Interactions of traditional and biodegradable microplastics with neonicotinoid pesticides.

Neonicotinoid pesticides (NNPs) and microplastics (MPs) are two emerging contaminants in agricultural environment. However, the interaction between MPs (especially biodegradable plastics) and NNPs is currently unclear. Therefore, taking thiacloprid (THI) as an example of NNPs, this study explores the adsorption-desorption process and mechanism of NNPs on MPs (traditional and biodegradable plastics), and analyzed the main factors affecting the adsorption (pH, salinity and dissolved organic matter). In addition, by using diffusive gradients in thin-films device, this study assessed the impact of MPs on the bioavailability of NNPs in soil. The results showed that the maximum adsorption capacity of polyamide 6 (96.49 µg g-1) for THI was greater than that of poly (butylene adipate co-terephthalate) (88.78 µg g-1). Aging increased the adsorption amount of THI (5.53 %-15.8 %) due to the higher specific surface area and reduced contact angle of MPs, but the adsorption mechanism remained unchanged. The desorption amount of THI from MPs in simulated intestinal fluid is 1.30-1.36 times. The MPs in soil alter the distribution of THI in the soil, increasing the bioavailability of THI while inhibiting its degradation. The results highlighted the significance of examining the combined pollution caused by MPs and NNPs.

Closed Bipolar Nanoelectrode Array for Ultra-Sensitive Detection of Alkaline Phosphatase and Two-Dimensional Imaging of Epidermal Growth Factor Receptors.

The combination of closed bipolar electrodes (cBPE) with electrochemiluminescence (ECL) imaging has demonstrated remarkable capabilities in the field of bioanalysis. Here, we established a cBPE-ECL platform for ultrasensitive detection of alkaline phosphatase (ALP) and two-dimensional imaging of epidermal growth factor receptor (EGFR). This cBPE-ECL system consists of a high-density gold nanowire array in anodic aluminum oxide (AAO) membrane as the cBPE coupled with ECL of highly luminescent cadmium selenide quantum dots (CdSe QDs) luminophores to achieve cathodic electro-optical conversion. When an enzyme-catalyzed amplification effect of ALP with 4-aminophenyl phosphate monosodium salt hydrate (p-APP) as the substrate and 4-aminophenol (p-AP) as the electroactive probe is introduced, a significant improvement of sensing sensitivity with a detection limit as low as 0.5 fM for ALP on the cBPE-ECL platform can be obtained. In addition, the cBPE-ECL sensing system can also be used to detect cancer cells with an impressive detection limit of 50 cells/mL by labeling ALP onto the EGFR protein on A431 human epidermal cancer cell membranes. Thus, two-dimensional (2D) imaging of the EGFR proteins on the cell surface can be achieved, demonstrating that the established cBPE-ECL sensing system is of high resolution for spatiotemporal cell imaging.

Small extracellular vesicles derived from microRNA-22-3p-overexpressing mesenchymal stem cells protect retinal ganglion cells by regulating MAPK pathway.

Glaucoma is the leading cause of irreversible blindness and is characterized by progressive retinal ganglion cell (RGC) loss and retinal nerve fiber layer thinning. Currently, no existing treatment is effective for the preservation of RGCs. MicroRNA-22-3p (miR22) and small extracellular vesicles derived from mesenchymal stem cells (MSC-sEVs) have neuroprotective effects. In this study, we apply miR22-overexpressing MSC-sEVs in an N-methyl-D-aspartic acid (NMDA)-induced RGC injury model to assess their short-term therapeutic effects and explore the underlying mechanisms. We find that mice in the miR22-sEVs-treated group have thicker retinas, fewer apoptotic cells, more reserved RGCs, better retinal function, and lower expression levels of Bax and caspase-3. MiR22-sEVs treatment promotes viability, inhibits apoptosis and inhibits Bax and caspase-3 expression in RGC-5 cells. MiR22 targets mitogen-activated protein kinase kinase kinase 12 to inhibit apoptosis by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Collectively, our results suggest that miR22-sEVs ameliorate NMDA-induced RGC injury through the inhibition of MAPK signaling pathway-mediated apoptosis, providing a potential therapy for glaucoma and other diseases that involve RGC damage.

