A distinct mechanism of epigenetic reprogramming silences PAX2 and initiates endometrial carcinogenesis.

Functional inactivation of tumor suppressor genes drives cancer initiation, progression, and treatment responses. Most tumor suppressor genes are inactivated through 1 of 2 well-characterized mechanisms: DNA-level mutations, such as point mutations or deletions, and promoter DNA hypermethylation. Here, we report a distinct third mechanism of tumor suppressor inactivation based on alterations to the histone rather than DNA code.

Correlation between Histopathological Features and Clinical Outcomes in Patients with Oral Squamous Cell Carcinoma.

Introduction: Oral squamous cell carcinoma (OSCC) is a prevalent malignancy, with histopathological features playing a crucial role in predicting clinical outcomes. Tumor budding, lymphovascular invasion, and depth of invasion are key indicators used to assess prognosis and therapeutic response. The objective of this research is to examine the correlation between these histopathological parameters and patient outcomes.

Glomerular Hematuria for the Diagnosis of Glomerulonephritis.

Introduction: Reports on the performance of glomerular hematuria for the diagnosis of glomerulonephritis (GN) show heterogeneity in the results and used urological pathologies as controls. We hypothesized that identification of urinary acanthocytes (uACANTHO) and/or urinary red blood cell casts (uRBCCs) by comprehensive microscopic examination of the urinary sediment (uMICRO) can differentiate glomerular disease from non-glomerular renal pathology.

Methods: Records of patients seen for consultation for acute kidney injury or proteinuria/hematuria who had specimens examined by uMICRO and a kidney biopsy performed within 2 weeks of uMICRO were extracted.

The Germline and Somatic Origins of Prostate Cancer Heterogeneity.

This study uncovered 223 recurrently mutated driver regions using the largest cohort of prostate tumors to date. It reveals associations between germline SNPs, somatic drivers, and tumor aggression, offering significant insights into how prostate tumor evolution is shaped by germline factors and the timing of somatic mutations.

Detection of pulmonary hypertension in preterm infants with bronchopulmonary dysplasia using oxygen saturation data.

Background: Pulmonary hypertension (PH) complicates the clinical course of bronchopulmonary dysplasia (BPD) in preterm infants, increasing risk of mortality and other morbidities. Early detection of PH may provide the clinical opportunity for earlier initiation of PH targeted therapies.

Methods: We analyzed variability patterns of oxygen saturation data in 41 preterm infants with BPD and associated PH and 57 infants with BPD alone using irregularity indices to identify PH.

Developing a Wearable Sensor-Based Digital Biomarker of Opioid Dependence.

Background: Repeated opioid exposure leads to a variety of physiologic adaptations that develop at different rates and may foreshadow risk of opioid-use disorder (OUD), including dependence and withdrawal. Digital pharmacovigilance strategies that use noninvasive sensors to identify physiologic adaptations to opioid use represent a novel strategy to facilitate safer opioid prescribing. This study aims to identify wearable sensor-derived features associated with opioid dependence by comparing opioid-naïve individuals to chronic opioid users with acute pain and developing a machine-learning model to distinguish between the 2 groups.

Evaluation of a digital tool for detecting stress and craving in SUD recovery: An observational trial of accuracy and engagement.

Background: Digital health interventions offer opportunities to expand access to substance use disorder (SUD) treatment, collect objective real-time data, and deliver just-in-time interventions: however implementation has been limited. RAE (Realize, Analyze, Engage) Health is a digital tool which uses continuous physiologic data to detect high risk behavioral states (stress and craving) during SUD recovery.

Methods: This was an observational study to evaluate the digital stress and craving detection during outpatient SUD treatment.

Dimensions of muddy brown granular casts in patients with acute tubular injury.

Background: The presence of "muddy" brown granular casts (MBGC) in the urine sediment is pathognomonic for acute tubular injury (ATI). Although MBGC have been noted for years, there are no reports regarding their length nor width. The objective of this study was to measure MBGC using images obtained by light microscopy and investigate associations with clinically relevant parameters.

Participatory hackathon to determine ecological relevant endpoints for a neurotoxin to aquatic and benthic invertebrates.

The aim of this study is twofold: i) to determine innovative yet sensitive endpoints for sulfoxaflor and ii) to develop best practices for innovative teaching in ecotoxicology. To this end, a group of 52 MSc students participated in an environmental hackathon, during which they did creative toxicity testing on 5 freshwater invertebrate species: Daphnia magna, Chironomus riparius, Asellus aquaticus, Lymnaea stagnalis, and Anisus vortex. Involving the students in an active learning environment stimulated increased creativity and productivity.

Urinary Vacuolar Casts Are a Unique Type of Casts in Advanced Proteinuric Glomerulopathies.

Key Points: Vacuolar casts are a distinct type of casts identifiable by urinary sediment microscopy. Identification of urinary vacuolar casts is associated with the presence of an advanced and severe form of a proteinuric glomerular disease.

Background: Identification of casts by urinary sediment microscopy is a valuable diagnostic clinical tool for the evaluation of kidney disease.

Information Based Similarity Analysis of Oxygen Saturation Recordings to Detect Pulmonary Hypertension in Preterm Infants.

Pulmonary hypertension (PH) is a complex cardiovascular condition associated with multiple morbidities and mortality risk in preterm infants. PH often complicates the clinical course of infants who have bronchopulmonary dysplasia (BPD), a more common lung disease in these neonates, causing respiratory deterioration and an even higher risk of mortality. While risk factors and prevalence of PH are not yet well defined, early screening and management of PH in infants with BPD are recommended by consensus guidelines from the American Heart Association.

