A phase 3 study (PATHWAY) of palbociclib plus tamoxifen in patients with HR-positive/HER2-negative advanced breast cancer.

Palbociclib combined with endocrine therapy is approved for treating patients with hormone-receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer; however, data on palbociclib combined with tamoxifen are limited. We investigated the efficacy and safety of palbociclib-tamoxifen in patients with HR+/HER2- advanced breast cancer. This double-blind phase 3 study included 184 women who were randomly assigned 1:1 to receive palbociclib-tamoxifen or placebo-tamoxifen. Pre/perimenopausal women also received goserelin. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. Median PFS was 24.4 months (95% confidence interval [CI], 13.1-32.4) with palbociclib-tamoxifen and 11.1 months (95% CI, 7.4-14.6) with placebo-tamoxifen (hazard ratio [HR], 0.60; 95% CI, 0.43-0.85; P = 0.002). Palbociclib-tamoxifen improved PFS in patients who were treated with first-line or second-line endocrine therapy and pre-, peri-, and postmenopausal patients. Though OS data are still immature (median not reached in both groups), an overall risk reduction of 27% (HR, 0.73; 95% CI, 0.44-1.21) with palbociclib-tamoxifen was observed at the time of PFS analysis. The most common grade 3/4 adverse event with palbociclib-tamoxifen was neutropenia (89.0% [none were febrile] versus 1.1% with placebo-tamoxifen). There were no deaths owing to adverse events in either group. Among patients with HR+/HER2- advanced breast cancer, palbociclib-tamoxifen resulted in significantly longer PFS than tamoxifen alone. Early OS data showed a trend favoring palbociclib-tamoxifen. Trial registration: ClinicalTrials.gov number, NCT03423199. Study registration date: February 06, 2018.

Real-world experience with CDK4/6 inhibitors in hormone receptor-positive metastatic and recurrent breast cancer: findings from an Asian population.

PURPOSE: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy have demonstrated significant clinical benefits in progression-free and overall survival. This study investigates the outcomes associated with two kinds of CDK4/6i in patients with hormone receptor (HR)-positive metastatic and relapsed breast cancer to inform real-world evidence of treatment strategies. METHODS: This retrospective study included 340 Taiwanese patients with HR-positive advanced breast cancer from the Taipei Veterans General Hospital, between 2018 and 2023. We analyzed patient characteristics, treatment strategies and outcomes associated with two CDK4/6i. The efficacy of patients who experienced economic burden and interrupted CDK4/6i treatment after 2 years of National Health Insurance (NHI) reimbursement was also investigated. RESULTS: Patients receiving ribociclib and palbociclib showed no significant differences in age, histology, body mass index(BMI), or pathologic status. The distribution of disease status and endocrine therapy partners was comparable between the two groups. Dose reduction was similar, while patients with palbociclib tended to discontinue CDK4/6i usage, and those with ribociclib tended to switch to the other CDK4/6i or endocrine partners. There was no significant difference in progression-free survival (PFS) between the two CDK4/6i in the first-line setting. Adverse prognostic factors were increasing HER2 IHC score, higher Ki-67 levels, visceral and liver metastasis, prior chemotherapy, and endocrine therapy resistance, while higher BMI, bone-only metastasis, and letrozole treatment were associated with a lower risk of progression. The limited follow-up time in our study was insufficient to assess the outcomes of patients treated with interrupted CDK4/6i for up to two years under the NHI reimbursement policy. CONCLUSION: Treatment outcomes between the two types of CDK4/6i did not differ significantly, indicating the safety and efficacy of CDK4/6i for the Asian population. Ribociclib and palbociclib showed similar efficacy in PFS in the real-world setting.

Comparison of the efficacy, safety and quality of life of pegylated liposomal doxorubicin-cyclophosphamide versus epirubicin-cyclophosphamide in patients with early stage HER2-negative breast cancer: A prospective, randomized, multicenter, Phase II study.

