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Recently, deep federated learning has attracted much attention from researchers in the fields of wireless communications, where the relaying technique has been shown as a powerful technology to assist the wireless signals and enhance the transmission quality, which is very important to the development of mobile edge computing (MEC) based Internet of Things (IoT) networks. In a relaying-aided MEC-IoT system, it is of vital importance to deeply investigate the system signal-to-noise ratio (SNR) at the receiver side, as it mainly determines the system performance metrics, such as capacity (or achievable data rate), outage probability, and bit-error-rate (BER). To this end, we first investigate the instantaneous convergence error, by deeply studying the relationship between the instantaneous two-hop relaying channels. We then investigate the statistical convergence error, by performing the statistical expectation with respect to the two-hop relaying channels. We finally present some results to show that the analysis of the convergence error is effective. The work in this paper can provide some theoretical foundation for deep federated learning and computing networks.

Recently, mobile edge computing (MEC) has been widely applied into Internet of Things (IoT) networks, which has attracted a lot of attention from researchers. A critical challenge in the MEC-aided IoT networks is that the performance analysis is often complicated, where it is quite difficult for us to obtain some analytical or closed-form solution to the performance analysis, such as outage probability and bit error rate. This has been the bottleneck of the development of MEC-aided IoT networks. To address this challenge, we deeply investigate the Chebyshev-Gauss approximation method and derive the analytical solution to implement this powerful and useful approximation. We then give several examples to show the effectiveness of the Chebyshev-Gauss approximation in the performance analysis for the MEC-aided IoT systems. The results in this work can serve as an important reference and reveal some important inherent mechanisms for the MEC-aided IoT networks.

Graph representation learning received increasing attentions in recent years. Most of existing methods ignore the complexity of the graph structures and restrict graphs in a single constant-curvature representation space, which is only suitable to particular kinds of graph structure indeed. Additionally, these methods follow the supervised or semi-supervised learning paradigm, and thereby notably limit their deployment on the unlabeled graphs in real applications. To address these aforementioned limitations, we take the first attempt to study the self-supervised graph representation learning in the mixed-curvature spaces. In this paper, we present a novel Self-supervised Mixed-curvature Graph Neural Network (SelfMGNN). Instead of working on one single constant-curvature space, we construct a mixed-curvature space via the Cartesian product of multiple Riemannian component spaces and design hierarchical attention mechanisms for learning and fusing the representations across these component spaces. To enable the self-supervisd learning, we propose a novel dual contrastive approach. The mixed-curvature Riemannian space actually provides multiple Riemannian views for the contrastive learning. We introduce a Riemannian projector to reveal these views, and utilize a well-designed Riemannian discriminator for the single-view and cross-view contrastive learning within and across the Riemannian views. Finally, extensive experiments show that SelfMGNN captures the complicated graph structures in reality and outperforms state-of-the-art baselines., Comment: Accepted by AAAI 2022, 11 pages

Vitamin K is involved in the formation of coronary artery calcification which is an independent predictor of coronary heart disease. This study aims to explore the association between coronary artery calcification score and serum concentrations of vitamin K1, menaquinone-4 (MK-4) and menaquinone-7 (MK-7) in middle-aged and elderly Chinese population.A total of 116 patients who underwent CT coronary angiography were consecutively enrolled. Serum concentrations of vitamin K1, MK-4 and MK-7 were determined by high performance liquid chromatography tandem mass spectrometry. The relationships between coronary artery calcification score and serum vitamin K concentrations were analyzed.Significantly lower serum vitamin K1 concentration was found in the patients with CACS 400, comparing with the other CACS categories, respectively. Log (CACS + 1) was significantly higher in MK-4 0.05 ng/ml group compared with MK-4 ≥ 0.05 ng/ml group [2.03(0.21, 2.58) vs 1.31(0.00, 2.19), P 0.05]. In subjects with established coronary calcification (defined as CACS 10), vitamin K1 was found to be an independent factor contributing to higher CACS (r = -0.288, P = 0.013).In this retrospective analysis, serum vitamin K1 and MK-4 concentrations were significantly lower in middle-aged and elderly cohorts with increasing calcification scores. The significant effect of vitamin K1 on CACS was only found in individuals who already had calcification. Whether the detection of circulating vitamin K in patients with preexisting coronary calcification could guide vitamin K supplementation needs further exploration.

Background Juvenile spondyloarthropathies (JSpA) are defined as a heterogeneous group of diseases that start before the age of 16. The study aimed to identify key genes and pathways that are influenced by circRNAs and to screen potential therapeutic agents for JSpA. The study likely involved the analysis of circRNA expression profiles, identification of circRNA-miRNA-mRNA regulatory networks, and functional annotation of differentially expressed genes. The results of the study may have provided insights into the molecular mechanisms underlying JSpA and potential therapeutic targets for this disease.Methods In this study, sequencing data of circRNA, miRNA, and mRNA were obtained from the GEO datasets. The data were then analyzed to identify candidates for constructing a circRNA-miRNA-mRNA network based on circRNA-miRNA interactions and miRNA-mRNA interactions. Functional enrichments of genes were performed using the DAVID database. A PPI network was constructed using the STRING database and visualized using Cytoscape software. The MCODE plugin app was used to explore hub genes in the PPI network. The expression changes in immune cells were assessed using the online CIBERSORT algorithm to obtain the proportion of various types of immune cells. Finally, the Connectivity Map L1000 platform was used to identify potential agents for JSpA treatment. Overall, this study aimed to provide a comprehensive understanding of the molecular mechanisms underlying JSpA and to identify potential therapeutic agents for this disease.Results A total of 225 differentially expressed circRNAs (DEcircRNAs), 23 differentially expressed miRNAs (DEmiRNAs) and 1324 differentially expressed mRNAs (DEmRNAs) were identified. We integrated 5 overlapped circRNAs, 7 miRNAs and 299 target mRNAs into a circRNA–miRNA–mRNA network. We next identified 10 hub genes based on the PPI network. KEGG pathway analysis revealed that the DEGs were mainly associated with JAK-STAT signal pathway. We found that neutrophils accounted for the majority of all infiltrating cells. In addition, we discovered several chemicals as potential treatment options for JSpA.Conclusions Through this bioinformatics analysis, we suggest a regulatory role for circRNAs in the pathogenesis and treatment of JSpA from the view of a competitive endogenous RNA (ceRNA) network.

