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Abstract Background A high body mass index (hBMI) is one of the major risk factors for ischemic stroke (IS), although independent estimates of the global burden and trend of IS attributable to hBMI are unclear. Methods Study data were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study and analysed by age, sex, year, and geographical location. The sociodemographic index (SDI) and the human development index (HDI) were used as indicators of national socioeconomic status. Geographic distributions and trends were assessed by calculating the estimated annual percentage change (EAPC). Associations between the age-standardized death rate (ASMR) or disability-adjusted life year rate (DALY) and socioeconomic status were analysed. Results Deaths and DALYs increased worldwide from 1990–2021, with increases of 95.74% for the former and 133.00% for the latter; the ASMR and ASDR decreased, with an ASMR and ASDR-related EAPCs of -1.10 (95% CI: -1.24–-0.96) and 0.04 (95% CI:-0.47–0.55), respectively; women had greater numbers of deaths and DALYs, and the majority of deaths and DALYs were shared by those aged ≥ 70. The highest burden rates were shared by Eastern Europe, North Africa, the Middle East, and Central Asia. The ASMR-related EAPCs were associated with the ASMR in 1990 (R = -0.35, P

Abstract Objective This study aims to compare the efficacy of the Age-adjusted Charlson Comorbidity Index (ACCI) and the Elixhauser-Van Walraven Comorbidity Index (ECI-VW) in predicting mortality risk among patients undergoing heart valve surgery. Methods Clinical data were extracted from the INSPIRE Database using R language. The Receiver Operating Characteristic (ROC) Curve was employed to assess the predictive accuracy of ACCI and ECI-VW for in-hospital all-cause mortality and post-surgical all-cause mortality at 7 and 28 days. Subgroup analysis was conducted to validate the application efficacy, and the optimal cutoff value was identified. Results The study included 996 patients, with 931 survivors and 65 cases of in-hospital all-cause mortality. The area under the curve (AUC) for ACCI in predicting in-hospital all-cause mortality was 0.658 (95% CI: 0.584, 0.732), while the AUC for ECI-vw in predicting the same outcome was 0.663 (95% CI: 0.584, 0.741). For predicting all-cause mortality within 7 days post-surgery, the AUC of ACCI was 0.680 (95% CI: 0.04, 0.56), and for ECI-vw, it was 0.532 (95% CI: 0.353, 0.712). Regarding the prediction of all-cause mortality within 28 days after surgery, the AUC for ACCI was 0.724 (95% CI: 0.622, 0.827), and for ECI-vw, it was 0.653 (95% CI: 0.538, 0.69). Patients were categorized into two groups based on the ACCI cutoff value of 3.5, including Group 1 (ACCI 3.5 points, 173 cases). The overall survival rate for these two patient groups was calculated using the Kaplan-Meier method, revealing that the 28-day postoperative survival rate for patients in Group 1 was significantly higher than that for patients in Group 2 (P

Abstract Magnetic fields from the linear motor, suspended electromagnet, and collector shoe arcing are the three main electromagnetic interference (EMI) sources for the medium–low-speed maglev train interior. Under their collective influence, the field intensity may exceed the standard threshold, consequently affecting the operational reliability of the train system. However, in previous studies, the EMI sources were analyzed separately, and studies regarding the influence of factors such as the motor states and the train body (TB) shielding against arcing EMI were lacking. Therefore, in this paper, all three EMI source are considered, and an EM disturbance source modeling scheme is proposed using the COMSOL software platform. Its effectiveness is demonstrated and the train interior magnetic field is analyzed, primarily with respect to prior simulations and tests. Subsequent analyses enable a comparative assessment of the individual contributions of each EMI source to the overall interference, considering the EMI control standards. The influence of other EMI source parameters, such as different motor states, is analyzed, and the potential for modifying the material composition and structural thickness of the TB is explored to determine the appropriate EMI inhibition strategy.

