Signal2signal: Pushing the Spatiotemporal Resolution to the Limit by Single Chemical Hyperspectral Imaging.

There is growing interest in developing a high-performance self-supervised denoising algorithm for real-time chemical hyperspectral imaging. With a good understanding of the working function of the zero-shot Noise2Noise-based denoising algorithm, we developed a self-supervised Signal2Signal (S2S) algorithm for real-time denoising with a single chemical hyperspectral image. Owing to the accurate distinction and capture of the weak signal from the random fluctuating noise, S2S displays excellent denoising performance, even for the hyperspectral image with a spectral signal-to-noise ratio (SNR) as low as 1.12. Under this condition, both the image clarity and the spatial resolution could be significantly improved and present an almost identical pattern with a spectral SNR of 7.87. The feasibility of real-time denoising during imaging was well demonstrated, and S2S was applied to monitor the photoinduced exfoliation of transition metal dichalcogenide, which is hard to accomplish by confocal Raman spectroscopy. In general, the real-time denoising capability of S2S offers an easy way toward in situ/in vivo/operando research with much improved spatial and temporal resolution. S2S is open-source at https://github.com/3331822w/Signal2signal and will be accessible online at https://ramancloud.xmu.edu.cn/tutorial.

CircRNA and Stroke: New Insight of Potential Biomarkers and Therapeutic Targets.

Stroke, the second-largest cause of death and the leading cause of disability globally, presents significant challenges in terms of prognosis and treatment. Identifying reliable prognosis biomarkers and treatment targets is crucial to address these challenges. Circular RNA (circRNA) has emerged as a promising research biomarkers and therapeutic targets because of its tissue specificity and conservation. However, the potential role of circRNA in stroke prognosis and treatment remains largely unexplored. This review briefly elucidate the mechanism underlying circRNA's involvement in stroke pathophysiology. Additionally, this review summarizes the impact of circRNA on different forms of strokes, including ischemic stroke and hemorrhagic stroke. And, this article discusses the positive effects of circRNA on promoting cerebrovascular repair and regeneration, maintaining the integrity of the blood-brain barrier (BBB), and reducing neuronal injury and immune inflammatory response. In conclusion, the significance of circRNA as a potential prognostic biomarker and a viable therapeutic target was underscored.

Public Opinion Through Art: Exploring Chinese University Students' Perspectives on COVID-19 Mass Nucleic Acid Testing.

In the context of the global COVID-19 pandemic, this study focuses on Chinese university students, employing graphic elicitation as a qualitative research method to analyze their hand-drawn paintings and related descriptions. Augmented by A/r/tography and metacognitive methods, the research aims to unveil the participants' collective memory, as well as the perspectives and responses of these students to policies related to the pandemic. By specifically examining this particular demographic, the study incorporates Fairclough's ethical theory, applying deontological ethics, consequentialist ethics, and virtue ethics to establish a comprehensive framework for evaluating adjustments to pandemic response policies. This research not only enhances our understanding of how these university students perceive and adapt to COVID-19 policies but also provides valuable insights for decision-makers. The particular methodology, combining graphic elicitation and metacognitive research, contributes to policy assessment and ethical analysis, offering a nuanced perspective on the interplay between individual perceptions, policy responses, and ethical considerations amid the complexities of a public health crisis.

Syndecan-1 as an immunogene in Triple-negative breast cancer: regulation tumor-infiltrating lymphocyte in the tumor microenviroment and EMT by TGFb1/Smad pathway.