Quiescent cancer stem cells (CSC) play important roles in tumorigenesis, relapse, and resistance to chemoradiotherapy. However, the determinants of CSC quiescence and how they sustain themselves to generate tumors and relapse beyond resistance to chemoradiotherapy remains unclear. Here, we found that SET domain–containing protein 4 (SETD4) epigenetically controls breast CSC (BCSC) quiescence by facilitating heterochromatin formation via H4K20me3 catalysis. H4K20me3 localized to the promoter regions and regulated the expression of a set of genes in quiescent BCSCs (qBCSC). SETD4-defined qBCSCs were resistant to chemoradiotherapy and promoted tumor relapse in a mouse model. Upon activation, a SETD4-defined qBCSC sustained itself in a quiescent state by asymmetric division and concurrently produced an active daughter cell that proliferated to produce a cancer cell population. Single-cell sequence analysis indicated that SETD4+ qBCSCs clustered together as a distinct cell type within the heterogeneous BCSC population. SETD4-defined quiescent CSCs were present in multiple cancer types including gastric, cervical, ovarian, liver, and lung cancers and were resistant to chemotherapy. SETD4-defined qBCSCs had a high tumorigenesis potential and correlated with malignancy and chemotherapy resistance in clinical breast cancer patients. Taken together, the results from our previous study and current study on six cancer types reveal an evolutionarily conserved mechanism of cellular quiescence epigenetically controlled by SETD4. Our findings provide insights into the mechanism of tumorigenesis and relapse promoted by SETD4-defined quiescent CSCs and have broad implications for clinical therapies.Significance:These findings advance our knowledge on the epigenetic determinants of quiescence in cancer stem cell populations and pave the way for future pharmacologic developments aimed at targeting drug-resistant quiescent stem cells.

Supplementary Table S1 and Supplementary Figure S1 to S11

BackgroundEpidemiological evidence on alpha (α)-tocopherol intake and cognitive performance in older individuals is controversial and the effect of periodontitis in this chain is sparse and limited. The goal of this study was to characterize the association between α-tocopherol intake and cognitive performance and the mediating role of periodontitis in a nationally representative sample of older adults.MethodsData from the National Health and Nutrition Examination Survey (NHANES), 2011–2014, were used. Multivariate logistic regression analysis was performed to explore the association of α-tocopherol intake, periodontal measures (mean attachment loss [AL] and mean probing depth [PD]), and clinical periodontitis defined by the European Workshop in Periodontology with poor cognitive performance evaluated by Consortium to Establish a Registry for Alzheimer’s disease (CERAD); the animal fluency test (AFT); and the Digit Symbol Substitution test (DSST) and the correlation between α-tocopherol intake and clinical periodontitis. Multiple linear regression analysis was used to explore the relationship between α-tocopherol intake and periodontal measures. Mediation analysis was used to test the effects of periodontal measures on the association between α-tocopherol intake and cognitive measures.ResultsA total of 1,749 older participants (≥60 years of age) with complete periodontal diagnosis, dietary retrospective survey, and cognitive tests were included. In the fully adjusted model, the odds ratio (OR) with 95% confidence interval (CI) of CERAD score, AFT score and DSST score were 0.214 (0.137–0.327), 0.378 (0.241–0.585) and 0.298 (0.169–0.512) for the highest versus lowest tertile of α-tocopherol intake, respectively. And participants with clinical periodontitis were more likely to exhibit lower DSST score (OR = 1.689; 95 CI%: 1.018–2.771) than those without periodontitis. Mean AL (OR = 1.296; 95 CI%: 1.102–1.524) and PD (OR = 1.667; 95 CI%: 1.18–2.363) were negatively correlated with DSST, and were estimated to mediate 9.1 and 8.2% of the total association between α-tocopherol intake and cognitive performance, respectively.ConclusionFinding of the present study suggested that participants with low α-tocopherol intake were at higher risk for developing cognitive decline. Moreover, periodontitis mediated the association between α-tocopherol intake and cognitive performance.

BACKGROUND: Argininemia, a rare urea cycle disorder resulting from an arginase-1 deficiency, is characterized by a progressive spastic paraplegia. While advances in diagnosis and treatment have increased the management of this condition, not all symptoms are resolved in response to traditional therapies. Interestingly, there exist some rare reports on the use of liver transplantation (LT) for the treatment of argininemia. METHODS: We conducted a retrospective study of eleven patients with argininemia receiving a LT as performed at our center over the period from January 2015 to November 2019. These patients were included due to their poor responses to protein restriction diets and alternative therapies of nitrogen scavengers. Detailed information on coagulation, liver function, histopathological and morphological examination of liver samples, and other clinical presentations were extracted from these patients. A grading scale was used for evaluating the neurological status, classification of physical growth and quality of life of these patients in response to the LT. RESULTS: Prior to LT, high levels of arginine were detected in all of argininemia patients and liver enzymes were elevated in nine of those patients. Nine patients presented with coagulation dysfunction without bleeding symptoms. Spastic paraplegia, irritability, intellectual developmental disability, and growth deficits were hallmarks of these nine patients, while four patients showed repeated, generalized tonic-clonic seizures before the operation. Seven novel mutations were found in these patients. The indication for LT in this series of patients was a presentation of progressive neurological impairments. After LT, the coagulation index and plasma arginine levels returned to normal and episodes of seizure were controlled in four patients. To date, all patients have survived and their LT has resulted a restoration of arginine metabolism and liver function, along with preventing further neurological deterioration, all of which provided an opportunity for future recuperation. Overall, the neurological status, growth deficits and quality of life were all significantly improved after LT with no evidence of severe complications. CONCLUSIONS: LT can serve as an effective treatment for argininemia in patients who respond poorly to traditional therapy. An early intervention of LT should be conducted in these patients to prevent neurological damage and improve their quality of life.

