Multi-gene phylogenetic and taxonomic contributions to Xylaria (Ascomycota) associated with fallen fruits from China.

Morphological and phylogenetic analyses on samples of Xylaria species associated with fallen fruits from China were carried out, and two new species were described, namely X.aleuriticola and X.microcarpa. Xylariaaleuriticola is found on fallen fruits of Aleuritesmoluccana, and characterized by stromata dichotomously branched several times with long acute sterile apices, fertile parts roughened with perithecia and tomentose, and ellipsoid to fusiform ascospores. Xylariamicrocarpa differs in its very small stromata with dark brown tomentum, light brown ascospores with an inconspicuous straight germ slit, and grows on leguminous pods. The differences between the new species and morphologically similar species are discussed. Phylogenetic analyses on ITS-RPB2-TUB sequences confirmed that the two species are clearly separated from other species of the genus Xylaria. Xylarialiquidambaris is reported as a new record from China. A key to the Xylaria species associated with fallen fruits and seeds reported from China is provided to facilitate future studies of the genus.

Deep learning promoted target volumes delineation of total marrow and total lymphoid irradiation for accelerated radiotherapy: A multi-institutional study.

BACKGROUND AND PURPOSE: One of the current roadblocks to the widespread use of Total Marrow Irradiation (TMI) and Total Marrow and Lymphoid Irradiation (TMLI) is the challenging difficulties in tumor target contouring workflow. This study aims to develop a hybrid neural network model that promotes accurate, automatic, and rapid segmentation of multi-class clinical target volumes. MATERIALS AND METHODS: Patients who underwent TMI and TMLI from January 2018 to May 2022 were included. Two independent oncologists manually contoured eight target volumes for patients on CT images. A novel Dual-Encoder Alignment Network (DEA-Net) was developed and trained using 46 patients from one internal institution and independently evaluated on a total of 39 internal and external patients. Performance was evaluated on accuracy metrics and delineation time. RESULTS: The DEA-Net achieved a mean dice similarity coefficient of 90.1 % ± 1.8 % for internal testing dataset (23 patients) and 91.1 % ± 2.5 % for external testing dataset (16 patients). The 95 % Hausdorff distance and average symmetric surface distance were 2.04 ± 0.62 mm and 0.57 ± 0.11 mm for internal testing dataset, and 2.17 ± 0.68 mm, and 0.57 ± 0.20 mm for external testing dataset, respectively, outperforming most of existing state-of-the-art methods. In addition, the automatic segmentation workflow reduced delineation time by 98 % compared to the conventional manual contouring process (mean 173 ± 29 s vs. 12168 ± 1690 s; P < 0.001). Ablation study validate the effectiveness of hybrid structures. CONCLUSION: The proposed deep learning framework achieved comparable or superior target volume delineation accuracy, significantly accelerating the radiotherapy planning process.

Widely metabolomic combined with transcriptome analysis to build a bioactive compound regulatory network for the fruit growth cycle in Pseudocydonia sinensis.

Neglected and underutilised plants such as Pseudocydonia sinensis (Chinese quince) have garnered global interest as invaluable sources of natural bioactive compounds. Herein, a wide-targeted metabolomics-based approach revealed 1199 concurrent metabolites, with further analysis of their fluctuations across with the five stages of fruit growth. The bioactive compounds in Chinese quince primarily comprised sugars and organic acids, flavonoids, and terpenoids. Moreover, 395 metabolites were identified as having medicinal properties and rutin was the most content of them. Transcriptome analysis further provided a molecular basis for the metabolic changes observed during fruit development. By thoroughly analysing metabolite and transcriptome data, we revealed changes in bioactive compounds and related genes throughout fruit development. This study has yielded valuable insights into the ripening process of Chinese quince fruit, presenting substantial implications for industrial applications, particularly in quality control.

ATF5-Mediated Mitochondrial Unfolded Protein Response (UPRmt) Protects Neurons Against Oxygen-Glucose Deprivation and Cerebral Ischemia.