BACKGROUND: Immune checkpoint inhibitors are the most studied forms of immunotherapy for triple-negative breast cancer (TNBC). The Cancer Genome Map (TCGA) and METABRIC project provide large-scale cancer samples that can be used for comprehensive and reliable immunity-related gene research. METHODS: We analyzed data from TCGA and METABRIC and established an immunity-related gene prognosis model for breast cancer. The SDC1 expression in tumor and cancer associated fibroblasts (CAFs) was then observed in 282 TNBC patients by immunohistochemistry. The effects of SDC1 on MDA-MB-231 proliferation, migration and invasion were evaluated. Qualitative real-time PCR and western blotting were performed to identify mRNA and protein expression, respectively. RESULTS: SDC1, as a key immunity-related gene, was significantly correlated with survival in the TCGA and METABRIC databases, while SDC1 was found to be highly expressed in TNBC in the METABRIC database. In the TNBC cohort, patients with high SDC1 expression in tumor cells and low expression in CAFs had significantly lower disease-free survival (DFS) and fewer tumor-infiltrating lymphocytes (TILs). The downregulation of SDC1 decreased the proliferation of MDA-MB-231, while promoting the migration of MDA-MB-231 cells by reducing the gene expression of E-cadherin and TGFb1 and activating p-Smad2 and p-Smad3 expression. CONCLUSION: SDC1 is a key immunity-related gene that is highly expressed TNBC patients. Patients with high SDC1 expression in tumors and low expression in CAFs had poor prognoses and low TILs. Our findings also suggest that SDC1 regulates the migration of MDA-MB-231 breast cancer cells through a TGFb1-Smad and E-cadherin-dependent mechanism.

Role of Transcription Factor Nrf2 in Pyroptosis in Spinal Cord Injury by Regulating GSDMD.

Spinal cord injury (SCI) is a prevalent disease that debilitates millions of people. Nuclear factor E2-related factor 2 (Nrf2) is an important regulator of SCI. The current study sought to elaborate on the effects of Nrf2 on gasdermin D (GSDMD)-mediated microglia pyroptosis to repair SCI. The SCI rat model was established via the percussion of the T10 spinal cord and in vitro SCI model was established on BV-2 cells via lipopolysaccharide (LPS)/adenosine triphosphate (ATP) treatment. Nrf2 expression in SCI rats and BV-2 cells was overexpressed via pcDNA3.1-Nrf2 injection. Functional assays were carried out to evaluate SCI rat pathological injury, BV-2 cell viability, the release of lactate dehydrogenase (LDH), and pyroptotic factors. The binding relations of Nrf2 and microRNA (miR)-146a and miR-146a and GSDMD were verified. BV-2 pyroptosis was analyzed after the combined experiment of miR-146a-inhibitor and pcDNA3.1-GSDMD. Our experiments revealed that Nrf2 was downregulated in SCI, and Nrf2 overexpression relieved SCI pathological injury, promoted BV-2 cell viability, inhibited the release of LDH, and repressed pyroptosis. Mechanically, Nrf2 bound to the miR-146a promoter and promoted miR-146a expression, and miR-146a targeted GSDMD transcription. Rescue experiments revealed that miR-146a knockdown or GSDMD overexpression annulled the inhibitory function of Nrf2 overexpression in LPS/ATP-induced microglia pyroptosis. Overall, our findings initially highlighted that Nrf2 inhibited GSDMD-mediated microglia pyroptosis and accelerated SCI repair by repressing miR-146a.

Contrast-enhanced lymphatic US can improve the preoperative diagnostic performance for sentinel lymph nodes in early breast cancer.

