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BACKGROUND AND AIMS: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). APPROACH AND RESULTS: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. CONCLUSIONS: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

BackgroundBone marrow aspiration and biopsy remain the gold standard for the diagnosis of hematological diseases despite the development of flow cytometry (FCM) and molecular and gene analyses. However, the interpretation of the results is laborious and operator dependent. Furthermore, the obtained results exhibit inter- and intravariations among specialists. Therefore, it is important to develop a more objective and automated analysis system. Several deep learning models have been developed and applied in medical image analysis but not in the field of hematological histology, especially for bone marrow smear applications. ObjectiveThe aim of this study was to develop a deep learning model (BMSNet) for assisting hematologists in the interpretation of bone marrow smears for faster diagnosis and disease monitoring. MethodsFrom January 1, 2016, to December 31, 2018, 122 bone marrow smears were photographed and divided into a development cohort (N=42), a validation cohort (N=70), and a competition cohort (N=10). The development cohort included 17,319 annotated cells from 291 high-resolution photos. In total, 20 photos were taken for each patient in the validation cohort and the competition cohort. This study included eight annotation categories: erythroid, blasts, myeloid, lymphoid, plasma cells, monocyte, megakaryocyte, and unable to identify. BMSNet is a convolutional neural network with the YOLO v3 architecture, which detects and classifies single cells in a single model. Six visiting staff members participated in a human-machine competition, and the results from the FCM were regarded as the ground truth. ResultsIn the development cohort, according to 6-fold cross-validation, the average precision of the bounding box prediction without consideration of the classification is 67.4%. After removing the bounding box prediction error, the precision and recall of BMSNet were similar to those of the hematologists in most categories. In detecting more than 5% of blasts in the validation cohort, the area under the curve (AUC) of BMSNet (0.948) was higher than the AUC of the hematologists (0.929) but lower than the AUC of the pathologists (0.985). In detecting more than 20% of blasts, the AUCs of the hematologists (0.981) and pathologists (0.980) were similar and were higher than the AUC of BMSNet (0.942). Further analysis showed that the performance difference could be attributed to the myelodysplastic syndrome cases. In the competition cohort, the mean value of the correlations between BMSNet and FCM was 0.960, and the mean values of the correlations between the visiting staff and FCM ranged between 0.952 and 0.990. ConclusionsOur deep learning model can assist hematologists in interpreting bone marrow smears by facilitating and accelerating the detection of hematopoietic cells. However, a detailed morphological interpretation still requires trained hematologists.

Tropical cyclone (TC) projections with atmosphere-only models are associated with uncertainties due to their inability to represent TC-ocean interactions. However, global coupled models, which represent TC-ocean interactions, can produce basin-scale sea surface temperature biases in seasonal to centennial simulations that lead to challenges in representing TC activity. Therefore, focusing on recent individual major hurricane events, we investigated the influence of TC-ocean coupling on the response of TCs to anthropogenic change using atmosphere-only and coupled atmosphere-ocean regional model simulations. Under an extremely warm scenario, coupling does not influence the signs of projected TC rainfall and intensity responses. Coupling, however, does influence the magnitude of projected intensity and especially rainfall. Within a 500 km radius region of the TCs, the projected rainfall increases in coupled simulations are 3–47 % less than in the atmosphere-only simulations, driven by enhanced TC-induced sea surface temperature cooling in the former. However, the influence of coupling on the magnitude of projected rainfall could vary considerably over the regions of highest rainfall generated by TCs.

Neonicotinoid insecticides are among the most used insecticides and their residues are frequently found in surface water due to their persistence and mobility. Neonicotinoid insecticides exhibit toxicity to a wide range of aquatic invertebrates at environmentally relevant levels, and therefore their contamination in surface water is of significant concern. In this study, we investigated the spatiotemporal distribution of six neonicotinoids in a large wetland system, the Prado Wetlands, in Southern California, and further evaluated the wetlands' efficiency at removing these insecticides. Total neonicotinoid concentrations in water ranged from 3.17 to 46.9 ng L-1 at different locations within the wetlands, with imidacloprid and dinotefuran among the most detected. Removal was calculated based on concentrations as well as mass flux. The concentration-based removal values for a shallow pond (vegetation-free), moderately vegetated cells, densely vegetated cells, and the entire wetland train were 16.9%, 34.2%, 90.2%, and 61.3%, respectively. Principal component analysis revealed that pH and temperature were the primary factors affecting neonicotinoids removal. Results from this study demonstrated the ubiquitous presence of neonicotinoids in surface water impacted by urban runoff and wastewater effluent and highlighted the efficiency of wetlands in removing these trace contaminants due to concerted effects of uptake by wetland plants, photolysis, and microbial degradation.

Natural environments play a crucial role in transmission of antimicrobial resistance (AMR). Development of methods to manage antibiotic resistance genes (ARGs) in natural environments are usually limited to the laboratory or field scale, partially due to the complex dynamics of transmission between different environmental compartments. Here, we conducted a nine-year longitudinal profiling of ARGs at a watershed scale, and provide evidence that restrictions on livestock farms near water bodies significantly reduced riverine ARG abundance. Substantial reductions were revealed in the relative abundance of genes conferring resistance to aminoglycosides (42%), MLSB (36%), multidrug (55%), tetracyclines (53%), and other gene categories (59%). Additionally, improvements in water quality were observed, with distinct changes in concentrations of dissolved reactive phosphorus, ammonium, nitrite, pH, and dissolved oxygen. Antibiotic residues and other pharmaceuticals and personal care products (PPCPs) maintain at a similarly low level. Microbial source tracking demonstrates a significant decrease in swine fecal indicators, while human fecal pollution remains unchanged. These results suggest that the reduction in ARGs was due to a substantial reduction in input of antibiotic resistant bacteria and genes from animal excreta. Our findings highlight the watershed as a living laboratory for understanding the dynamics of AMR, and for evaluating the efficacy of environmental regulations, with implications for reducing environmental risks associated with AMR on a global scale.

