High-Resolution OCT Reveals Age-Associated Variation in the Region Posterior to the External Limiting Membrane.

Purpose: To evaluate visibility of a sub-band posterior to the external limiting membrane (ELM) and assess its age-associated variation.

Methods: In a retrospective cross-sectional study, normal eyes were imaged using a high-resolution spectral-domain optical coherence tomography (SD-OCT) prototype (2.7-µm axial resolution).

Evaluating the reliability of a microperimetry-based method for assessing visual function in the junctional zone of geographic atrophy lesions.

Purpose: To assess the repeatability of a microperimetry methodology for quantifying visual function changes in the junctional zone of eyes with geographic atrophy (GA) in the clinical trial context.

Methods: A post hoc analysis of the OAKS phase III trial was conducted, which enrolled patients with GA secondary to age-related macular degeneration. Microperimetry using a standard 10 - 2 fovea centered grid was performed at baseline and follow-up visits.

Evaluating the Reliability of a Microperimetry-Based Method for Assessing Visual Function in the Junctional Zone of Geographic Atrophy Lesions.

Purpose: To assess the repeatability of a microperimetry methodology for quantifying visual function changes in the junctional zone of eyes with geographic atrophy (GA) in the clinical trial context.

Methods: A post hoc analysis of the OAKS phase III trial was conducted, which enrolled patients with GA secondary to age-related macular degeneration. Microperimetry using a standard 10-2 fovea centered grid was performed at baseline and follow-up visits.

Anti-Poiseuille flow by spin Hall effect.

Hydrodynamics is known to emerge in electron flow when the electron-electron interaction dominates over the other momentum-nonconserving scatterings. The hydrodynamic equation that describes the electric current includes viscosity, extending beyond the Ohmic flow. The laminar flow of such a viscous electron fluid in a sample with finite width is referred to as the Poiseuille flow, where the flow velocity is maximum at the center and decreases towards the edges of the sample.

Identification of peptide-based hepatitis B virus capsid inhibitors based on the viral core protein.

In this study, we have identified two novel peptides, 19Ac (comprising residues 91-105) and 20Ac (encompassing residues 96-110), from a systematically designed peptide library based on the Hepatitis B virus (HBV) core protein, that inhibit the assembly of HBV capsid. Peptide 20Ac exhibited about twofold the inhibitory potency of 19Ac and proved effective against both standard and morphothiadin (GLS4)-resistant HBV strains. Molecular dynamics simulations revealed that despite their overlapping sequence, 19Ac and 20Ac bonded to different regions of the core protein, thereby inhibiting capsid assembly through distinct mechanisms.

Delta-like ligand 3 (DLL3) landscape in pulmonary and extra-pulmonary neuroendocrine neoplasms.

Delta-like Ligand 3 (DLL3) targeting therapies are promising in small cell lung cancer (SCLC) treatment. However, DLL3 expression in SCLC and other neuroendocrine neoplasms (NEN) is heterogeneous and not well characterized. We describe the landscape of DLL3 at the mRNA and protein levels across SCLC, large cell neuroendocrine carcinoma (LCNEC), and non-small cell lung cancer.

Multiregional transcriptomic profiling provides improved prognostic insight in localized non-small cell lung cancer.

Lung Cancer remains the leading cause of cancer deaths in the USA and worldwide. Non-small cell lung cancer (NSCLC) harbors high transcriptomic intratumor heterogeneity (RNA-ITH) that limits the reproducibility of expression-based prognostic models. In this study, we used multiregional RNA-seq data (880 tumor samples from 350 individuals) from both public (TRACERx) and internal (MDAMPLC) cohorts to investigate the effect of RNA-ITH on prognosis in localized NSCLC at the gene, signature, and tumor microenvironment levels.

QUANTIFICATION OF CAPILLARY BLOOD FLOW SPEEDS IN DIABETIC RETINOPATHY USING VARIABLE INTERSCAN TIME ANALYSIS OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Purpose: To investigate retinal capillary plexus capillary flow speed and vessel density in diabetic retinopathy and normal subjects using variable interscan time analysis optical coherence tomography angiography (OCTA).

