A Unified Single-stage Learning Model for Estimating Fiber Orientation Distribution Functions on Heterogeneous Multi-shell Diffusion-weighted MRI

Diffusion-weighted (DW) MRI measures the direction and scale of the local diffusion process in every voxel through its spectrum in q-space, typically acquired in one or more shells. Recent developments in micro-structure imaging and multi-tissue decomposition have sparked renewed attention to the radial b-value dependence of the signal. Applications in tissue classification and micro-architecture estimation, therefore, require a signal representation that extends over the radial as well as angular domain. Multiple approaches have been proposed that can model the non-linear relationship between the DW-MRI signal and biological microstructure. In the past few years, many deep learning-based methods have been developed towards faster inference speed and higher inter-scan consistency compared with traditional model-based methods (e.g., multi-shell multi-tissue constrained spherical deconvolution). However, a multi-stage learning strategy is typically required since the learning process relied on various middle representations, such as simple harmonic oscillator reconstruction (SHORE) representation. In this work, we present a unified dynamic network with a single-stage spherical convolutional neural network, which allows efficient fiber orientation distribution function (fODF) estimation through heterogeneous multi-shell diffusion MRI sequences. We study the Human Connectome Project (HCP) young adults with test-retest scans. From the experimental results, the proposed single-stage method outperforms prior multi-stage approaches in repeated fODF estimation with shell dropoff and single-shell DW-MRI sequences

Sustained complete response to first-line immunochemotherapy for highly aggressive TP53/MDM2-mutated upper tract urothelial carcinoma with ERBB2 mutations, luminal immune-infiltrated contexture, and non-mesenchymal state: a case report and literature review

BackgroundUpper tract urothelial carcinoma (UTUC) is a rare malignancy. The management of metastatic or unresectable UTUC is mainly based on evidence extrapolated from histologically homologous bladder cancer, including platinum-based chemotherapy and immune checkpoint inhibitor alone, whereas UTUC exhibits more invasiveness, worse prognosis, and comparatively inferior response to treatments. First-line immunochemotherapy regimens have been attempted in clinical trials for unselected naïve-treated cases, but their efficacies relative to standard chemo- or immuno-monotherapy still remain controversial. Here, we present a case of highly aggressive UTUC for whom comprehensive genetic and phenotypic signatures predicted sustained complete response to first-line immunochemotherapy.Case presentationA 50-year-old man received retroperitoneoscopic nephroureterectomy and regional lymphadenectomy for high-risk locally advanced UTUC. Postoperatively, he developed rapid progression of residual unresectable metastatic lymph nodes. Pathologic analysis and next-generation sequencing classified the tumor as highly aggressive TP53/MDM2-mutated subtype with features more than expression of programmed death ligand-1, including ERBB2 mutations, luminal immune-infiltrated contexture, and non-mesenchymal state. Immunochemotherapy combining gemcitabine, carboplatin, and off-label programmed death-1 inhibitor sintilimab was initiated, and sintilimab monotherapy was maintained up to 1 year. Retroperitoneal lymphatic metastases gradually regressed to complete response. Blood-based analyses were performed longitudinally for serum tumor markers, inflammatory parameters, peripheral immune cells, and circulating tumor DNA (ctDNA) profiling. The ctDNA kinetics of tumor mutation burden and mean variant allele frequency accurately predicted postoperative progression and sustained response to the following immunochemotherapy, which were mirrored by dynamic changes in abundances of ctDNA mutations from UTUC-typical variant genes. The patient remained free of recurrence or metastasis as of this publishing, over 2 years after the initial surgical treatment.ConclusionImmunochemotherapy may be a promising first-line option for advanced or metastatic UTUC selected with specific genomic or phenotypic signatures, and blood-based analyses incorporating ctDNA profiling provide precise longitudinal monitoring

Spatial Pathomics Toolkit for Quantitative Analysis of Podocyte Nuclei with Histology and Spatial Transcriptomics Data in Renal Pathology

