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In the digital age, experts in digital learning tools, or learning technologists (LTs), play an increasingly important role in the creation and delivery of online learning in health professions education. However, their expertise in the selection, curation and implementation of digital tools is often underutilized due to imbalanced relationships and lack of effective collaboration between faculty and LTs. Here, we describe how the co-production model can be applied to build equal and synergistic partnerships between faculty and LTs, so as to optimize the use of digital affordances and enhance online learning. Submitted/Accepted version

高雄長庚紀念醫院品質管理中心以「創新品質與病人安全管理專業」運用「資訊智能資源整合」發展「卓越醫療品質特色」等成果，榮獲2022年第23屆國家醫療品質獎―卓越中心之殊榮。中心核心團隊發展專業特色如：「智能指標管理，做為高層決策之依據」、「建立病安通報系統，確保病人安全」、「研發醫病共享決策(Shared Decision Making, SDM)輔助工具，創立國際中文版翻譯」、「開發急性腎損傷(acute kidney injury, AKI)智能照護系統」、「營造優質病安文化」、「積極人才培育專業證照」等，引領全院進行跨領域專業多元合作，提供最高品質的醫療服務。榮獲「卓越中心」象徵本院為實現正向醫品病安文化價值，全方位提升醫療品質及病人安全成效之肯定，期望藉此經驗分享，引領同儕，追求更卓越的醫療品質。 The center of quality management, Kaohsiung Chang Gung Memorial Hospital has utilized its innovation and professionalism in quality and patient safety management to facilitate smart information and resource integration, achieving outstanding healthcare quality. In 2022, these achievements enabled the center to win the 23rd National Healthcare Quality Award in the Excellent Center category. The core management team of the center has developed the following professional features: smart index management for providing referential data to hospital executives when making decisions; establishing a patient safety report system to ensure the safety of all patients; developing the patient decision aids (PDAs) for shared decision making (SDM) and translating the international PDAs into Mandarin Chinese version; developing an acute kidney injury care system; fostering adequate patient safety culture; and promoting talent cultivation and professional certification. The center guides the entire hospital staff to participate in interdisciplinary collaboration to provide healthcare services of the highest quality. Winning the Excellent Center Award signifies approval of the efforts made by the hospital to promote positive healthcare culture and values through enhancing every aspect of healthcare quality and patient safety. By sharing its experience, the center hopes to play a leading role in the healthcare industry and help other institutions strive for excellent healthcare quality. &nbsp

Qing-Fei-Shen-Shi decoction (QFSS) consists of Prunus armeniaca L., Gypsum Fibrosum, Smilax glabra Roxb., Coix lacryma-jobi L., Benincasa hispida (Thunb.) Cogn., Plantago asiatica L., Pyrrosia lingua (Thunb.) Farw., Houttuynia cordata Thunb., Fritillaria thunbergii Miq., Cicadae Periostracum, and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle. QFSS shows significant clinical efficacy in the treatment of asthma. However, the specific mechanism of QFSS on asthma remains unclear. Recently, multiomics techniques are widely used in elucidating the mechanisms of Chinese herbal formulas. The use of multiomics techniques can better illuminate the multicomponents and multitargets of Chinese herbal formulas. In this study, ovalbumin (OVA) was first employed to induce an asthmatic mouse model, followed by a gavage of QFSS. First, we evaluated the therapeutic effects of QFSS on the asthmatic model mice. Second, we investigated the mechanism of QFSS in treating asthma by using an integrated 16S rRNA sequencing technology and untargeted metabolomics. Our results showed that QFSS treatment ameliorated asthma in mice. In addition, QFSS treatment affected the relative abundances of gut microbiota including Lactobacillus, Dubosiella, Lachnospiraceae_NK4A136_group, and Helicobacter. Untargeted metabolomics results showed that QFSS treatment regulated the metabolites such as 2-(acetylamino)-3-[4-(acetylamino) phenyl] acrylic acid, D-raffinose, LysoPC (15 : 1), methyl 10-undecenoate, PE (18 : 1/20 : 4), and D-glucose6-phosphate. These metabolites are associated with arginine and proline metabolism, arginine biosynthesis, pyrimidine metabolism, and glycerophospholipid metabolism. Correlation analysis indicated that arginine and proline metabolism and pyrimidine metabolism metabolic pathways were identified as the common metabolic pathways of 16s rRNA sequencing and untargeted metabolomics. In conclusion, our results showed that QFSS could ameliorate asthma in mice. The possible mechanism of QFSS on asthma may be associated with regulating the gut microbiota and arginine and proline metabolism and pyrimidine metabolism. Our study may be useful for researchers to study the integrative mechanisms of Chinese herbal formulas based on modulating gut microbiota and metabolism.