BACKGROUND: The mitochondrial unfolded protein response (UPRmt) is an evolutionarily conserved mitochondrial response that is critical for maintaining mitochondrial and energetic homeostasis under cellular stress after tissue injury and disease. Here, we ask whether UPRmt may be a potential therapeutic target for ischemic stroke. METHODS: We performed the middle cerebral artery occlusion and oxygen-glucose deprivation models to mimic ischemic stroke in vivo and in vitro, respectively. Oligomycin and meclizine were used to trigger the UPRmt. We used 2,3,5-triphenyltetrazolium chloride staining, behavioral tests, and Nissl staining to evaluate cerebral injury in vivo. The Cell Counting Kit-8 assay and the Calcein AM Assay Kit were conducted to test cerebral injury in vitro. RESULTS: Inducing UPRmt with oligomycin protected neuronal cultures against oxygen-glucose deprivation. UPRmt could also be triggered with meclizine, and this Food and Drug Administration-approved drug also protected neurons against oxygen-glucose deprivation. Blocking UPRmt with siRNA against activating transcription factor 5 eliminated the neuroprotective effects of meclizine. In a mouse model of focal cerebral ischemia, pretreatment with meclizine was able to induce UPRmt in vivo, which reduced infarction and improved neurological outcomes. CONCLUSIONS: These findings suggest that the UPRmt is important in maintaining the survival of neurons facing ischemic/hypoxic stress. The UPRmt mechanism may provide a new therapeutic avenue for ischemic stroke.

Utility of PSMA PET/CT in Staging and Restaging of Renal Cell Carcinoma: A Systematic Review and Metaanalysis.

Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of multiple solid tumors, including renal cell carcinoma (RCC). Studies have demonstrated promising results on the utility of PSMA-targeted PET/CT imaging in RCC. This report aims to provide a systematic review and metaanalysis on the utility and detection rate of PSMA PET/CT imaging in staging or evaluation of primary RCC and restaging of metastatic or recurrent RCC. Methods: Searches were performed in PubMed, Embase, and abstract proceedings (last updated, August 2023). Studies that provided a lesion-level detection rate of PSMA radiotracers in staging or restaging of RCC were included in the metaanalysis. The overall pooled detection rate with a 95% CI was estimated, and subgroup analysis was performed when feasible. Results: Nine studies comprising 152 patients (133 clear cell RCC [ccRCC], 19 other RCC subtypes) were included in the metaanalysis. The pooled detection rate of PSMA PET/CT in evaluation of primary or metastatic RCC was estimated to be 0.83 (95% CI, 0.67-0.92). Subgroup analysis showed a pooled PSMA detection rate of 0.74 (95% CI, 0.57-0.86) in staging or evaluation of primary RCC lesions and 0.87 (95% CI, 0.73-0.95) in restaging of metastatic or recurrent RCC. Analysis based on the type of radiotracer showed a pooled detection rate of 0.85 (95% CI, 0.62-0.95) for 68Ga-based PSMA tracers and 0.92 (95% CI, 0.76-0.97) for 18F-DCFPyL PET/CT. Furthermore, in metastatic ccRCC, the available data support a significantly higher detection rate for 18F-DCFPyL PET/CT than for conventional imaging modalities (2 studies). Conclusion: Our preliminary results show that PSMA PET/CT could be a promising alternative imaging modality for evaluating RCC, particularly metastatic ccRCC. Large prospective studies are warranted to confirm clinical utility in the staging and restaging of RCC.

Novel off-Targeting Events Identified after Genome Wide Analysis of CRISPR-Cas Edited Pigs.

CRISPR-Cas technology has transformed our ability to introduce targeted modifications, allowing unconventional animal models such as pigs to model human diseases and improve its value for food production. The main concern with using the technology is the possibility of introducing unwanted modifications in the genome. In this study, we illustrate a pipeline to comprehensively identify off-targeting events on a global scale in the genome of three different gene-edited pig models. Whole genome sequencing paired with an off-targeting prediction software tool filtered off-targeting events amongst natural variations present in gene-edited pigs. This pipeline confirmed two known off-targeting events in IGH knockout pigs, AR and RBFOX1, and identified other presumably off-targeted loci. Independent validation of the off-targeting events using other gene-edited DNA confirmed two novel off-targeting events in RAG2/IL2RG knockout pig models. This unique strategy offers a novel tool to detect off-targeting events in genetically heterogeneous species after genome editing.