Abstract Low-dose CT (LDCT) is increasingly recognized as the preferred method for detecting pulmonary nodules. However, distinguishing whether a nodule is benign or malignant often necessitates repeated scans or invasive tissue sampling procedures. Therefore, there is a pressing need for non-invasive techniques to minimize unnecessary interventions. This study aim to investigate the expression profile of exosomal snoRNA in the serum of patients with benign and malignant pulmonary nodules. We identified a total of 278 snoRNAs in serum exosomes, revealing significant differences in snoRNA levels between patients with malignant and benign nodules. Specifically, the upregulated snoRNAs U78 and U37 were validated through qRT-PCR and were found significantly elevated in the serum of patients with malignant pulmonary nodules, positioning them as promising biomarkers for the early detection of lung cancer. This study underscores the potential of serum exosomal U78 and U37 as critical tools for assessing the risk of pulmonary nodules identified through CT screening.

Abstract Background NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. Methods Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. Results Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P

Abstract Background Omicron variant impacts populations with its rapid contagiousness, and part of patients suffered from persistent symptoms termed as long COVID. The molecular and immune mechanisms of this currently dominant global variant leading to long COVID remain unclear, due to long COVID heterogeneity across populations. Methods We recruited 66 participants in total, 22 out of 66 were healthy control without COVID-19 infection history, and 22 complaining about long COVID symptoms 6 months after first infection of Omicron, referred as long COVID (LC) Group. The left ones were defined as non-long COVID (NLC) Group. We profiled them via plasma neutralizing antibody titer, SARS-CoV-2 viral load, transcriptomic and proteomics screening, and machine learning. Results No serum residual SARS-CoV-2 was observed in the participants 6 months post COVID-19 infection. No significant difference in neutralizing antibody titers was found between the long COVID (LC) Group and the non-long COVID (NLC) Group. Transcriptomic and proteomic profiling allow the stratification of long COVID into neutrophil function upregulated (NU-LC) and downregulated types (ND-LC). The NU-LC, identifiable through a refined set of 5 blood gene markers (ABCA13, CEACAM6, CRISP3, CTSG and BPI), displays evidence of relatively higher neutrophil counts and function of degranulation than the ND-LC at 6 months after infection, while recovered at 12 months post COVID-19. Conclusion The transcriptomic and proteomic profiling revealed heterogeneity among long COVID patients. We discovered a subgroup of long COVID population characterized by neutrophil activation, which might associate with the development of psychiatric symptoms and indicate a higher inflammatory state. Meanwhile, a cluster of 5 genes was manually curated as the most potent discriminators of NU-LC from long COVID population. This study can serve as a foundational exploration of the heterogeneity in the pathogenesis of long COVID and assist in therapeutic targeting and detailed epidemiological investigation of long COVID.

Abstract As a class of biologically active molecules with significant immunomodulatory and anti-inflammatory effects, anti-inflammatory peptides have important application value in the medical and biotechnology fields due to their unique biological functions. Research on the identification of anti-inflammatory peptides provides important theoretical foundations and practical value for a deeper understanding of the biological mechanisms of inflammation and immune regulation, as well as for the development of new drugs and biotechnological applications. Therefore, it is necessary to develop more advanced computational models for identifying anti-inflammatory peptides. In this study, we propose a deep learning model named DAC-AIPs based on variational autoencoder and contrastive learning for accurate identification of anti-inflammatory peptides. In the sequence encoding part, the incorporation of multi-hot encoding helps capture richer sequence information. The autoencoder, composed of convolutional layers and linear layers, can learn latent features and reconstruct features, with variational inference enhancing the representation capability of latent features. Additionally, the introduction of contrastive learning aims to improve the model's classification ability. Through cross-validation and independent dataset testing experiments, DAC-AIPs achieves superior performance compared to existing state-of-the-art models. In cross-validation, the classification accuracy of DAC-AIPs reached around 88%, which is 7% higher than previous models. Furthermore, various ablation experiments and interpretability experiments validate the effectiveness of DAC-AIPs. Finally, a user-friendly online predictor is designed to enhance the practicality of the model, and the server is freely accessible at http://dac-aips.online .