INTRODUCTION: This multicenter, phase II randomized, non-inferiority study reports from the first prospective two-armed randomized control trial that compared the efficacy, safety and quality-of-life of pegylated liposomal doxorubicin (PLD)-based and epirubicin-based as adjuvant chemotherapy for stage I-II Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer. METHODS: Patients with stage I/II HER2-negative breast cancer received PLD (37.5mg/m2, Q3W, 5 cycles, LC arm) plus cyclophosphamide (600mg/m2) or epirubicin (90mg/m2, Q3W, 4 cycles, EC arm) plus cyclophosphamide (600mg/m2). Randomization was stratified by lymph node, ER and PR status. The primary endpoint was disease-free survival (DFS), and secondary endpoints were overall survival (OS), safety profiles, and quality of life (QoL). QoL was assessed using the EORTC QLQ-C30 and QLQ-BR23 questionnaires. RESULTS: A total of 256 patients were assigned to LC (n=148) and EC (n=108). There was no difference in 5-year DFS and OS rate between two groups. LC-based adjuvant regimens had significantly less alopecia, less grade 3-4 hematologic adverse events (AEs). Significantly improved QoL was observed in the LC arm during and after treatment for symptoms including fatigue, nausea and vomiting, and systemic therapy side effects. CONCLUSION: Comparable efficacy and safety between adjuvant PLD and epirubicin for stage I-II HER2-negative breast cancer was observed. There was no difference in 5-year DFS and OS rate between the two treatment arms. However, less grade 3-4 AEs and a trend of favorable QoL symptom scales were observed in the LC arm, suggesting that PLD-containing regimen could become a new standard treatment for early stage HER2-negative breast cancer patients.

Trastuzumab deruxtecan versus trastuzumab emtansine in Asian patients with HER2-positive metastatic breast cancer.

The global phase 3 DESTINY-Breast03 study (ClinicalTrials.gov; NCT03529110) showed statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) with trastuzumab deruxtecan (T-DXd) over trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. Here, we report a subgroup analysis of Asian patients enrolled in DESTINY-Breast03. In total, 309 patients (149 in the T-DXd arm and 160 in the T-DM1 arm) from Asian countries and regions were randomized. At data cutoff (July 25, 2022), the median duration of follow-up in the Asian subpopulation was 29.0 months with T-DXd and 26.0 months with T-DM1. The PFS (determined by blinded independent central review) hazard ratio was 0.30 (95% confidence interval 0.22-0.41) favoring T-DXd over T-DM1 (median PFS 25.1 vs. 5.4 months). Median OS was not reached in the T-DXd arm and was 37.7 months in the T-DM1 arm. The median treatment duration was 15.4 months with T-DXd and 5.5 months with T-DM1. The incidence of grade ≥3 drug-related treatment-emergent adverse events was similar between both treatment arms (49.0% vs. 46.5%) and was consistent with the overall DESTINY-Breast03 population. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 12.9% of patients treated with T-DXd and 2.5% treated with T-DM1, with a higher incidence in Japanese patients; none of these were grade ≥4 events. These efficacy and safety data reinforce the favorable benefit-risk profile of T-DXd in HER2-positive mBC, including in the Asian subgroup.

A novel method to evaluate the transverse pedicle angles of the lower lumbar vertebrae using digital radiography.

To investigate a novel approach for establishing the transverse pedicle angle (TPA) of the lower lumbar spine using preoperative digital radiography (DR). Computed Tomography (CT) datasets of the lower lumbar were reconstructed using MIMICS 17.0 software and then imported into 3-matic software for surgical simulation and anatomical parameter measurement. A mathematical algorithm of TPA based on the Pythagorean theorem was established, and all obtained data were analyzed by SPSS software. The CT dataset from 66 samples was reconstructed as a digital model of the lower lumbar vertebrae (L3-L5), and the AP length/estimated lateral length for L3 between the right and left sides was statistically significant (P = 0.015, P = 0.005). The AP length of the right for L4 was smaller than that of the left after a paired t test was executed (P = 0.006). Both the width of the pedicle and the length of the pedicle (P2C1) were consistent with TPA (L3

Spatial and Single-Cell Investigations Illuminate Theragnostic value and Immune Landscape of Mitochondrial Dynamin-Like GTPase in Breast Cancer.