Methods: High speed swept source OCTA imaging using multiple interscan times was performed over a 5 mm × 5 mm field-of-view with 600 kHz A-scan rate. Second-generation variable interscan time analysis OCTA was used to measure a surrogate marker for capillary blood flow speed, variable interscan time analysis flow speed (VFS), in the superficial and intermediate capillary plexuses VFS , and deep capillary plexus VFS .

Ensembling U-Nets for microaneurysm segmentation in optical coherence tomography angiography in patients with diabetic retinopathy.

Diabetic retinopathy is one of the leading causes of blindness around the world. This makes early diagnosis and treatment important in preventing vision loss in a large number of patients. Microaneurysms are the key hallmark of the early stage of the disease, non-proliferative diabetic retinopathy, and can be detected using OCT angiography quickly and non-invasively.

Evaluating the Effect of Strain Shirota on the Physical Consistency of Stool in Healthy Participants with Hard or Lumpy Stools: A Double-Blind, Randomized, Placebo-Controlled Study.

We have earlier established a direct measurement method for assessing stool physical consistency using a texture analyzer (TAXT). The present study aimed to evaluate the stool softening effect of strain Shirota (LcS) using TAXT in a double-blind, randomized, placebo-controlled study. Sixty-four healthy participants with a Bristol stool form scale (BSFS) 1/2 ≥ 50% during screening consumed fermented milk containing LcS or a placebo beverage daily for 8 weeks.

Topographic Measurement of the Subretinal Pigment Epithelium Space in Normal Aging and Age-Related Macular Degeneration Using High-Resolution OCT.

Purpose: A micrometer scale hyporeflective band within the retinal pigment epithelium basal lamina - Bruch's membrane complex (RPE-BL-BrM) was topographically measured in aging and age-related macular degeneration (AMD).

Methods: In a prospective cross-sectional study, 90 normal eyes from 76 subjects (range = 23-90 years) and 53 dry AMD eyes from 47 subjects (range = 62-91 years) were enrolled. Isotropic volume raster scans over 6 mm × 6 mm (500 × 500 A-scans) were acquired using a high-resolution (2.

A Pan-Cancer Patient-Derived Xenograft Histology Image Repository with Genomic and Pathologic Annotations Enables Deep Learning Analysis.

Patient-derived xenografts (PDX) model human intra- and intertumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histologic imaging via hematoxylin and eosin (H&E) staining is routinely performed on PDX samples, which could be harnessed for computational analysis. Prior studies of large clinical H&E image repositories have shown that deep learning analysis can identify intercellular and morphologic signals correlated with disease phenotype and therapeutic response.

LGBTQ+ individuals are not explicitly represented in emergency medicine simulation curricula.

Background: Medical educational societies have emphasized the inclusion of marginalized populations, including the lesbian, gay, bisexual, transgender and queer (LGBTQ+) population, in educational curricula. Lack of inclusion can contribute to health inequality and mistreatment due to unconscious bias. Little didactic time is spent on the care of LGBTQ+ individuals in emergency medicine (EM) curricula.

CoCo-ST: Comparing and Contrasting Spatial Transcriptomics data sets using graph contrastive learning.

Traditional feature dimension reduction methods have been widely used to uncover biological patterns or structures within individual spatial transcriptomics data. However, these methods are designed to yield feature representations that emphasize patterns or structures with dominant high variance, such as the normal tissue spatial pattern in a precancer setting. Consequently, they may inadvertently overlook patterns of interest that are potentially masked by these high-variance structures.

Preoperative diagnosis of adhesion severity between the abdominal wall and intestinal tract with novel abdominal ultrasound methodology to enhance surgical safety.

Background: Adhesions between the abdominal wall and intestinal tract from previous surgeries can complicate reoperations; however, predicting the extent of adhesions preoperatively is difficult. This study aimed to develop a straightforward approach for predicting adhesion severity using a novel abdominal ultrasound technique that quantifies the displacement of motion vectors of two organs to enhance surgical safety. The efficacy of this methodology was assessed experimentally and clinically.