Tumor therapeutics often target the primary tumor bulk but fail to eradicate therapy-resistant cancer stem cells (CSCs) in quiescent state. These can then become activated to initiate recurrence and/or metastasis beyond therapy. Here, we identified and isolated chemoradiotherapy-resistant CSCs in quiescent state with high capacity of tumor-initiation and tumorsphere formation from three types of breast tumors in mice. Experiments of knockdown and rescue revealed DEK, a nuclear protein, as essential for CSC activation. Exogenous DEK was then used to trigger quiescence exit of CSCs. ChIP-seq and ATAC-seq showed that DEK directly binds to chromatin, facilitating its genome-wide accessibility. The resulting epigenetic events upregulate the expression of cellular activation-related genes including MYC targets, whereas cellular quiescence-related genes including the p53 signaling pathway are silenced. However, twinned with DEK-induced activation, formerly resistant CSCs were then destroyed by chemotherapy in vitro. In mice, traditional chemoradiotherapy concurrent with the injection of DEK-containing exosomes resulted in eradication of primary tumors together with formerly resistant CSCs without recurrence or metastasis. Our findings advance knowledge of the mechanism of quiescent CSC activation and may provide novel clinical opportunities for removal of quiescence-linked therapy resistance.

Rare earth-doped upconversion nanoparticles (UCNPs) have the advantages of a narrow emission peak, large anti-Stokes displacement, negligible autofluorescence and photobleaching, which make them popular in biomedical fields. With the development of biological technology and nanotechnology, great progress has been achieved in use of rare earth-doped UCNPs in the treatment and diagnosis of various diseases. To date, based on the light conversion characteristics of upconverted rare earth nanocrystals, their medical applications are mainly focused on the detection and treatment of tumors. In view of the above situation, this paper focuses on reviewing UCNPs applications for the treatment and detection of various diseases, including atherosclerosis, inflammation, bacterial infections, viruses, and tumors. Finally, challenges and opportunities regarding the use of UCNPs in diseases treatment and detection are discussed. Overall, our goal is to provide readers with a fresh perspective on recent developments in the treatment and detection of various diseases with rare earth-doped upconversion materials.

BACKGROUND Mature teratoma composed of all three basic germ cell layers of the head and neck is a rare disease. Teratomas involving the temporal bone are particularly scarce. CASE SUMMARY A 48-year-old male patient with a history of chronic otitis of the left ear from infancy, for which he had been operated on twice, was referred to our hospital for chronic otitis, cholesteatoma and a middle ear mass. Computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed a eustachian tube teratoma, in which the anterior lower part and posterior upper part were connected by a thin membranaceous tissue. The mass was removed completely under general anesthesia by mastoidectomy. As of last follow-up (2 years post-surgery), the disease had not relapsed. CONCLUSION Pre-operative CT and MRI are necessary for eustachian tube teratoma. Complete surgical resection provided excellent prognosis.

Floral ontogeny can assist in understanding formation of mature floral structure and provide taxonomic and evolutionary insights at the species and genus level. In this study, floral ontogeny of Magnolia liliiflora, M. maudiae and M. figo was investigated using scanning electron microscopy. The results showed that tepal primordia of these species are initiated asynchronously in whorls, whereas stamen and carpel primordia are initiated spirally and centripetally. Variation in tepal number in M. maudiae was also observed at the early stage of differentiation. Our study demonstrates that floral ontogeny is remarkably homogenous in Magnoliaceae, and thus it cannot serve as a basis for classification at the genus or lower taxonomic levels. Nonetheless, the transition of floral development from typical spiral flowers to typical whorled flowers is of great significance for understanding evolution of angiosperm flowers.

Clinical and experimental evidence suggested that anesthesia choice can influence cancer progression and patients’ outcomes by modulating tumor microenvironment and tumorigenic pathways. Curative resection is the mainstay of therapy for hepatocellular carcinoma (HCC), which is an intractable disease due to high recurrence and poor prognosis. However, different anesthetics may play different roles in alleviating surgery-induced stress response and inflammatory cytokines release that are considered to be closely associated with proliferation, invasion and metastasis of tumor cells. Propofol, sevoflurane, non-steroidal anti-inflammatory drugs and local anesthetics have shown to exert anti-tumor effect on HCC mainly through regulating microRNAs or signaling pathways, while other inhalational agents, dexmedetomidine and opioids have the potential to promote tumor growth. In terms of anesthetic methods and analgesia strategies, propofol based total intravenous anesthesia and thoracic epidural analgesia could be preferred for HCC patients undergoing open liver resection rather than inhalational anesthesia. Local anesthesia techniques have great potential to attenuate perioperative stress response, hence they may contribute to more favorable outcomes. This review summarized the relations between different anesthesia choices and HCC patients’ long-term outcomes as well as their underlying mechanisms. Due to the complexity of molecules interactions and signaling pathways, further studies are warranted to confirm these results so as to optimize anesthesia strategy for HCC patients.