Abstract Stroke is the second leading cause of death worldwide, and China has the highest stroke incidence in the world. The systemic inflammatory response index (SIRI), systemic inflammatory response index (SIRI), systemic immune-inflammatory index (SII), neutrophil-to-high-density lipoprotein ratio (NHR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) have clinical in predicting the prognosis of acute ischaemic stroke (AIS) patients. No studies have compared the predictive value of these six composite inflammatory markers. This study included 516 AIS patients with AIS symptoms for 2 defining poor prognosis. The results of the univariate analysis showed that all six composite inflammatory indices, SIRI, SII, NHR, NLR, PLR and MLR, were associated with a poor prognosis in patients with AIS. All six composite inflammatory indicators correlated with the short-term prognosis of AIS patients. The six composite inflammation indicators were included in the binary logistic regression, and the results showed that SIRI, NLR and PLR were found to be independent risk factors for poor short-term prognosis in AIS patients. Among the six inflammatory markers, SIRI, NLR and PLR were the most clinically valuable for predicting the short-term prognosis of patients with AIS. Peripheral blood indices are easy to obtain clinically and can provide important clinical value for early prognosis and treatment adjustment.

Abstract In plants due to their sessile nature, secondary metabolites are important components against different abiotic and biotic stress, such as extended darkness. For this reason, the variation of secondary metabolite content of the Arabidopsis thaliana HapMap natural population following 0-and 6-d darkness treatment were detected and the raw data of different accessions at two timepoints were deposited in the Zenodo database. Moreover, the annotated secondary metabolites of these samples are presented in this data descriptor, which we believe will be a usefully re-usable resource for future integrative analysis with dark-treated transcripts, proteins or other phenotypic data in order to comprehensively illustrate the multiomic landscape of Arabidopsis in response to the stresses exerted by extended darkness.

Abstract Alzheimer’s disease (AD) is the most common cause of dementia characterized by amyloid-β (Aβ) deposition, tau hyperphosphorylation, and neuroinflammation. Naringenin (NRG), a natural flavonoid widely present in citrus fruits, has been reported can penetrate the blood-brain barrier and exert anti-inflammatory effects in the central nervous system. Here, we investigate the protective effects of long-term NRG treatment on AD. The novel object recognition test and Morris water maze test reveal that NRG treatment can improve the learning and memory ability of APP/PS1 mice. Besides, we find that NRG can significantly reduce Aβ deposition, microglial and astrocytic activation, and pro-inflammatory cytokine levels in APP/PS1 mice. Results further show that NRG effectively decreases pro-inflammatory cytokines in LPS/Aβ-stimulated BV2 cells. Lastly, the molecular mechanistic study reveals that NRG attenuates neuroinflammatory responses via inhibition of the MAPK signaling pathway in vivo and in vitro. Overall, NRG may emerge as a promising compound for the prevention and treatment of AD.

Abstract Background The interplay between diet and the gut microbiota in multiple sclerosis (MS) is poorly understood. We aimed to assess the interrelationship between diet, the gut microbiota, and MS. Methods We conducted a case-control study including 95 participants (44 pediatric-onset MS cases, 51 unaffected controls) enrolled from the Canadian Pediatric Demyelinating Disease Network study. All had completed a food frequency questionnaire ≤21-years of age, and 59 also provided a stool sample. Results Here we show that a 1-point increase in a Mediterranean diet score is associated with 37% reduced MS odds (95%CI: 10%–53%). Higher fiber and iron intakes are also associated with reduced MS odds. Diet, not MS, explains inter-individual gut microbiota variation. Several gut microbes abundances are associated with both the Mediterranean diet score and having MS, and these microbes are potential mediators of the protective associations of a healthier diet. Conclusions Our findings suggest that the potential interaction between diet and the gut microbiota is relevant in MS.

