Surgical management of umbilical endometrioma within an umbilical hernia.

A nulliparous woman in her 40s is referred to gynaecological oncology secondary to umbilical pain and bleeding with menses. Examination revealed a blood-filled cystic mass within an umbilical hernia consistent with umbilical endometrioma. The patient exhausted medical management options, then pursued surgical management via umbilectomy, excision of umbilical endometriosis, lysis of adhesions and umbilical hernia repair.

Prognostic values of molecular subtypes and SWI/SNF protein expression in de-differentiated/undifferentiated endometrial carcinoma.

Aims: Classification and risk stratification of endometrial carcinoma (EC) has transitioned from histopathological features to molecular classification, e.g. the ProMisE classifier, identifying four prognostic subtypes: POLE mutant (POLEmut) with almost no recurrence or disease-specific death events, mismatch repair deficient (MMRd) and no specific molecular profile (NSMP), with intermediate outcome and p53 abnormal (p53abn) with poor outcomes.

Molecular Identification of Infection Using Nanopore Sequencing: A Case Report and Literature Review.

(previously known as ) infection is not common in Hong Kong. is a fish-borne cestode parasite that infects humans after consuming raw or insufficiently cooked fish containing plerocercoids. We reported a case of infection in a 40-year-old woman who presented with a complaint of epigastric pain and diarrhea.

Novel antimalarial 3-substituted quinolones isosteres with improved pharmacokinetic properties.

Aryl quinolone derivatives can target the cytochrome bc complex of Plasmodium falciparum, exhibiting excellent in vitro and in vivo antimalarial activity. However, their clinical development has been hindered due to their poor aqueous solubility profiles. In this study, a series of bioisosteres containing saturated heterocycles fused to a 4-pyridone ring were designed to replace the inherently poorly soluble quinolone core in antimalarial quinolones with the aim to reduce π-π stacking interactions in the crystal packing solid state, and a synthetic route was developed to prepare these alternative core derivatives.

Serum CA125 levels in the context of ProMisE molecular classification provides pre-operative prognostic information that can direct endometrial cancer management.

Objective: Previous research suggests serum CA125 reflects extra-uterine disease in patients with endometrial carcinoma (EC). Our objective was to determine if CA125 can identify patients with extra-uterine and/or nodal metastases, the association of this biomarker with EC molecular subtype, and to explore an optimal cutoff in this context.

Methods: We assessed the association of CA125 levels with clinicopathologic and outcomes data on a cohort of 1107 molecularly classified EC.

Evaluation of the safety, tolerability, pharmacokinetics and pharmacodynamics of SM17 in healthy volunteers: results from pre-clinical models and a first-in-human, randomized, double blinded clinical trial.

Background: Alarmins mediate type 2 T helper cell (Th2) inflammation and serve as upstream signaling elements in allergic inflammation and autoimmune responses. The alarmin interleukin (IL)-25 binds to a multi-domain receptor consisting of IL-17RA and IL-17RB subunits, resulting in the release of Th2 cytokines IL-4, IL-5, IL-9 and IL-13 to drive an inflammatory response. Therefore, the blockage of IL-17RB via SM17, a novel humanized monoclonal antibody, offers an attractive therapeutic target for Th2-mediated diseases, such as asthma.

Diversity in Naturally Acquired Immunity to Group B Streptococcus: A Comparative Study of Women from Bangladesh, Malawi, and the United Kingdom.

Background: Significant disparities in Group B Streptococcus (GBS) colonisation and neonatal disease rates have been documented across different geographical regions. For example, Bangladesh reports notably lower rates compared to the United Kingdom (UK) and Malawi. This study investigates whether this epidemiological variability correlates with the immune response to GBS in these regions.

Papillary and ductal patterns of mesonephric-like adenocarcinomas are often overlooked: a retrospective revaluation of over 1000 endometrial carcinomas.

