Gestational trophoblastic disease: understanding the molecular mechanisms of placental tumours.

Gestational trophoblastic disease (GTD) describes a group of rare benign and cancerous lesions originating from the trophoblast cells of the placenta. These neoplasms are unconventional entities, being one of the few instances in which cancer develops from the cells of another organism, the foetus. Although this condition was first described over 100 years ago, the specific genetic and non-genetic drivers of this disease remain unknown to this day.

Analyzing Pathophysiology and Immune Cells and Their Cytokines and Mediators in Precision-Cut Slices of the Murine Lung.

Understanding the dynamic pathophysiology of diseases in the lung, such as asthma and chronic asthma, chronic obstructive pulmonary disease, and lung cancer, is crucial for the treatment, analysis, and outcome of these diseases. Unlike other traditional models, we suggest a protocol that is sustainable and reproducible and offers different analysis methods while maintaining in vivo lung architecture and immune dynamics. This protocol allows one to study the pathophysiological changes, including changes to the immune cells, cytokines, and mediators, in 30 precision-cut lung slices from a single murine lung.

Living donor uterus transplant research project in Singapore: Progress of the first case.

Introduction: To report the progress of the human living uterus transplant research project in Singapore.

Material And Methods: The uterus transplant research project began in 2012 with a collaboration between the Swedish and Singapore teams. Ethics approval was obtained from the SingHealth Centralised Institutional Review Board, the SingHealth Transplant and the Singapore General Hospital Biomedical Ethics Committee to perform 5 uterus transplant procedures in a collaborative multi-site research study at the Singapore General Hospital.

TP53 Mutations in Myeloproliferative Neoplasms: Context-Dependent Evaluation of Prognostic Relevance.

The clinical relevance of TP53 mutations (TP53) in myeloproliferative neoplasms (MPN) and their prognostic interaction with MPN subtype designation has not been systematically studied. In the current study, 114 patients with MPN harboring TP53 (VAF ≥ 2%) were evaluated for overall survival (OS), calculated from the time of TP53 detection: chronic phase myelofibrosis (MF-CP; N = 61); blast-phase (MPN-BP; N = 31) or accelerated-phase (MPN-AP; N = 16) MPN, and polycythemia vera/essential thrombocythemia (PV/ET; N = 6). Sixty-five (57%) patients harbored International Consensus Classification (ICC)-defined multihit TP53 and 56 (49%) monosomal/complex karyotype (MK/CK).

The role of 27-hydroxycholesterol in hypercholesterolemia-associated exacerbation of apical periodontitis and therapeutic potential of felodipine.

Background/purpose: Studies have demonstrated a relation between hypercholesterolemia and development of apical periodontitis (AP), but the underlying mechanism is uncertain. 27-hydroxycholesterol (27HC), produced by cytochrome P450 27A1 (CYP27A1)-catalyzed hydroxylation of cholesterol, is known to possess pro-inflammatory activity. Felodipine is an anti-hypertensive agent able to inhibit CYP27A1.

From microscope to masterpiece: Validating the role of artistic competition in enhancing dental students' engagement in histological study.

Background/purpose: Our previous study found that the integration of arts into the dental education through an innovative photomicrograph competition can increase the dental students' interests in learning microscopic lessons. This study aimed to validate whether the same photomicrograph competition still had its effectiveness to promote the students' interests in learning microscopic lessons.

Materials And Methods: A photomicrograph competition was organized for the 477 dental students.

CIDEC/FSP27 exacerbates obesity-related abdominal aortic aneurysm by promoting perivascular adipose tissue inflammation.

Abdominal aortic aneurysm (AAA) is strongly correlated with obesity, partially due to the abnormal expansion of abdominal perivascular adipose tissue (PVAT). Cell death-inducing DNA fragmentation factor-like effector C (CIDEC), also known as fat-specific protein 27 (FSP27) in rodents, is specifically expressed in adipose tissue where it mediates lipid droplet fusion and adipose tissue expansion. Whether and how CIDEC/FSP27 plays a role in AAA pathology remains elusive.