Due to the rapid economic development and urban construction and the high exploitation rate of groundwater and geothermal resource, Jimo district existed a potential threat of surface deformation. To clarify the characteristics and causations of surface deformation, this study firstly used SBAS-InSAR (Small Baseline Subset-Interferometric Synthetic Aperture Radar) technology to analyze the surface defor-mation distribution in the whole research area. Then, three areas with different surface cover conditions were selected to analyze the causations of surface deformation. Lastly, taking central urban area as the key research area, surface deformation causations were analyzed in detail based on PS-InSAR (Persistent Scatter-Interferometric Synthetic Aperture Radar) technology. The study found that, in coastal mollisol area, farmland area, and hot spring area, the maximum subsidence velocity reached up to 46.8 mm/a, 24 mm/a, and 19.1 mm/a, respectively. The factors, including surface loading, precipitation, and the groundwater level, were the causations of surface deformation in different research areas. The trend of the surface deformation curve was consistent with that of the groundwater level curve in the central urban area, but the response time of surface deformation lagged behind the change of groundwater level by approximately 4 months.

Smart security based on object detection is one of the important applications of edge computing in IoT. Anchors in object detection refer to points on the feature map, which can be used to generate anchor boxes and serve as training samples. Current object detection models do not consider the aspect ratio of the ground-truth boxes in anchor assignment and are not well-adapted to objects with very different shapes. Therefore, this paper proposes the Lightweight Anchor Dynamic Assignment algorithm (LADA) for object detection. LADA does not change the structure of the original detection model; first, it selects an equal proportional center region based on the aspect ratio of the ground-truth box, then calculates the combined loss of anchors, and finally divides the positive and negative samples more efficiently by dynamic loss threshold without additional models. The algorithm solves the problems of poor adaptability and difficulty in the selection of the best positive samples based on IoU assignment, and the sample assignment for eccentric objects and objects with different aspect ratios was more reasonable. Compared with existing sample assignment algorithms, the LADA algorithm outperforms the MS COCO dataset by 1.66% over the AP of the baseline FCOS, and 0.76% and 0.24% over the AP of the ATSS algorithm and the PAA algorithm, respectively, with the same model structure, which demonstrates the effectiveness of the LADA algorithm.

Background Stroke is one of the major diseases that endangers human health. It is widely reported that enriched environment (EE) can improve the neurological function in different brain injury models. Recently, relevant researches have indicated that MAPK pathway is closely related to the inflammatory response in nervous system related diseases. However, whether pre exposure to EE (EE pretreatment) has a preventive effect, and its mechanism are not clear. Therefore, this study aimed to determine the possible benefits and related mechanisms of EE in preventing brain injury after acute ischemia-reperfusion. Methods Adult Sprague Dawley rats were kept in enriched or standardized environments for 21 days. Then the middle cerebral artery of rats was occluded for one hour and 30 min, and then reperfusion was performed. Then their neurological deficit score was evaluated. Cerebral edema, along with ELISA and protein quantities of p38MAPK, JNK, ERK, IL-1β, TNF-α, and co-localization of Iba1 were assessed. Changes in neuroinflammation and apoptosis were also detected in the penumbra cortex. Results Our research showed that EE pretreatment significantly alleviated acute cerebral ischemia-reperfusion injury in rats. Including the reduction of brain edema and apoptosis, and the improvement of neurological scores. In addition, the protein level of p38MAPK was significantly down regulated in EE pretreatment group, and the downstream protein STAT1 had the same trend. In addition, immunofluorescence results showed that Iba1 in EE pretreatment group decreased, the ELISA results showed that the classical proinflammatory cytokines increased significantly, while anti-inflammatory cytokines in EE pretreatment group increased, and the same results were obtained by Western blot analysis. Conclusion On the whole, our research demonstrated that EE pretreatment can have a protective effect on the organism by inhibiting the p38 MAPK/STAT1 pathway. Thus, EE can be one of the most promising means of disease prevention. Secondly, p38MAPK/STAT1 pathway may be a latent target for the prevention of acute ischemic stroke.