Aims: Mesonephric-like adenocarcinoma (MLA) of the endometrium is often a diagnostic challenge, due to its morphological resemblance to other more common Müllerian neoplasms. This study aimed to retrospectively identify overlooked MLA in a large endometrial carcinoma cohort, using a combination of immunohistochemistry (IHC), morphology and KRAS sequencing.

Methods And Results: IHC was conducted on 1094 endometrial carcinomas, identifying 16 potential MLA cases based on GATA3+ and/or TTF1+ and ER- staining patterns, which subsequently underwent detailed histological review, KRAS sequencing and ProMisE molecular classification.

Divergent lineage trajectories and genetic landscapes in human gastric intestinal metaplasia organoids associated with early neoplastic progression.

Background: Gastric intestinal metaplasia (IM) is a precancerous stage spanning a morphological spectrum that is poorly represented by human cell line models.

Objective: We aim to establish and characterise human IM cell models to better understand IM progression along the cancer spectrum.

Design: A large human gastric IM organoid (IMO) cohort (n=28), their clonal derivatives and normal gastric organoids (n=42) for comparison were established.

Phage-derived polysaccharide depolymerase potentiates ceftazidime efficacy against Acinetobacter baumannii pneumonia via low-serum-dependent mechanisms.

The emergence of multidrug-resistant Acinetobacter baumannii (MDR-AB), which most commonly manifests as pneumonia, has posed significant clinical challenges and called for novel treatment strategies. Phage depolymerases, which degrade bacterial surface carbohydrates, have emerged as potential antimicrobial agents. However, their preclinical application is limited to systemic infections due to their dependency on serum-mediated bacterial killing.

Advancements in Targeting Macrophage Senescence for Age-Associated Conditions.

Macrophages, a critical subset of innate immune cells, play a pivotal role in cytokine production during disease progression, tissue injury, and pathogen invasion. Their intricate involvement in the manifestation of chronic low-grade inflammation associated with the aging process is widely acknowledged. Notably, in aged tissues, macrophages exhibit an altered phenotype characterized by an augmented synthesis of pro-inflammatory cytokines and chemokines, a profile intimately associated with a phenomenon known as inflammaging.

Validation and clinical performance of a single test, DNA based endometrial cancer molecular classifier.

Objectives: We have previously shown that DNA based, single test molecular classification by next generation sequencing (NGS) (Proactive Molecular risk classifier for Endometrial cancer (ProMisE) NGS) is highly concordant with the original ProMisE classifier and maintains prognostic value in endometrial cancer. Our aim was to validate ProMisE NGS in an independent cohort and assess the performance of ProMisE NGS in real world clinical practice to address if there were any practical challenges or learning points for implementation.

Methods: We evaluated DNA extracted from an external research cohort of 211 endometrial cancer cases diagnosed in 2016 from Germany, Switzerland, and Austria, across seven European centers, comparing standard molecular classification (NGS for status, immunohistochemistry for mismatch repair and p53) with ProMisE NGS (NGS for and microsatellite instability assay) for concordance metrics and Kaplan-Meier survival statistics across molecular subtypes.

Effect of prefabricated auxiliary devices in different optical properties and shapes on the accuracy of intraoral scanning of the edentulous arch with multiple implants: An in-vitro study.

Objectives: This study aimed to evaluate the impact of prefabricated auxiliary devices (PADs) in different optical properties and shapes on the accuracy of digital implant impressions.

Methods: An edentulous maxillary all-on-4 master model was fabricated. PADs were 3D-printed in different resin materials (Grey, Translucent, White, Yellow) and shapes (Cuboid, Cylinder, Sphere) using a 3D printer (AccuFab-C1s, 3DShining, Hangzhou, China).

Clinical implementation of the Validated Intraoperative Bleeding Scale: Perioperative patient management and effective team communication from the nurses' perspective.

Major bleeding represents a critical scenario that can quickly evolve into life threatening, thereby compromising patient safety. A Validated Intraoperative Bleeding Scale called VIBe Scale was introduced and studied as part of a quality improvement initiative. This study evaluated the clinical implementation of the VIBe Scale in perioperative patient management and team communication from the nurses' perspectives.