Risk Factors of Hemophagocytic Lymphohistiocytosis in Adults with Fever of Unknown Origin: A Retrospective Study.

Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a critical syndrome with a high mortality rate. In clinical practice, some patients with fever of unknown origin (FUO) can develop HLH, further complicating the diagnosis and treatment. However, studies on HLH in adults with FUO are limited.

New insights into freshwater ascomycetes: discovery of novel species in diverse aquatic habitats.

During investigations of freshwater fungi in Hunan and Yunnan provinces, China, sp. nov. (Nectriaceae), sp.

Nebulized aminoglycosides for ventilator-associated pneumonia: Methodological considerations and lessons from experimental studies.

Aminoglycosides are concentration-dependent antibiotics exerting a bactericidal effect when concentrations at the site of infection are equal to or greater than 5 times the minimum inhibitory concentrations (MIC). When administered intravenously, they exhibit poor lung penetration and high systemic renal and ototoxicity, imposing to restrict their administration to 5 days. Experimental studies conducted in anesthetized and mechanically ventilated sheep and pigs provide evidence that high doses of nebulized aminoglycosides induce a rapid and potent bacterial killing in the infected lung parenchyma.

Using Anal Cytology and Human Papillomavirus DNA and E6/E7 mRNA Detection to Optimize High-Resolution Anoscopy Referrals in Men Who Have Sex With Men With HIV.

Background: This study was conducted to evaluate screening procedures for anal high-grade squamous intraepithelial lesions (HSILs) with anal liquid-based cytology (aLBC) and biomarkers to identify candidates for high-resolution anoscopy (HRA).

Methods: This cross-sectional study included men who have sex with men with HIV. Participants underwent HRA, aLBC, and biomarker testing.

The complexities of elexacaftor/tezacaftor/ivacaftor therapeutic drug monitoring in a person with cystic fibrosis and pulmonary disease.

Therapeutic drug monitoring (TDM) of elexacaftor/tezacaftor/ivacaftor (ETI) remains challenging due to a lack of clarity around the parameters that govern ETI plasma concentrations, whilst the use of concomitant CYP3A inducers rifabutin and rifampicin is not recommended. We present the complexities of TDM for ETI performed in a person with cystic fibrosis and refractory pulmonary disease. Utilising National Association of Testing Authorities (NATA) accredited assays and target considerations published by the Therapeutic Goods Administration (TGA), Australia, ETI plasma concentration variability was monitored over the course of an acute admission with added complexity from an antibiotic regimen including rifabutin, a moderate cytochrome P450 3A (CYP3A) inducer, and clofazimine, a mild CYP3A inhibitor.

Five-year complete remission of super-giant hepatocellular carcinoma with hepatectomy followed by sorafenib plus camrelizumab: A case report.

Background: Cirrhotic patients with super-giant hepatocellular carcinoma (HCC) and portal vein invasion generally have a poor prognosis. This paper presents a patient with super-giant HCC and portal vein invasion, who underwent hepatectomy followed by a combination of sorafenib and camrelizumab, resulting in complete remission (CR) for 5 years.

Case Summary: A 40-year-old male with compensated hepatitis B-related cirrhosis was diagnosed with HCC, Barcelona Clinic Liver Cancer stage C.

Primary Diffuse Leptomeningeal Melanomatosis Leading to Raised Intracranial Pressure in a Pediatric Patient.

A critical clinical consideration, in addition to other common risk factors predisposing individuals to idiopathic intracranial hypertension (IIH), involves the potential co-occurrence of increased intracranial pressure and elevated cerebrospinal fluid protein levels in the presence of underlying malignancies. Primary diffuse leptomeningeal melanomatosis, an exceptionally rare condition with few reported cases in the pediatric population, illustrates this scenario. Timely decision-making based on clinical suspicion to perform a biopsy and involving a skilled pathologist for accurate reporting are essential steps toward achieving a definitive diagnosis.