(1) Background: To assess the efficacy of the quantitative parameters of intravoxel incoherent motion (IVIM) diffusion-weighted imaging for hepatocellular carcinoma (HCC) diagnosis after transarterial chemoembolization (TACE). (2) Methods: Fifty HCC patients after TACE were included and underwent MRI. All of the patients were scanned with the IVIM-DWI sequence and underwent TACE retreatment within 1 week. Referring to digital subtraction angiography (DSA) and MR enhanced images, two readers measured the f, D, and D* values of the tumor active area (TAA), tumor necrotic area (TNA), and adjacent normal hepatic parenchyma (ANHP). Then, the distinctions of the TAA, TNA, and ANHP were compared and we analyzed the differential diagnosis of the parameters in three tissues. (3) Results: For values of f and D, there were significant differences between any of the TAA, TNA, and ANHP (p < 0.05). The values of f and D were the best indicators for identifying the TAA and TNA, with AUC values of 0.959 and 0.955, respectively. The values of f and D performed well for distinguishing TAA from ANHP, with AUC values of 0.835 and 0.753, respectively. (4) Conclusions: Quantitative IVIM-DWI was effective for evaluating tumor viability in HCC patients treated with TACE and may be helpful for non-invasive monitoring of the tumor viability.

Head and neck squamous cell carcinomas (HNSCC) are the most common type of head and neck cancer with an unimproved prognosis over the past decades. Although the role of cancer-associated-fibroblast (CAF) has been demonstrated in HNSCC, the correlation between CAF-derived gene expression and patient prognosis remains unknown.A total of 528 patients from TCGA database and 270 patients from GSE65858 database were contained in this study. After extracting 66 CAF-related gene expression data from TCGA database, consensus clustering was performed to identify different HNSCC subtypes. Limma package was used to distinguish the differentially expression genes (DEGs) between these subtypes, followed by Lasso regression analysis to construct a prognostic model. The model was validated by performing Kaplan-Meier survival, ROC and risk curve, univariate and multivariate COX regression analysis. GO, KEGG, GSEA, ESTIMATE and ssGSEA analyses was performed to explort the potential mechanism leading to different prognosis.Based on the 66 CAF-related gene expression pattern we stratitied HNSCC patients into two previously unreported subtypes with different clinical outcomes. A prognostic model composed of 15 DEGs was constructed and validated. In addition, bioinformatics analysis showed that the prognostic risk of HNSCC patients was also negatively correlated to immune infiltration, implying the role of tumor immune escape in HNSCC prognosis and treatment option.The study develops a reliable prognostic prediction tool and provides a theoretical treatment guidance for HNSCC patients.

Dual-specificity Phosphatases (DUSPs) are not only the key regulators of dephosphorylating and inactivating mitogen-activated protein kinases (MAPKs), but play a crucial role in the immune response. However, the role of DUSP genes in Japanese flounder (PoDUSPs) is still unclear. In this study, 28 DUSP genes in Japanese flounder were identified and classified based on the whole genome database. Phylogenetic analysis and protein structure analysis revealed that DUSPs had highly conserved domains in teleosts. Molecular evolution analysis indicated that the PoDUSP genes were conservative during evolution and were functional-constrained. Meanwhile, PoDUSP genes were found to express in different embryonic and larval stages which might play the role of sentinel in healthy organisms. Furthermore, PoDUSP genes' expression profiles after temperature stress and Edwardsiella tarda (E. tarda) infection were determined in Japanese flounder without precedent, and the results demonstrated that Podusp1, Podusp2 and Podusp16 were more respective to temperature variation whereas Podusp1 and Podusp6 were more respective to E. tarda infection. In summary, our results provide useful resources for understanding the immune responsibilities of DUSP genes in flatfish.