Arthroscopic inferior leaf meniscectomy of the involved anterior horn in the lateral meniscus horizontal tear via an accessary extreme far anteromedial portal.

BACKGROUND: An accessory extreme far anteromedial portal can improve visualisation and ease inferior leaf meniscectomy in patients with lateral meniscal anterior horn horizontal tears. However, the therapeutic outcomes of adding an accessory extreme far anteromedial portal remain unclear. This study aimed to evaluate the clinical efficacy of adding an accessory extreme far anteromedial portal for treating lateral meniscal horizontal tears involving the anterior horns. METHODS: This retrospective study included 101 patients with anterior horn involvement in lateral meniscal horizontal tears who underwent arthroscopic unstable inferior leaf meniscectomy between January 2016 and December 2020. The pathologies were diagnosed using physical examinations and magnetic resonance imaging. The anterior horn involved in the lateral meniscal horizontal tears was treated using inferior leaf meniscectomy. The primary endpoints were changes in the visual analogue scale, Lysholm, International Knee Documentation Committee, and Tegner scores at the final follow-up. The secondary endpoint was meniscal cure rate at 3 months postoperatively. The preoperative and postoperative functional scores were compared. The occurrence of complications was recorded. RESULTS: All patients were followed up for an average of 4.9 ± 1.2 years (range 2.3-7.5 years). After 4 months, none of the patients experienced pain, weakness, instability, or tenderness in the lateral joint line, achieving an imaging cure rate of 98%. At the final follow-up, significant postoperative improvements were observed in the average values of the visual analogue scale score (3.5 ± 0.7 vs. 0.7 ± 0.6), Lysholm score (62.7 ± 4.4 vs. 91.8 ± 3.1), International Knee Documentation Committee score (61.9 ± 3.7 vs. 91.7 ± 9.5), and Tegner score (2.0 ± 0.7 vs. 6.1 ± 0.7). Excellent Lysholm scores were obtained in 81 patients, and good outcomes were obtained in 18 patients, with an excellent-to-good rate of 98.0%. CONCLUSIONS: Inferior leaf resection via the accessory far anteromedial portal is a safe treatment option for the involved anterior horn in lateral meniscal horizontal tears. This approach enhances visibility and facilitates surgical procedures, with minimal complications.

Molecular and morphological data reveal two new species of Tropicoporus (Hymenochaetaceae, Basidiomycota) from Australia and tropical Asia.

Phylogenetic analyses and morphological examination confirmed two new species in the tropical polypore genus Tropicoporus, T.oceanianus and T.zuzaneae, from Australia and tropical Asia, respectively. A phylogenetic analysis based on the two DNA markers including the nuclear ribosomal internal transcribed spacer (ITS) region and the large subunit (nLSU) gene shows that these two new species form two independent lineages nested in the genus Tropicoporus. T.oceanianus is characterized by perennial and ungulate basidiomata, the occasional presence of hymenial setae, a trimitic hyphal structure in the context and a dimitic hyphal system in the trama, and broadly ellipsoid to subglobose basidiospores measuring 5.2-6 × 4-5 µm. T.zuzaneae is characterized by perennial and resupinate basidiomata with distinct receding margin, glancing pores, very thin to almost lacking subiculum, a dimitic hyphal structure, the absence of any setal elements, broadly ellipsoid to subglobose basidiospores measuring 3.8-4.9 × 3-4.2 µm. The differences among the new species and their phylogenetically related and morphologically similar species are discussed.

Remote ischemic conditioning improves cerebral hemodynamics in symptomatic intracranial atherosclerosis: A PET/CT-guided randomized controlled study.