Background: As we delve into the intricate world of mitochondrial inner membrane proteins, particularly Optic Atrophy types 1 and 3 (OPA1/3), we uncover their pivotal role in maintaining mitochondrial dynamic equilibrium and fusion, crucial for cellular energy production and synthesis. Despite extensive scrutiny, the significance of OPA1/3 in breast cancer (BRCA) and its interplay with the immune microenvironment remain elusive. Materials and Methods: We meticulously sourced BRCA data from renowned repositories such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA), leveraging cutting-edge techniques including single-cell RNA-sequencing (scRNA-seq), spatial transcriptomics, and pharmacogenomics. Through multifaceted data analysis, we endeavored to unravel the intricate role and potential value of OPA1/3 in BRCA tumorigenesis and progression. Results: Our investigation reveals a conspicuous upregulation of OPA1/3 expression in BRCA, correlating with dismal prognoses. Kaplan-Meier plot analysis underscores that heightened OPA1/3 levels are associated with poor survival rates. Both clinical specimens and biobank biopsies corroborate the elevated expression of OPA1/3 in breast cancer patients. Moreover, scRNA-seq unveils a strong correlation between OPA1/3 and macrophage infiltration in the BRCA immune milieu, alongside its association with the cellular communication network involving CXCL, TGFb, VEGF, and IL16. Conclusion: In light of these findings, OPA1/3 emerges as a promising contender for therapeutic targeting and as a potential diagnostic, prognostic, and survival biomarker in BRCA. The implications of our study underscore the pressing need to explore these novel biomarkers to enhance patient outcomes.

Multi-omic profiling of breast tumor microenvironment uncovers a role of mitochondrial calcium gatekeepers.

In this study, we aimed to elucidate the role of mitochondrial calcium uptake 1/2 (MiCU1/2) in breast cancer (BRCA) by employing a comprehensive multi-omics approach. Unlike previous research, we utilized a novel web application tailored for whole tumor tissue, single-cell, and spatial transcriptomics analysis to investigate the association between MiCU1/2 and the tumor immune microenvironment (TIME). Our gene set enrichment analysis (GSEA) provided insights into the primary biological effects of MiCU1/2, while our CRISPR-based drug screening repository identified potential effective drugs. Our study revealed that high MiCU1/2 expression serves as an independent diagnostic biomarker, correlating with advanced clinical status and indicating poorer recurrence-free survival (RFS) rates in BRCA patients. Additionally, spatial transcriptome analysis highlighted the heightened expression of MiCU1/2 in tumors and its relevance in surrounding immune cells. Furthermore, using the CIBERSORT algorithm, we discovered a positive correlation between MiCU1/2 levels and macrophage infiltration, underscoring their potential impact on immune infiltration. We also identified expression patterns of immune-related genes associated with responses against various immune cell types, including CXCL, MIF, GDF, SPP1, and IL16. Finally, our pharmacogenomic screening identified potential small molecule drugs capable of effectively targeting breast cancer cells with elevated MiCU1/2 expression. Overall, our study establishes MiCU1/2 as a promising novel biomarker for BRCA diagnosis and prognostic prediction, as well as a potential therapeutic target, highlighting the importance of exploring these pathways to advance patient care and outcomes in BRCA treatment.

Automatic segmentation of MRI in prospective breast volume evaluation: Comparison of different assessments for immediate breast reconstruction.

BACKGROUND: Assessment of breast volume is essential in preoperative planning of immediate breast reconstruction (IBR) surgery to achieve satisfactory cosmetic outcome. This study introduced a breast volume measurement tool that can be used to perform automatic segmentation of magnetic resonance images (MRI) and calculation of breast volume. We compared the accuracy and reliability of this measurement method with four other conventional modalities. METHODS: Patients who were scheduled to undergo mastectomy with IBR between 2016 and 2021 were enrolled in the study. Five different breast volume assessments, including automatic segmentation of MRI, manual segmentation of MRI, 3D surface imaging, mammography, and the BREAST-V formula, were used to evaluate different breast volumes. The results were validated using water displacement volumes of the mastectomy specimens. RESULTS: In this pilot study, a total of 50 female patients met the inclusion criteria and contributed 54 breast specimens to the volumetric analysis. There was a strong linear association between the MRI and water displacement methods (automatic segmentation: r = 0.911, p < 0.001; manual segmentation: r = 0.924, p < 0.001), followed by 3D surface imaging (r = 0.858, p < 0.001), mammography (r = 0.841, p < 0.001), and Breast-V formula (r = 0.838, p < 0.001). Breast volumes measured using automatic and manual segmentation of MRI had lower mean relative errors (30.3% ± 22.0% and 28.9% ± 19.8, respectively) than 3D surface imaging (38.9% ± 31.2), Breast-V formula (44.8% ± 25.8), and mammography (60.3% ± 37.6). CONCLUSION: Breast volume assessment using the MRI methods had better accuracy and reliability than the other methods used in our study. Breast volume measurement using automatic segmentation of MRI could be more efficient compared to the conventional methods.