Background: Tumor regression grade (TRG) correlates with prognosis in patients with locally advanced rectal cancer (LARC), but there is controversy regarding the use of magnetic resonance imaging (MRI) for determining TRG. This study to evaluate the diagnostic value of change rate in signal intensity (SI) and volume (V) from MRI to TRG following preoperative chemoradiotherapy (CRT) in patiens with LARC.Materials and methods: This retrospective analysis examined 82 LARC patients who were admitted to our institution between Oct 2017 and Oct 2019. Patients underwent pre- and post-CRT T2-weighted (T2W), diffusion-weighted (DW)/apparent diffusion coefficient (ADC), and contrast-enhanced T1-weighted (ceT1W) MRI. Change rate of volume and relative SI ratio(%△V and %△SIR) from each sequence were determined. All LARCs were confirmed pathologically and classified into TRG 0, 1, 2 and 3. Descriptive statistics and receiver operating characteristic (ROC) analysis, with calculation of area under the curve (AUC), were used to compare the diagnostic performances. Results: Sixteen patients had TRG-0, 15 had TRG-1, 35 had TRG-2, and 16 had TRG-3. Except for ADC-%△SIR, the remaining%△V and %△SIR on T1W, DWI, and ceT1W had significant differences among the four groups. %△V and/or %△SIR did not distinguish TRG-1 from TRG-2 nor TRG-2 from TRG-3, but differences between other TRGs were identified by %△V and/or %△SIR on T2W, DWI, and ceT1W. The combined use of DW-%△V and T2W-%△SIR provided the best diagnostic performance in distinguishing of TRG-0 from TRG-2 (AUC: 0.954) and from TRG-3 (AUC: 1.000).Conclusions: Preoperative MRI of LARC patients can determine TRG and may improve selection of the preoperative therapy.

Background: While radiotherapy has been studied in the treatment of locally advanced pancreatic ductal adenocarcinoma (PDAC), few studies have analyzed the effects of radiotherapy on PDAC in patients with liver metastases. This study aimed to determine whether PDAC patients with liver metastases have improved survival after radiotherapy treatment. Methods: The data of 8535 patients who were diagnosed with PDAC with liver metastases between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis and Cox proportional hazards regression analysis of cancer-specific mortality and overall survival were performed, and propensity score matching (PSM) was used to reduce selection bias. Results: After PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) in the radiotherapy group were longer than those in the nonradiotherapy group (OS: 6 months vs. 4 months; mCSS: 6 months vs. 5 months, both p < 0.05), respectively. The multivariate analysis showed that cancer-specific mortality rates were higher in the nonradiotherapy group than in the radiotherapy group (HR: 1.174, 95% CI: 1.035–1.333, p = 0.013). The Cox regression analysis according to subgroups showed that the survival benefits (OS and CSS) of radiotherapy were more significant in patients with tumor sizes greater than 4 cm (both p < 0.05). Conclusions: PDAC patients with liver metastases, particularly those with tumor sizes greater than 4 cm, have improved cancer-specific survival (CSS) rates after receiving radiotherapy.

The immune profile in primary resected hypopharyngeal squamous cell carcinoma (HPSCC) and its prognostic value remain to be defined.We enrolled 100 patients with HPSCC underwent primary surgical resection at our department. HPSCC samples were examined using immunohistochemistry for the expressions of CD8, Foxp3, CD163, CD66B, programmed death ligand-1 (PD-L1), and interferon (IFN)-γ. The immune pattern of the tumor microenvironment (TME) was discriminated into inflamed and non-inflamed tumors based on the presence or absence of parenchymal CD8We found that 74% of HPSCC cases in our cohort were characterized by an immune-inflamed TME. Immune-inflamed patterns demonstrated an inferior survival with a significantly increased density of CD163The immune-inflamed pattern is the predominant preexisting immune phenotype in HPSCC and demonstrates immunosuppressive immune cell recruitment.

Autophagy is an essential degradation pathway that assists eukaryote survival under multiple stress conditions. Autophagosomes engulfing cargoes accomplish degradation only when they have matured through fusing with lysosomes or vacuoles. However, the molecular machinery mediating autophagosome maturation in plants remains unknown. Using the combined approaches of mass spectrometry, biochemistry, reverse genetics and microscopy, we uncover that UVRAG, a subunit of the class III phosphatidylinositol 3-kinase complexes in Nicotiana benthamiana, plays an essential role in autophagsome maturation via ATG14-assisted recruitment to autophagosomes and by facilitating RAB7 activation. An interaction between N. benthamiana UVRAG and ATG14 was observed in vitro and in vivo, which strikingly differed from their mutually exclusive appearance in different PI3KC3 complexes in yeast and mammals. This interaction increased the localisation of UVRAG on autophagosomes and enabled the convergence of autophagic and late endosomal structures, where they contributed to fusions between these two types of organelles by recruiting the essential membrane fusion factors RAB7 GTPase and the homotypic fusion and protein sorting (HOPS) complex. In addition, we uncovered a joint contribution of ATG14 and UVRAG to geminiviral infection, beyond autophagy. Our study provides insights into the mechanisms of autophagosome maturation in plants and expands the understanding of organisations and roles of the PI3KC3 complexes.