Patients with symptomatic intracranial arterial stenosis (sICAS) suffer embarrassed hemodynamic status and acute ischemic stroke (AIS) recurrence. We aimed to assess the efficacy of remote ischemic conditioning (RIC) on improving this status by evaluating cerebral blood flow (CBF) and cerebral glucose metabolism (CGM) via PET/CT. Adult patients with unilateral sICAS in middle cerebral artery and/or intracranial segment of internal carotid artery-related AIS or transient ischemic attack within 6 months prior to randomization were enrolled. Individuals who received intravenous thrombolysis or endovascular treatment, or sICAS caused by cardiac embolism, small vessel occlusion, or other determined causes were excluded. Twenty-three eligible patients were randomly assigned to standard medical treatment (SMT) (n = 10) or RIC group (n = 13). The RIC protocol consisted of 5 cycles, each for 5-min bilateral upper limb ischemia and 5-min reperfusion period, twice a day, with a total duration of 3 months. Ten healthy volunteers were enrolled as healthy control group. We tested CBF and CGM at the rest stage and the methazolamide-induced stress stage. All patients received PET/CT at baseline and three-month followup. Both CBF and CGM in ipsilateral hemisphere of sICAS patients were significantly decreased at the rest stage and the stress stage (p < .05), which were improved by three-month RIC (p < .05). The lesions decreased notably in RIC group compared to SMT group (p < .05). RIC ameliorated the hemodynamic status and glucose metabolism in regions at high risk of infarction, which might improve the resistance capacity towards ischemic load in sICAS patients.

An N-Shaped Lightweight Network with a Feature Pyramid and Hybrid Attention for Brain Tumor Segmentation.

Brain tumor segmentation using neural networks presents challenges in accurately capturing diverse tumor shapes and sizes while maintaining real-time performance. Additionally, addressing class imbalance is crucial for achieving accurate clinical results. To tackle these issues, this study proposes a novel N-shaped lightweight network that combines multiple feature pyramid paths and U-Net architectures. Furthermore, we ingeniously integrate hybrid attention mechanisms into various locations of depth-wise separable convolution module to improve efficiency, with channel attention found to be the most effective for skip connections in the proposed network. Moreover, we introduce a combination loss function that incorporates a newly designed weighted cross-entropy loss and dice loss to effectively tackle the issue of class imbalance. Extensive experiments are conducted on four publicly available datasets, i.e., UCSF-PDGM, BraTS 2021, BraTS 2019, and MSD Task 01 to evaluate the performance of different methods. The results demonstrate that the proposed network achieves superior segmentation accuracy compared to state-of-the-art methods. The proposed network not only improves the overall segmentation performance but also provides a favorable computational efficiency, making it a promising approach for clinical applications.

Chitosan-Based Structural Color Films for Humidity Sensing with Antiviral Effect.

This scientific investigation emphasizes the essential integration of nature's influence in crafting multifunctional surfaces with bio-inspired designs for enhanced functionality and environmental advantages. The study introduces an innovative approach, merging color decoration, humidity sensing, and antiviral properties into a unified surface using chitosan, an organo-biological polymer, to create cost-effective multilayered films through sol-gel deposition and UV photoinduced deposition of metal nanoparticles. The resulting chitosan films showcase diverse structural colors and demonstrate significant antiviral efficiency, with a 50% and 85% virus inhibition rate within a rapid 20 min reaction, validated through fluorescence cell expression and real-time qPCR (polymerase chain reaction) assays. Silver-deposited chitosan films further enhance antiviral activity, achieving remarkable 91% and 95% inhibition in independent assays. These films exhibit humidity-responsive color modifications across a 25-90% relative humidity range, enabling real-time monitoring validated through simulation studies. The proposed three-in-one functional surface can have versatile applications in surface decoration, medicine, air conditioning, and the food industry. It can serve as a real-time humidity sensor for indoor and outdoor surfaces, find use in biomedical devices for continuous humidity monitoring, and offer antiviral protection for frequently handled devices and tools. The customizable colors enhance visual appeal, making it a comprehensive solution for diverse applications.

Construction of Hollow Ultrasmall Co3O4 Nanoparticles Immobilized in BN for CO2 Conversion.

Rational design and fabrication of metal-organic framework-derived metal oxide (MO) materials featuring a hollow structure and active support can significantly enhance their catalytic activity for specific reactions. Herein, a series of Co3O4 nanoparticles (NPs) immobilized in boron nitride (denoted as Co3O4@BN) with highly open and precisely controllable structures were constructed by an in situ self-assembly method combined with a controlled annealing process. The obtained Co3O4@BN not only possesses a hollow structure but also shows highly dispersed Co3O4 NPs and high loadings of up to 34.3 wt %. Owing to the ultrafine particle size and high dispersity, the optimized Co3O4@BN exhibits high catalytic activity for the cycloaddition of CO2 to epoxides under mild conditions (i.e., 100 °C and CO2 balloon), resulting in at least 4.5 times higher yields (99%) of styrene carbonate than that of Co3O4 synthesized by the pristine ZIF-67. This strategy sheds light on the rational design of hollow MO materials for various advanced applications.