OBJECTIVES: To evaluate the preoperative diagnostic value of contrast-enhanced lymphatic ultrasound (CEUS) for the sentinel lymph node (SLN) status in early breast cancer. MATERIALS AND METHODS: We prospectively recruited 102 consecutive patients with clinically node-negative early breast cancer from July 2021 to October 2021. All patients underwent conventional US and percutaneous CEUS examinations. The CEUS of SLNs were classified into four enhancement patterns: homogeneous (I), featured inhomogeneous (II), focal defect (III), and no enhancement (IV). The diagnostic performance of conventional US and CEUS for SLN metastasis was assessed by receiver operating characteristic (ROC) curves and decision curves. RESULTS: A total of 78 women were enrolled in this study, including 55, 18, and 5 patients with negative axilla, 1-2, and ≥ 3 metastastic SLNs pathologically, respectively. The identification rate of SLNs by CEUS was 100%. Patterns I and II can select 91.7% (44/48) of patients with disease-free axilla, while patterns III and IV had higher percentages of metastasis (65.2%, p < 0.001 and 57.1%, p < 0.002, respectively). For the SLN metastatic burden, 100% (48/48) of patients with pattern I/II had ≤ 2 metastatic SLNs. Compared with conventional US, the CEUS enhancement patterns showed significant improvement in diagnosing metastatic SLNs (0.813 vs 0.601, p < 0.001). CEUS had greater clinical benefits and correctly reclassified 48% of metastatic SLNs (p < 0.001) without sacrificing the classification accuracy of negative SLNs (p = 0.25), and could improve prediction accuracy by 0.42 (p < 0.001). CONCLUSIONS: CEUS demonstrated better diagnostic performance and greater clinical benefits than conventional US for the preoperative diagnosis of SLNs, showing its potential to select candidates for precluding axillary surgery in early breast cancer. KEY POINTS: • The homogeneous and featured inhomogeneous enhancement of SLNs are highly suggestive of negative LNs, while focal defect (p < 0.001) and no enhancement (p < 0.002) patterns had higher percentages of metastasis. • The proportion of SLNs with highly suspicious signs on conventional US increases as the type of enhancement pattern increases (no suspicious signs in pattern I/II, 34.8% in pattern III, and 85.7% in pattern IV). • Compared with conventional US, CEUS improved the area under the receiver operating characteristic curve (0.813 vs. 0.601, p < 0.001) and had greater clinical benefits (IDI = 0.42, p < 0.001) for the diagnosis of axillary metastasis.

Risk stratification of gallbladder masses by machine learning-based ultrasound radiomics models: a prospective and multi-institutional study.

OBJECTIVE: This study aimed to evaluate the diagnostic performance of machine learning (ML)-based ultrasound (US) radiomics models for risk stratification of gallbladder (GB) masses. METHODS: We prospectively examined 640 pathologically confirmed GB masses obtained from 640 patients between August 2019 and October 2022 at four institutions. Radiomics features were extracted from grayscale US images and germane features were selected. Subsequently, 11 ML algorithms were separately used with the selected features to construct optimum US radiomics models for risk stratification of the GB masses. Furthermore, we compared the diagnostic performance of these models with the conventional US and contrast-enhanced US (CEUS) models. RESULTS: The optimal XGBoost-based US radiomics model for discriminating neoplastic from non-neoplastic GB lesions showed higher diagnostic performance in terms of areas under the curves (AUCs) than the conventional US model (0.822-0.853 vs. 0.642-0.706, p < 0.05) and potentially decreased unnecessary cholecystectomy rate in a speculative comparison with performing cholecystectomy for lesions sized over 10 mm (2.7-13.8% vs. 53.6-64.9%, p < 0.05) in the validation and test sets. The AUCs of the XGBoost-based US radiomics model for discriminating carcinomas from benign GB lesions were higher than the conventional US model (0.904-0.979 vs. 0.706-0.766, p < 0.05). The XGBoost-US radiomics model performed better than the CEUS model in discriminating GB carcinomas (AUC: 0.995 vs. 0.902, p = 0.011). CONCLUSIONS: The proposed ML-based US radiomics models possess the potential capacity for risk stratification of GB masses and may reduce the unnecessary cholecystectomy rate and use of CEUS. CLINICAL RELEVANCE STATEMENT: The machine learning-based ultrasound radiomics models have potential for risk stratification of gallbladder masses and may potentially reduce unnecessary cholecystectomies. KEY POINTS: • The XGBoost-based US radiomics models are useful for the risk stratification of GB masses. • The XGBoost-based US radiomics model is superior to the conventional US model for discriminating neoplastic from non-neoplastic GB lesions and may potentially decrease unnecessary cholecystectomy rate for lesions sized over 10 mm in comparison with the current consensus guideline. • The XGBoost-based US radiomics model could overmatch CEUS model in discriminating GB carcinomas from benign GB lesions.

Modern cities modelled as "super-cells" rather than multicellular organisms: Implications for industry, goods and services.