Comparative analysis of gut microbiome of mangrove brachyuran crabs revealed patterns of phylosymbiosis and codiversification.

The acquisition of microbial symbionts enables animals to rapidly adapt to and exploit novel ecological niches, thus significantly enhancing the evolutionary fitness and success of their hosts. However, the dynamics of host-microbe interactions and their evolutionary implications remain largely underexplored in marine invertebrates. Crabs of the family Sesarmidae (Crustacea: Brachyura) are dominant inhabitants of mangrove forests and are considered keystone species there. Their rapid diversification, particularly after adopting a plant-feeding lifestyle, is believed to have been facilitated by symbiotic gut microbes, enabling successful colonization of intertidal and terrestrial environments. To investigate the patterns and mechanisms shaping the microbial communities and the role of microbes in the evolution of Sesarmidae, we characterized and compared the gut microbiome compositions across 43 crab species from Sesarmidae and other mangrove-associated families using 16S metabarcoding. We found that the gut microbiome assemblages in crabs are primarily determined by host identity, with a secondary influence from environmental factors such as microhabitat and sampling location, and to a lesser extent influenced by biological factors such as sex and gut region. While patterns of phylosymbiosis (i.e. when microbial community relationships recapitulate the phylogeny of their hosts) were consistently observed in all beta-diversity metrics analysed, the strength of phylosymbiosis varied across crab families. This suggests that the bacterial assemblages in each family were differentially shaped by different degrees of host filtering and/or other evolutionary processes. Notably, Sesarmidae displayed signals of cophylogeny with its core gut bacterial genera, which likely play crucial functional roles in their hosts by providing lignocellulolytic enzymes, essential amino acids, and fatty acids supplementation. Our results support the hypothesis of microbial contribution to herbivory and terrestrialization in mangrove crabs, highlighting the tight association and codiversification of the crab holobiont.

Multiplex Digital PCR-Based Development and discussion of the Detection of Genetic Association Between Staphylococcus aureus and mecA.

Methicillin-resistant Staphylococcus aureus (MRSA) is a predominant nosocomial infection-causing bacteria. The aim of this study was to develop a novel single-bacteria multiplex digital PCR assays (SMD-PCR), which is capable of simultaneously detecting and discriminating Methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA. This protocol employed TaqMan probes to detect SAOUHSC_00106 and mecA genes, with the latter being linked to methicillin resistance. A total of 72 samples from various specimen types were evaluated. The accuracy rates for the sputum samples, pus samples, swab samples, ear secretion samples, and catheter samples were 94.44%, 100%, 92%, 100%, and 100%, respectively. Our results showed that the clinical practicability of SMD-PCR has applicability to the rapid detection of MRSA without DNA extraction or bacterial culture, and can be utilized for the rapid detection of Staphylococcus aureus and the timely identification of MRSA in clinical samples, thereby providing an advanced platform for the rapid diagnosis of clinical MRSA infection.

Spatial and single-cell explorations uncover prognostic significance and immunological functions of mitochondrial calcium uniporter in breast cancer.

The mitochondrial calcium uniporter (MCU) is a transmembrane protein facilitating the entry of calcium ions into mitochondria from the cell cytosol. Maintaining calcium balance is crucial for enhancing cellular energy supply and regulating cell death. The interplay of calcium balance through MCU and the sodium-calcium exchanger is known, but its regulation in the breast cancer tumor microenvironment remains elusive. Further investigations are warranted to explore MCU's potential in BRCA clinical pathology, tumor immune microenvironment, and precision oncology. Our study, employing a multi-omics approach, identifies MCU as an independent diagnostic biomarker for breast cancer (BRCA), correlated with advanced clinical status and poor overall survival. Utilizing public datasets from GEO and TCGA, we discern differentially expressed genes in BRCA and examine their associations with immune gene expression, overall survival, tumor stage, gene mutation status, and infiltrating immune cells. Spatial transcriptomics is employed to investigate MCU gene expression in various regions of BRCA, while spatial transcriptomics and single-cell RNA-sequencing methods explore the correlation between MCUs and immune cells. Our findings are validated through the analysis of 59 BRCA patient samples, utilizing immunohistochemistry and bioinformatics to examine the relationship between MCU expression, clinicopathological features, and prognosis. The study uncovers the expression of key gene regulators in BRCA associated with genetic variations, deletions, and the tumor microenvironment. Mutations in these regulators positively correlate with different immune cells in six immune datasets, playing a pivotal role in immune cell infiltration in BRCA. Notably, high MCU performance is linked to CD8 + T cells infiltration in BRCA. Furthermore, pharmacogenomic analysis of BRCA cell lines indicates that MCU inactivation is associated with increased sensitivity to specific small molecule drugs. Our findings suggest that MCU alterations may be linked to BRCA progression, unveiling new diagnostic and prognostic implications for MCU in BRCA. The study underscores MCU's role in the tumor immune microenvironment and cell cycle progression, positioning it as a potential tool for BRCA precision medicine and drug screening.