Cytonuclear Interactions and Subgenome Dominance Shape the Evolution of Organelle-Targeted Genes in the Brassica Triangle of U.

The interaction and coevolution between nuclear and cytoplasmic genomes are one of the fundamental hallmarks of eukaryotic genome evolution and, 2 billion yr later, are still major contributors to the formation of new species. Although many studies have investigated the role of cytonuclear interactions following allopolyploidization, the relative magnitude of the effect of subgenome dominance versus cytonuclear interaction on genome evolution remains unclear. The Brassica triangle of U features 3 diploid species that together have formed 3 separate allotetraploid species on similar evolutionary timescales, providing an ideal system for understanding the contribution of the cytoplasmic donor to hybrid polyploid. Here, we investigated the evolutionary pattern of organelle-targeted genes in Brassica carinata (BBCC) and 2 varieties of Brassica juncea (AABB) at the whole-genome level, with particular focus on cytonuclear enzyme complexes. We found partial evidence that plastid-targeted genes experience selection to match plastid genomes, but no obvious corresponding signal in mitochondria-targeted genes from these 2 separately formed allopolyploids. Interestingly, selection acting on plastid genomes always reduced the retention rate of plastid-targeted genes encoded by the B subgenome, regardless of whether the Brassica nigra (BB) subgenome was contributed by the paternal or maternal progenitor. More broadly, this study illustrates the distinct selective pressures experienced by plastid- and mitochondria-targeted genes, despite a shared pattern of inheritance and natural history. Our study also highlights an important role for subgenome dominance in allopolyploid genome evolution, even in genes whose function depends on separately inherited molecules.

Outcomes of extracorporeal membrane oxygenation support in pediatric hemato-oncology patients.

BACKGROUND: In this study, we reviewed the outcomes of pediatric patients with malignancies who underwent hematopoietic stem cell transplantation (HSCT) and extracorporeal membrane oxygenation (ECMO). METHODS: We retrospectively analyzed the records of pediatric hemato-oncology patients treated with chemotherapy or HSCT and who received ECMO in the pediatric intensive care unit (PICU) at Seoul National University Children's Hospital from January 2012 to December 2020. RESULTS: Over a 9-year period, 21 patients (14 males and 7 females) received ECMO at a single pediatric institute; 10 patients (48%) received veno-arterial (VA) ECMO for septic shock (n=5), acute respiratory distress syndrome (ARDS) (n=3), stress-induced myopathy (n=1), or hepatopulmonary syndrome (n=1); and 11 patients (52%) received veno-venous (VV) ECMO for ARDS due to pneumocystis pneumonia (n=1), air leak (n=3), influenza (n=1), pulmonary hemorrhage (n=1), or unknown etiology (n=5). All patients received chemotherapy; 9 received anthracycline drugs and 14 (67%) underwent HSCT. Thirteen patients (62%) were diagnosed with malignancies and 8 (38%) were diagnosed with non-malignant disease. Among the 21 patients, 6 (29%) survived ECMO in the PICU and 5 (24%) survived to hospital discharge. Among patients treated for septic shock, 3 of 5 patients (60%) who underwent ECMO and 5 of 10 patients (50%) who underwent VA ECMO survived. However, all the patients who underwent VA ECMO or VV ECMO for ARDS died. CONCLUSIONS: ECMO is a feasible treatment option for respiratory or heart failure in pediatric patients receiving chemotherapy or undergoing HSCT.

The MpNAC72/MpERF105-MpMYB10b module regulates anthocyanin biosynthesis in Malus 'Profusion' leaves infected with Gymnosporangium yamadae.

