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Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.

Background. Advances in cancer research have allowed for early diagnosis and improved treatment of cutaneous melanoma (CM). However, its invasiveness and recurrent metastasis, along with rising resistance to newer therapies, have lent urgency to the search for novel biomarkers and the underlying molecular mechanisms of CM. Methods. Single nucleotide polymorphism- (SNP-) related genes were obtained from the sequencing data of 428 CM samples in The Cancer Genome Atlas. Functional enrichment of these genes was analysed in clusterProfiler. Additionally, a protein-protein interaction (PPI) network was constructed with the Search Tool for the Retrieval of Interacting Gene (STRING) database. Gene Expression Profiling Interactive Analysis (GEPIA) was used to identify the expression and prognostic value of mutated genes. Finally, the Tumour Immune Estimation Resource (TIMER) analysed the relationship between gene expression and immune cell infiltration. Results. We constructed a PPI network from the top 60 SNP-related genes. Mutated genes were mainly involved in calcium and oxytocin signalling pathways, as well as circadian entrainment. In addition, three SNP-related genes, BRAF, FLG, and SORL1, were significantly associated with patient prognosis. BRAF and SORL1 were positively associated with infiltration abundance of B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells, whereas FLG expression was negatively associated. Furthermore, higher immune cell infiltration was positively correlated with good prognosis. Conclusions. Our study provides vital bioinformatic data and a relevant theoretical basis to further explore the molecular pathogenesis of CM and improve patient prognosis.

Purpose There are a paucity of data and a pressing need to evaluate response to neoadjuvant chemotherapy (NACT) and determine long-term outcomes in young Black women with early-stage breast cancer (EBC). Methods We analyzed data from 2196 Black and White women with EBC treated at the University of Chicago over the last 2 decades. Patients were divided into groups based on race and age at diagnosis: Black women $$\le$$ ≤ 40 years, White women $$\le$$ ≤ 40 years, Black women $$\ge$$ ≥ 55 years, and White women $$\ge$$ ≥ 55 years. Pathological complete response rate (pCR) was analyzed using logistic regression. Overall survival (OS) and disease-free survival (DFS) were analyzed using Cox proportional hazard and piecewise Cox models. Results Young Black women had the highest risk of recurrence, which was 22% higher than young White women (p = 0.434) and 76% higher than older Black women (p = 0.008). These age/racial differences in recurrence rates were not statistically significant after adjusting for subtype, stage, and grade. In terms of OS, older Black women had the worst outcome. In the 397 women receiving NACT, 47.5% of young White women achieved pCR, compared to 26.8% of young Black women (p = 0.012). Conclusions Black women with EBC had significantly worse outcomes compared to White women in our cohort study. There is an urgent need to understand the disparities in outcomes between Black and White breast cancer patients, particularly in young women where the disparity in outcome is the greatest.

Since its establishment in 1837, Hermes has been adhering to quality, culture is driven, handmade, and adhere to the development of high-end, from the original harness store development into today's famous super luxury giant. This paper analyzes Hermes from two aspects, its own financial situation and the surrounding industry market. In terms of financial performance, Hermes showed a good recovery from the negative effect of COVID in 2020, creating a leading position over the industry in sales revenue. Combined with well turnover and debt-paying ability, the business performance is generally in stable growth. In terms of the market analysis, the SWOT and industrial competitor analysis was made to point out the actual utilities of Hermes’ strategies. Hermes insists on the family's absolute control of the brand to ensure the maintenance of the family business model. In strategies, the membership system and hunger marketing to increase user engagement, the little discount style also creates a noble image of the brand.

The type IV IFN (IFN-υ) is reported in vertebrates from fish to primary mammals with IFN-υR1 and IL-10R2 as receptor subunits. In this study, the proximal promoter of IFN-υ was identified in the amphibian model, Xenopus laevis, with functional IFN-sensitive responsive element and NF-κB sites, which can be transcriptionally activated by transcription factors, such as IFN regulatory factor (IRF)1, IRF3, IRF7, and p65. It was further found that IFN-υ signals through the classical IFN-stimulated gene (ISG) factor 3 (ISGF3) to induce the expression of ISGs. It seems likely that the promoter elements of the IFN-υ gene in amphibians is similar to type III IFN genes, and that the mechanism involved in IFN-υ induction is very much similar to type I and III IFNs. Using recombinant IFN-υ protein and the X. laevis A6 cell line, >400 ISGs were identified in the transcriptome, including ISGs homologous to humans. However, as many as 268 genes were unrelated to human or zebrafish ISGs, and some of these ISGs were expanded families such as the amphibian novel TRIM protein (AMNTR) family. AMNTR50, a member in the family, was found to be induced by type I, III, and IV IFNs through IFN-sensitive responsive element sites of the proximal promoter, and this molecule has a negative role in regulating the expression of type I, III, and IV IFNs. It is considered that the current study contributes to the understanding of transcription, signaling, and functional aspects of type IV IFN at least in amphibians.