Analysis of Heavy Metal Characteristics and Health Risk Assessment of Dried Fish Marketed in Guangzhou, China.

This study investigated heavy metal contamination in dried fish sold in Guangzhou, China, and evaluated the resultant non-carcinogenic and carcinogenic health risks. Dried fish samples were purchased from Baiyun, Tianhe, Panyu, and Yuexiu districts in Guangzhou, where the population is substantial. They were randomly acquired in bustling supermarkets and farmers' markets, targeting the most popular dried fish in these areas. Sixty samples from five dried fish types (Stolephorus chinensis, Thamnaconus modestus, Nemipterus-virgatus, river fish, Ctenopharyngodon idella) were analyzed for chromium (Cr), arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) content. Quantification of the heavy metals were carried out by inductively coupled plasma mass spectrometry (ICP-MS) for Cr, As, Cd, and Pb, and an automatic mercury analyzer for Hg. The median concentration of these heavy metals in dried fish were 0.358 mg/kg, 2.653 mg/kg, 0.032 mg/kg, 0.083 mg/kg, and 0.042 mg/kg, respectively. Pollution severity was ranked as dried Nemipterus-virgatus > dried Stolephorus chinensis > dried Thamnaconus modestus > dried river fish > dried Ctenopharyngodon idella, with As being the most predominant pollutant. All fish types showed severe As pollution. Non-carcinogenic risks were identified in the consumption of dried Nemipterus-virgatus and dried Stolephorus chinensis for both genders, while potential carcinogenic risks were associated with four of the fish types. Women faced higher health risks than men from dried fish consumption. Consequently, we advise consumers to minimize their intake of dried fish and regulatory agencies conduct regular monitoring of heavy metal levels in commercially available dried fish to avert potential health risks.

Key Issues of Economic Evaluations for Health Technology Assessment in China: A Nationwide Expert Survey.

OBJECTIVES: Health technology assessment (HTA) is increasingly crucial in medicine price negotiations in China, yet prior appraisals revealed national discrepancies on key economic evaluation issues: willingness-to-pay (WTP) threshold, pricing models for multi-indication medicines, and comparator selection principles. This study aims to collect expert opinions on these issues for future HTA evaluations. METHODS: A nationwide anonymous web-based survey encompassing experts across academia, HTA, consultancy/contract research organization (CRO)/industry, service provider and payer. In 2023, a generic invitation containing a web link to the questionnaire was disseminated via WeChat using convenience and snowball sampling. Agreement rates for questionnaire views were analyzed using descriptive statistics. The relationship between participants' responses and demographics was examined using appropriate logistic models. RESULTS: 303 responses were received from experts in 34 cities. Key expert views include: a suggested base WTP threshold ranging from 0.5 to 1.5 times GDP (52.1% agreement); elevated thresholds for childhood diseases, rare diseases, end-of-life diseases, and first-in-class medicines (FICs) (>78.0% agreement); a single pricing model for multi-indication medicines (60.4% agreement); consideration of multiple medicines as comparators (79.9% agreement); and avoiding the use of centrally procured medicines as comparators for medicines with a time-to-market under three years (71.0% agreement). Participants who are service provider had lower odds of selecting higher thresholds (OR: 0.26; P<0.01) compared with responders from consultancy/CRO/industry. CONCLUSIONS: Expert views indicate the need for substantial changes in China's current HTA methods, highlighting the need for increased investment in HTA processes and expertise cultivation.

Actn2 defects accelerates H9c2 hypertrophy via ERK phosphorylation under chronic stress.