Pharmacogenetics is a potential driver of the "East Asian paradox," in which East Asian acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy (DAPT) with clopidogrel following percutaneous coronary intervention (PCI) demonstrate higher levels of platelet reactivity on treatment than Western patients, yet have lower ischemic risk and higher bleeding risk at comparable doses. However, the impact of pharmacogenetics, particularly regarding CYP2C19 genotype, on the pharmacodynamics of P2Y12 inhibitors has not been extensively studied in Taiwanese ACS patients as yet.CYP2C19 genotyping and pharmacogenetic analysis was conducted on 102 subjects from the Switch Study, a multicenter, single-arm, open-label intervention study that examined the effects on platelet activity and clinical outcomes of switching from clopidogrel (75 mg daily) to low-dose prasugrel (3.75 mg daily) for maintenance DAPT after PCI in 203 Taiwanese ACS patients.Genotyping results revealed that 43.1% were CYP2C19 extensive metabolizers (EM), while 56.9% were reduced metabolizers (RM). After switching to prasugrel, mean P2Y12 reaction units (PRU) values were significantly reduced in both EM and RM populations, while the proportion of high on-treatment platelet reactivity (HPR) patients significantly declined in RM patients. No increase in bleeding risk after switching was observed during follow-up. Multivariate analysis indicated that for RM patients, low estimated glomerular filtration rate (eGFR) and low hemoglobin were associated with greater HPR risk on clopidogrel, but not after switching to prasugrel.Switching to low-dose prasugrel from clopidogrel reduced mean PRU levels and proportion of HPR patients, with more significant reduction in RM patients.

This study aims to dynamically assess tumor changes after variable treatments with vascular endothelial growth factor (VEGF) inhibitor and/or immune checkpoint inhibitor (ICI) using multimodal imaging of MRI and

Significant pancreatic islet dysfunction and loss shortly after transplantation to the liver limit the widespread implementation of this procedure in the clinic. Nonimmune factors such as reactive oxygen species and inflammation have been considered as the primary driving force for graft failure. The adipokine adiponectin plays potent roles against inflammation and oxidative stress. Previous studies have demonstrated that systemic administration of adiponectin significantly prevented islet loss and enhanced islet function at post-transplantation period. In vitro studies indicate that adiponectin protects islets from hypoxia/reoxygenation injury, oxidative stress as well as TNF-α-induced injury. By applying adenovirus mediated transfection, we now engineered islet cells to express exogenous adiponectin gene prior to islet transplantation. Adenovirus-mediated adiponectin transfer to a syngeneic suboptimal islet graft transplanted under kidney capsule markedly prevented inflammation, preserved islet graft mass and improved islet transplant outcomes. These results suggest that adenovirus-mediated adiponectin gene therapy would be a beneficial clinical engineering approach for islet preservation in islet transplantation.

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are intestinal complications characterized by chronic inflammation, autophagy abnormality, and lysosomal stress, which are derived from genetic predisposition and environmental risk factors. It is generally precepted that dietary green vegetable is beneficial for physiological homeostasis. In this study, we found that dextran sulfate sodium (DSS)-induced colitis and altered intestinal epithelia in mice were attenuated by oral administration of chlorophyllin (CHL), a water-soluble derivate of chlorophyll. In DSS-treated mice, autophagy was persistently activated in intestinal tissues and associated with bowel disorders. Conversely, supplement of CHL in diet or gavage suppressed intestinal inflammation, downregulated autophagy flux in intestinal tissue, and relieved endoplasmic reticulum stress. In vitro studies show that CHL could activate Akt and mTOR pathways, leading to downregulation of autophagic and lysosomal flux. Thus, consumption of green vegetables and chlorophyllin may be beneficial for IBD recovery in part through alleviation of inflammation and autolysosomal flux.