In order to improve the signal processing effect and efficiency of Coriolis mass flowmeter, a signal processing system of Coriolis mass flowmeter based on time-varying signal model is designed. Based on the analysis of the structure and working principle of Coriolis mass flowmeter, the environmental factors affecting the performance of Coriolis mass flowmeter are discussed. Based on the above analysis, the signal processing environment is designed, including serial signal processing environment and dual core parallel signal processing environment. Then the effective signal processing of Coriolis mass flowmeter is completed from three aspects: initial processing, phase calculation and frequency tracking. The experimental results show that after the time-varying signal model is applied, a complete signal frame can be collected in less than 50 ms in the pre-processing process, and the signal processing frame can be completed in less than 80 ms in the post-processing process. This shows that the signal processing time of the system is short, and the phase difference detection accuracy of the signal processing system based on the time-varying signal model is high, which is of great value to further improve the application effect of Coriolis mass flowmeter.

IFN-stimulated genes (ISGs) can act as effector molecules against viral infection and can also regulate pathogenic infection and host immune response. N-Myc and STAT interactor (Nmi) is reported as an ISG in mammals and in fish. In this study, the expression of Nmi was found to be induced significantly by the infection of Siniperca chuatsi rhabdovirus (SCRV), and the induced expression of type I IFNs after SCRV infection was reduced following Nmi overexpression. It is observed that Nmi can interact with IRF3 and IRF7 and promote the autophagy-mediated degradation of these two transcription factors. Furthermore, Nmi was found to be interactive with IFP35 through the CC region to inhibit IFP35 protein degradation, thereby enhancing the negative role in type I IFN expression after viral infection. In turn, IFP35 is also capable of protecting Nmi protein from degradation through its N-terminal domain. It is considered that Nmi and IFP35 in fish can also interact with each other in regulating negatively the expression of type I IFNs, but thus in enhancing the replication of SCRV.

The digital trade ecosystem’s development relies on the growth of cross-border e-commerce platforms. To ensure the continued growth of China’s digital trade, it is crucial to consider the service capabilities of digital platforms and the digital transformation capabilities of cross-border e-commerce firms. This study explores the impact of these factors on the performance of cross-border e-commerce companies, with digital transformation capability acting as a mediator. Empirical research reveals that the service capability of digital platforms is composed of supply chain communication and cost control abilities, which partially mediate the relationship between digital platform serviceability and cross-border e-commerce enterprise performance. Moreover, both the service capabilities of digital platforms and the digital transformation capabilities of cross-border e-commerce companies have a positive and significant impact on enterprise performance.

A star-shaped polymer (Star-PEG-PCL2) was synthesized to with PCL and PEG, and used as a stationary phase for gas chromatography. The statically coated Star-PEG-PCL2 column exhibited an efficiency of 2260 plates/m determined by naphthalene at 120 °C and moderate polarity. The Star-PEG-PCL2 column showed high resolution performance for isomers of a wide ranging polarity, including methylnaphthalenes, halogenated benzenes, nitrobenzene, phenols, and anilines, and displayed dual-nature selectivity for a mixture of 17 analytes. Also, the Star-PEG-PCL2 column exhibited good separation performance and column inertness for Grob test mixture and a series of cis-/trans-isomers. In addition, it exhibited advantageous separation performance over the commercial HP-35 and PEG-20M columns for chloroaniline and bromoaniline isomers through its unique three-dimensional framework. In conclusion, it has good potential as a new stationary phase for separating a variety of analytes because of its special structure and excellent separation performance.