BACKGROUND: In humans, ACTN2 mutations are identified as highly relevant to a range of cardiomyopathies such as DCM and HCM, while their association with sudden cardiac death has been observed in forensic cases. Although ACTN2 has been shown to regulate sarcomere Z-disc organization, a causal relationship between ACTN2 dysregulation and cardiomyopathies under chronic stress has not yet been investigated. OBJECTIVE: In this work, we explored the relationship between Actn2 dysregulation and cardiomyopathies under dexamethasone treatment. METHODS: Previous cases of ACTN2 mutations were collected and the conservative analysis was carried out by MEGA 11, the possible impact on the stability and function of ACTN2 affected by these mutations was predicted by Polyphen-2. ACTN2 was suppressed by siRNA in H9c2 cells under dexamethasone treatment to mimic the chronic stress in vitro. Then the cardiac hypertrophic molecular biomarkers were elevated, and the potential pathways were explored by transcriptome analysis. RESULTS: Actn2 suppression impaired calcium uptake and increased hypertrophy in H9c2 cells under dexamethasone treatment. Concomitantly, hypertrophic molecular biomarkers were also elevated in Actn2-suppressed cells. Further transcriptome analysis and Western blotting data suggested that Actn2 suppression led to the excessive activation of the MAPK pathway and ERK cascade. In vitro pharmaceutical intervention with ERK inhibitors could partially reverse the morphological changes and inhibit the excessive cardiac hypertrophic molecular biomarkers in H9c2 cells. CONCLUSION: Our study revealed a functional role of ACTN2 under chronic stress, loss of ACTN2 function accelerated H9c2 hypertrophy through ERK signaling. A commercial drug, Ibudilast, was identified to reverse cell hypertrophy in vitro.

Interfacial-Assembly-Induced In Situ Transformation from Aligned 1D Nanowires to Quasi-2D Nanofilms.

As the dimensionality of materials generally affects their characteristics, thin films composed of low-dimensional nanomaterials, such as nanowires (NWs) or nanoplates, are of great importance in modern engineering. Among various bottom-up film fabrication strategies, interfacial assembly of nanoscale building blocks holds great promise in constructing large-scale aligned thin films, leading to emergent or enhanced collective properties compared to individual building blocks. As for 1D nanostructures, the interfacial self-assembly causes the morphology orientation, effectively achieving anisotropic electrical, thermal, and optical conduction. However, issues such as defects between each nanoscale building block, crystal orientation, and homogeneity constrain the application of ordered films. The precise control of transdimensional synthesis and the formation mechanism from 1D to 2D are rarely reported. To meet this gap, we introduce an interfacial-assembly-induced interfacial synthesis strategy and successfully synthesize quasi-2D nanofilms via the oriented attachment of 1D NWs on the liquid interface. Theoretical sampling and simulation show that NWs on the liquid interface maintain their lowest interaction energy for the ordered crystal plane (110) orientation and then rearrange and attach to the quasi-2D nanofilm. This quasi-2D nanofilm shows enhanced electric conductivity and unique optical properties compared with its corresponding 1D geometry materials. Uncovering these growth pathways of the 1D-to-2D transition provides opportunities for future material design and synthesis at the interface.

Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography.

INTRODUCTION: There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. METHODS: In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. RESULTS: Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p < 0.001). CONCLUSION: Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.

Unconventional superconductivity in chiral molecule-TaS2 hybrid superlattices.