This phase 3 confirmatory diabetes mellitus treatment study compared the safety and efficacy of Rapilin and NovoRapid insulin asparts in combination with metformin.This 24-week, open-label, randomized, active-controlled, noninferiority phase 3 confirmatory study conducted across centers in China aimed to enroll patients with type 2 diabetes mellitus and blood sugar glucose inadequately controlled by oral antidiabetic drugs. Randomized patients received subcutaneous mealtime Rapilin or NovoRapid (3:1) injections, with metformin. The primary objectives were to demonstrate noninferiority (margin of 0.4%) in HbA1c change from baseline and compare safety profiles of Rapilin versus NovoRapid after 24 weeks. Secondary outcomes included 2-h postprandial plasma glucose (PPG), fasting plasma glucose (FPG), and patients achieving HbA1c7.0% and ≤6.5%.590 patients with type 2 diabetes mellitus were randomized to Rapilin (Rapilin demonstrated non-inferior glycemic control, and matching safety and immunogenicity to NovoRapid in patients with type 2 diabetes mellitus also receiving metformin over 24 weeks.ChiCTR20003129041.

Tabular data is arguably one of the most commonly used data structures in various practical domains, including finance, healthcare and e-commerce. The inherent heterogeneity allows tabular data to store rich information. However, based on a recently published tabular benchmark, we can see deep neural networks still fall behind tree-based models on tabular datasets. In this paper, we propose Trompt--which stands for Tabular Prompt--a novel architecture inspired by prompt learning of language models. The essence of prompt learning is to adjust a large pre-trained model through a set of prompts outside the model without directly modifying the model. Based on this idea, Trompt separates the learning strategy of tabular data into two parts. The first part, analogous to pre-trained models, focus on learning the intrinsic information of a table. The second part, analogous to prompts, focus on learning the variations among samples. Trompt is evaluated with the benchmark mentioned above. The experimental results demonstrate that Trompt outperforms state-of-the-art deep neural networks and is comparable to tree-based models., ICML'23 (poster)

Diabetes mellitus (DM) is a systemic metabolic disease with high mortality and morbidity. Extracellular vesicles (EVs) have emerged as a novel class of signaling molecules, biomarkers and therapeutic agents. EVs-mediated intercellular and interorgan crosstalk of pancreatic islets plays a crucial role in the regulation of insulin secretion of β-cells and insulin action in peripheral insulin target tissues, maintaining glucose homeostasis under physiological conditions, and it’s also involved in pathological changes including autoimmune response, insulin resistance and β-cell failure associated with DM. In addition, EVs may serve as biomarkers and therapeutic agents that respectively reflect the status and improve function and viability of pancreatic islets. In this review, we provide an overview of EVs, discuss EVs-mediated intercellular and interorgan crosstalk of pancreatic islet under physiological and diabetic conditions, and summarize the emerging applications of EVs in the diagnosis and treatment of DM. A better understanding of EVs-mediated intercellular and interorgan communication of pancreatic islets will broaden and enrich our knowledge of physiological homeostasis maintenance as well as the development, diagnosis and treatment of DM.

At present, the majority of known clinical drugs originated from cultivated species of a few bacterial lineages. It is vital for the development of new pharmaceuticals to explore the biosynthetic potential of naturally uncultivable microorganisms using new techniques.

Specific nitrification inhibitors (NIs) have been widely used to disentangle the contribution of ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB) as well as nitrite oxidizers to the nitrification process in specific environments. However, if these previously reported NIs can also be used to evaluate the activity of the newly discovered complete ammonia oxidizers (comammox) Nitrospira, remains understudied. Here we evaluated various NIs for their impact and specificity regarding inhibition of comammox Nitrospira in batch cultures of pure and mixed strains of AOA, AOB and comammox. Using these batch cultures, we observed that chlorate could specifically inhibit the ammonia oxidation and nitrite oxidation activity of comammox Nitrospira, while it had no effect on the tested AOA and AOB strains. This inhibitory effect of chlorate on comammox Nitrospira was subsequently confirmed based on 13CO2-DNA-stable isotope probing (13C-DNA-SIP) analysis. Furthermore, by applying a set of specific NIs, the nitrification and nitrous oxide (N2O) production rates of comammox Nitrospira in coastal wetlands were estimated as 17.45 ng N g-1 h-1(26.9 % of the total rate) and 0.0083 µmol-1 L h-1 (28.5%). Altogether, we identified and applied an effective and specific inhibitor of comammox Nitrospira, which allowed quantifying comammox activity in wetlands of the Yangtze Estuary, shedding new light on the ecological roles of comammox bacteria in coastal wetland environments.