The widespread emergence of smart devices for ECG has sparked demand for intelligent single-lead ECG-based diagnostic systems. However, it is challenging to develop a single-lead-based ECG interpretation model for multiple diseases diagnosis due to the lack of some key disease information. In this work, we propose inter-lead Multi-View Knowledge Transferring of ECG (MVKT-ECG) to boost single-lead ECG's ability for multi-label disease diagnosis. This training strategy can transfer superior disease knowledge from multiple different views of ECG (e.g. 12-lead ECG) to single-lead-based ECG interpretation model to mine details in single-lead ECG signals that are easily overlooked by neural networks. MVKT-ECG allows this lead variety as a supervision signal within a teacher-student paradigm, where the teacher observes multi-lead ECG educates a student who observes only single-lead ECG. Since the mutual disease information between the single-lead ECG and muli-lead ECG plays a key role in knowledge transferring, we present a new disease-aware Contrastive Lead-information Transferring(CLT) to improve the mutual disease information between the single-lead ECG and muli-lead ECG. Moreover, We modify traditional Knowledge Distillation to multi-label disease Knowledge Distillation (MKD) to make it applicable for multi-label disease diagnosis. The comprehensive experiments verify that MVKT-ECG has an excellent performance in improving the diagnostic effect of single-lead ECG.

Additional file 1: Drp1 promoter sequence.

Additional file 1: Supplement Table S1. The distribution of the ESSDAI score for each domain of 39 patients with childhood-onset primary Sjögren’s syndrome.

Let $\mathfrak{H}$ be the Heisenberg group. From the standard CR structure $\mathcal{H}$ of $\mathfrak{H}$ we construct the complex hyperbolic structure of the Siegel domain. Additionally, using the same minimal data for $\mathfrak{H}$, that is, its Sasakian structure, we provide the Siegel domain with yet another Kähler structure: this structure is of unbounded negative sectional curvature, and its complex structure does not commute with the standard complex structure. However, we show that those two Kähler structures are {\rm PCR} Kähler equivalent, that is to say, essentially the same when restricted to $\mathcal{H}$., 22 pages

Bile acids play crucial roles in various metabolisms, as well as Lactobacillus in the intestine. But studies on their roles in acute coronary syndrome (ACS) are still insufficient. The aim of this study was to investigate their role and potential association with the severity of coronary lesions and the prognosis of ACS. Three hundred and sixty ACS patients were selected. Detection of gut Lactobacillus levels was done through 16S rDNA sequence analysis. Evaluation of the extent of lesions was done using the SYNTAX (SS) score. Mediation analysis was used to assess the relationship between serum total bile acid (TBA), Lactobacillus, atherosclerotic lesions and prognosis of ACS. Logistic regressive analysis disclosed that serum TBA and Lactobacillus were independent predictors of coronary lesions (high vs. low SS: serum TBA adjusted odds ratio (aOR) = 0.8, 95% confidence interval (CI): 0.6–0.9, p < .01; Lactobacillus: aOR = 0.9, 95% CI: 0.9–1.0, p = .03). According to multivariate Cox regression analysis, they were negatively correlated with the overall risk of all-cause death (serum TBA: adjusted hazard ratio (aHR) = 0.1, 95% CI: 0.0–0.6, p = .02; Lactobacillus: aHR = 0.6, 95% CI: 0.4–0.9, p = .01), especially in acute myocardial infarction (AMI) but not in unstable angina pectoris (UAP). Ulteriorly, mediation analysis showed that serum TBA played an important role as a mediation effect in the following aspects: Lactobacillus (17.0%, p < .05) → SS association (per 1 standard deviation (SD) increase), Lactobacillus (43.0%, p < .05) → all-cause death (per 1 SD increase) and Lactobacillus (45.4%, p < .05) → cardiac death (per 1 SD increase). The lower serum TBA and Lactobacillus level in ACS patients, especially in AMI, was independently linked to the risk of coronary lesions, all-cause death and cardiac death. In addition, according to our mediation model, serum TBA served as a partial intermediate in predicting coronary lesions and the risk of death by Lactobacillus, which is paramount to further exploring the mechanism of Lactobacillus and bile acids in ACS.KEY MESSAGESLower level of serum total bile acid (TBA) was highly associated with the severity of coronary lesions, myocardial damage, inflammation and gut Lactobacillus in acute coronary syndrome (ACS) patients, especially in acute myocardial infarction (AMI).Lower level of serum TBA was highly associated with mortality (including all-cause death and cardiac death) in patients with ACS, especially with AMI.Serum TBA had a partial mediating effect rather than regulating effect between gut Lactobacillus and coronary lesions and prognosis of ACS. Lower level of serum total bile acid (TBA) was highly associated with the severity of coronary lesions, myocardial damage, inflammation and gut Lactobacillus in acute coronary syndrome (ACS) patients, especially in acute myocardial infarction (AMI). Lower level of serum TBA was highly associated with mortality (including all-cause death and cardiac death) in patients with ACS, especially with AMI. Serum TBA had a partial mediating effect rather than regulating effect between gut Lactobacillus and coronary lesions and prognosis of ACS.