Chiral superconductors, a unique class of unconventional superconductors in which the complex superconducting order parameter winds clockwise or anticlockwise in the momentum space1, represent a topologically non-trivial system with intrinsic time-reversal symmetry breaking (TRSB) and direct implications for topological quantum computing2,3. Intrinsic chiral superconductors are extremely rare, with only a few arguable examples, including UTe2, UPt3 and Sr2RuO4 (refs. 4-7). It has been suggested that chiral superconductivity may exist in non-centrosymmetric superconductors8,9, although such non-centrosymmetry is uncommon in typical solid-state superconductors. Alternatively, chiral molecules with neither mirror nor inversion symmetry have been widely investigated. We suggest that an incorporation of chiral molecules into conventional superconductor lattices could introduce non-centrosymmetry and help realize chiral superconductivity10. Here we explore unconventional superconductivity in chiral molecule intercalated TaS2 hybrid superlattices. Our studies reveal an exceptionally large in-plane upper critical field Bc2,|| well beyond the Pauli paramagnetic limit, a robust π-phase shift in Little-Parks measurements and a field-free superconducting diode effect (SDE). These experimental signatures of unconventional superconductivity suggest that the intriguing interplay between crystalline atomic layers and the self-assembled chiral molecular layers may lead to exotic topological materials. Our study highlights that the hybrid superlattices could lay a versatile path to artificial quantum materials by combining a vast library of layered crystals of rich physical properties with the nearly infinite variations of molecules of designable structural motifs and functional groups11.

Ti3C2Tx Coated with TiO2 Nanosheets for the Simultaneous Detection of Ascorbic Acid, Dopamine and Uric Acid.

Two-dimensional MXenes have become an important material for electrochemical sensing of biomolecules due to their excellent electric properties, large surface area and hydrophilicity. However, the simultaneous detection of multiple biomolecules using MXene-based electrodes is still a challenge. Here, a simple solvothermal process was used to synthesis the Ti3C2Tx coated with TiO2 nanosheets (Ti3C2Tx@TiO2 NSs). The surface modification of TiO2 NSs on Ti3C2Tx can effectively reduce the self-accumulation of Ti3C2Tx and improve stability. Glassy carbon electrode was modified by Ti3C2Tx@TiO2 NSs (Ti3C2Tx@TiO2 NSs/GCE) and was able simultaneously to detect dopamine (DA), ascorbic acid (AA) and uric acid (UA). Under concentrations ranging from 200 to 1000 µM, 40 to 300 µM and 50 to 400 µM, the limit of detection (LOD) is 2.91 µM, 0.19 µM and 0.25 µM for AA, DA and UA, respectively. Furthermore, Ti3C2Tx@TiO2 NSs/GCE demonstrated remarkable stability and reliable reproducibility for the detection of AA/DA/UA.

CMRxRecon: A publicly available k-space dataset and benchmark to advance deep learning for cardiac MRI.

Cardiac magnetic resonance imaging (CMR) has emerged as a valuable diagnostic tool for cardiac diseases. However, a significant drawback of CMR is its slow imaging speed, resulting in low patient throughput and compromised clinical diagnostic quality. The limited temporal resolution also causes patient discomfort and introduces artifacts in the images, further diminishing their overall quality and diagnostic value. There has been growing interest in deep learning-based CMR imaging algorithms that can reconstruct high-quality images from highly under-sampled k-space data. However, the development of deep learning methods requires large training datasets, which have so far not been made publicly available for CMR. To address this gap, we released a dataset that includes multi-contrast, multi-view, multi-slice and multi-coil CMR imaging data from 300 subjects. Imaging studies include cardiac cine and mapping sequences. The 'CMRxRecon' dataset contains raw k-space data and auto-calibration lines. Our aim is to facilitate the advancement of state-of-the-art CMR image reconstruction by introducing standardized evaluation criteria and making the dataset freely accessible to the research community.

Inducing superconductivity in quantum anomalous Hall regime.

Interfacing the quantum anomalous Hall insulator with a conventional superconductor is known to be a promising manner for realizing a topological superconductor, which has been continuously pursued for years. Such a proximity route depends to a great extent on the control of the delicate interfacial coupling of the two constituents. However, a recent experiment reported the failure to reproduce such a topological superconductor, which is ascribed to the negligence of the electrical short by the superconductor in the theoretical proposal. Here, we reproduce this topological superconductor with attention to the interface control. The resulted conductance matrix under a wide magnetic field range agrees with the fingerprint of this topological superconductor. This allows us to develop a phase diagram that unveils three regions parameterized by various coupling limits, which not only supports the feasibility to fabricate the topological superconductor by proximity but also fully explains the origin of the previous debate. The present work provides a comprehensible guide on fabricating the topological superconductor.