Podocytes, specialized epithelial cells that envelop the glomerular capillaries, play a pivotal role in maintaining renal health. The current description and quantification of features on pathology slides are limited, prompting the need for innovative solutions to comprehensively assess diverse phenotypic attributes within Whole Slide Images (WSIs). In particular, understanding the morphological characteristics of podocytes, terminally differentiated glomerular epithelial cells, is crucial for studying glomerular injury. This paper introduces the Spatial Pathomics Toolkit (SPT) and applies it to podocyte pathomics. The SPT consists of three main components: (1) instance object segmentation, enabling precise identification of podocyte nuclei; (2) pathomics feature generation, extracting a comprehensive array of quantitative features from the identified nuclei; and (3) robust statistical analyses, facilitating a comprehensive exploration of spatial relationships between morphological and spatial transcriptomics features.The SPT successfully extracted and analyzed morphological and textural features from podocyte nuclei, revealing a multitude of podocyte morphomic features through statistical analysis. Additionally, we demonstrated the SPT's ability to unravel spatial information inherent to podocyte distribution, shedding light on spatial patterns associated with glomerular injury. By disseminating the SPT, our goal is to provide the research community with a powerful and user-friendly resource that advances cellular spatial pathomics in renal pathology. The implementation and its complete source code of the toolkit are made openly accessible at https://github.com/hrlblab/spatial_pathomics

Urinary microbiota signatures associated with different types of urinary diversion: a comparative study

BackgroundRadical cystectomy and urinary diversion (UD) are gold standards for non-metastatic muscle-invasive bladder cancer. Orthotopic neobladder (or Studer), ileal conduit (or Bricker) and cutaneous ureterostomy (CU) are mainstream UD types. Little is known about urinary microbiological changes after UD. MethodsIn this study, urine samples were collected from healthy volunteers and patients with bladder cancer who had received aforementioned UD procedures. Microbiomes of samples were analyzed using 16S ribosomal RNA gene sequencing, and microbial diversities, distributions and functions were investigated and compared across groups. ResultsHighest urine microbial richness and diversity were observed in healthy controls, followed by Studer patients, especially those without hydronephrosis or residual urine, α-diversity indices of whom were remarkably higher than those of Bricker and CU groups. Studer UD type was the only independent factor favoring urine microbial diversity. The urine microflora structure of the Studer group was most similar to that of the healthy individuals while that of the CU group was least similar. Studer patients and healthy volunteers shared many similar urine microbial functions, while Bricker and CU groups exhibited opposite characteristics. ConclusionOur study first presented urinary microbial landscapes of UD patients and demonstrated the microbiological advantage of orthotopic neobladder. Microbiota might be a potential tool for optimization of UD management

Determination of the 95% effective dose of remimazolam tosylate in anesthesia induction inhibits endotracheal intubation response in senile patients

Background and Purpose: The prevalence of elderly patients prompts anesthesiologists to determine the optimal dose of medication due to the altered pharmacokinetics and pharmacodynamics of this population. The present study aimed to determine the 95% effective dose (ED95) of remimazolam tosylate in anesthesia induction to inhibit endotracheal intubation-related cardiovascular reaction in frail and non-frail senile patients.Methods: A prospective sequential allocation dose-finding study of remimazolam tosylate was conducted on 80 elderly patients who received general anesthesia between May and June 2022 at the First Affiliated Hospital of Nanchang University. The initial dose was 0.3 mg/kg. The blood pressure and heart rate fluctuations during intubation were either <20% (negative cardiovascular response) or ≥20% (positive cardiovascular response). If positive, the dose of the next patient was increased by 0.02 mg/kg, while if negative, it was reduced by 0.02 mg/kg according to the 95:5 biased coin design (BCD). The ED95 and 95% confidence intervals (CIs) were determined using R-Foundation isotonic regression and bootstrapping methods.Results: The ED95 of remimazolam tosylate to inhibit the response during tracheal intubation was 0.297 mg/kg (95% CI: 0.231–0.451 mg/kg) and 0.331 mg/kg (95% CI: 0.272–0.472 mg/kg) in frail and non-frail senile patients, respectively.Conculation and Implications: The CI of the two groups overlap, and no difference was detected in the ED95 of remimazolam tosylate in inhibiting endotracheal intubation-related cardiovascular response in frail and non-frail senile patients. These results suggested that remimazolam tosylate is an optimal anesthesia inducer for all elderly patients.Clinical Trial Registration:https://www.chictr.org.cn, identifier ChiCTR2200055709