Abstract The aim of this study was to assess the correlation between gut microbial taxonomy and various ovarian responses to controlled ovarian stimulation. A total of 22 IVF cycles with a follicle-to-oocyte index (FOI)

Background: Involvement of the recurrent laryngeal nerve (RLN) in papillary thyroid carcinoma (PTC) is an important prognostic factor and is associated with a higher risk of recurrence. This study aimed to retrospectively analyze the outcomes of patients treated with hemithyroidectomy (HT) in PTC patients with an exclusive RLN invasion who could not tolerate staged surgery, did not wish to undergo another operation, or had other reasons. Methods: A retrospective review was conducted on 163 patients with PTC and exclusive RLN involvement at our institution between 2013 and 2019. Patients were divided into a total thyroidectomy (TT) group and HT group. The clinicopathologic factors and prognostic outcomes were compared between the two groups. A propensity score-matched analysis was carried out to reduce selection bias, with the following covariates: gender, age, tumor size, multifocality, central lymph node metastasis (CLNM), and RLN resection. The Kaplan–Meier method was used for a comparison of recurrence outcomes. Results: In the baseline data of the 163 PTC patients, tumor size (p < 0.001), multifocality (p = 0.011), CLNM (p < 0.001), and RLN resection (p < 0.008) in the TT and HT groups differed significantly, whereas age and gender did not differ between the two groups. The TT group reported significantly higher temporary and permanent hypoparathyroidism than the HT group (p < 0.001 and p = 0.042, respectively). With 72-month median follow-up, 11 (6.7%) patients developed recurrence. After propensity score matching, 24 patients with HT and 43 patients with TT were included. Recurrence-free survival (RFS) in the matched samples showed no difference between the TT and HT groups (p = 0.092). Conclusion: Our results indicate that HT may be a feasible treatment for PTC patients with exclusive RLN involvement in specific circumstances without significantly increasing the risk of recurrence. Performing a thorough preoperative examination is crucial to exclude multifocal tumors and lymph node metastasis before undergoing HT.

Abstract C-1 Glycals serve as pivotal intermediates in synthesizing diverse C-glycosyl compounds and natural products, necessitating the development of concise, efficient and user-friendly methods to obtain C-1 glycosides is essential. The Suzuki-Miyaura cross-coupling of glycal boronates is notable for its reliability and non-toxic nature, but glycal donor stability remains a challenge. Herein, we achieve a significant breakthrough by developing stable glycal boronates, effectively overcoming the stability issue in glycal-based Suzuki–Miyaura coupling. Leveraging the balanced reactivity and stability of our glycal boronates, we establish a robust palladium-catalyzed glycal-based Suzuki-Miyaura reaction, facilitating the formation of various C(sp 2)-C(sp), C(sp 2)-C(sp 2 ), and C(sp 2)-C(sp 3) bonds under mild conditions. Notably, we expand upon this achievement by developing the DNA-compatible glycal-based cross-coupling reaction to synthesize various glycal-DNA conjugates. With its excellent reaction reactivity, stability, generality, and ease of handling, the method holds promise for widespread appication in the preparation of C-glycosyl compounds and natural products.

Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy involving approximately 80 pathogenic genes. Whole-exome sequencing (WES) and confirmatory Sanger sequencing analysis was applied to identify the disease-causing mutations in a Chinese patient with lower limb weakness. We present an 18-year-old male with a 2.5-year history of progressive lower limb weakness and an unsteady gait. Upon admission, a physical examination revealed hands tremulousness, bilateral calf muscle wasting and weakness, pes cavus, and elevated serum creatine kinase (CK) levels. Electromyography demonstrated axonal neuropathy affecting both upper and lower limbs. A de novo heterozygous missense mutation was identified in the MORC2 gene, NM_001303256.3: c.1199A>G, NP_001290186.1: p.Gln400Arg. Consequently, these clinical and genetic findings suggested a diagnosis of hereditary peripheral neuropathy, CMT type 2Z. Oral mecobalamin and coenzyme Q10 was initiated as subsequent treatment. Our study firstly reports the MORC2 c.1199A>G mutation occurring de novo, highlighting its causal association with CMT2Z, and prompting its reclassification as likely pathogenic. Oral mecobalamin and coenzyme Q10 might be a potential treatment approach for early-stage CMT2Z. We recommend genetic testing for CMT patients to identify the genetic etiology, thereby improving clinical management and facilitating genetic counseling.