Integrated analysis of single-cell and bulk RNA sequencing data reveals a cellular senescence-related signature in hepatocellular carcinoma.

The mortality of hepatocellular carcinoma (HCC) is on the rise globally, particularly in the Western world, with etiology gradually shifting from virus-related liver diseases to metabolic disorders such as non-alcoholic fatty liver disease. Early detection of HCC is challenging, and effective prognostic indicators are currently lacking, urgently necessitating reliable markers to assist in treatment planning and clinical management. Here, we introduce hepatocellular carcinoma senescence genes (HSG) to assess cellular senescence in HCC and devise a hepatocellular carcinoma senescence score (HSS) for prognostic prediction. Higher HSS levels signify poorer prognosis and increased tumor proliferation activity. Additionally, we observe alterations in the tumor immune microenvironment with higher HSS levels, such as increased infiltration of Treg, potentially providing a basis for immunotherapy. Furthermore, we identify key genes, such as PTTG1, within the senescence gene set and demonstrate their regulatory roles in HCC cells and Treg through experimentation. In summary, we establish a scoring system based on hepatocellular carcinoma senescence genes for prognostic prediction in HCC, potentially offering guidance for clinical treatment planning.

Lighting Up Nucleolus To Report Mitochondria Damage Using a Mitochondria-to-Nucleolus Migration Probe.

Visualization of the mitochondrial state is crucial for tracking cell life processes and diagnosing disease, while fluorescent probes that can accurately assess mitochondrial status are currently scarce. Herein, a fluorescent probe named "SYN" was designed and prepared, which can target mitochondria via the mitochondrial membrane potential. Upon pathology or external stimulation, SYN can be released from the mitochondria and accumulate in the nucleolus to monitor the status of mitochondria. During this process, the brightness of the nucleolus can then serve as an indicator of mitochondrial damage. SYN has demonstrated excellent photostability in live cells as well as an extremely inert fluorescence response to bioactive molecules and the physiological pH environment of live cells. Spectroscopic titration and molecular docking studies have revealed that SYN can be lit up in nucleoli due to the high viscosity of the nucleus and the strong electrostatic interaction with the phosphate backbone of RNA. This probe is expected to be an exceptional tool based on its excellent imaging properties for tracking mitochondrial state in live cells.

Photosensitizing metal covalent organic framework with fast charge transfer dynamics for efficient CO2 photoreduction.

Designing artificial photocatalysts for CO2 reduction is challenging, mainly due to the intrinsic difficulty of making multiple functional units cooperate efficiently. Herein, three-dimensional metal covalent organic frameworks (3D MCOFs) were employed as an innovative platform to integrate a strong Ru(ii) light-harvesting unit, an active Re(i) catalytic center, and an efficient charge separation configuration for photocatalysis. The photosensitive moiety was precisely stabilized into the covalent skeleton by using a rational-designed Ru(ii) complex as one of the building units, while the Re(i) center was linked via a shared bridging ligand with an Ru(ii) center, opening an effective pathway for their electronic interaction. Remarkably, the as-synthesized MCOF exhibited impressive CO2 photoreduction activity with a CO generation rate as high as 1840 µmol g-1 h-1 and 97.7% selectivity. The femtosecond transient absorption spectroscopy combined with theoretical calculations uncovered the fast charge-transfer dynamics occurring between the photoactive and catalytic centers, providing a comprehensive understanding of the photocatalytic mechanism. This work offers in-depth insight into the design of MCOF-based photocatalysts for solar energy utilization.

Identification Of Endothelial Cell Immune-related Gene Signature for Lung Adenocarcinoma by Integrated Analysis of Single-cell and Bulk RNA Sequencing Data.