The structure and "metabolism" (movement and conversion of goods and energy) of urban areas has caused cities to be identified as "super-organisms", placed between ecosystems and the biosphere, in the hierarchy of living systems. Yet most such analogies are weak, and render the super-organism model ineffective for sustainable development of cities. Via a cluster analysis of 15 shared traits of the hierarchical living system, we found that industrialized cities are more similar to eukaryotic cells than to multicellular organisms; enclosed systems, such as factories and greenhouses, paralleling organelles in eukaryotic cells. We further developed a "super-cell" industrialized city model: a "eukarcity" with citynucleus (urban area) as a regulating centre, and organaras (enclosed systems, which provide the majority of goods and services) as the functional components, and cityplasm (natural ecosystems and farmlands) as the matrix. This model may improve the vitality and sustainability of cities through planning and management.

Value of CEUS features in diagnosing thyroid nodules with halo sign on B-mode ultrasound.

BACKGROUND: The results of halo sign in the differential diagnosis of thyroid nodules were conflicting, and the value of contrast-enhanced ultrasound (CEUS) in characterization of thyroid nodules with halo has not been fully evaluated. This study was therefore designed to investigate the value of contrast-enhanced ultrasound features in the differential diagnosis of thyroid nodules with halo sign on B-mode ultrasound. MATERIAL AND METHODS: Seventy-four consecutive thyroid nodules with halo sign on B-mode ultrasound were pathologically confirmed by surgery or fine needle aspiration, including 43 benign and 31 malignant lesions. All these lesions underwent pre-operative CEUS examination. The CEUS features, including enhanced time, enhanced intensity and homogeneity, and presence of enhancing ring, were compared between benign and malignant ones. RESULTS: Enhanced intensity was significant different between benign and malignant lesions with halo. Hypo-enhancement was more frequently detected in malignant nodules than that in benign ones, compared with iso-enhancement and hyper-enhancement (p = 0.013, and = 0.014, respectively). Detection rate of high-enhancing ring was significantly higher in benign nodules than that in malignant group (p = 0.001). While in nodules > 10 mm, only high-enhancing ring was the distinguishing feature between benign and malignant nodules. CONCLUSIONS: Enhanced intensity and high-enhancing ring may be helpful in the differential diagnosis of thyroid nodules with halo sign on B-mode ultrasound.

SDH5 down-regulation mitigates the damage of osteoporosis via inhibiting the MyD88/NF-κB signaling pathway.

BACKGROUND: Osteoporosis has become a serious public health problem especially in postmenopausal women. This work aims to assess both the function and mechanism of SDH5 in osteoporosis. METHODS: The animal model of osteoporosis in Sprague-Dawley rats was established by utilizing ovariectomy (OVX). The trabecular bone morphometry had been determined by micro-CT, and tibia injury of rats was detected through HE and alcian blue staining. Meanwhile, the levels of oxidative stress factors, including malondialdehyde, catalase, glutathione peroxidase (GSH-Px), and superoxide (SOD), were detected by ELISA. The proliferation and apoptosis of osteoblasts isolated from OVX-induced rats were found out by CCK-8 and flow cytometry, respectively. The expression of SDH5, Osterix, Type I collagen (CoL1A1), osteocalcin (OC), SOD1, SOD2, p-MyD88/MyD88, and p-NF-κB p65/NF-κB p65 was assessed by Western blot. The effect and mechanism of SDH5 knockdown on osteoporosis were verified by lipopolysaccharide treatment. RESULTS: In the osteoporosis rat model, the expression of SDH5 had an up-regulated tend. A higher bone mineral density value was found in the SDH5 knockdown group. SDH5 inhibition ameliorated bone loss, mitigated bone histopathological injury, alleviated oxidative stress, and elevated osteogenic marker protein expression in vivo and in vitro. SDH5 down-regulation also promoted the proliferation and restrained apoptosis of osteoblasts extracted from OVX-induced rats. Furthermore, we found that the underlying mechanism was associated with the inhibition of the MyD88/NF-κB pathway. CONCLUSION: Down-regulation of SDH5 mitigates the damage of osteoporosis both in vivo and in vitro via inhibiting the MyD88/NF-κB signaling activation.

Effects of Twin-Block with an expanding device on the upper airway in growing children with skeletal class II malocclusion-a retrospective study based on the consistency of three-dimensional and two-dimensional data.