Segment Anything Model (SAM) for Digital Pathology: Assess Zero-shot Segmentation on Whole Slide Imaging

The segment anything model (SAM) was released as a foundation model for image segmentation. The promptable segmentation model was trained by over 1 billion masks on 11M licensed and privacy-respecting images. The model supports zero-shot image segmentation with various segmentation prompts (e.g., points, boxes, masks). It makes the SAM attractive for medical image analysis, especially for digital pathology where the training data are rare. In this study, we evaluate the zero-shot segmentation performance of SAM model on representative segmentation tasks on whole slide imaging (WSI), including (1) tumor segmentation, (2) non-tumor tissue segmentation, (3) cell nuclei segmentation. Core Results: The results suggest that the zero-shot SAM model achieves remarkable segmentation performance for large connected objects. However, it does not consistently achieve satisfying performance for dense instance object segmentation, even with 20 prompts (clicks/boxes) on each image. We also summarized the identified limitations for digital pathology: (1) image resolution, (2) multiple scales, (3) prompt selection, and (4) model fine-tuning. In the future, the few-shot fine-tuning with images from downstream pathological segmentation tasks might help the model to achieve better performance in dense object segmentation

Baicalein-corrected gut microbiota may underlie the amelioration of memory and cognitive deficits in APP/PS1 mice

Background: Baicalein is an active ingredient extracted from the root of S. baicalensis Georgi, which exhibits cardiovascular protection, anti-inflammatory, and anti-microbial properties. Our previous study showed that chronic treatment of Baicalein ameliorated cognitive dysfunction in a mouse model of Alzheimer's disease (AD). However, it remains unknown whether Baicalein ameliorates cognitive deficits in AD mouse models by altering gut microbiota and its metabolites.Methods: Behavioral tests, metagenomic and untargeted metabolomics analyses were used to evaluate the effects of Baicalein on the APP/PS1 mice.Results: Our research showed that treatment of Baicalein for 2 weeks ameliorated cognition and memory in a dose-dependent manner, as indicated by the significant increases in the Discrimination index and Number of crossings and decrease in latency to the previous platform location in 8-month of age APP/PS1 mice in novel object recognition and water maze tests. The metagenomic analysis showed the abundance of the dominant phyla in all groups, including Bacteroidetes (14.59%–67.02%) and Firmicutes (20.19%–61.39%). LEfSe analysis of metagenomics identified three species such as s__Roseburia_sp_1XD42_69, s__Muribaculaceae_bacterium_Isolate_104_HZI, s__Muribaculaceae_bacterium_Isolate_110_HZI as Baicalein-treated potential biomarkers. Metabolite analysis revealed the increment of metabolites, including glutamate, thymine and hexanoyl-CoA.Conclusion: The effects of Baicalein on memory and cognition may relate to the metabolism of nucleotides, lipids and glucose

Minimal residual disease monitoring in childhood Philadelphia chromosome-positive acute lymphoblastic leukemia: prognostic significance and correlation between multiparameter flow cytometry and real-time quantitative polymerase chain reaction

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Accelerated Degradation Test and Predictive Failure Analysis of B10 Copper-Nickel Alloy under Marine Environmental Conditions

This paper studies the corrosion behavior of B10 copper-nickel alloy in marine environment. Accelerated degradation test under marine environmental conditions was designed and performed based on the accelerated testing principle and the corrosion degradation mechanism. With the prolongation of marine corrosion time, the thickness of Cu2O film increased gradually. Its corrosion product was Cu2(OH)3Cl, which increased in quantity over time. Cl− was the major factor responsible for the marine corrosion of copper and copper alloy. Through the nonlinear fitting of corrosion rate and corrosion quantity (corrosion weight loss), degradation data of different corrosion cycles, the quantitative effects of two major factors, i.e., dissolved oxygen (DO) and corrosion medium temperature, on corrosion behavior of copper alloy were analyzed. The corrosion failure prediction models under different ambient conditions were built. One-day corrosion weight loss under oxygenated stirring conditions was equivalent to 1.31-day weight loss under stationary conditions, and the corrosion rate under oxygenated conditions was 1.31 times higher than that under stationary conditions. In addition, corrosion medium temperature had a significant effect on the corrosion of B10 copper sheet