Background: The role of endothelial cells in tumor progression is considerable, yet the effect of endothelial cell immune-related genes (EIRGs) is still unclear. This research aimed to scrutinize the prognostic value of EIRGs in lung adenocarcinoma (LUAD) and provide further insights into the abovementioned uncertainties. Methods: After single-cell RNA sequencing (scRNA-seq) samples were obtained from the Gene Expression Omnibus (GEO) database, they were integrated with bulk RNA sequencing data from The Cancer Genome Atlas (TCGA). Prognostic markers were determined and a prognostic model was developed. From this model, a nomogram was constructed. We analyzed the biological mechanism of the EIRGs in LUAD, including functional enrichment, tumor mutational burden (TMB), tumor microenvironment (TME) analyses and drug sensitivity. We validated the signature by validating the external cohort GSE31210 and RT-qPCR. Results: After analyzing the model constructed from eight EIRGs, we observed that high-risk group (HG) LUAD patients (a risk score exceeding 4.65) exhibited unfavorable outcomes according to Kaplan‒Meier survival curves. This outcome was confirmed by GSE31210. The nomogram based on the model demonstrated significant predictive value. HG was influenced primarily by steroid hormone biosynthesis and ECM receptor interactions. The TMB in HGs was greater than that in the LG. Analysis of drug sensitivity revealed the direction for individualized treatment for both risk cohorts. Variations in the expression of EIRGs have been confirmed via RT-qPCR in several LUAD cell lines. Conclusions: The prognostic model and nomogram above are valuable for determining the survival rate and treatment options for LUAD patients.

Adipose-Derived Stem Cell Exosomes Facilitate Diabetic Wound Healing: Mechanisms and Potential Applications.

Wound healing in diabetic patients is frequently hampered. Adipose-derived stem cell exosomes (ADSC-eoxs), serving as a crucial mode of intercellular communication, exhibit promising therapeutic roles in facilitating wound healing. This review aims to comprehensively outline the molecular mechanisms through which ADSC-eoxs enhance diabetic wound healing. We emphasize the biologically active molecules released by these exosomes and their involvement in signaling pathways associated with inflammation modulation, cellular proliferation, vascular neogenesis, and other pertinent processes. Additionally, the clinical application prospects of the reported ADSC-eoxs are also deliberated. A thorough understanding of these molecular mechanisms and potential applications is anticipated to furnish a theoretical groundwork for combating diabetic wound healing.

Construction of a novel nomogram for predicting overall survival in patients with Siewert type II AEG based on LODDS: a study based on the seer database and external validation.

Background: In recent years, the incidence of adenocarcinoma of the esophagogastric junction (AEG) has been rapidly increasing globally. Despite advances in the diagnosis and treatment of AEG, the overall prognosis for AEG patients remains concerning. Therefore, analyzing prognostic factors for AEG patients of Siewert type II and constructing a prognostic model for AEG patients is important. Methods: Data of primary Siewert type II AEG patients from the SEER database from 2004 to 2015 were obtained and randomly divided into training and internal validation cohort. Additionally, data of primary Siewert type II AEG patients from the China Medical University Dandong Central Hospital from 2012 to 2018 were collected for external validation. Each variable in the training set underwent univariate Cox analysis, and variables with statistical significance (p < 0.05) were added to the LASSO equation for feature selection. Multivariate Cox analysis was then conducted to determine the independent predictive factors. A nomogram for predicting overall survival (OS) was developed, and its performance was evaluated using ROC curves, calibration curves, and decision curves. NRI and IDI were calculated to assess the improvement of the new prediction model relative to TNM staging. Patients were stratified into high-risk and low-risk groups based on the risk scores from the nomogram. Results: Age, Differentiation grade, T stage, M stage, and LODDS (Log Odds of Positive Lymph Nodes)were independent prognostic factors for OS. The AUC values of the ROC curves for the nomogram in the training set, internal validation set, and external validation set were all greater than 0.7 and higher than those of TNM staging alone. Calibration curves indicated consistency between the predicted and actual outcomes. Decision curve analysis showed moderate net benefit. The NRI and IDI values of the nomogram were greater than 0 in the training, internal validation, and external validation sets. Risk stratification based on the nomogram's risk score demonstrated significant differences in survival rates between the high-risk and low-risk groups. Conclusion: We developed and validated a nomogram for predicting overall survival (OS) in patients with Siewert type II AEG, which assists clinicians in accurately predicting mortality risk and recommending personalized treatment strategies.