Apple rust is a serious fungal disease affecting Malus plants worldwide. Infection with the rust pathogen Gymnosporangium yamadae induces the accumulation of anthocyanins in Malus to resist rust disease. However, the mechanism of anthocyanin biosynthesis regulation in Malus against apple rust is still unclear. Here, we show that MpERF105 and MpNAC72 are key regulators of anthocyanin biosynthesis via the ethylene-dependent pathway in M. 'Profusion' leaves under rust disease stress. Exogenous ethephon treatment promoted high expression of MpERF105 and MpNAC72 and anthocyanin accumulation in G. yamadae-infected M. 'Profusion' leaves. Overexpression of MpERF105 increased the total anthocyanin content of Malus plant material and acted by positively regulating its target gene, MpMYB10b. MpNAC72 physically interacted with MpERF105 in vitro and in planta, and the two form a protein complex. Coexpression of the two leads to higher transcript levels of MpMYB10b and higher anthocyanin accumulation. In addition, overexpression of MpERF105 or MpNAC72 enhanced the resistance of M. 'Profusion' leaves to apple rust. In conclusion, our results elucidate the mechanism by which MpERF105 and MpNAC72 are induced by ethylene in G. yamadae-infected M. 'Profusion' leaves and promote anthocyanin accumulation by mediating the positive regulation of MpMYB10b expression.

Genomic insights into local adaptation and phenotypic diversity of Wenchang chickens.

Wenchang chicken, a prized local breed in Hainan Province of China renowned for its exceptional adaptability to tropical environments and good meat quality, is deeply favored by the public. However, an insufficient understanding of its population architecture and the unclear genetic basis that governs its typical attributes have posed challenges in the protection and breeding of this precious breed. To address these gaps, we conducted whole-genome resequencing on 200 Wenchang chicken samples derived from 10 distinct strains, and we gathered data on an array of 21 phenotype traits. Population genomics analysis unveiled distinctive population structures in Wenchang chickens, primarily attributed to strong artificial selection for different feather colors. Selection sweep analysis identified a group of candidate genes, including PCDH9, DPF3, CDIN1, and SUGCT, closely linked to adaptations that enhance resilience in tropical island habitats. Genome-wide association studies (GWAS) highlighted potential candidate genes associated with diverse feather color traits, encompassing TYR, RAB38, TRPM1, GABARAPL2, CDH1, ZMIZ1, LYST, MC1R, and SASH1. Through the comprehensive analysis of high-quality genomic and phenotypic data across diverse Wenchang chicken resource groups, this study unveils the intricate genetic backgrounds and population structures of Wenchang chickens. Additionally, it identifies multiple candidate genes linked to environmental adaptation, feather color variations, and production traits. These insights not only provide genetic reference for the purification and breeding of Wenchang chickens but also broaden our understanding of the genetic basis of phenotypic diversity in chickens.

Self-assembly of peptide nanomaterials at biointerfaces: molecular design and biomedical applications.

Self-assembly is an important strategy for constructing ordered structures and complex functions in nature. Based on this, people can imitate nature and artificially construct functional materials with novel structures through the supermolecular self-assembly pathway of biological interfaces. Among the many assembly units, peptide molecular self-assembly has received widespread attention in recent years. In this review, we introduce the interactions (hydrophobic interaction, hydrogen bond, and electrostatic interaction) between peptide nanomaterials and biological interfaces, summarizing the latest advancements in multifunctional self-assembling peptide materials. We systematically demonstrate the assembly mechanisms of peptides at biological interfaces, such as proteins and cell membranes, while highlighting their application potential and challenges in fields like drug delivery, antibacterial strategies, and cancer therapy.

Clonal haematopoiesis of indeterminate potential and atrial fibrillation: an east Asian cohort study.