Vina-FPGA-Cluster: Multi-FPGA Based Molecular Docking Tool with High-Accuracy and Multi-Level Parallelism.

AutoDock Vina (Vina) stands out among numerous molecular docking tools due to its precision and comparatively high speed, playing a key role in the drug discovery process. Hardware acceleration of Vina on FPGA platforms offers a high energy-efficiency approach to speed up the docking process. However, previous FPGA-based Vina accelerators exhibit several shortcomings: 1) Simple uniform quantization results in inevitable accuracy drop; 2) Due to Vina's complex computing process, the evaluation and optimization phase for hardware design becomes extended; 3) The iterative computations in Vina constrain the potential for further parallelization. 4) The system's scalability is limited by its unwieldy architecture. To address the above challenges, we propose Vina-FPGA-cluster, a multi-FPGA-based molecular docking tool enabling high-accuracy and multi-level parallel Vina acceleration. Standing upon the shoulders of Vina-FPGA, we first adapt hybrid fixed-point quantization to minimize accuracy loss. We then propose a SystemC-based model, accelerating the hardware accelerator architecture design evaluation. Next, we propose a novel bidirectional AG module for data-level parallelism. Finally, we optimize the system architecture for scalable deployment on multiple Xilinx ZCU104 boards, achieving task-level parallelism. Vina-FPGA-cluster is tested on three representative molecular docking datasets. The experiment results indicate that in the context of RMSD (for successful docking outcomes with metrics below 2Å), Vina-FPGA-cluster shows a mere 0.2% lose. Relative to CPU and Vina-FPGA, Vina-FPGA-cluster achieves 27.33× and 7.26× speedup, respectively. Notably, Vina-FPGA-cluster is able to deliver the 1.38× speedup as GPU implementation (Vina-GPU), with just the 28.99% power consumption.

Different radius of curvature at the talus trochlea from northern Chinese population measured using 3D model.

BACKGROUND: To analyze the curvature characteristics of the talus trochlea in people from northern China in different sex and age groups. METHODS: Computed tomography scanning data of talus from 61 specimens were collected and constructed as a three-dimensional model by Materialise's Interactive Medical Image Control System(MIMICS) software, anteromedial(AM), posteromedial(PM), anterolateral(AL), and posterolateral(PL) edge, anterior edge of medial trochlea, posterior edge of medial trochlea and anterior edge of lateral trochlea were defined according to the anatomical landmarks on trochlear surface. The curvature radii for different areas were measured using the fitting radius and measure module. RESULTS: There were significant differences among the talus curvatures in the six areas (F = 54.905, P = 0.000), and more trends in the analytical results were as follows: PM > PL > MP > AL > MA > AM. The average PL radius from specimens aged > 38 years old was larger than that from specimens aged < = 38 years (t=-2.303, P = 0.038). The talus curvature of the AM for males was significantly larger than that for females (t = 4.25, P = 0.000), and the curvature of the AL for males was larger than that for females (t = 2.629, P = 0.010). For observers aged < = 38 years, the AM curvature of the right talus in the male group was significantly larger than that in the female group (P < 0.01). In age < = 38years group, the MA curvature of right talus in male was significantly larger than in female group(P < 0.01), fitting radius of talus for male (21.90 ± 1.97 mm) was significantly greater than female of this(19.57 ± 1.26 mm)(t = 6.894, P = 000). The average radius of the talus in the male population was larger than that in the female population. CONCLUSION: There was no significant relationship between age and talus curvature for males and females. The radius of curvature in the posterior area was significantly larger than that in the anterior area. We recommend that this characteristic of the talus trochlea should be considered when designing the talus component in total ankle replacement (TAR).