OBJECTIVES: Skeletal class II malocclusion is one of the most common malocclusions. Among the functional appliances for skeletal class II malocclusion, the Twin-Block appliance with a maxillary expander is effective in repositioning the mandible forward. In this study, we focused our efforts on investigating the effects of Twin-Block appliances with maxillary expanders on the upper airway in growing children with skeletal class II malocclusion by tracing and measuring lateral cephalograms after evaluating the consistency of three-dimensional CBCT data and two-dimensional lateral cephalogram data. MATERIALS AND METHODS: A total of 102 patients ranging from 9 to 15 years old (11.37 ± 2.80, male/female ratio = 1:1) with skeletal class II malocclusion were selected to evaluate the consistency of CBCT data and lateral cephalogram data. The strongly and moderately correlated segments were then selected to study the effects of Twin-Block with a maxillary expander on the upper airway in 66 growing children with skeletal class II malocclusion (11.31 ± 1.23 years old, male/female ratio = 1:1) by lateral cephalograms. RESULTS: The results showed a strong significant correlation in the nasopharynx (r = 0.708) and moderate significant correlations in the overall upper airway (r = 0.641), palatopharynx (r = 0.553), and glossopharynx (r = 0.575) but a weak correlation in the hypopharynx (r = 0.323). The corresponding determination coefficient (R2) was also determined by scatter plot analysis. Moreover, compared with the pretreatment data (T1), the total area of the upper airway and the areas of the nasopharynx, palatopharynx, and glossopharynx after functional treatment (T2) increased statistically and significantly. CONCLUSIONS: Lateral cephalograms can reflect the volume of the nasopharynx and oropharynx in skeletal class II children to a certain extent, while Twin-Block appliances with maxillary expanders can widen the volume of the nasopharynx and oropharynx significantly. CLINICAL RELEVANCE: The lateral cephalogram is reliable for analyzing the nasopharynx, palatopharynx, and glossopharynx in orthodontic clinical practice. Twin-Block appliances with maxillary expanders have a positive effect on skeletal class II patients with airway stenosis.

Vehicle Trajectory Prediction via Urban Network Modeling.

Taxis are an important component of the transportation system, and empty taxis represent a significant waste of transportation resources. To alleviate the imbalance between supply and demand and relieve traffic congestion, real-time prediction of taxi trajectories is necessary. Most existing trajectory prediction studies focus on extracting time-series information but do not capture spatial information sufficiently. In this paper, we focus on the construction of an urban network and propose an urban topology-encoding spatiotemporal attention network (UTA) to address destination prediction problems. Firstly, this model discretizes the production and attraction units of transportation, combining them with key nodes in the road network to form an urban topological network. Secondly, GPS records are matched to the urban topological map to construct a topological trajectory, which significantly improves trajectory consistency and endpoint certainty, helping to model destination prediction problems. Thirdly, semantic information concerning surrounding space is attached to effectively mine the spatial dependencies of trajectories. Finally, after the topological encoding of city space and trajectories, this algorithm proposes a topological graph neural network to model the attention calculation with the trajectory context, comprehensively considering the spatiotemporal characteristics of the trajectories and improving prediction accuracy. We solve the prediction problems with the UTA model and also compare it with some other classical models, such as the HMM, RNN, LSTM, and transformer. The results suggest that all the models work well in combination with the proposed urban model (with a rough increase of 2%), while the UTA model is less affected by data sparsity.

Observation of the clinical features of dupilumab-associated facial erythema.