Background Prostate cancer (PCa) is usually considered as cold tumor. Malignancy is associated with cell mechanic changes that contribute to extensive cell deformation required for metastatic dissemination. Thus, we established stiff and soft tumor subtypes for PCa patients from perspective of membrane tension. Methods Nonnegative matrix factorization algorithm was used to identify molecular subtypes. We completed analyses using software R 3.6.3 and its suitable packages. Results We constructed stiff and soft tumor subtypes using eight membrane tension-related genes through lasso regression and nonnegative matrix factorization analyses. We found that patients in stiff subtype were more prone to biochemical recurrence than those in soft subtype (HR 16.18; p Conclusions From the perspective of cell membrane tension, we found that stiff and soft tumor subtypes were closely associated with BCR-free survival for PCa patients, which might be important for the future research in the field of PCa.

We reconstructed gene regulatory networks for 80 TCGA and 37 DKFZ leiomyosarcoma samples, and used these networks as input to PORCUPINE (Principal Components Analysis to Obtain Regulatory Contributions Using Pathway-based Interpretation of Network Estimates) method to identify pathways driving leiomyosarcoma heterogeneity. In short, PORCUPINE combines knowledge on biological pathways with permutation-based network analysis to identify pathways that exhibit significant regulatory heterogeneity across a patient population. This repository contains following: “rse_gene.RData” - A RangedSummarizedExperiment-class object for the TCGA RNA-seq data. “LMS_37_readCount.txt”- Raw expression count data for 37 DKFZ-LMS samples. This file contains a 57,820 by 38 dataframe, where the first column is gene ID. “GN_ensemblID_symbol.txt”- A 55,476 by 2 dataframe where the first column is Ensemble ID and the second column is gene symbol, corresponding to features in “LMS_37_readCount.txt”. “preprocessing_and_normalization.R” - R script with preprocessing and normalization workflow of the data. “prior.txt” - Prior information on potential regulatory interactions, obtained from scanning known TF motifs to promoter regions in the human genome. This prior network was previously published in Lopes-Ramos et al. 2021 Cancer Research (PMID 34493595). This file contains a 11,151,077 by 3 dataframe, where the first column is the transcription factor's gene IDs, the second column is the target gene IDs and third column shows the presence (1) or absence (0) of a motif of a TF in a promoter region of a gene. “exp.txt” - Gene expression data, contains a 17,899 by 11,322 dataframe including normalized expression data for each sample. The first column is a gene ID. “ppi.txt” – protein-protein interactions between TFs obtained from StringDb (https://string-db.org/), as in Lopes-Ramos et al. 2021 (PMID 34493595). The file contains a 80,037 by 3 dataframe with three columns, where the first two columns contain protein IDs and the third column contains a score for each interaction. “80_tcga_lms_net.RData” - patient-specific gene regulatory networks for 80 TCGA leiomyosarcoma samples. This file contains a 11,151,077 by 80 dataframe that includes edge weights for each sample. Edge order corresponds to edge order in the edges.RData file. “37_dkfz_lms_net.RData” - patient-specific gene regulatory networks for 37 DKFZ leiomyosarcoma samples. This file contains a 11,151,077 by 37 dataframe that includes edge weights for each sample. Edge order corresponds to edge order in the edges.RData file. “edges.RData” - regulatory edge information, includes a 11,151,077 by 3 dataframe with three columns: reg (the transcription factor's gene IDs), tar (the target gene IDs), prior (information from “prior” network). "PORCUPINE.zip" - PORCUPINE R package, This work was supported by the Norwegian Research Council, Helse Sør-Øst, and University of Oslo through the Centre for Molecular Medicine Norway (187615), the Norwegian Research Council (313932), Familien Blix Fond, as well as the Emmy Noether Programme Grant from the German Research Foundation (DFG, No. CH 2302/1-1).

Type 2 diabetes (T2DM) clinically exhibits a higher incidence of hepatocellular carcinoma (HCC), contributing to a lousy prognosis in patients harboring both diseases. Microflora-based therapy draws attention with low side effects. Accumulating evidence shows that Lactobacillus brevis can improve blood glucose and body weight of the T2DM mice model and reduce several cancer incidences. However, the therapeutic effect of Lactobacillus brevis in affecting the prognosis of T2DM+HCC remains unknown. In this study, we aim to explore this question via an established T2DM+HCC mice model. We observed a significant alleviation after the probiotic intervention. Lactobacillus brevis improves blood glucose and insulin resistance and ameliorates Mechanically. Combined with a multi-omics approach including 16SrDNA, GC-MS, and RNA-seq, we identified distinct intestinal microflora composition and metabolites after Lactobacillus brevis intervention. Furthermore, we found that Lactobacillus brevis delayed disease progression by regulating MMP9 and NOTCH 1 signaling pathways, potentially through gut microflora and BA interaction. This study indicates that Lactobacillus brevis may improve the prognosis of T2DM + HCC, providing novel therapeutic opportunities via targeting intestinal flora for patients with T2DM+HCC.