Analgesia-nociception index accurately predicts inadequate pectoralis muscle fascia block (PECS) in patients undergoing breast surgery: A prospective observational study.

BACKGROUND: Postoperative opioid administration has been largely replaced by regional anesthesia techniques. We aimed to determine whether intraoperative Analgesia-Nociception Index (ANI) can aid in early evaluation of the effectiveness of regional blocks such as the pectoralis muscle fascia block (PECS, pectoserratus and interpectoral plane blocks) and predicting the need for analgesics postoperatively. METHODS: This prospective observational study enrolled 30 women (age: 20-80 years) undergoing unilateral, non-intubated, breast tumor excision alone or in conjunction with sentinel lymph node biopsy. PECS block was performed following sedation. ANI readings were obtained at 1-min intervals, and polar coordinates were assigned to the distance from the nipple (0.5-cm intervals) and o'clock position (15-min intervals) for each reading. Pain scores were assessed using a numeric rating scale from 0 to 10, and analgesics were administered depending on pain score post-operatively. RESULTS: 8 (27%), 19 (63%), and 3 (10%) patients received morphine, tramadol, and no analgesics, respectively. In total, 954 ANI measurements were obtained. At the proposed cut-off of 50, the sensitivity and specificity of the ANI nadir for need of post-operative opioids were 0.875 and 0.932, respectively. Block effectiveness was most satisfactory in the upper lateral quadrant of the breast with nipple-areolar complex (NAC) sparing effect. Most average ANI measurements for the NAC were <50. No patient experienced postoperative nausea/vomiting, although one reported dizziness. CONCLUSIONS: The intraoperative ANI nadir <50 was strongly correlated with need for postoperative opioids. The ANI may aid in objectively evaluating the effectiveness of pectoralis muscle fascial blocks and predicting postoperative need for analgesics.

An improved point cloud denoising method in adverse weather conditions based on PP-LiteSeg network.

Reliable point cloud data (PCD) generated by LiDAR are crucial to perceiving surroundings when autonomous driving systems are a concern. However, adverse weather conditions can impact the detection range of LiDAR, resulting in a significant amount of noisy data that substantially deteriorates the quality of PCD. Point cloud denoising algorithms used for challenging weather conditions suffer from poor accuracy and slow inferences. The manuscript proposes a Series Attention Fusion Denoised Network (SAFDN) based on a semantic segmentation model in real-time, called PP-LiteSeg. The proposed approach provides two key components to the model. The insufficient feature extraction issue in the general-purpose segmentation models is first addressed when dealing with objects with more noise, so the WeatherBlock module is introduced to replace the original layer used for feature extraction. Hence, this module employs dilated convolutions to enhance the receptive field and extract multi-scale features by combining various convolutional kernels. The Series Attention Fusion Module (SAFM) is presented as the second component of the model to tackle the problem of low segmentation accuracy in rainy and foggy weather conditions. The SAFM sequentially applies channel and spatial attention mechanisms to enhance the model's sensitivity to crucial features. Furthermore, weighted feature fusion is employed to enhance the model's efficiency in integrating low-level and high-level feature information configurations. Experimental evaluations were conducted on the publicly available DENSE dataset. The results demonstrate that the improved model achieved an 11.1% increase in denoising accuracy measured by MIOU and an inference speed of 205.06 FPS when compared to the PP-LiteSeg model. As a result, the noise recognition accuracy and denoising capability in real-time are enhanced.

Metagenomic analysis of gut microbiome illuminates the mechanisms and evolution of lignocellulose degradation in mangrove herbivorous crabs.