Introduction: Dupilumab is the first biologic agent used to clinically treat moderate and severe atopic dermatitis (AD) and is currently the only biologic agent used for this condition. Many studies have reported that moderate-to-severe AD was significantly improved after dupilumab injection, although head/neck dermatitis occurred with itching, flushing, and scaling. Moreover, because all the symptoms occur after dupilumab treatment, they are called "dupilumab facial redness (DFR)". Aim: To retrospectively analyse the clinical characteristics and treatment of facial erythema in patients with atopic dermatitis treated with dupilumab. Material and methods: The clinical data of patients with moderate-to-severe atopic dermatitis treated with dupilumab (600 mg for the first time, 300 mg every 2 weeks thereafter) in the department of dermatology from July 2020 to May 2022 were obtained. We described their characteristics and analysed their symptomatic treatment measures and efficacy. Results: Twenty-one patients with DFR were included. Most clinical manifestations were erythema and pruritus, which differed from the symptoms of typical moderate-to-severe AD. After treatment, drug withdrawal, and dressing change, the symptoms of 17 patients were effectively controlled or completely improved, while these of 4 did not improve. Conclusions: Although the mechanism of DFR is still unclear, symptomatic treatment is partially effective, and medication discontinuation and switching to Janus kinase inhibitors are acceptable for some patients.

Long-term survival of screen-detected synchronous and metachronous bilateral non-palpable breast cancer among Chinese women: a hospital-based study (2003-2017).

PURPOSE: Screen-detected unilateral non-palpable breast cancer (NPBC) shows favorable prognosis, whereas bilateral breast cancer (BBC), especially synchronous BBC (SBBC) manifests worse survival than unilateral breast cancer (BC). It remains unclear whether screen-detected bilateral NPBC has compromised survival and requires intensified treatment or favorable prognosis and needs de-escalating therapy. METHODS: From 2003 to 2017, 1,075 consecutive NPBC patients were retrospectively reviewed. There were 988 patients with unilateral NPBC (UniNPBC), and 87 patients with ipsilateral NPBC + any contralateral BC [(N + AnyContra) PBC], including 32 patients with bilateral NPBC (BiNPBC) and 55 patients with ipsilateral NPBC + contralateral palpable cancer [(N + Contra) PBC]. Median follow-up time was 91 (48-227) months. Clinicopathological characteristics were compared between UniNPBC and BBC, whereas relapse-free survival (RFS) and overall survival (OS) among BBC subgroups. RFS and OS factors of BBC were identified. RESULTS: Compared to UniNPBC, patients with screen-detected bilateral BC had more invasive (85.1%, 74.8%), ER negative (26.4%, 17.1%), PR negative (36.8%, 23.5%), triple-negative (21.6%, 8.5%) BC as well as less breast conserving surgery (17.2%, 32.4%), radiotherapy (13.8%, 32.0%) and endocrine therapy (71.3%, 83.9%). 10 year RFS and OS rates of (N + AnyContra) PBC (72.8%, 81.5%), (N + Contra) PBC (60.6%, 73.9%), and synchronous (N + Contra) PBC (58.1%, 70.1%) were significantly compromised compared to UniNPBC (91.0%, 97.2%). RFS factors of BBC included pN3 (p = 0.048), lymphovascular invasion (p = 0.008) and existence of contralateral palpable interval BC (p = 0.008), while the OS relevant factor was pN3 (p = 0.018). CONCLUSION: Screen-detected bilateral NPBC including SynBiNPBC and MetaBiNPBC showed good prognosis as UniNPBC so that the therapy of BiNPBC could be de-escalated and optimized according to UniNPBC. Contrarily, screen-detected ipsilateral NPBC with contralateral palpable BC [(N + Contra) PBC] manifested unfavorable survival worse than UniNPBC and synchronous (N + Contra) PBC had the worst survival among all subgroups, implying that these were actually bilateral interval BC and required intensified treatment.

Rationale and design of a phase II trial of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for N0/N1mi, HER2 + early breast cancer (PHAEDRA).