The cryosphere's surface (snow, sea ice, and water) regulates global climate through several feedback mechanisms. Broadband albedo is a critical parameter determining the radiative energy balance of the complex atmosphere-cryosphere system, but there is currently no reliable, operational albedo retrieval product capable of assessing the global sea-ice albedo with sufficient spatial-temporal resolution for studies of sea-ice dynamics and for use in global climate models. A framework was established for remote sensing of sea ice albedo that integrates sea-ice physics with high computational efficiency, and can be applied to any optical sensor that measures appropriate radiance data. A scientific machine learning (SciML) approach was developed and trained on a large synthetic dataset (SD) constructed using a coupled atmosphere-surface radiative transfer model (RTM). The resulting RTM/SciML framework combines the RTM with a multi-layer artificial neural network SciML model. In comparison to the NASA MODIS MCD43 albedo product, this framework does not depend on observations from multiple days, and can be applied to single angular observations obtained under clear-sky conditions. Compared to the existing melt pond fraction-based approach for albedo retrieval, the RTM/SciML framework has the advantage of being applicable to a wide variety of cryosphere surfaces, both heterogeneous and homogeneous. Validation of the RTM/SciML albedo product using MODIS and SGLI data against measurements obtained from aircraft campaigns revealed excellent agreement, with mean absolute error of 0.047 for above 2000 clear-sky pixels.

Title: Epidemiology and Prognosis of HER2-Low Breast Cancer (BC) in the National Cancer Data Base (NCDB) Background: Characterization of HER2 status has focused on HER2 overexpressing BC, which are uniquely sensitive to HER2-directed therapy. However, approximately 60% of BC traditionally characterized as HER2-negative express low levels of HER2 on immunohistochemistry (IHC). Although these ‘HER2-low’ cancers are insensitive to traditional HER2 blockade, a recent randomized clinical trial showed that antibody drug conjugates such as trastuzumab deruxtecan (T-DXd) are effective in this population. Given the heterogenity of low level HER2 expression and the impact of T-DXd on outcomes in this population, further data on the epidemiology and prognosis of HER2-low BC is needed. Methods: We conducted a retrospective cohort study of patients (pts) in the NCDB diagnosed from 2010 to 2019 with invasive BC classified as HER2-negative, and with HER2 IHC results available. We compared demographics and other clinical characteristics of HER2 0 vs HER2-low (defined as IHC score of 1+ or 2+) cases in this cohort. A logistic regression was used to quantify the independent association of demographic and clinical factors with HER2-low status, and odds ratios (OR) and 95% confidence intervals (CI) were reported. Overall survival (OS) was compared for HER2 0 vs HER2-low by receptor subtype and stage, and a multivariable Cox model was fit to also control for age, race/ethnicity, comorbidity score, treatment facility type, grade, and histologic type. In pts who received neoadjuvant chemotherapy (NAC), a logistic regression was used to determine if pathological complete response (pCR) rate was different between HER2-low and HER2 0 pts. Results: We identified 1,191,389 pts, including 394,937 HER2 0 and 796,452 HER2-low; median follow-up was 54 months with 84.1% of pts surviving. Hispanic and Black pts and pts with higher grade, non-ductal, triple-negative breast cancer (TNBC) and affect minority Hispanic and Black women (table 1). On multivariable analysis, TNBC (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.47 – 0.49), lobular (OR 0.74, 95% CI 0.73 – 0.75) and other non-ductal histology (OR 0.66, 95% CI 0.64 – 0.67) had lower likelihood of HER2-low status. Hispanic ethnicity remained associated with lower likelihood of HER2-low (OR 0.89, 95% CI 0.87 – 0.91), whereas Black race was associated with a slight increased likelihood of HER2-low status (OR 1.06, 95% CI 1.04 – 1.08). In multivariable survival analysis of TNBC patients, HER2-low BC was associated with improved OS for stage 2 (hazard ratio [HR] 0.93, 95% CI 0.90 – 0.96), stage 3 (HR 0.92, 95% CI 0.88 – 0.96) and stage 4 (HR 0.92, 95% CI 0.87 – 0.97) cancer. By contrast, survival analysis of hormone receptor positive cancer showed that HER2-low BC was associated with improved OS only for stage 4 disease (HR 0.96, 95% CI 0.92 – 0.99). In 62,667 pts receiving NAC, HER2-low status was associated with a lower likelihood of pCR (OR 0.88, 95% CI 0.84 – 0.92). Conclusions: HER2-low BC is most frequently HR+ with a ductal histology, and is associated with a lower likelihood of response to chemotherapy but an improved OS, especially for metastatic cases. This lower pCR in the HER2-low population could be explained by a higher proportion of these tumors being HR+. There are racial/ethnic differences in the incidence of HER2-low BC, largely mediated by differences in rates of TNBC, and fewer Black and Hispanic pts will be candidates for therapies targeting low level HER2 expression. Citation Format: Daniel Peiffer, Frederick M. Howard, Nan Chen, Olwen M. Hahn, Rita Nanda, Olufunmilayo I. Olopade, Dezheng Huo. HER2-11 Epidemiology and Prognosis of HER2-Low Breast Cancer (BC) in the National Cancer Data Base (NCDB) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr HER2-11.