BackgroundObesity is a prevalent health problem in patients with schizophrenia, and calorie restriction diet (CRD) achieved effective weight loss and metabolic improvement; however, these have not been rigorously evaluated in obese patients with schizophrenia.ObjectiveTo measure the effects of CRD on weight loss and metabolic status in hospitalized obese women with schizophrenia during a 4-week period.MethodsParticipants were randomly assigned to two groups in a 1:1 ratio. The intervention group (n = 47) was asked to follow a CRD and the control group (n = 48) a normal diet for 4 weeks. Outcomes of body weight, body composition, as well as metabolic parameters were measured at baseline and following the intervention period.ResultsForty-five participants completed the 4-week research in both the intervention and control groups. Compared to the normal diet, adherence to the CRD significantly decreased body weight (2.38 ± 1.30 kg), body mass index (0.94 ± 0.52 kg/m2), waist circumference (4.34 ± 2.75 cm), hip circumference (3.37 ± 2.36 cm), mid-upper circumferences, triceps skin-fold thickness, fat mass and free fat mass with large effect sizes (p = ηp2 range between 0.145 and 0.571), as well as total cholesterol (0.69 ± 0.70 mmol/L) with a medium effect size (p = 0.028, ηp2 = 0.054). There were no differences between the CRD and control groups in terms of pre-post changes in triglycerides, high- and low-density lipoprotein-cholesterols, as well as systolic and diastolic blood pressures (p > 0.05).ConclusionCRD is preventative of weight gain, but not apparent in intervention for metabolic status in hospitalized obese women with schizophrenia.Clinical trial registration: http://www.chictr.org.cn, ChiCTR-INR-16009185.

One of the long-standing interests of biogeography is to explore diversity patterns and uncover their underlying mechanisms. Despite intensive studies on the responses of eukaryotic communities to chlorophyll a concentrations, we know little about how changes in seawater chlorophyll a concentrations affect free-living bacteria (FLB) and particle-associated bacteria (PAB) diversity patterns in natural systems.

In this article, we investigate the incoming boundary value problem for the stationary linearized Boltzmann equations in $ \Omega \subseteq \mathbb{R}^{3}$. For a $C^2$ bounded domain with boundary of positive Gaussian curvature, the existence theory is established in $H^{1}(\Omega \times \mathbb{R}^{3})$ provided that the diameter of the domain $\Omega$ is small enough., Comment: 19 pages, 1 figure

In recent years, automatic detection of threats in X-ray baggage has become important in security inspection. However, the training of threat detectors often requires extensive, well-annotated images, which are hard to procure, especially for rare contraband items. In this paper, a few-shot SVM-constraint threat detection model, named FSVM is proposed, which aims at detecting unseen contraband items with only a small number of labeled samples. Rather than simply finetuning the original model, FSVM embeds a derivable SVM layer to back-propagate the supervised decision information into the former layers. A combined loss function utilizing SVM loss is also created as the additional constraint. We have evaluated FSVM on the public security baggage dataset SIXray, performing experiments on 10-shot and 30-shot samples under three class divisions. Experimental results show that compared with four common few-shot detection models, FSVM has the highest performance and is more suitable for complex distributed datasets (e.g., X-ray parcels).

Vortex generators (VGs) are a passive method by which to alleviate boundary layer separation (BLS). The device-induced streamwise vortices propagate downstream. There is then lift-off from the surface and the vortex decays. The effectiveness of VGs depends on their geometrical configuration, spacing, and flow characteristics. In a high-speed flow regime, the VGs must be properly positioned upstream of the BLS region. Measurements using discrete pressure taps and pressure-sensitive paint (PSP) show that there is an increase in the upstream surface pressure and the downstream favorable pressure gradient. The effective distance for a flat plate in the presence of three VG configurations is determined, as is the height of the device (conventional and micro VGs).