Defining and responding to the contextual drivers for implementation of antimicrobial stewardship in 14 neonatal units in South Africa.

Background: Research on the contextual drivers of antimicrobial stewardship (AMS) programme interventions in neonatal units is limited.

Methods: As part of a prospective mixed-methods multidisciplinary neonatal AMS (NeoAMS) interventional study in 14 South African hospitals, we applied a three-phased process to assess implementation barriers and contextual drivers experienced by participating health professionals. The study included: (Phase one; P1) a survey of pre-intervention barriers and enablers; (P2) written feedback during the study intervention phase; and (P3) semi-structured exit interviews.

Integration of single-cell transcriptome and chromatin accessibility and its application on tumor investigation.

The advent of single-cell sequencing techniques has not only revolutionized the investigation of biological processes but also significantly contributed to unraveling cellular heterogeneity at unprecedented levels. Among the various methods, single-cell transcriptome sequencing stands out as the best established, and has been employed in exploring many physiological and pathological activities. The recently developed single-cell epigenetic sequencing techniques, especially chromatin accessibility sequencing, have further deepened our understanding of gene regulatory networks.

New Mediastinal and Hilar Lymphadenopathy After Adjuvant Pembrolizumab in a Patient With Stage III Clear Cell Renal Cell Carcinoma.

The advent of immune checkpoint inhibitors (ICIs) has transformed the management of advanced and high-risk renal cell carcinoma (RCC). In the adjuvant setting, ICIs, such as pembrolizumab, aim to reduce the risk of recurrence following potentially curative nephrectomy. However, this therapeutic approach introduces unique challenges, particularly related to immune-related adverse events (irAEs).

Descending Necrotizing Mediastinitis: A Rare Yet Lethal Complication Demanding Timely Intervention.

Descending necrotizing mediastinitis (DNM) is a rare and potentially life-threatening condition characterized by the rapid spread of infection within the mediastinum. This severe form of mediastinitis poses a significant challenge to clinicians due to its aggressive nature and potential for rapid deterioration. In this case report, we present a challenging case of descending necrotizing mediastinitis in a 39-year-old patient with persistent pyrexia and an extended hospital stay in the intensive care unit (ICU), cardiothoracic unit (CTU), and surgical intensive care unit (SICU).

Emerging Trend of Central Precocious Puberty: A Retrospective Study of Cases Diagnosed Before and During the COVID-19 Pandemic in a Portuguese Tertiary-Level Hospital.

Introduction: In light of the recent evidence suggesting an increase in idiopathic central precocious puberty (ICPP) during the COVID-19 pandemic, this study aimed to assess the incidence of newly diagnosed ICPP cases and compare differences in demographic, anthropometric, and clinical characteristics pre-pandemic and during the pandemic.

Methods: We conducted a retrospective study at a national reference pediatric endocrinology unit in Portugal to evaluate the proportion of referrals for precocious puberty (PP) and, within this group, the number of ICPP cases diagnosed before (group 1: January 2018 to March 2020) and during the pandemic (group 2: April 2020 to June 2022). Additionally, we compared the demographic, anthropometric, and clinical characteristics of ICPP patients between the two groups.

The immune landscape of fetal chorionic villous tissue in term placenta.

Introduction: The immune compartment within fetal chorionic villi is comprised of fetal Hofbauer cells (HBC) and invading placenta-associated maternal monocytes and macrophages (PAMM). Recent studies have characterized the transcriptional profile of the first trimester (T1) placenta; however, the phenotypic and functional diversity of chorionic villous immune cells at term (T3) remain poorly understood.

Methods: To address this knowledge gap, immune cells from human chorionic villous tissues obtained from full-term, uncomplicated pregnancies were deeply phenotyped using a combination of flow cytometry, single-cell RNA sequencing (scRNA-seq, CITE-seq) and chromatin accessibility profiling (snATAC-seq).