Comprehensive histopathological analysis of gastric cancer in European and Latin America populations reveals differences in PDL1, HER2, p53 and MUC6 expression.

Introduction: Gastric cancer (GC) burden is currently evolving with regional differences associated with complex behavioural, environmental, and genetic risk factors. The LEGACy study is a Horizon 2020-funded multi-institutional research project conducted prospectively to provide comprehensive data on the tumour biological characteristics of gastroesophageal cancer from European and LATAM countries.

Material And Methods: Treatment-naïve advanced gastroesophageal adenocarcinoma patients were prospectively recruited in seven European and LATAM countries.

Ferguson Plot Analysis of Chaperone ClpB from Moderate Halophile.

The Ferguson plot is a simple method for determining the molecular weight of native proteins and their complexes. In this study, we tested the validity of the Ferguson plot based on agarose native gel electrophoresis using multimeric chaperone protein, ClpB, derived from a moderate halophile that forms a native hexamer. The Ferguson plot showed a single band with a molecular weight of 1,500 kDa, approximately twice the size of the native hexamer.

Demographic and clinical trends of young breast cancer patients from the national cancer database: disproportionate effect on minority populations.

Purpose: There is an increasing incidence of young breast cancer (YBC) patients with uncertainty surrounding the factors and patterns that are contributing.

Methods: We obtained characteristics and survival data from 206,156 YBC patients (≤ 40 years of age) diagnosed between 2005 and 2019 from the National Cancer Database (NCDB). Patients were subdivided into two comparison groups based on year of diagnosis (2005-2009, Old vs.

Defining the Zone of Acute Peripheral Nerve Injury Using Fluorescence Lifetime Imaging in a Crush Injury Sheep Model.

Purpose: Current technologies to define the zone of acute peripheral nerve injury intraoperatively are limited by surgical experience, time, cumbersome electrodiagnostic equipment, and interpreter reliability. In this pilot study, we evaluated a real-time, label-free optical technique for intraoperative nerve injury imaging. We hypothesize that fluorescence lifetime imaging (FLIm) will detect a difference between the time-resolved fluorescence signatures for acute crush injuries versus uninjured segments of peripheral nerves in sheep.

Identification of Cannabis Product Characteristics and Pricing on Dark Web Markets.

Growing cannabis use has made it the most widely cultivated and trafficked illicit drug globally according to the World Health Organization, with 147 million people consuming cannabis-derived products (CDPs) in various product forms and constituency. Despite restrictions in certain countries, unregulated access can still be found on the dark web which specializes in trafficking of illicit goods. The objective was to systematically collect data from multiple marketplaces to identify types of cannabis products offered for sale.

Evaluation of Safety and Efficacy of a Single Lorecivivint Injection in Patients with Knee Osteoarthritis: A Multicenter, Observational Extension Trial.

Introduction: Lorecivivint (LOR), a CDC-like kinase/dual-specificity tyrosine kinase (CLK/DYRK) inhibitor thought to modulate inflammatory and Wnt pathways, is being developed as a potential intra-articular knee osteoarthritis (OA) treatment. The objective of this trial was to evaluate long-term safety of LOR within an observational extension of two phase 2 trials.

Methods: This 60-month, observational extension study (NCT02951026) of a 12-month phase 2a trial (NCT02536833) and 6-month phase 2b trial (NCT03122860) was administratively closed after 36 months as data inferences became limited.

Retrospective Cohort Study on the Predictive Value of Primary Non-response to Initial Biologic for Future Biologic Use in Patients with Inflammatory Bowel Disease.

Background: The armamentarium of medical therapies to treat inflammatory bowel disease (IBD) continues to grow, which has expanded treatment options, particularly after first biologic failure. Currently, there are limited studies investigating the predictive value of first biologic primary non-response (PNR) on subsequent biologic success. Our objective was to determine if PNR to the first biologic for IBD is predictive of response to subsequent biologic therapy.

Clinical Pharmacokinetics of Atogepant in Healthy Japanese and White Adults.

Introduction: Atogepant is a calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine in adults in the USA, EU, and several other countries. The objectives of this study were to evaluate the pharmacokinetics (PK) and dose proportionality of atogepant in healthy Japanese participants, evaluate the safety and tolerability of atogepant in Japanese participants, and explore the differences in the PK and safety of atogepant in Japanese vs white participants.

Methods: A total of 50 participants (40 Japanese and 10 white) were enrolled into five cohorts; Japanese cohorts were randomized in a 4:1 ratio to atogepant (10 mg, 30 mg, or 60 mg daily dosing and 60 mg twice daily) or placebo.

Contamination assessment and source identification of metals and metalloids in submicron road dust (PM) in Moscow Megacity.