BACKGROUND: Sesarmid crabs dominate mangrove habitats as the major primary consumers, which facilitates the trophic link and nutrient recycling in the ecosystem. Therefore, the adaptations and mechanisms of sesarmid crabs to herbivory are not only crucial to terrestrialization and its evolutionary success, but also to the healthy functioning of mangrove ecosystems. Although endogenous cellulase expressions were reported in crabs, it remains unknown if endogenous enzymes alone can complete the whole lignocellulolytic pathway, or if they also depend on the contribution from the intestinal microbiome. We attempt to investigate the role of gut symbiotic microbes of mangrove-feeding sesarmid crabs in plant digestion using a comparative metagenomic approach. RESULTS: Metagenomics analyses on 43 crab gut samples from 23 species of mangrove crabs with different dietary preferences revealed a wide coverage of 127 CAZy families and nine KOs targeting lignocellulose and their derivatives in all species analyzed, including predominantly carnivorous species, suggesting the crab gut microbiomes have lignocellulolytic capacity regardless of dietary preference. Microbial cellulase, hemicellulase and pectinase genes in herbivorous and detritivorous crabs were differentially more abundant when compared to omnivorous and carnivorous crabs, indicating the importance of gut symbionts in lignocellulose degradation and the enrichment of lignocellulolytic microbes in response to diet with higher lignocellulose content. Herbivorous and detritivorous crabs showed highly similar CAZyme composition despite dissimilarities in taxonomic profiles observed in both groups, suggesting a stronger selection force on gut microbiota by functional capacity than by taxonomy. The gut microbiota in herbivorous sesarmid crabs were also enriched with nitrogen reduction and fixation genes, implying possible roles of gut microbiota in supplementing nitrogen that is deficient in plant diet. CONCLUSIONS: Endosymbiotic microbes play an important role in lignocellulose degradation in most crab species. Their abundance is strongly correlated with dietary preference, and they are highly enriched in herbivorous sesarmids, thus enhancing their capacity in digesting mangrove leaves. Dietary preference is a stronger driver in determining the microbial CAZyme composition and taxonomic profile in the crab microbiome, resulting in functional redundancy of endosymbiotic microbes. Our results showed that crabs implement a mixed mode of digestion utilizing both endogenous and microbial enzymes in lignocellulose degradation, as observed in most of the more advanced herbivorous invertebrates.

Clinical outcomes and patient-reported outcomes after oncoplastic breast surgery in breast cancer patients: A matched cohort study.

BACKGROUND: Surgery is the recommended treatment for breast cancer, the most common cancer in women in Taiwan and the leading cause of cancer-related deaths. Although breast-conserving surgery (BCS) has good prognosis, in some cases, BCS may cause more significant deformities and interfere with the patient's psychosocial well-being. Oncoplastic breast surgery (OBS) is the treatment option in these cases. This study aimed to determine the outcomes of OBS and BCS regardless of clinical and patient-reported esthetic outcomes. METHODS: Between 2015 and 2020, 50 patients who underwent OBS at our hospital after complete treatment were enrolled. With 1:2 matched ratios, 100 patients were enrolled in the BCS control group. Clinical outcomes were analyzed. The BREAST-Q questionnaire was then assessed 6 months after the completion of treatment for subjective patient-reported outcomes. RESULTS: Due to the matching process, no difference was noted between the two groups in terms of demographic data such as age, comorbidities, or tumor characteristics. There were no significant differences in the local recurrence rate, disease-free survival, overall survival, positive margin rate, rewide excision rate, conversion to mastectomy rate, or complication rate (major or minor) between both groups. However, the OBS group showed higher satisfaction with breasts in the BREAST-Q questionnaire ( p < 0.001). The mean follow-up time was 38.77 ± 14.70 months in the BCS group and 29.59 ± 14.06 months in the OBS group. CONCLUSION: OBS seems to be a safe and feasible surgery in breast cancer patients because clinical outcomes are compatible with BCS. Moreover, the OBS group had better patient-reported outcomes in terms of satisfaction.

Early left ventricular microvascular dysfunction in diabetic pigs: a longitudinal quantitative myocardial perfusion CMR study.