Unveiling the Power of Model-Agnostic Multiscale Analysis for Enhancing Artificial Intelligence Models in Breast Cancer Histopathology Images.

Developing AI models for digital pathology has traditionally relied on single-scale analysis of histopathology slides. However, a whole slide image is a rich digital representation of the tissue, captured at various magnification levels. Limiting our analysis to a single scale overlooks critical information, spanning from intricate high-resolution cellular details to broad low-resolution tissue structures. In this study, we propose a model-agnostic multiresolution feature aggregation framework tailored for the analysis of histopathology slides in the context of breast cancer, on a multicohort dataset of 2038 patient samples. We have adapted 9 state-of-the-art multiple instance learning models on our multi-scale methodology and evaluated their performance on grade prediction, TP53 mutation status prediction and survival prediction. The results prove the dominance of the multiresolution methodology, and specifically, concatenating or linearly transforming via a learnable layer the feature vectors of image patches from a high (20x) and low (10x) magnification factors achieve improved performance for all prediction tasks across domain-specific and imagenet-based features. On the contrary, the performance of uniresolution baseline models was not consistent across domain-specific and imagenet-based features. Moreover, we shed light on the inherent inconsistencies observed in models trained on whole-tissue-sections when validated against biopsy-based datasets. Despite these challenges, our findings underscore the superiority of multiresolution analysis over uniresolution methods. Finally, cross-scale analysis also benefits the explainability aspects of attention-based architectures, since one can extract attention maps at the tissue- and cell-levels, improving the interpretation of the model's decision. The code and results of this study can be found at github.com/tsikup/multiresolution_histopathology.

What was the global burden of kidney cancer attributable to high body mass index from 1990 to 2019? There existed some points noteworthy.

Purpose: With the prevalence of high body mass index (HBMI) increasing over the past 30 years, it is essential to examine the impact of obesity on kidney cancer. This study aims to explore the attributable burden of kidney cancer associated with HBMI and its proportion at different levels. Methods and materials: The data used in this research were obtained from the Global Burden of Diseases Study 2019. We utilized DisMod-MR 2.1, a Bayesian meta-regression tool, to estimate the burden of kidney cancer attributable to HBMI, which was measured by age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR). Correlation analysis was conducted by the Spearman rank order correlation method. The temporal trends were analyzed by estimating the estimated annual percentage change (EAPC). Results: Globally in 2019, there were a total of 31.7 thousand deaths and 751.89 thousand disability-adjusted life years (DALYs) attributable to kidney cancer caused by HBMI, increased by 183.1 and 164%, respectively. Over the period from 1990 to 2019, the burden of kidney cancer attributable to HBMI increased in all regions, with the most significant increases occurring in Low-middle socio-demographic index (SDI) and Low SDI regions. At the national level, countries with lower SDI had lower ASMR and ASDR compared to developed nations. However, the EAPC values, which indicate the rate of increase, were significantly higher in these countries than in developed nations. Furthermore, across all years from 1990 to 2019, males experienced a greater and more rapidly increasing burden of kidney cancer attributable to HBMI than females. Conclusion: As the population grows and dietary patterns shift, the burden of kidney cancer attributable to HBMI is expected to become even more severe. Males and developed regions have borne a heavier burden from 1990 to 2019. However, the EAPC values for both ASMR and ASDR were higher in males but not in regions with higher SDI values.