The assessment and prevention of mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been standardized. This study aimed to evaluate MBD one year after kidney transplantation (KT) and identify the influencing factors of MBD. A total of 95 KTRs in our center were enrolled. The changes in bone mineral density (BMD) and bone metabolism biochemical markers, including serum calcium (Ca), phosphorus(P), 25-hydroxyvitamin D(25(OH)vitD), intact parathyroid hormone (iPTH), bone alkaline phosphatase, osteocalcin (OC), type I collagen N-terminal peptide and type I collagen C-terminal peptide (CTx), over one year after KT were assessed. The possible influencing factors of BMD were analyzed. The relationships between bone metabolism biochemical markers were evaluated. The indicators between groups with or without iPTH normalization were also compared. MBD after KT was manifested as an increased prevalence of hypophosphatemia and bone loss, persistent 25(OH)vitD deficiency, and partially decreased PTH and bone turnover markers (BTMs). Femoral neck BMD was positively correlated with body mass index (BMI) and postoperative 25(OH)vitD, and negatively correlated with postoperative PTH. Lumbar spine BMD was positively correlated with BMI and preoperative TG, and negatively correlated with preoperative OC and CTx. BMD loss was positively associated with glucocorticoid accumulation. Preoperative and postoperative iPTH was negatively correlated with postoperative serum P and 25(OH)vitD, and positively correlated with postoperative Ca and BTMs. The recipients without iPTH normalization, who accounted for 41.0% of all KTRs, presented with higher Ca, lower P, higher BTMs, advanced age, and a higher prevalence of preoperative parathyroid hyperplasia. MBD persisted after KT, showing a close relationship with hyperparathyroidism, high bone turnover, and glucocorticoid accumulation.

Additional File 1: Figure S1. Normal distribution of CC (SPAD value) in different environments. Figure S2. QQ plots of the chlorophyll content (CC) for five models in different environments. Figure S3. Differences in the chlorophyll content (CC) associated with key candidate genes. Figure S4. R2 values for all SNPs in the QTL of the significant QTN. Figure S5. Manhattan plots of the CC for six models in different environments or involving different methods.

Additional file 2.

We propose a nontrivial two-qubit gate scheme in which Rydberg atoms are subject to designed pulses resulting from geometric evolution processes. By utilizing a hybrid robust non-adiabatic and adiabatic geometric operations on the control atom and target atom, respectively, we improve the robustness of two-qubit Rydberg gate against Rabi control errors as well as blockade errors in comparison with the conventional two-qubit blockade gate. Numerical results with the current state-of-the-art experimental parameters corroborates the above mentioned robustness. We also evaluated the influence induced by the motion-induced dephasing and the dipole-dipole interaction and imperfection excitation induced leakage errors, which both could decrease the gate fidelity. Our scheme provides a promising route towards systematic control error (Rabi error) as well as blockade error tolerant geometric quantum computation on neutral atom system., Comment: 14 pages, 13 figures, 2 tables. Accepted by Physical Review Applied

Additional file 1 (Table S1-S4).

We study tail risk dynamics in high-frequency financial markets and their connection with trading activity and market uncertainty. We introduce a dynamic extreme value regression model accommodating both stationary and local unit-root predictors to appropriately capture the time-varying behaviour of the distribution of high-frequency extreme losses. To characterize trading activity and market uncertainty, we consider several volatility and liquidity predictors, and propose a two-step adaptive $L_1$-regularized maximum likelihood estimator to select the most appropriate ones. We establish the oracle property of the proposed estimator for selecting both stationary and local unit-root predictors, and show its good finite sample properties in an extensive simulation study. Studying the high-frequency extreme losses of nine large liquid U.S. stocks using 42 liquidity and volatility predictors, we find the severity of extreme losses to be well predicted by low levels of price impact in period of high volatility of liquidity and volatility.

Additional file 2 (Figure S1-S2).

Additional file 1. Boxplot of number of bacterial taxa in milk samples and sequenced bacterial-based mock communities. Samples are grouped by bacterial biomass, for milk samples this corresponds to number of cfu in 100µL of cultured milk and for mock communities from input number of bacterial cells. Number of bacterial taxa retrieved from rarefied data. No growth n = 41, 1-10 cfu n = 53, 11-50 cfu c = 7, >50 cfu n = 3, for all bacterial-based mock communities n = 2.

Supplementary Material 1

Graph clustering is a longstanding research topic, and has achieved remarkable success with the deep learning methods in recent years. Nevertheless, we observe that several important issues largely remain open. On the one hand, graph clustering from the geometric perspective is appealing but has rarely been touched before, as it lacks a promising space for geometric clustering. On the other hand, contrastive learning boosts the deep graph clustering but usually struggles in either graph augmentation or hard sample mining. To bridge this gap, we rethink the problem of graph clustering from geometric perspective and, to the best of our knowledge, make the first attempt to introduce a heterogeneous curvature space to graph clustering problem. Correspondingly, we present a novel end-to-end contrastive graph clustering model named CONGREGATE, addressing geometric graph clustering with Ricci curvatures. To support geometric clustering, we construct a theoretically grounded Heterogeneous Curvature Space where deep representations are generated via the product of the proposed fully Riemannian graph convolutional nets. Thereafter, we train the graph clusters by an augmentation-free reweighted contrastive approach where we pay more attention to both hard negatives and hard positives in our curvature space. Empirical results on real-world graphs show that our model outperforms the state-of-the-art competitors., Comment: Accepted by IJCAI'23

Additional file 1: Table S. Clinical data of 8 children with blau syndrome in our center.

Additional file 1.

Additional file 2. ANOSIM with BrayCurtis similarity index after grouping by individual cow. PCoA of the same data is found in Figure 4A in the main text. Bonferroni corrected p-values above diagonal, R values below, significant differences marked with red.