The evolution of lung adenocarcinoma precursors is associated with chromosomal instability and transition from innate to adaptive immune response/evasion.

Studying lung adenocarcinoma (LUAD) early carcinogenesis is challenging, primarily due to the lack of LUAD precursors specimens. We amassed multi-omics data from 213 LUAD and LUAD precursors to identify molecular features underlying LUAD precancer evolution. We observed progressively increasing mutations, chromosomal aberrations, whole genome doubling and genomic instability from precancer to invasive LUAD, indicating aggravating chromosomal instability (CIN).

Rapid examination of lung tissues by nonlinear microscopy.

Objectives: Traditional histopathology is a time-intensive and labor-intensive process involving tissue formalin fixation, paraffin embedding, and microtoming into thin sections for H&E staining. Frozen section analysis is a modality used during surgery to quickly evaluate tissue, but it has limitations, such as the size and number of the specimens that can be analyzed as well as difficulties with fatty and bony tissues. Our objective was to investigate the performance of nonlinear microscopy, a fluorescence microscopy technique, for the rapid examination of resected lung tumors.

Prognostic analysis of radiation-induced liver damage following carbon-ion radiotherapy for hepatocellular carcinoma.

Background: Radiation-induced liver damage (RILD) occasionally occurs following carbon-ion radiotherapy (CIRT) for liver tumors, such as hepatocellular carcinoma (HCC), in patients with impaired liver function disease. However, the associated risk factors remain unknown. The present study aimed to determine the risk factors of RILD after CIRT.

Supplements Are Not a Synonym for Safe: Suspected Liver Injury From Ashwagandha.

Background: As patients look more to alternative herbal and dietary supplements to boost energy and mood, reports are increasing of unintended adverse effects, particularly to the liver.

Case Presentation: We report a case of a 48-year-old man with a history of severe alcohol use disorder who presented to the emergency department with a cholestatic pattern of liver injury in the setting of alcohol and use of a testosterone-boosting supplement containing ashwagandha.

Conclusions: Drug-induced liver damage should be considered in patients with alcohol use disorder who present with a cholestatic pattern of liver injury.

Late-Stage Derivatization of Oleanolic Acid-Based Anti-HIV-1 Compounds.

A 12-keto-type oleanolic acid derivative (4) has been identified as a potent anti-human immunodeficiency virus type-1 (HIV-1) compound that demonstrates synergistic effects with several types of HIV-1 neutralizing antibodies. In the present study, we used a common key synthetic intermediate to carry out the late-stage derivatization of an anti-HIV compound based on the chemical structure of a 12-keto-type oleanolic acid derivative. To execute this strategy, we designed a diketo-type oleanolic acid derivative (5) for chemoselective transformation, targeting the carboxy group and the hydroxyl group on the statine unit, as well as the 3-carbonyl group on the oleanolic acid unit, as orthogonal synthetic handles.

Data retrieval from archival renal biopsies using nonlinear microscopy.

Thorough examination of renal biopsies may improve understanding of renal disease. Imaging of renal biopsies with fluorescence nonlinear microscopy (NLM) and optical clearing enables three-dimensional (3D) visualization of pathology without microtome sectioning. Archival renal paraffin blocks from 12 patients were deparaffinized and stained with Hoechst and Eosin for fluorescent nuclear and cytoplasmic/stromal contrast, then optically cleared using benzyl alcohol benzyl benzoate (BABB).

Field testing the transferability of behavioural science knowledge on promoting vaccinations.

As behavioural science is increasingly adopted by organizations, there is a growing need to assess the robustness and transferability of empirical findings. Here, we investigate the transferability of insights from various sources of behavioural science knowledge to field settings. Across three pre-registered randomized controlled trials (RCTs, N = 314,824) involving a critical policy domain-COVID-19 booster uptake-we field tested text-based interventions that either increased vaccinations in prior field work (RCT1, NCT05586204), elevated vaccination intentions in an online study (RCT2, NCT05586178) or were favoured by scientists and non-experts (RCT3, NCT05586165).