Evaluation of indoor Rn and Rn concentrations in Dakshina Kannada, Karnataka, India.

Naturally occurring radioactive gases which tend to build up (radon and thoron) in indoor environs can cause deleterious health effects including the development of lung cancer. The present study aims to measure Rn and Rn levels in dwellings in different seasons in the environs of Dakshina Kannada region of India. The Rn and Rn concentrations were measured in the monsoon, autumn, winter, and summer seasons using Solid State Nuclear Track Detector (SSNTD, LR-115 type II) films fixed in single-entry pinhole cylindrical twin-cup dosimeters.

Comparison of oxygen supplementation in very preterm infants: Variations of oxygen saturation features and their application to hypoxemic episode based risk stratification.

Background: Oxygen supplementation is commonly used to maintain oxygen saturation (SpO) levels in preterm infants within target ranges to reduce intermittent hypoxemic (IH) events, which are associated with short- and long-term morbidities. There is not much information available about differences in oxygenation patterns in infants undergoing such supplementations nor their relation to observed IH events. This study aimed to describe oxygenation characteristics during two types of supplementation by studying SpO signal features and assess their performance in hypoxemia risk screening during NICU monitoring.

Refractoriness of Hyperkalemia and Hyperphosphatemia in Dialysis-Dependent AKI Associated with COVID-19.

Background: Persistent hyperkalemia (hyperK) and hyperphosphatemia (hyperP) despite renal replacement therapy (RRT) was anecdotally reported in COVID-19 and acute kidney injury (AKI) requiring RRT (CoV-AKI-RRT). However, observation bias could have accounted for the reports. Thus, we systematically examined the rate and severity of hyperK and hyperP in patients with CoV-AKI-RRT in comparison with the pre-COVID-19 era.

Prostate Cancer Transcriptomic Regulation by the Interplay of Germline Risk Alleles, Somatic Mutations, and 3D Genomic Architecture.

Unlabelled: Prostate cancer is one of the most heritable human cancers. Genome-wide association studies have identified at least 185 prostate cancer germline risk alleles, most noncoding. We used integrative three-dimensional (3D) spatial genomics to identify the chromatin interaction targets of 45 prostate cancer risk alleles, 31 of which were associated with the transcriptional regulation of target genes in 565 localized prostate tumors.

Stochastic Modeling of Inter-Hypoxemia Intervals in Preterm Infants.

Hypoxemia, characterized by low blood oxygen levels is pervasive in preterm infants and is associated with development of multiple adverse cardiovascular morbidities. In clinical practice, it is often quantified using frequency, pattern and time spent in it. A predictive tool of hypoxemia occurrence will aid clinicians in risk stratifying infant oxygenation patterns and improving personalized care.

Stress and the CITI.

Transcription-coupled cellular stress is associated with several physiological and pathological features, including membraneless biomolecular condensates. In the study by Yasuhara et al., the authors have described specific nuclear condensates in multiple cell types upon inhibition of RNA polymerase II transcription, discovered their main constituent proteins, and elucidated their functions.

Concomitant Identification of Muddy Brown Granular Casts and Low Fractional Excretion of Urinary Sodium in AKI.

Background: Fractional excretion of urinary sodium (FENa) is a widely utilized clinical test to evaluate acute kidney injury (AKI). A low FENa (<1%) is deemed consistent with prerenal azotemia and inconsistent with acute tubular injury (ATI). Muddy brown granular casts (MBGC) on microscopic examination of urinary sediment (MicrExUrSed) are highly suggestive of ATI.

FOXA2 suppresses endometrial carcinogenesis and epithelial-mesenchymal transition by regulating enhancer activity.

FOXA2 encodes a transcription factor mutated in 10% of endometrial cancers (ECs), with a higher mutation rate in aggressive variants. FOXA2 has essential roles in embryonic and uterine development. However, FOXA2's role in EC is incompletely understood.

Identification of tolerance levels on the cold-water coral Desmophyllum pertusum (Lophelia pertusa) from realistic exposure conditions to suspended bentonite, barite and drill cutting particles.

Cold-water coral (CWC) reefs are numerous and widespread along the Norwegian continental shelf where oil and gas industry operate. Uncertainties exist regarding their impacts from operational discharges to drilling. Effect thresholds obtained from near-realistic exposure of suspended particle concentrations for use in coral risk modeling are particularly needed.

Immunohistochemical evaluation of myofibroblasts in odontogenic keratocyst, dentigerous cyst and different clinical variants of ameloblastoma: A comparative study.

Background: Odontogenic cysts and tumors exhibit varying degrees of aggressiveness in their biological behavior. Odontogenic keratocyst (OKC), dentigerous cyst (DC), ameloblastoma are most common odontogenic cysts and tumors to occur in the oral cavity. Myofibroblasts (MFs) in the connective tissue stroma participate in the matrix degradation process by secreting matrix metalloproteinase 2, transforming growth factor beta1 and may contribute to variation in their biological behavior.

Disruptin, a cell-penetrating peptide degrader of EGFR: Cell-Penetrating Peptide in Cancer Therapy.

Disruptin is a cell-permeable decoy peptide designed to destabilize activated EGFR, both by inhibiting Hsp90 chaperoning and dissociating the active asymmetric EGFR dimer, which leads to an increase in engagement of activated EGFR with the proteolytic degradation machinery and subsequent loss from the cells. Disruptin is an N-terminally biotinylated nonadecapeptide, with 8 amino acids from the αC-helix-β4 sheet loop of EGFR (S-C) fused to a TAT undecapeptide. The S-R loop is at the interface with juxtamembrane domains in the active EGFR dimers and is a binding site for Hsp90.