Current state-of-the-art models for natural language understanding require a preprocessing step to convert raw text into discrete tokens. This process known as tokenization relies on a pre-built vocabulary of words or sub-word morphemes. This fixed vocabulary limits the model's robustness to spelling errors and its capacity to adapt to new domains. In this work, we introduce a novel open-vocabulary language model that adopts a hierarchical two-level approach: one at the word level and another at the sequence level. Concretely, we design an intra-word module that uses a shallow Transformer architecture to learn word representations from their characters, and a deep inter-word Transformer module that contextualizes each word representation by attending to the entire word sequence. Our model thus directly operates on character sequences with explicit awareness of word boundaries, but without biased sub-word or word-level vocabulary. Experiments on various downstream tasks show that our method outperforms strong baselines. We also demonstrate that our hierarchical model is robust to textual corruption and domain shift., Comment: Accepted to ACL 2023 Main Conference

BACKGROUND Cytomegalovirus (CMV) infection is common in liver transplant (LT)_ recipients, and biliary complications occur in a large number of patients. It has been reported that CMV-DNA is more detectable in bile than in blood. AIM To investigate the effects of CMV infection on biliary complications by comparing the levels of CMV-DNA in the bile and blood of patients after LT. METHODS We conducted a retrospective analysis of 57 patients who underwent LT, 10 of these patients had no biliary complications and 47 patients had biliary complications. We also compared the levels of CMV-DNA in patients’ bile and blood, which were sampled concurrently. We used RNAscope technology to identify CMV in paraffin-embedded liver sections. RESULTS CMV-DNA was not detected in bile samples and was detected in 2 blood samples from patients without biliary complications. In the 47 patients with biliary complications, CMV-DNA was detected in 22 bile samples and 8 blood samples, both bile and blood samples were positive for CMV-DNA in 6 patients. The identification rate of CMV-DNA in blood was 17.0%, and was 46.8% in bile. Moreover, tissue samples from 4 patients with biliary complications tested positive using RNAscope technology but were negative with hematoxylin and eosin staining. During the follow-up period, graft failure occurred in 13 patients with biliary complications, 8 of whom underwent retransplantation, and 3 died. CMV-DNA in bile was detected in 9 of 13 patients with graft failure. CONCLUSION In patients with biliary complications, the identification rate of CMV-DNA in bile was higher than that in blood. Blood CMV-DNA negative patients with biliary complications should still be monitored for CMV-related biliary tract diseases. Potential occult CMV infection may also be a contributing etiological factor in the development of graft failure.

BACKGROUND AND PURPOSE Psoriasis is a chronic inflammatory skin disease associated with both innate and adaptive immune responses. The stimulator of interferon genes (STING) protein engages in sensing of cytosolic DNA to initiate dsDNA-driven immune responses. In vitro and in vivo anti-psoriasis effects of STING antagonist H-151 were explored. EXPERIMENTAL APPROACH We analysed the gene expression profile of STING and related downstream targets in the skin samples of healthy people and psoriasis patients from the GEO database. Cellular inhibitory activity of H-151 on STING pathway was confirmed via qPCR and western blotting. The preventive effect of topical application of H-151 on imiquimod-induced psoriatic mice was examined through histological, immunohistochemical, immunofluorescent, flow cytometric analysis, ELISA Kits and other approaches. Preliminary mechanistic studies were also performed. KEY RESULTS Gene expressions of STING and its downstream target were up-regulated in lesional skin samples from psoriasis patients. Topical administration of H-151 attenuated the skin lesions in imiquimod-induced psoriatic mouse model, while the secretion of pro-inflammatory cytokines (IL-17, IL-23 and IL-6), infiltration of M1 macrophages and differentiation of Th17 cells were significantly suppressed by H-151 treatment. Mechanistically, H-151 inhibited STING/NF-κB signalling in both keratinocytes and immune cells. CONCLUSION AND IMPLICATIONS H-151 displayed anti-inflammatory activity in both keratinocytes and immune cells, and decreased the severity of psoriatic response in vivo. Inhibition of STING signalling pathway may represent a novel therapeutic approach to psoriasis and related complications.

Ovate family proteins (OFP) are plant-specific transcription factors involved in regulating morphologies of the lateral organs, plant growth and development. However, the functional roles of OFP genes in Betula luminifera, an important timber tree species, are not well studied. In this study, we identified 20 BlOFP genes and analyzed their phylogenetic relationship, gene structure, conserved motifs, and cis-elements. Further, expression analysis indicates that BlOFP genes were up-regulated in leaves on the one-year-old branch compared to leaves on the current-year branch and bract, except BlOFP7, BlOFP11, BlOFP14 and BlOFP12. The overexpression of BlOFP3 and BlOFP5 in Arabidopsis thaliana not only resulted in a slower growth rate but also produced sawtooth shape, flatter and darker green rosette leaves. Further investigation showed that the leaf thickness of the transgenic plants was more than double that of the wild type, which was caused by the increasement in the number and size of palisade tissue cells. Furthermore, the expression analysis also indicated that the expressions of several genes related to leaf development were significantly changed in the transgene plants. These results suggested the significant roles of BlOFP3 and BlOFP5 in leaf development. Moreover, protein-protein interaction studies showed that BlOFP3 interacts with BlKNAT5, and BlOFP5 interacts with BlKNAT5, BlBLH6 and BlBLH7. In conclusion, our study demonstrates that BlOFP3 and BlOFP5 were involved in leaf shape and thickness regulation by forming a complex with BlKNAT5, BlBLH6 and BlBLH7. In addition, our study serves as a guide for future functional genomic studies of OFP genes of the B. luminifera.