BackgroundCardiopulmonary bypass (CPB) triggers a strong inflammatory response in cardiovascular surgery patients during the perioperative period. This article mainly focuses on the perioperative application of novel inflammatory biomarkers in cardiovascular surgeries involving CPB.MethodsPatients were divided into a CPB group and a non-CPB group according to whether they underwent CPB during cardiovascular surgery. Novel inflammatory biomarkers and clinical results were recorded. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), platelet × neutrophil/lymphocyte ratio (SII), and monocyte × platelet × neutrophil/lymphocyte ratio (PIV) were calculated. The primary outcomes were perioperative prognosis between the CPB and non-CPB groups. The secondary outcomes included perioperative alterations of novel inflammatory biomarkers in the CPB group and predictive values of novel inflammatory biomarkers for postoperative infection and acute kidney injury.ResultsA total of 332 patients were initially included in the study. Before propensity score matching (PSM), there were 96 patients in the CPB group and 236 patients in the non-CPB group. After PSM, both groups included 58 patients each. Compared with the non-CPB group, the CPB group had a higher proportion of intraoperative transfusion of blood products (63.79% vs. 6.90%, P

The minimum fire extinguishing concentration is a key index for the development of next generation chemical clean fire extinguishing gases, which is usually got by the cup-burner. The fire suppression performance of low concentration of chemical gas is hard to be understood by the available methods. In this work, the fundamental acknowledgement of steady flame surface attacking mechanism by halon functional group is newly discussed by conducting a series of bench scale tests with a cylindrical channel under a varied fluorinated gases. The characteristics of flame propagation under differentiated air atmosphere environmental conditions is obtained. The influence of fluorine-containing gas flow rate on flame propagation speed is clarified. A dimensionless relationship including atomic radius, bond length, polarization degree, molar mass and molar volume are proposed to describe the influence of low concentration of fluorine-containing gas on flame propagation speed. It provides an insight for the understanding of the flame inhibition performance of low concentration halogenated gas.

Abstract Background Appendicular lean mass (ALM) is a good predictive biomarker for sarcopenia. And previous studies have reported the association between ALM and stroke or Alzheimer’s disease (AD), however, the causal relationship is still unclear, The purpose of this study was to evaluate whether genetically predicted ALM is causally associated with the risk of stroke and AD by performing Mendelian randomization (MR) analyses. Methods A two-sample MR study was designed. Genetic variants associated with the ALM were obtained from a large genome-wide association study (GWAS) and utilized as instrumental variables (IVs). Summary-level data for stroke and AD were generated from the corresponding GWASs. We used random-effect inverse-variance weighted (IVW) as the main method for estimating causal effects, complemented by several sensitivity analyses, including the weighted median, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. Multivariable analysis was further conducted to adjust for confounding factors, including body mass index (BMI), type 2 diabetes mellitus (T2DM), low density lipoprotein-C (LDL-C), and atrial fibrillation (AF). Results The present MR study indicated significant inverse associations of genetically predicted ALM with any ischemic stroke ([AIS], odds ratio [OR], 0.93; 95% confidence interval [CI], 0.89–0.97; P = 0.002) and AD (OR, 090; 95% CI 0.85–0.96; P = 0.001). Regarding the subtypes of AIS, genetically predicted ALM was related to the risk of large artery stroke ([LAS], OR, 0.86; 95% CI 0.77–0.95; P = 0.005) and small vessel stroke ([SVS], OR, 0.80; 95% CI 0.73–0.89; P

Abstract Glioma, particularly glioblastomas (GBM), is incurable brain tumor. The most targeted receptor tyrosine kinase (RTKs) drugs did not bring benefit to GBM patients. The mechanism of glioma growth continues to be explored to find more effective treatment. Here, we reported that Ser/Thr protein kinase YANK2 (yet another kinase 2) is upregulated in glioma tissues and promotes the growth and proliferation of glioma in vitro and in vivo. Further, we confirmed that oncogene Fyn directly activated YANK2 through phosphorylation its Y110, and Fyn-mediated YANK2 phosphorylation at Y110 site promotes glioma growth by increasing its stability. Finally, YANK2 was proved to be a novel upstream kinase of p70S6K and promotes glioma growth by directly phosphorylating p70S6K at T389. Taken together, we found a new mTOR-independent p70S6K activation pathway, Fyn-YANK2-p70S6K, which promotes glioma growth, and YANK2 is a potential oncogene and serves as a novel therapeutic target for glioma.