Two new diatom species belonging to the genus Gomphonemopsis are described, Gomphonemopsis nana sp. nov. and Gomphonemopsis gaoi sp. nov. These two species were compared in detail with congeners. Gomphonemopsis nana is distinguished by its high stria density and small size. This species was found so far to be epiphytic only on the eelgrass collected from Qingdao Bay (Yellow Sea). Gomphonemopsis gaoi is characterized by its isopolar valves, simple proximal raphe endings and acutely rounded apices. This taxon was separated from the exoskeleton of marine copepods sampled from the Futian Mangrove Nature Reserve (South China Sea). In addition, two new combinations, Gomphonemopsis oahuensis (Hustedt) Lang Li, Yuhang Li & Changping Chen, comb. nov. and Gomphonemopsis platypus (Østrup) Lang Li, Yuhang Li & Junxiang Lai, comb. nov. are proposed. This study increases the records and knowledge of Gomphonemopsis along the coast of China.

Abstract Background GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. Methods Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. Results First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). Conclusions The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients.

AbstractPurpose To offer consensus on the utilization of corticosteroids (CS) for treating non-infectious uveitis in the context of clinical practice in Taiwan. This entails examining the different administration methods, their advantages and disadvantages, and considering alternative treatments according to the prevailing evidence and health policies.Methods Ten ophthalmologists and one rheumatologist convened on December 11, 2022, to review and discuss literature on the topic. The databases explored were the Central Cochrane library, EMBASE, Medline, PUBMED, and Web of Science using relevant keywords. The search spanned from January 1996 to June 2023. After the initial results of the literature review were presented, open voting determined the final statements, with a statement being accepted if it secured more than 70% agreement. This consensus was then presented at significant meetings for further discussions before the final version was established.Results A flow chart and nine statements emerged from the deliberations. They address the importance of CS in uveitis management, guidelines for using topical CS, indications for both periocular or intravitreal and systemic therapies, and tapering and discontinuation methods for both topical and systemic CS.Conclusion While CS are a cornerstone for non-infectious uveitis treatment, their administration requires careful consideration, depending on the clinical situation and the specific type of uveitis. The consensus generated from this article provides a guideline for practitioners in Taiwan, taking into account local health policies and the latest research on the subject. It emphasizes the significance of strategic tapering, the potential for alternative therapies, and the importance of patient-centric care.

Introduction Postoperative pulmonary complications (PPCs) occur frequently in patients undergoing lung surgery under general anaesthesia and are strongly associated with longer postoperative hospital stays and increased mortality. The existing literature has shown that a higher level of preoperative physical activity (PA) plays a positive role in the low incidence of postoperative complications and the quality of life in patients undergoing lung surgery. However, the association between preoperative PA levels and the incidence of PPCs has rarely been studied, particularly in thoracoscopic lung surgery. This study aims to evaluate PA levels in patients undergoing thoracoscopic lung surgery using the International Physical Activity Questionnaire and to investigate the association between PA levels and the incidence of PPCs.Methods and analysis A total of 204 participants aged 18–80 years undergoing thoracoscopic lung surgery (thoracoscopic wedge resection, thoracoscopic segmentectomy and thoracoscopic lobectomy) will be included in the study. The primary outcome is the incidence of PPCs within the first 5 postoperative days. The secondary outcomes include the number of PPCs, the incidence of PPCs 1 month postoperatively, the arterial blood levels of inflammatory markers, the incidence of postoperative adverse events within the first 5 postoperative days, extubation time, unplanned admission to the intensive care unit, postoperative length of stay and mortality 1 month postoperatively.Ethics and dissemination The study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Shandong First Medical University on 31 March 2022 (YXLL-KY-2022(014)) and is registered at ClinicalTrials.gov. We plan to disseminate the data and findings of this study in international and peer-reviewed journals.Trial registration number The trial has been prospectively registered at the clinicaltrials.gov registry (NCT05401253).

Purpose: To investigate the treatment outcome, visual outcome, and adverse effects of five-fraction stereotactic radiosurgery (SRS) to medium- and large-sized uveal melanoma with a non-invasive eye immobilization device. Methods: Medical records of 14 patients with uveal melanoma receiving SRS with a total dose of 50 Gy in five fractions from 2008 to 2017 were retrospectively reviewed. A non-invasive eye fixation device was used to achieve and monitor eye immobilization. Results: Local tumor control rates were 85.7% and 75.0% at 2 and 5 years, respectively. The average tumor diameter decreased significantly from 10.0 ± 3.21 mm to 8.36 ± 3.71 mm (p = 0.038) 15 months after SRS, while the average tumor thickness decreased significantly from 5.45 ± 2.21 mm to 4.34 ± 2.29 (p = 0.036) 21 months after SRS. The 5-year metastasis-free survival was 87.5%. The mean best-corrected visual acuity (BCVA) deteriorated from logMAR 0.296 at baseline to logMAR 1.112 at the last individual follow-up visits (p