Background: Hormone receptor positive breast cancer constitutes about 70% of newly diagnosed early-stage disease in the United States, and gene-expression based recurrence assays such as Oncotype DX (ODX) are strongly recommended by guidelines to aid in treatment decisions. However, recurrence assays are costly, time-consuming, underutilized in low resource settings, and unavailable in developing countries. Deep Learning (DL) using hematoxylin and eosin (H&E) stained digital pathology has been shown to approximate gene expression patterns for multiple cancer types, and may provide a cost-effective, fast, and scalable method to predict risk of recurrence in community settings. Methods: We first developed a model for ODX using only DL on pathology, comprised of two Xception-based modules, trained on 1,039 slides from The Cancer Genome Atlas (TCGA) tessellated into 10x magnification image tiles. The first module predicts tumor likelihood, and was trained using pathologist annotations for tumor regions versus normal stroma. The second module was trained to predict ODX score, estimated from gene expression data within TCGA. Patient-level predictions were calculated by weighting the predicted recurrence score by tumor likelihood for all tiles within a slide. Separately, ODX score was predicted from clinical variables using the University of Tennessee Nomogram, which incorporates grade, progesterone receptor, size, age, and histologic subtype. Finally, we developed a combined model by fitting a logistic regression to the DL pathologic model and the clinical nomogram predictions. Performance of the clinical nomogram, pathologic, and combined models were then compared in a single-institution external validation cohort of patients diagnosed with breast cancer between 2006 and 2020, all of whom had the commercial ODX assay run. Results: We identified 428 cases for our diverse validation cohort (69% White, 24% Black, 6% Asian, and 3% Hispanic) with mean ODX score of 18. Chemotherapy was administered for 104 (24.3%) of patients, the remaining 323 (75.4%) received endocrine therapy alone. Area under the receiver operating characteristic curve (AUROC) for prediction of high ODX score (≥ 26) of the combined model was 0.83 (95% confidence interval [CI] 0.78 – 0.89) in the validation cohort, which was higher than either the DL pathology model (AUROC 0.80, 95% CI 0.75 – 0.85, p = 0.026) or the Tennessee nomogram (AUROC 0.77, 85% CI 0.70 – 0.83, p = 0.003). Performance was similar in Black (AUROC 0.86, 95% CI 0.78 – 0.94) and White (AUROC of 0.81, 95% CI 0.74 – 0.88) subgroups. The combined model was more accurate in prediction of recurrence-free interval in patients receiving endocrine therapy (hazard ratio [HR] 2.02 per standard deviation [SD], 95% CI 1.16 – 3.52, p = 0.013, Concordance [C]-index 0.75) than the clinical nomogram (HR 1.75 per SD, 95% CI 1.09 – 2.81, p = 0.021, C-index 0.68). No model was prognostic in patients receiving chemotherapy. Pathologist review of heatmaps of DL model predictions identified lymphovascular invasion, necrosis, high grade, and infiltrative borders as features contributing to model prediction of high risk. Conclusions: DL can improve on existing clinical prediction of breast cancer with low recurrence risk. This approach could improve the speed at which treatment decisions are made due to the time-consuming nature of genomic testing and simultaneously reduce the cost of care. Given the equal performance in racial subgroups, this approach has promise for application in global health settings where genomic assays are not widely available or are prohibitively expensive. Citation Format: Frederick M. Howard, James M. Dolezal, Sara Kochanny, Galina Khramtsova, Jasmine Vickery, Andrew Srisuwananukorn, Anna Woodard, Nan Chen, Rita Nanda, Charles Perou, Olufunmilayo I. Olopade, Dezheng Huo, Alexander Pearson. Multimodal Prediction of Breast Cancer Recurrence Assays and Risk of Recurrence [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-08.