BACKGROUND AND AIMS: Both clonal haematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. This study investigated the potential role of CHIP in the development and progression of AF. METHODS: Deep-targeted sequencing of 24 CHIP mutations (a mean depth of coverage = 1000×) was performed in 1004 patients with AF and 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (i) the prevalence of CHIP mutations between AF and non-AF subjects and (ii) clinical characteristics discriminated by CHIP mutations within AF patients. Furthermore, the risk of clinical outcomes-the composite of heart failure, ischaemic stroke, or death-according to the presence of CHIP mutations in AF was investigated from the UK Biobank cohort. RESULTS: The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. CHIP mutations with a variant allele fraction of ≥2.0% were found in 237 (23.6%) AF patients (DNMT3A, 13.5%; TET2, 6.6%; and ASXL1, 1.5%) and were more prevalent than non-AF subjects [356 (10.7%); P < .001] across the age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, and hypertension), CHIP mutations were 1.4-fold higher in AF [adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10-1.74, P < .01]. The ORs of CHIP mutations were the highest in the long-standing persistent AF (adjusted OR 1.50; 95% confidence interval 1.14-1.99, P = .004) followed by persistent (adjusted OR 1.44) and paroxysmal (adjusted OR 1.33) AF. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (adjusted OR 1.65; 95% confidence interval 1.05-2.60, P = .030). AF patients with CHIP mutations were older and had a higher prevalence of diabetes, a longer AF duration, a higher E/E', and a more severely enlarged left atrium than those without CHIP mutations (all P < .05). In UK Biobank analysis of 21 286 AF subjects (1297 with CHIP and 19 989 without CHIP), the CHIP mutation in AF is associated with a 1.32-fold higher risk of a composite clinical event (heart failure, ischaemic stroke, or death). CONCLUSIONS: CHIP mutations, primarily DNMT3A or TET2, are more prevalent in patients with AF than non-AF subjects whilst their presence is associated with a more progressive nature of AF and unfavourable clinical outcomes.

Rethinking automatic segmentation of gross target volume from a decoupling perspective.

Accurate and reliable segmentation of Gross Target Volume (GTV) is critical in cancer Radiation Therapy (RT) planning, but manual delineation is time-consuming and subject to inter-observer variations. Recently, deep learning methods have achieved remarkable success in medical image segmentation. However, due to the low image contrast and extreme pixel imbalance between GTV and adjacent tissues, most existing methods usually obtained limited performance on automatic GTV segmentation. In this paper, we propose a Heterogeneous Cascade Framework (HCF) from a decoupling perspective, which decomposes the GTV segmentation into independent recognition and segmentation subtasks. The former aims to screen out the abnormal slices containing GTV, while the latter performs pixel-wise segmentation of these slices. With the decoupled two-stage framework, we can efficiently filter normal slices to reduce false positives. To further improve the segmentation performance, we design a multi-level Spatial Alignment Network (SANet) based on the feature pyramid structure, which introduces a spatial alignment module into the decoder to compensate for the information loss caused by downsampling. Moreover, we propose a Combined Regularization (CR) loss and Balance-Sampling Strategy (BSS) to alleviate the pixel imbalance problem and improve network convergence. Extensive experiments on two public datasets of StructSeg2019 challenge demonstrate that our method outperforms state-of-the-art methods, especially with significant advantages in reducing false positives and accurately segmenting small objects. The code is available at https://github.com/shijun18/GTV_AutoSeg.

Gene expression bias between the subgenomes of allopolyploid hybrids is an emergent property of the kinetics of expression.

Hybridization coupled to polyploidy, or allopolyploidy, has dramatically shaped the evolution of flowering plants, teleost fishes, and other lineages. Studies of recently formed allopolyploid plants have shown that the two subgenomes that merged to form that new allopolyploid do not generally express their genes equally. Instead, one of the two subgenomes expresses its paralogs more highly on average. Meanwhile, older allopolyploidy events tend to show biases in duplicate losses, with one of the two subgenomes retaining more genes than the other. Since reduced expression is a pathway to duplicate loss, understanding the origins of expression biases may help explain the origins of biased losses. Because we expect gene expression levels to experience stabilizing selection, our conceptual frameworks for how allopolyploid organisms form tend to assume that the new allopolyploid will show balanced expression between its subgenomes. It is then necessary to invoke phenomena such as differences in the suppression of repetitive elements to explain the observed expression imbalances. Here we show that, even for phenotypically identical diploid progenitors, the inherent kinetics of gene expression give rise to biases between the expression levels of the progenitor genes in the hybrid. Some of these biases are expected to be gene-specific and not give rise to global differences in progenitor gene expression. However, particularly in the case of allopolyploids formed from progenitors with different genome sizes, global expression biases favoring one subgenome are expected immediately on formation. Hence, expression biases are arguably the expectation upon allopolyploid formation rather than a phenomenon needing explanation. In the future, a deeper understanding of the kinetics of allopolyploidy may allow us to better understand both biases in duplicate losses and hybrid vigor.