Genomic and biogeographic characterisation of the novel prasinovirus Mantoniella tinhauana virus 1.

Mamiellophyceae are a ubiquitous class of unicellular green algae in the global ocean. Their ecological importance is highlighted in studies focused on the prominent genera Micromonas, Ostreococcus, and Bathycoccus. Mamiellophyceae are susceptible to prasinoviruses, double-stranded DNA viruses belonging to the nucleocytoplasmic large DNA virus group.

Deep PSA response and extended time-to-nadir as robust predictors of survival in Asian patients with de novo metastatic hormone-sensitive prostate cancer receiving upfront intensified treatment.

Introduction: In de novo metastatic hormone-sensitive prostate cancer (mHSPC) treated with upfront intensification using androgen receptor signaling inhibitor or chemotherapy (Docetaxel), achieving a PSA nadir less than 0.2 ng/mL, indicative of superior survival in trials, may often be unattainable in real-world settings. We explored the predictive value of the degree of PSA decline and time to PSA nadir (TTPN) on oncological outcomes.

NetMIM: network-based multi-omics integration with block missingness for biomarker selection and disease outcome prediction.

Compared with analyzing omics data from a single platform, an integrative analysis of multi-omics data provides a more comprehensive understanding of the regulatory relationships among biological features associated with complex diseases. However, most existing frameworks for integrative analysis overlook two crucial aspects of multi-omics data. Firstly, they neglect the known dependencies among biological features that exist in highly credible biological databases.

The Supporting Emerging Adults With Diabetes (SEAD) Program: An Adult-Based Real-World Clinical Model That Improves Hospitalizations, Diabetes Technology Uptake, and Glycemic Outcomes in Underserved Young Adults With Type 1 Diabetes.

Objective: Underserved young adults (YA) with type 1 diabetes (T1D) experience the worst outcomes across the life span. We developed and integrated the Supporting Emerging Adults with Diabetes (SEAD) program into routine endocrinology care to address unmet social and medical challenges.

Research Design And Methods: This study was designed as a longitudinal cohort study, with prospective data collection over 4 years on YA in SEAD compared with usual endocrine care.

Normothermic ex vivo kidney perfusion preserves mitochondrial and graft function after warm ischemia and is further enhanced by AP39.

We previously reported that normothermic ex vivo kidney  perfusion (NEVKP) is superior in terms of organ protection compared to static cold storage (SCS), which is still the standard method of organ preservation, but the mechanisms are incompletely understood. We used a large animal kidney autotransplant model to evaluate mitochondrial function during organ preservation and after kidney transplantation, utilizing live cells extracted from fresh kidney tissue. Male porcine kidneys stored under normothermic perfusion showed preserved mitochondrial function and higher ATP levels compared to kidneys stored at 4 °C (SCS).

Childhood trauma, resilience, psychopathology and social functioning in schizophrenia: A network analysis.

The affective pathway to psychosis implicates affective symptoms and neuroticism as mediating steps between childhood trauma and symptoms of schizophrenia. Prior research seldom examined the interplay between childhood trauma, resilience, personality, social functioning and symptoms in schizophrenia patients. This study recruited 290 schizophrenia patients, and constructed a regularized partial correlation network of childhood trauma, resilience, big-five personality traits, symptoms and social functioning.

Cyclin A/B RxL Macrocyclic Inhibitors to Treat Cancers with High E2F Activity.

Cancer cell proliferation requires precise control of E2F1 activity; excess activity promotes apoptosis. Here, we developed cell-permeable and bioavailable macrocycles that selectively kill small cell lung cancer (SCLC) cells with inherent high E2F1 activity by blocking RxL-mediated interactions of cyclin A and cyclin B with select substrates. Genome-wide CRISPR/Cas9 knockout and random mutagenesis screens found that cyclin A/B RxL macrocyclic inhibitors (cyclin A/Bi) induced apoptosis paradoxically by cyclin B- and Cdk2-dependent spindle assembly checkpoint activation (SAC).