Background: Only a subset of patients with metastatic triple-negative breast cancers (TNBC) demonstrate response to FDA approved PD-1 immune checkpoint blockade (ICB), and few have durable responses. Data suggests that breast cancers have defects in antigen presentation and that antigen presenting cells especially the DC1 subtype of dendritic cells (DCs) are required for response to ICB. CD40 agonists activate antigen presenting cells including DCs and B cells and also repolarize macrophages to an anti-tumor phenotype. Flt3 ligand is a growth factor that increases differentiation and expansion of DCs. We recently demonstrated in pre-clinical TNBC models that the combination of liposomal-doxorubicin chemotherapy, a CD40 agonist, and a Flt3 ligand improves outcomes compared to alternate combinations. Methods: This is a single arm phase I pilot study of liposomal-doxorubicin, CDX-1140 (CD40 agonist), and CDX-301 (Flt3 ligand) combination therapy in patients with metastatic or unresectable locally advanced metastatic TNBC. Patients will be randomized to 3 lead-in arms (triplet therapy, doublet immunotherapy only, or liposomal-doxorubicin only) for 1 cycle prior to receiving triplet therapy with fresh tissue biopsies before and after the lead-in treatment. CDX-301 will be discontinued after 2 cycles; liposomal-doxorubicin and CDX-1140 will be continued until disease progression or clinically limiting toxicities. Primary endpoint is determination of a recommended phase 2 dose based on treatment-related adverse events including dose-limiting toxicities. Secondary endpoints include anti-tumor immune response after triplet therapy, after immunotherapy alone, and after liposomal-doxorubicin alone; median progression-free survival, overall response rate, duration of response, and clinical benefit rate. Key eligibility criteria are unresectable stage III or stage IV TNBC (ER ≤10%, PR ≤10%, HER2/neu negative), 1st to 3rd line metastatic treatment setting (1st line patients need to be PD-L1 negative by 22C3 assay), measurable disease by RECIST 1.1 criteria, consent for pre-treatment and on-treatment biopsies of amenable soft tissue tumor lesions, no prior treatment with an anti-CD40 antibody or a Flt3 ligand, no anthracycline treatment in the metastatic setting, no prior progression while on anthracycline-based therapy or within 6 months of completing neoadjuvant chemotherapy, and no history of non-infectious pneumonitis or current pneumonitis. This trial will enroll up to 45 patients across multiple sites (NCT05029999). Citation Format: Sangeetha Reddy, Meredith Carter, Isaac Chan, Nisha Unni, Namrata Peswani, Dawn Klemow, Samira Syed, Shahbano Shakeel, Farjana Fattah, Chul Ahn, Yisheng Fang, Heather McArthur, Nicole Sinclair, Michael Yellin, Denise Yardley, Nan Chen, Joyce O’Shaughnessy, Rita Nanda, Suzanne D. Conzen, Carlos Arteaga. Phase 1 trial of anthracycline chemotherapy in combination with CD40 agonist and Flt3 ligand in metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-17-01.

In this study, modifications of the Held scaling (Held) are proposed and tested against simulations of f-plane, two-layer quasigeostrophic turbulence. The aim is to better constrain the eddy mixing length and rms barotropic velocity in response to varied quadratic and linear bottom drag. The proposed modifications allow eddies to be partially barotropized, to relax the commonly invoked barotropization approximation, and consider a drag-dependent cascade rate per energy input, to account for the lack of an inertial range. Quantitative comparisons with the vortex gas scaling are also carried out. It is shown that the progressively weakened sensitivity in eddy scales to increased drag strength is mainly a result of eddy partial barotropization. For both drag forms except toward the limit of weak linear drag, accounting for partial barotropization alone leads to good predictions of eddy velocity, although not of mixing length. It also partly resolves the degeneracy of balance constraints for linear drag because partial barotropization acts like scale-dependent damping. Adding a cascade correction, which is interpreted as allowing for changes in spectral room for cascade, further improves the mixing length representation. Overall, the proposed theory can augment the existing scalings by extending the eddy scale predictions to O(1) quadratic drag and has skills generally comparable to the vortex gas scaling for linear drag. However, toward the weak linear drag limit where eddies approach complete barotropization, the proposed theory breaks down but the vortex gas performs well. Potential issues concerning the applicability of vortex gas to this limit are discussed.