Chinese bayberry (Myrica rubra) is an important tree in South China, with its fruit being of nutritional and high economic value. The early maturing varieties of Chinese bayberry are characterized by early flowering. In this study, early ripening (ZJ), medium ripening (BQ) and late ripening (DK) varieties were used as test materials, while young leaves in the floral bud morphological differentiation period were selected for transcriptome sequencing. A total of 4,538 differentially expressed genes were detected. Based on clustering analysis and comparisons with genes reportedly related to flowering in Arabidopsis thaliana, 25 homologous genes were identified. Of these, one was down-regulated in DK but up-regulated in ZJ and BQ, with the results also reflected in the relative expression determined by qRT-PCR. The gene contained the SBP domain and the target site of miR156, named MrSPL4. Primers were designed to clone the gene whose total length and the length of the CDS sequence were 1,664 bp and 555 bp respectively. An overexpression vector (35S:: 35S::MrSPL4-pCambia2301-KY) was then constructed and successfully transfected into tobacco to obtain MrSPL4-positive plants. In this case, the relative expression of MrSPL4 was up regulated by 3,862.0-5,938.4 times. The height of positive plants was also significantly higher than that of wild-type (WT) plants, with the bud stage occurring 12 days earlier. Altogether, the results indicated that the gene influenced growth and flowering, which provided a theoretical basis for the regulation of flowering in Chinese bayberry.

IntroductionLow back pain (LBP) is the most prevalent form of chronic pain in active-duty military personnel worldwide. Electroacupuncture (EA) and neuromuscular electrical stimulation (NMES) are the two most widely used treatment methods in the military, while evidence for their benefits is lacking. The aim of this randomized clinical trial is to investigate the effectiveness of EA vs. NMES in reducing pain intensity among active-duty navy personals with chronic LBP.MethodsThe study is designed as a single-center, randomized controlled trial. The primary outcome is a positive categorical response for treatment success in the first-time follow-up, which is predesignated as a two-point or greater decrease in the NRS score and combined with a score > 3 on the treatment satisfaction scale. The secondary outcomes include pain intensity, rate of treatment success, and Oswestry Disability Index (ODI) fear-avoidance beliefs questionnaire (FABQ) score along with muscular performance. The first follow-up starts on the first day after completing the last treatment session, and then the 4-weeks and 12-weeks follow-up are applied via telephone visit.ResultsEighty-five subjects complete the treatment diagram and are included in the analysis. For the primary outcome, no difference has been found between EA and NMES, with 65.1% (28 in 43) individuals reporting a positive response to EA treatment, while 53.5% (23 in 43) in NMES. However, for longer follow-ups, superiority in positive response of EA has been found in 4-weeks (26 in 39, 66.7% vs. 16 in 40, 40%; P = 0.018) and 12-weeks (24 in 36, 66.7% vs. 12 in 36, 33.3%; P = 0.005) follow-up. In the regression analysis, baseline pain intensity and FABQ score are identified to be highly associated with positive treatment outcomes. Finally, the subgroup analysis suggests that EA treatment is associated with better long-term outcomes in patients with LBP with a severe pain score (NRS score >4, Figure 4B) and stronger fear-avoidance beliefs.ConclusionBoth the EA and NMES are associated with a positive response in treating military LBP, and the former offers lasting benefits in the later follow-ups. Thus, electroacupuncture is a more recommended treatment for military LBP. A lot of research is needed to verify an efficient and standardized treatment session, with more information and evidence about indications for these treatments.Trial registrationChiCTR, (ChiCTR2100043726); registered February 27, 2021.

Several immune checkpoint inhibitors targeting programmed death ligand 1 (PD-L1)/programmed death 1 have successfully improved the prognosis of oesophageal squamous cell carcinoma (ESCC) with approval in certain countries. However, whether the expression of PD-L1 is associated with the degree of benefit is unclear yet and a unified standard of antibody and cut-off value of PD-L1 detection is also lacking. The current meta-analysis then aimed to explore the association between PD-L1 expression and clinicopathological features as well as prognosis in ESCC. A systematic search on PubMed, Embase, Cochrane Library and Web of Science databases was performed up to 30 March 2021. The correlation between PD-L1 expression and clinicopathological features, as well as prognosis in ESCC, was estimated with the random-effects model. A total of 5368 patients from 31 retrospective studies were enrolled. The overexpression of PD-L1 was significantly associated with lymph node metastasis (OR 1.342, 95% CI 0.995 to 1.809, p=0.050) and distant metastasis (OR 1.516, 95% CI 1.001 to 2.294, p=0.050). The pooled HR showed that PD-L1 overexpression was significantly correlated with poor overall survival (OS) of patients with ESCC (HR 1.306, 95% CI 1.108 to 1.539, p The overexpression of PD-L1 was correlated with lymph node and distant metastasis as well as poor survival of ESCC.

Circulating microRNAs (miRNAs) are a class of noncoding RNAs and many miRNAs have been frequently reported to be potential biomarkers for drug-induced liver injury (DILI) in clinical patients. However, the usefulness of miRNAs as biomarkers for DILI in preclinical toxicological studies using non-human primates is controversial owing to the limited information. This study was initiated to determine the potential of circulating miR-122, miR-192, miR-885, miR-151, miR-378, miR-365, and miR-31 as a biomarker for carbon tetrachloride (CCl4)–induced liver injury in Macaca fascicularis. The ten Macaca fascicularis were orally given 15% CCl4 (10 mL/kg) to establish the DILI. The serum at 48 h after administration when a single hepatocyte showed histopathological necrosis and vacuolation was isolated and quantified for serum miRNAs by next-generation sequencing (NGS) analysis. It was revealed that miR-122, miR-192, miR-885, miR-151, miR-378, miR-365, miR-31, and miR-802 were upregulated in the circulating serum at 48 h. The serum in different time points was collected to analyze the levels of alanine aminotransferase (ALT) and the eight miRNAs. The concentration of ALT was detected by automatic biochemistry analyzer and the miRNA level was quantified by real-time reverse-transcription PCR. All quantitative PCR values were normalized to inter-control miR-39 and calculated with the comparative Ct method. The miR-802 was not detected at each time point in the following real-time PCR amplification because of unknown reasons and would not involve any other comparison analysis in the present study. Serum ALT increased significantly from 24 h after CCl4-induced liver injury and reached top value at 48 h. The increasing fold changes of miR-122 were more than 8-fold from 2 h after administration and that of miR-885 were over 5-fold from 6 h. The top fold change of miR-122 was approximate 813-fold at 24 h and miR-885 was approximately 89-fold at 48 h. The miR-192 increased over a 4-fold change from 2 h and the top fold change reached approximately 119-fold at 48 h in this study. The miR-378 increased significantly at 4 h after administration and the top fold change of miR-378 was lower than the maximum fold change of ALT. The miR-365, miR-151, and miR-31 showed no correlation with serum ALT. This study indicates that serum miR-122, miR-885, and miR-192 have a stronger potential as sensitive candidate biomarkers for predicting CCl4-induced liver injury in Macaca fascicularis. The miR-378 shows a similar diagnostic value to serum ALT. The miR-151, miR-365, and miR-31 have no diagnostic value to CCl4-induced liver injury in Macaca fascicularis.