Abstract Coagulation alterations manifest early after severe burns and are closely linked to mortality outcomes. Nevertheless, the precise characterization of coagulation changes associated with early mortality remains elusive. We examined alterations in indicators linked to mortality outcomes at both the transcriptomic and clinical characteristic levels. At the transcriptomic level, we pinpointed 28 differentially expressed coagulation-related genes (DECRGs) following burn injuries and endeavored to validate their causal relationships through Mendelian randomization. DECRGs tied to survival exhibit a significant association with neutrophil function, wherein the expression of CYP4F2 and P2RX1 serves as robust predictors of fatal outcomes. In terms of clinical indicators, early levels of D-dimer and alterations in serum calcium show a strong correlation with mortality outcomes. Coagulation depletion and fibrinolytic activation, stemming from the hyperactivation of coagulation pathways post-severe burns, are strongly linked to patient mortality. Monitoring these early coagulation markers with predictive value can effectively identify individuals necessitating priority critical care.

Abstract Despite the high therapeutic response achieved with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapy in relapsed and refractory multiple myeloma (R/R MM), primary resistance and relapse exist with single-target immunotherapy. Here, we design bispecific BC19 CAR T cells targeting BCMA/CD19 and evaluate antimyeloma activity in vitro and in vivo. Preclinical results indicate that BC19 CAR specifically recognize target antigens, and BC19 CAR T cells mediate selective killing of BCMA or CD19-positive cancer cells. BC19 CAR T cells also exhibit potent antigen-specific anti-tumor activity in xenograft mouse models. We conduct an open-label, single-arm, phase I/II study of BC19 CAR T cells in 50 patients with R/R MM (ChiCTR2000033567). The primary endpoint was safety. BC19 CAR T cells are well tolerated with grade 3 or higher cytokine release syndrome in 8% of patients and grade 1 neurotoxic events in 4% of patients, which meet the pre-specified primary endpoint. Secondary endpoints include overall response rate (92%), median progression-free survival (19.7 months), median overall survival (19.7 months) and median duration of response (not reached). Our study demonstrates that bispecific BC19 CAR T cells are feasible, safe and effective in treating patients with R/R MM.

Abstract Background Intravenous immunoglobulin (IVIG) is the primary treatment for Kawasaki disease (KD). However, 10–20% of KD patients show no response to IVIG treatment, making the early prediction of IVIG resistance a key focus of KD research. Our aim is to explore the application of the C-reactive protein to albumin ratio (CAR) for predicting IVIG resistance in children with KD through meta-analysis. Methods Cochrane Library, PubMed, MEDLINE, EMbase, CNKI, WanFang, the Chinese Biomedical Database, and CQVIP were searched up to November 2023 for cohort studies on predicting IVIG-resistant KD using the CAR. Articles were selected based on pre-established inclusion and exclusion criteria after extracting literature data and assessing them using the QUADAS-2.0 tool for evaluating the accuracy of diagnostic tests. Stata 15.0 software was used for meta-analysis. Results Four Chinese and English literature reports were included in this meta-analysis. The results revealed the presence of a threshold effect and high heterogeneity among the included studies. The combined sensitivity for CAR predicting IVIG-resistant KD was calculated as 0.65 (95% CI 0.58–0.72), specificity as 0.71 (95% CI 0.57–0.81), and the area under the curve (AUC) as 0.70 (95% CI 0.66–0.74) using the random-effects model. The combined positive likelihood ratio was 2.22 (95% CI 1.35–3.65), the combined negative likelihood ratio was 0.49 (95% CI 0.35–0.69), and the diagnostic odds ratio was 5 (95% CI 2–10). Conclusion CAR is an auxiliary predictive indicator with moderate diagnostic value that provides guidance in the early treatment of the disease, demonstrating a certain predictive value that warrants further investigation. However, CAR cannot yet be considered as a definitive diagnostic or exclusionary marker for IVIG-resistant KD. Therefore, multi-center, large sample, and high-quality long-term follow-up trials are warranted to confirm the current findings.