Background and objectivesHigh-dose dual therapy [proton pump inhibitor (PPI) + amoxicillin] is recommended as a Helicobacter pylori rescue treatment. However, its efficacy is still controversial. The aim of this study was to evaluate the efficacy and safety of triple therapy containing high dose of PPI and amoxicillin plus metronidazole compared with dual therapy in rescue treatment.MethodsTwo hundred and sixty-eight patients who failed at least two courses of H. pylori treatment were recruited and randomly allocated into two 14-day groups: esomeprazole 40 mg twice daily and amoxicillin 1000 mg three times daily plus metronidazole 400 mg three times daily (EAM group); or esomeprazole 40 mg twice daily and amoxicillin 1000 mg three times daily (EA group). The agar-dilution method was performed as an antibiotic susceptibility test. The 13C urea breath test was used to assess H. pylori eradication at 6 weeks after the treatment. The study was registered at clinicaltrials.gov (NCT04024527).ResultsH. pylori eradication rates in the EAM group were 85.8% (115/134, 95% CI 79.9%–91.7%) in ITT analysis and 92.6% (113/122, 95% CI 87.9%–97.3%) in PP analysis, significantly higher than those of the EA group, which were 73.1% (98/134, 95% CI 65.6%–80.6%) and 83.1% (98/118, 95% CI 76.8%–89.8%) (P = 0.005, 0.011). Resistance rates of amoxicillin and metronidazole were 6.6% (13/196) and 89.8% (176/196). Metronidazole resistance did not affect the eradication rates in the EAM group. Both groups had similar moderate and severe adverse events and similar compliance.ConclusionsA triple therapy containing high dose of PPI and amoxicillin plus metronidazole could be a potential rescue therapy worldwide even in a high metronidazole-resistance region.

This study firstly developed a hiPSC-derived lineage-specific SMC-on-a-chip model and identified the segmental aortic heterogeneity. The model can be used for disease modelling, drug testing and personalised treatment.

To evaluate and map the reporting and methodological quality of network meta-analysis (NMA) on acupuncture.Published acupuncture NMAs were searched through eight databases from inception to February 2022. The reporting and methodological quality of included studies was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Network Meta-Analysis (PRISMA-NMA) statement and the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) checklist.A total of 113 NMAs were identified. Most (99, 87.61%) studies were performed in China. Most studies focused on multiple acupuncture techniques (82.30%), and the main studied ailments were pain and poststroke sequelae (20.24%). The median (interquartile range (IQR)) score of the reporting quality was 26.5 (25-28.5). However, poor reporting rates in the protocol and registration (33.63%) and geometry of the network (35.40%), especially for China-based studies, were identified. The methodological quality of only 2 (1.77%) English studies was high. The reporting rate of Chinese studies was below 15% on each of items 4, 7, 10, and 12.The reporting quality of the NMAs was moderate, but the methodological quality was very low. The reporting and methodological quality of future NMAs, especially for Chinese studies, need further improvement.

Little is known about the pathogenesis underlying cognitive impairment in major depressive disorder (MDD). We aimed to explore the mechanisms of cognitive impairments among patients with MDD by investigating the dynamics of overlapping brain sub-networks.Forty unmedicated patients with MDD and 28 healthy controls (HC) were enrolled in this study. Cognitive function was measured using the Chinese versions of MATRICS Consensus Cognitive Battery (MCCB). All participants were scanned using a whole-head resting-state magnetoencephalography (MEG) machine. The dynamism of neural sub-networks was analyzed based on the detection of overlapping communities in five frequency bands of oscillatory brain signals.MDD demonstrated poorer cognitive performance in six domains compared to HC. The difference in community detection (functional integration mode) in MDD was frequency-dependent. MDD showed significantly decreased community dynamics in all frequency bands compared to HC. Specifically, differences in the visual network (VN) and default mode network (DMN) were detected in all frequency bands, differences in the cognitive control network (CCN) were detected in the alpha2 and beta frequency bands, and differences in the bilateral limbic network (BLN) were only detected in the beta frequency band. Moreover, community dynamics in the alpha2 frequency band were positively correlated with verbal learning and reasoning problem solving abilities in MDD.Our study found that decreasing in the dynamics of overlapping sub-networks may differ by frequency bands. The aberrant dynamics of overlapping neural sub-networks revealed by frequency-specific MEG signals may provide new information on the mechanism of cognitive impairments that result from MDD.

A novel C–N bond activation strategy was established by developing new organic photoredox catalyst (Cz-NI-Ph), which provides a concise approach for the synthesis of amides from tertiary amines.