influence or even determine its legal analysis. If that is true, then scholars who are interested in case outcomes should study the Court’s language. But the Court’s rhetoric does not just shape case outcomes; it also alters the way we understand, engage with, and view one another. When the Court uncritically invokes traditional narratives about women and mothers, it may—for better or for worse—perpetuate and reconstitute a world where certain assumptions govern. When it actively distances itself from traditional narratives, as it does in gender discrimination cases and early abortion cases, it creates legal and rhetorical space for women to enact various modes of motherhood and womanhood. And when the Court ignores the inherited language of motherhood, it frames legal debates as if women’s interests are not at stake and, in doing so, obscures women’s perspectives, needs, and lived experiences. Scholars interested in the ways law shapes relationships and facilitates identity formation should pay attention to these constitutive effects. [ABSTRACT FROM AUTHOR]

Abrupt and rapid changes in human societies are among the most exciting population phenomena. Human populations tend to show rapid expansions from low to high population density along with increased social complexity in just a few generations. Such demographic transitions appear as a remarkable feature of Homo sapiens population dynamics, most likely fuelled by the ability to accumulate cultural/technological innovations that actively modify their environment. We are especially interested in establishing if the demographic transitions of pre-historic populations show the same dynamic signature of the Industrial Revolution transition (a positive relationship between population growth rates and size). Our results show that population growth patterns across different pre-historic societies were similar to those observed during the Industrial Revolution in developed western societies. These features, which appear to have been operating during most of our recent demographic history from hunter–gatherers to modern industrial societies, imply that the dynamics of cooperation underlay sudden population transitions in human societies. This article is part of the theme issue 'Evolution and sustainability: gathering the strands for an Anthropocene synthesis'. [ABSTRACT FROM AUTHOR]

Anthropogenic planetary disruptions, from climate change to biodiversity loss, are unprecedented challenges for human societies. Some societies, social groups, cultural practices, technologies and institutions are already disintegrating or disappearing as a result. However, this coupling of socially produced environmental challenges with disruptive social changes—the Anthropocene condition—is not new. From food-producing hunter–gatherers, to farmers, to urban industrial food systems, the current planetary entanglement has its roots in millennia of evolving and accumulating sociocultural capabilities for shaping the cultured environments that our societies have always lived in (sociocultural niche construction). When these transformative capabilities to shape environments are coupled with sociocultural adaptations enabling societies to more effectively shape and live in transformed environments, the social–ecological scales and intensities of these transformations can accelerate through a positive feedback loop of 'runaway sociocultural niche construction'. Efforts to achieve a better future for both people and planet will depend on guiding this runaway evolutionary process towards better outcomes by redirecting Earth's most disruptive force of nature: the power of human aspirations. To guide this unprecedented planetary force, cultural narratives that appeal to human aspirations for a better future will be more effective than narratives of environmental crisis and overstepping natural boundaries. This article is part of the theme issue 'Evolution and sustainability: gathering the strands for an Anthropocene synthesis'. [ABSTRACT FROM AUTHOR]

The overall trajectory for the human–environment interaction has been punctuated by demographic boom-and-bust cycles, phases of growth/overshooting as well as of expansion/contraction in productivity. Although this pattern has been explained in terms of an interplay between population growth, social upscaling, ecosystem engineering and climate variability, the evoked demographic–resource-complexity mechanisms have not been empirically tested. By integrating proxy data for population sizes, palaeoclimate and internal societal factors into empirical modelling approaches from the population dynamic theory, we evaluated how endogenous (population sizes, warfare and social upscaling) and exogenous (climate) variables module the dynamic in past agrarian societies. We focused on the inland Atacama Desert, where populations developed agriculture activities by engineering arid and semi-arid landscapes during the last 2000 years. Our modelling approach indicates that these populations experienced a boom-and-bust dynamic over the last millennia, which was coupled to structure feedback between population sizes, hydroclimate, social upscaling, warfare and ecosystem engineering. Thus, the human–environment loop appears closely linked with cooperation, competition, limiting resources and the ability of problem-solving. This article is part of the theme issue 'Evolution and sustainability: gathering the strands for an Anthropocene synthesis'. [ABSTRACT FROM AUTHOR]

How did human societies evolve to become a major force of global change? What dynamics can lead societies on a trajectory of global sustainability? The astonishing growth in human population, economic activity and environmental impact has brought these questions to the fore. This theme issue pulls together a variety of traditions that seek to address these questions using different theories and methods. In this Introduction, we review and organize the major strands of work on how the Anthropocene evolved, how evolutionary dynamics are influencing sustainability efforts today, and what principles, strategies and capacities will be important to guide us towards global sustainability in the future. We present a set of synthetic insights and highlight frontiers for future research efforts which could contribute to a consolidated synthesis. This article is part of the theme issue 'Evolution and sustainability: gathering the strands for an Anthropocene synthesis'. [ABSTRACT FROM AUTHOR]