BACKGROUND: The de-escalation treatment in patients with low-risk HER2-positive early breast cancer (eBC) is an attractive strategy to avoid unnecessary treatment and improve the quality of life of patients. Pyrotinib, a novel irreversible pan-HER2 tyrosine kinase inhibitor (TKI), has shown efficacy in patients with advanced HER2-positive breast cancer. Meanwhile, nanoparticle albumin-bound (nab)-paclitaxel reveals survival benefit over solvent-based paclitaxel and eliminates the toxicities associated with the solvent. However, the efficacy and safety of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for low-risk HER2 + eBC patients have not been evaluated. METHODS: This is a multicenter, open-label, single-arm phase II study. A sample size of 261 patients with tumor ≤ 3 cm, lymph node-negative (N0) or micrometastatic (N1mi), HER2 + breast cancer will be recruited. Eligible patients will receive nab-paclitaxel 260 mg/m2 once every 3 weeks for 12 weeks and pyrotinib 400 mg once daily for one year. The primary endpoint is invasive disease-free survival. A sub-study will be conducted to investigate different prophylactic strategies for diarrhea, which is the most common adverse event of pan-HER TKIs. One hundred and twenty patients from the main study will be randomly (1:1) allocated to receive loperamide either during the first cycle (4 mg tid on days 1-7, then 4 mg bid on days 8-21) or the first 2 cycles (4 mg tid on days 1-7, then 4 mg bid on days 8-42). The primary endpoint of the sub-study is the incidence of grade ≥ 3 diarrhea. DISCUSSION: This is the first prospective study of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for patients with low-risk HER2-positive eBC. It would probably provide robust evidence for de-escalating strategy of HER2-positive eBC and appropriate management for pyrotinib-related diarrhea. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04659499 . Registered on December 9, 2020.

Sentinel Lymph Node Positive Rate Predicts Non-Sentinel Lymph Node Metastasis in Breast Cancer.

BACKGROUND: To investigate retrospectively an association between the number of metastatic sentinel lymph nodes (SLNs) per total number of SLNs per patient (i.e., the SLN positive rate, or SLN-PR) and non-SLN metastasis in breast cancer. METHODS: A large population (n = 2250) underwent SLN dissection from January 1, 2014 to January 1, 2020; 627 (27.87%) had at least one positive SLN (SLN+). Among these, 283 underwent axillary lymph node (ALN) dissection, and formed the test group. Four external validation groups comprised 43 patients treated in 2019. SLN mappings were examined using methylene blue and indocyanine green. Lymph node ultrasound, SLN-PR, and pathological characteristics were compared between patients with and without non-SLN metastasis. An SLN-PR cutoff value was calculated using receiver operating characteristic (ROC) curves. Associations between clinicopathological variables and SLN-PR with non-SLN metastasis were analyzed by multivariate logistic regression model. RESULTS: The median age was 47 years (IQR: 42-56 y). The median number of resected SLNs was 4. Patients with positive non-SLNs (126/283, 44.52%) had a median of 2 positive node. SLN-PR > 0.333 was a risk factor for non-SLN positivity (area under the ROC curve, 0.726); and carried significantly higher risk of non-SLN metastasis (P < 0.001). This was validated in the external group. CONCLUSIONS: SLN-PR > 0.333 was associated with greater risk of non-SLN metastasis. This provides a reference to non-SLN metastasis in patients with SLN metastasis, an indication for ALN dissection and choice of adjuvant treatment.

Comprehensive profiling of alternative splicing landscape during secondary dormancy in oilseed rape (Brassica napus L.).

Alternative splicing is a general mechanism that regulates gene expression at the post-transcriptional level, which increases the transcriptomic diversity. Oilseed rape (Brassica napus L.), one of the main oil crops worldwide, is prone to secondary dormancy. However, how alternative splicing landscape of oilseed rape seed changes in response to secondary dormancy is unknown. Here, we analyzed twelve RNA-seq libraries from varieties "Huaiyou-SSD-V1" and "Huaiyou-WSD-H2" which exhibited high (> 95%) and low (< 5%) secondary dormancy potential, respectively, and demonstrated that alternative splicing changes led to a significant increase with the diversity of the transcripts in response to secondary dormancy induction via polyethylene glycol 6000 (PEG6000) treatment. Among the four basic alternative splicing types, intron retention dominates, and exon skipping shows the rarest frequency. A total of 8% of expressed genes had two or more transcripts after PEG treatment. Further analysis revealed that global isoform expression percentage variations in alternative splicing in differently expressed genes (DEGs) is more than three times as much as those in non-DEGs, suggesting alternative splicing change is associated with the transcriptional activity change in response to secondary dormancy induction. Eventually, 342 differently spliced genes (DSGs) associated with secondary dormancy were identified, five of which were validated by RT-PCR. The number of the overlapped genes between DSGs and DEGs associated with secondary dormancy was much less than that of either DSGs or DEGs, suggesting that DSGs and DEGs may independently regulates secondary dormancy. Functional annotation analysis of DSGs revealed that spliceosome components are overrepresented among the DSGs, including small nuclear ribonucleoprotein particles (snRNPs), serine/arginine-rich (SR) proteins, and other splicing factors. Thus, it is proposed that the spliceosome components could be exploited to reduce secondary dormancy potential in oilseed rape. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01314-8.