The content of 39 metals and metalloids (MMs) in submicron road dust (PM fraction) was studied in the traffic zone, residential courtyards with parking lots, and on pedestrian roads in parks in Moscow. The geochemical profiles of PM vary slightly between different types of roads and courtyards but differ significantly from those in parks. In Moscow, compared to other cities worldwide, submicron road dust contains less As, Sb, Mo, Cr, Cd, Sn, Tl, Ca, Rb, La, Y, U, but more Cu, Zn, Co, Fe, Mn, Ti, Zr, Al, V.

Medical & Socioeconomic Risk Factors Associated with Lack of Neurodevelopmental Evaluation Following Neonatal Cardiac Surgery.

Neonates with congenital heart disease (CHD) who undergo cardiopulmonary bypass (CPB) are at high-risk for unfavorable neurodevelopmental (ND) outcomes and are recommended for ND evaluation (NDE); however, poor rates have been reported. We aimed to identify risk factors associated with lack of NDE. This single-center retrospective observational study included neonates < 30 days old who underwent CPB and survived to discharge between 2012 and 2018.

3D CT to 2D X-ray image registration for improved visualization of tibial vessels in endovascular procedures.

Purpose: During endovascular revascularization interventions for peripheral arterial disease, the standard modality of X-ray fluoroscopy (XRF) used for image guidance is limited in visualizing distal segments of infrapopliteal vessels. To enhance visualization of arteries, an image registration technique was developed to align pre-acquired computed tomography (CT) angiography images and to create fusion images highlighting arteries of interest.

Methods: X-ray image metadata capturing the position of the X-ray gantry initializes a multiscale iterative optimization process, which uses a local-variance masked normalized cross-correlation loss to rigidly align a digitally reconstructed radiograph (DRR) of the CT dataset with the target X-ray, using the edges of the fibula and tibia as the basis for alignment.

Nobiletin: a potential erythropoietin receptor activator protects renal cells against hypoxia.

Tangerine peel is a traditional Chinese herb and has been widely applied in foods and medicine for its multiple pharmacological effects. Erythropoietin receptor (EPOR), a member of the cytokine receptor family, is widely expressed in multiple tissues in especial kidney and plays protective effects in adverse physiological and pathological conditions. We hypothesized that it might be EPOR agonists existing in Tangerine peel bring such renal benefits.

Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers.

Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib.

Lateral decubitus: its influence on hemodynamic and respiratory function during retroperitoneal robotic assisted laparoscopic pyeloplasty (R-RALP) in children.

Retroperitoneal robotic-assisted laparoscopic pyeloplasty (R-RALP) is the commonest urologic procedure performed in children, entailing retroperitoneal CO2 insufflation and lateral decubitus, whose effects on cardiopulmonary variables are poorly known. We, therefore, studied hemodynamic and respiratory changes due to CO2 insufflation and lateral decubitus in children undergoing R-RALP and their effects on regional tissue oxygenation. Between 1/2021 and 7/2024, children affected by ureteropelvic joint obstruction (UPJO) underwent a pyeloplasty by R-RALP at Necker Enfants Malades Hospital (Paris, France), using a standardized surgical technique and a lung-protecting anesthetic protocol aimed to prevent hypercarbia.

Carpal tunnel syndrome diagnosis as a risk factor for falls.

Purpose: Subclinical peroneal neuropathy without overt foot drop has been linked to increased fall risk in adults, yet remains under reported due to subtle symptoms and lack of awareness. Patients with carpal tunnel syndrome (CTS) often experience other nerve entrapments, prompting this study to evaluate CTS (a proxy for peroneal nerve entrapment) as a significant predictor of time to first fall.

Methods: Data from the Merative MarketScan Research Databases (2007-2021) were used to identify adult patients using ICD-9/10 codes.

From "Airway scares me" to "I would say I'm pretty comfortable": quality improvement for reducing time to obtain equipment for adult advanced airway management in a rural emergency department.

Background: Management of the adult airway is one of the most stressful and time-critical procedures in emergency medicine. In the Cowichan District Hospital, a rural hospital in British Columbia, Emergency Department (ED) staff were uncomfortable with acquiring the equipment needed for adult advanced airway management and the mean length of time to acquire the equipment was 319 s. The aim of this quality improvement (QI) project was to decrease the time to obtain the equipment needed for adult advanced airway management by nurses and physicians in the Cowichan District Hospital ED to less than 90 s by May 2023.

Emergency department ophthalmoscopy: physician confidence and clinical practices.