BACKGROUND: Microvascular pathology is one of the main characteristics of diabetic cardiomyopathy; however, the early longitudinal course of diabetic microvascular dysfunction remains uncertain. This study aimed to investigate the early dynamic changes in left ventricular (LV) microvascular function in diabetic pig model using the cardiac magnetic resonance (CMR)-derived quantitative perfusion technique. METHODS: Twelve pigs with streptozotocin-induced diabetes mellitus (DM) were included in this study, and longitudinal CMR scanning was performed before and 2, 6, 10, and 16 months after diabetic modeling. CMR-derived semiquantitative parameters (upslope, maximal signal intensity, perfusion index, and myocardial perfusion reserve index [MPRI]) and fully quantitative perfusion parameters (myocardial blood flow [MBF] and myocardial perfusion reserve [MPR]) were analyzed to evaluate longitudinal changes in LV myocardial microvascular function. Pearson correlation was used to analyze the relationship between LV structure and function and myocardial perfusion function. RESULTS: With the progression of DM duration, the upslope at rest showed a gradually increasing trend (P = 0.029); however, the upslope at stress and MBF did not change significantly (P > 0.05). Regarding perfusion reserve function, both MPRI and MPR showed a decreasing trend with the progression of disease duration (MPRI, P = 0.001; MPR, P = 0.042), with high consistency (r = 0.551, P < 0.001). Furthermore, LV MPR is moderately associated with LV longitudinal strain (r = - 0.353, P = 0.022), LV remodeling index (r = - 0.312, P = 0.033), fasting blood glucose (r = - 0.313, P = 0.043), and HbA1c (r = - 0.309, P = 0.046). Microscopically, pathological results showed that collagen volume fraction increased gradually, whereas no significant decrease in microvascular density was observed with the progression of DM duration. CONCLUSIONS: Myocardial microvascular reserve function decreased gradually in the early stage of DM, which is related to both structural (but not reduced microvascular density) and functional abnormalities of microvessels, and is associated with increased blood glucose, reduced LV deformation, and myocardial remodeling.

Neuropathic Pain Affects Quality of Life in Breast Cancer Survivors with Chemotherapy-Induced Peripheral Neuropathy.

BACKGROUND: Despite the significant impact of chemotherapy-induced peripheral neuropathy on the quality of life for breast cancer survivors, there is a notable lack of comprehensive research. Therefore, a crucial need exists for further systematic investigation and inquiry into this matter. AIMS: This study examined predictors of quality of life in breast cancer survivors with chemotherapy-induced peripheral neuropathy. DESIGN: A cross-sectional, correlational design. SETTINGS: This study was conducted at a medical center in northern Taiwan and a teaching hospital in northeastern Taiwan. PARTICIPANTS/SUBJECTS: One hundred and thirty adult women with breast cancer, who have undergone chemotherapy and obtained a Total Neuropathy Scale-Clinical Version score>0, were enrolled. METHODS: Neuropathic pain, sleep disturbances, depression, and quality of life were evaluated using multiple regression analysis to identify quality of life predictors. Clinical importance was established using the minimally important difference of Functional Assessment of Cancer Therapy-Breast. RESULTS: The study indicated that improving depression (B = -10.87, p < .001) and neuropathic pain (B = -8.33, p = .004) may enhance the quality of life of breast cancer survivors with chemotherapy-induced peripheral neuropathy. Moreover, the individual's marital status and family history of breast cancer were identified as predictive factors. CONCLUSIONS: This study illuminates quality of life determinants for breast cancer survivors with chemotherapy-induced peripheral neuropathy, advocating comprehensive care and addressing depression and neuropathic pain for better outcomes.

Genomic Alterations of Tumors in HER2-Low Breast Cancers.

The aim of this study was to elucidate molecular profiling in HER2-low tumors based on a promising dataset. A total of 615 consecutive HER2-negative breast cancer samples were assayed. The genomic mutations in the two groups with different HER2 expression levels (HER2-0 vs. HER2-low) were compared. The mutation types obtained via next-generation targeted sequencing were correlated with the clinicopathological features of the patients with HER2-0 and HER2-low breast cancer. The results showed that there was a significantly higher percentage of receptor-positive (ER/PR) tumors and more low-level Ki-67 tumors, but a lower incidence of stage I/II tumors in the HER2-low group compared to the HER2-0 group. There was a significantly higher frequency of 17.62% (65/369) for PIK3CA_SNA in the HER2-low group than in the HER2-0 group, which had a frequency of only 9.35% (23/246) (p = 0.006). When the called gene alterations in the triple-negative breast cancer (TNBC) group were compared with those in the luminal-like breast cancer group, there was a significantly high frequency of 28.17% (140/497) for ERBB2_SNA in a luminal-like group than in the TNBC group(16.95% (20/118)).We conclude that the early detection of PIK3CA mutations is likely to be important and might help therapeutic decision making in patients with HER2-low tumors.