Design, synthesis and pharmacological characterization of N-(3-ethylbenzo[d]isoxazol-5-yl) sulfonamide derivatives as BRD4 inhibitors against acute myeloid leukemia.

BRD4 plays a key role in the regulation of gene transcription and has been identified as an attractive target for cancer treatment. In this study, we designed 26 new compounds by modifying 3-ethyl-benzo[d]isoxazole core with sulfonamides. Most compounds exhibited potent BRD4 binding activities with ΔTm values exceeding 6 °C. Two crystal structures of 11h and 11r in complex with BRD4(1) were obtained to characterize the binding patterns. Compounds 11h and 11r were effective for BRD4(1) binding and showed remarkable anti-proliferative activity against MV4-11 cells with IC50 values of 0.78 and 0.87 µM. Furthermore, 11r (0.5-10 µM) concentration-dependently inhibited the expression levels of oncogenes including c-Myc and CDK6 in MV4-11 cells. Moreover, 11r (0.5-10 µM) concentration-dependently blocked cell cycle in MV4-11 cells at G0/G1 phase and induced cell apoptosis. Compound 11r may serve as a new lead compound for further drug development.

Spatial-Temporal Convolutional Transformer Network for Multivariate Time Series Forecasting.

Multivariate time series forecasting has long been a research hotspot because of its wide range of application scenarios. However, the dynamics and multiple patterns of spatiotemporal dependencies make this problem challenging. Most existing methods suffer from two major shortcomings: (1) They ignore the local context semantics when modeling temporal dependencies. (2) They lack the ability to capture the spatial dependencies of multiple patterns. To tackle such issues, we propose a novel Transformer-based model for multivariate time series forecasting, called the spatial-temporal convolutional Transformer network (STCTN). STCTN mainly consists of two novel attention mechanisms to respectively model temporal and spatial dependencies. Local-range convolutional attention mechanism is proposed in STCTN to simultaneously focus on both global and local context temporal dependencies at the sequence level, which addresses the first shortcoming. Group-range convolutional attention mechanism is designed to model multiple spatial dependency patterns at graph level, as well as reduce the computation and memory complexity, which addresses the second shortcoming. Continuous positional encoding is proposed to link the historical observations and predicted future values in positional encoding, which also improves the forecasting performance. Extensive experiments on six real-world datasets show that the proposed STCTN outperforms the start-of-the-art methods and is more robust to nonsmooth time series data.

A Comparative Study of Frequent Pattern Mining with Trajectory Data.

Sequential pattern mining (SPM) is a major class of data mining topics with a wide range of applications. The continuity and uncertain nature of trajectory data make it distinctively different from typical transactional data, which requires additional data transformation to prepare for SPM. However, little research focuses on comparing the performance of SPM algorithms and their applications in the context of trajectory data. This study selected some representative sequential pattern mining algorithms and evaluated them with various parameters to understand the effect of the involved parameters on their performances. We studied the resultant sequential patterns, runtime, and RAM consumption in the context of the taxi trajectory dataset, the T-drive dataset. It was demonstrated in this work that a method to discretize trajectory data and different SPM algorithms were performed on trajectory databases. The results were visualized on actual Beijing road maps, reflecting traffic congestion conditions. Results demonstrated contiguous constraint-based algorithms could provide a concise representation of output sequences and functions at low min_sup with balanced RAM consumption and execution time. This study can be used as a guide for academics and professionals when determining the most suitable SPM algorithm for applications that involve trajectory data.