Objectives: Fundoscopy is crucial in the emergency department to identify or rule out serious ocular and neurological conditions. Despite its clinical importance, fundoscopy is often omitted due to the technical challenges associated with traditional direct ophthalmoscopy, particularly for non-ophthalmologists. This study examines emergency physicians' practices, confidence levels, and training related to various modalities of fundoscopy including traditional direct ophthalmoscopes, binocular indirect ophthalmoscopes, panoptic ophthalmoscopes, slit lamp fundoscopy and fundus cameras; and explores the potential role of alternative modalities, such as fundus cameras, in Canadian emergency departments.

Investigating proteogenomic divergence in patient-derived xenograft models of ovarian cancer.

Within ovarian cancer research, patient-derived xenograft (PDX) models recapitulate histologic features and genomic aberrations found in original tumors. However, conflicting data from published studies have demonstrated significant transcriptional differences between PDXs and original tumors, challenging the fidelity of these models. We employed a quantitative mass spectrometry-based proteomic approach coupled with generation of patient-specific databases using RNA-seq data to investigate the proteogenomic landscape of serially-passaged PDX models established from two patients with distinct subtypes of ovarian cancer.

Leveraging U-Net and selective feature extraction for land cover classification using remote sensing imagery.

In this study, we explore an enhancement to the U-Net architecture by integrating SK-ResNeXt as the encoder for Land Cover Classification (LCC) tasks using Multispectral Imaging (MSI). SK-ResNeXt introduces cardinality and adaptive kernel sizes, allowing U-Net to better capture multi-scale features and adjust more effectively to variations in spatial resolution, thereby enhancing the model's ability to segment complex land cover types. We evaluate this approach using the Five-Billion-Pixels dataset, composed of 150 large-scale RGB-NIR images and over 5 billion labeled pixels across 24 categories.

N2GNet tracks gait performance from subthalamic neural signals in Parkinson's disease.

Adaptive deep brain stimulation (DBS) provides individualized therapy for people with Parkinson's disease (PWP) by adjusting the stimulation in real-time using neural signals that reflect their motor state. Current algorithms, however, utilize condensed and manually selected neural features which may result in a less robust and biased therapy. In this study, we propose Neural-to-Gait Neural network (N2GNet), a novel deep learning-based regression model capable of tracking real-time gait performance from subthalamic nucleus local field potentials (STN LFPs).

Adaptable electro-optic detection of THz radiation using a laser-written bull's-eye antenna.

We report a nonlinear terahertz (THz) detection device based on a metallic bull's-eye plasmonic antenna. The antenna, fabricated with femtosecond laser direct writing and deposited on a nonlinear gallium phosphide (GaP) crystal, focuses incoming THz waveforms within the sub-wavelength bull's eye region to locally enhance the THz field. Additionally, the plasmonic structure minimizes diffraction effects allowing a relatively long interaction length between the transmitted THz field and the co-propagating near-infrared gating pulse used in an electro-optic sampling configuration.

Segmentation aware probabilistic phenotyping of single-cell spatial protein expression data.

Spatial protein expression technologies can map cellular content and organization by simultaneously quantifying the expression of >40 proteins at subcellular resolution within intact tissue sections and cell lines. However, necessary image segmentation to single cells is challenging and error prone, easily confounding the interpretation of cellular phenotypes and cell clusters. To address these limitations, we present STARLING, a probabilistic machine learning model designed to quantify cell populations from spatial protein expression data while accounting for segmentation errors.

Therapeutic reduction of neurocan in murine intracerebral hemorrhage lesions promotes oligodendrogenesis and functional recovery.

Background: Intracerebral hemorrhage (ICH) causes prominent deposition of extracellular matrix molecules, particularly the chondroitin sulphate proteoglycan (CSPG) member neurocan. In tissue culture, neurocan impedes the properties of oligodendrocytes. Whether therapeutic reduction of neurocan promotes oligodendrogenesis and functional recovery in ICH is unknown.

Managing xylazine-involved overdoses in a community harm reduction setting: lessons from Tijuana, Mexico.

Background: Xylazine is a α2-adrenergic receptor agonist, used for sedation in veterinary contexts. Although it is increasingly found in overdose deaths across North America, the clinical management of xylazine-involved overdoses has not been extensively studied, especially in community-based harm reduction settings. Here we present a clinical series of xylazine-involved overdose and share the clinical approach and lessons learned by a community overdose response team in Tijuana, Mexico amidst the arrival of xylazine.

SINE retrotransposons import polyadenylation signals to 3'UTRs in dog (Canis familiaris).

Background: Messenger RNA 3' untranslated regions (3'UTRs) control many aspects of gene expression and determine where the transcript will terminate. The polyadenylation signal (PAS) AAUAAA (AATAAA in DNA) is a key regulator of transcript termination and this hexamer, or a similar sequence, is very frequently found within 30 bp of 3'UTR ends. Short interspersed element (SINE) retrotransposons are found throughout genomes in high copy numbers.