This Deliverable Report describes the work carried out in Task 5.4 (“Development of Decision Support System (DSS) for post-event rapid response also accounting for aftershocks”) within TURNkey WP5. The purpose of this task is to integrate the stakeholder performance metrics from Task 5.1 and the predictive models from Task 5.2 (performance of infrastructure systems) with the procedures for Rapid Earthquake Loss Prediction (RELP) (Task 4.5). The updated loss estimates that are output from WP4 constitute the initial state of the affected area (i.e., situational awareness), from which adequate actions may be taken during the crisis period. Accounting for various uncertainties (i.e., the known state of the systems and the variability in the effects of given decisions), the evaluation of various potential actions in a RRE context results in the design of a Decision Support System (DSS) that has the effect of orienting emergency responders towards the most efficient actions, thus reducing the time to emerge from the crisis phase. To this end, this task revolved around two specific focus areas, which are detailed in this report:  Design of a DSS for the post-earthquake accessibility of a road network (Section 3): following the general WP5 methodology, the DSS aims at identifying the best routes to navigate a degraded road network (accounting for uncertainty in the actual state of the road components) depending on the type of user (e.g., emergency responders, healthcare crew, general public, etc.).  Assessment of structural damage that occurs to infrastructure components under mainshock and future aftershock events (Sections 4 and 5): a Bayesian network-based probabilistic framework is developed for updating the risk of damage to bridges during aftershocks, allowing the integration of various types of information to reduce uncertainty in the calculations.

BackgroundAutoimmune gastritis (AIG) and Primary Sjögren’s syndrome (pSS) are both autoimmune diseases with low prevalence in China. Subacute combined degeneration (SCD) of the spinal cord is the most common neurological manifestation of vitamin B12 deficiency. Until now, a patient with pSS and complications of AIG including SCD has not been reported.Case PresentationA 69-year-old woman presented with palpitations and symmetrical and progressive numbness in her hands and feet. The patient had a sense of stepping on cotton and could not write or walk without help. We reviewed the patient’s history and analyzed her blood tests, imaging, gastroscopic findings, and pathological results. The patient fulfilled the criteria of AIG, pSS, spinal cord SCD and early pernicious anemia (PA) simultaneously. Although pSS can lead to reduction of vitamin B12, this is the first overlapping case of pSS with spinal cord SCD. After symptomatic treatment, the patient returned to a normal life.ConclusionsThis first report about the coexistence of pSS and complications of AIG including SCD and PA will promote a better understanding of the relationship between these diseases.

Developing different synthetic approaches to realize controlled or living polymerization is of great interest to polymer chemists to obtain polymers with defined molecular weight, narrow molecular weight distribution and unambiguous structures. Herein, we report an effective and efficient Lewis pair for methyl methacrylate (MMA) polymerization under ambient conditions by utilization of a new type of Lewis base, pyridinylidenaminophosphines (PyAPs). Among the currently investigated Lewis pair catalyzed MMA polymerization systems, Lewis pair (LP) catalysts based on PyAPs as Lewis bases (LBs) and organoaluminum compounds as Lewis acids (LAs), PyAPs possessing di-tertbutylphosphine (PyAP-tBu) LB and a moderately Lewis acidic and sterically hindered methylaluminum bis(2,6-di-tert-butyl-4-methylphenoxide) [MeAl(BHT)2] (BHT: 2,6-di-tert-butyl-4-methylphenol) LA have been demonstrated as the best LP catalysts in MMA Lewis pair polymerization (LPP). Moreover, the solid-state structure of the enolaluminate intermediate PyAP-tBu-CH2C(Me)C(OMe)OAl(BHT)2Me (INT1) was characterized by X-ray diffraction analysis. The polymerization of MMA exhibited activity up to 6400 h−1 TOF and a relatively high initiation efficiency, producing polymers with an ultrahigh molecular weight (Mn up to 790 kg mol−1) and narrow molecular weight distributions (Đ = 1.15). This polymerization with a controlled characteristic has been verified by several pieces of evidence, including chain-end analysis, a linear increase of Mnvs. monomer conversion and the monomer-to-initiator ratio and the synthesis of a diblock copolymer. In combination with MeAl(BHT)2 as the Lewis acid, PyAP-Cy and PyAP-iPr could polymerize MMA in the range of 800 equiv., to 1600 equiv., producing polymers with Mn up to 230 kg mol−1 and 240 kg mol−1, respectively. The electronic matching of the relative strength of LAs and LBs, as well as the steric interplays of Lewis pairs might account for the realization of controlled MMA polymerization.