Abstract Crystalline white organic light-emitting diodes (C-WOLEDs) are promising candidates for lighting and display applications. It is urgently necessary, however, to develop energy-saving and high-efficiency C-WOLEDs that have stable and powerful emission to meet commercial demands. Here, we report a crystalline host matrix (CHM) with embedded nanoaggregates (NA) structure for developing high-performance C-WOLEDs by employing a thermally activated delayed fluorescence (TADF) material and orange phosphorescent dopants (Phos.-D). The CHM-TADFNA-D WOLED exhibit a remarkable EQE of 12.8%, which is the highest performance WOLEDs based on crystalline materials. The device has a quick formation of excitons and a well-designed energy transfer process, and possesses a fast ramping of luminance and current density. Compared to recently reported high-performance WOLEDs based on amorphous material route, the C-WOLED achieves a low series-resistance Joule-heat loss ratio and an enhanced photon output, demonstrating its significant potential in developing the next-generation WOLEDs.

Abstract Background Plant diseases caused by pathogenic fungi are devastating. However, commonly used fungicides are harmful to the environment, and some are becoming ineffective due to fungal resistance. Therefore, eco-friendly biological methods to control pathogenic fungi are urgently needed. Results In this study, a strain, Paenibacillus sp. lzh-N1, that could inhibit the growth of the pathogenic fungus Mycosphaerella sentina (Fr) Schrorter was isolated from the rhizosphere soil of pear trees, and the complete genome sequence of the strain was obtained, annotated, and analyzed to reveal the genetic foundation of its antagonistic ability. The entire genome of this strain contained a circular chromosome of 5,641,488 bp with a GC content of 45.50%. The results of species identification show that the strain belongs to the same species as P. polymyxa Sb3-1 and P. polymyxa CJX518. Sixteen secondary metabolic biosynthetic gene clusters were predicted by antiSMASH, including those of the antifungal peptides fusaricidin B and paenilarvins. In addition, biofilm formation-related genes containing two potential gene clusters for cyclic lactone autoinducer, a gene encoding S-ribosylhomocysteine lyase (LuxS), and three genes encoding exopolysaccharide biosynthesis protein were identified. Conclusions Antifungal peptides and glucanase biosynthesized by Paenibacillus sp. lzh-N1 may be responsible for its antagonistic effect. Moreover, quorum sensing systems may influence the biocontrol activity of this strain directly or indirectly.

Background: Crops are constantly attacked by various pathogens. These pathogenic microorganisms, such as fungi, oomycetes, bacteria, viruses, and nematodes, threaten global food security by causing detrimental crop diseases that generate tremendous quality and yield losses worldwide. Chemical pesticides have undoubtedly reduced crop damage; however, in addition to increasing the cost of agricultural production, the extensive use of chemical pesticides comes with environmental and social costs. Therefore, it is necessary to vigorously develop sustainable disease prevention and control strategies to promote the transition from traditional chemical control to modern green technologies. Plants possess sophisticated and efficient defense mechanisms against a wide range of pathogens naturally. Immune induction technology based on plant immunity inducers can prime plant defense mechanisms and greatly decrease the occurrence and severity of plant diseases. Reducing the use of agrochemicals is an effective way to minimize environmental pollution and promote agricultural safety. Aim of review: The purpose of this work is to offer valuable insights into the current understanding and future research perspectives of plant immunity inducers and their uses in plant disease control, ecological and environmental protection, and sustainable development of agriculture. Key scientific concepts of review: In this work, we have introduced the concepts of sustainable and environment-friendly concepts of green disease prevention and control technologies based on plant immunity inducers. This article comprehensively summarizes these recent advances, emphasizes the importance of sustainable disease prevention and control technologies for food security, and highlights the diverse functions of plant immunity inducers-mediated disease resistance. The challenges encountered in the potential applications of plant immunity inducers and future research orientation are also discussed.

Background Relapsed/refractory acute lymphoblastic leukemia (R/R ALL) continues to be a major cause of mortality in children worldwide, with around 15% of ALL patients experiencing relapse and approximately 10% eventually dying from the disease. Early identification of R/R ALL in children has posed a longstanding clinical challenge.Method Genetic analysis of survival outcomes in pediatric patients with ALL from the TARGET-ALL dataset revealed five risk score factors identified through the intersection of differential genes (relapse/non-relapse) from the GSE17703 and GSE6092 databases. A risk score equation was formulated using these factors and validated against prognostic data from 46 ALL cases at our institution. Patients from multiple datasets were stratified into high and low-score groups based on this equation. Protein–protein interaction networks (PPI) were then constructed using the intersecting differential genes from all three datasets to identify hub nodes and predict interacting transcription factors. Additionally, genes related to cell pyroptosis with varying expression across these datasets were screened, and a multifactorial ROC curve (incorporating risk score and differential expression of pyroptosis-related genes) was generated. Furthermore, relationships among variables in the predictive model were depicted using a nomogram, and model efficacy was assessed through decision curve analysis (DCA).Results By analyzing the TARGET-ALL, GSE17703, and GSE6092 databases, we developed a prognostic risk assessment model for pediatric ALL incorporating BAG2, EPHA4, FBXO9, SNX10, and WNK1. Validation of this model was conducted using data from 46 pediatric ALL cases obtained from our institution. Following the identification of 27 differentially expressed genes, we constructed a PPI and identified the top 10 hub genes (PTPRC, BTK, LCK, PRKCQ, CD3D, CD27, CD3G, BLNK, RASGRP1, VPREB1). Using this network, we predicted the top 5 transcription factors (HOXB4, MYC, SOX2, E2F1, NANOG). ROC and DCA were conducted on pyroptosis-related genes exhibiting differential expression and risk scores. Subsequently, a nomogram was generated, demonstrating the effectiveness of the risk score in predicting prognosis for pediatric ALL patients.Conclusions We have developed a risk prediction model for pediatric R/R ALL utilizing the genes BAG2, EPHA4, FBXO9, SNX10, and WNK1. This model provides a scientific foundation for early identification of R/R ALL in children.

AbstractObjective The aim of this study was to explore the impact of growth hormone (GH) therapy on the onset and progression of puberty in girls with idiopathic short stature.Methods This study included 541 girls aged between 4.5 and 10.6 years who were receiving GH treatment, monitored over a 22-year follow-up period. Of these, 126 girls have been followed up to the onset of menarche. The participants were divided into two groups: a ISS control group (n = 66) and a group receiving daily GH treatment at a dose of 0.15 iu/kg (n = 60). We assessed the pubertal development and GH usage of these girls every three months.Results (1) There was no significant difference in the onset of puberty between the growth hormone (GH) treatment group and the control group; however, the average duration of puberty was longer in the treatment group compared to the control group. (2) During puberty, there were no significant differences in height growth between the treated and untreated groups. (3) The duration of GH treatment showed a significant negative correlation with the age at onset of gonadal development and the age at menarche in females within the treatment group.Conclusion GH treatment does not seem to accelerate the onset of puberty but may extend its duration, without significantly impacting height growth during puberty. Additionally, longer GH treatment duration is linked to earlier gonadal development and menarche in females.

ABSTRACTData on reinfection in large Asian populations are limited. In this study, we aimed to evaluate the reinfection rate, disease severity, and time interval between the infections in the symptomatic and asymptomatic populations which are firstl infected with BA.2 Omicron Variant. We retrospectively included adult patients with COVID-19 discharged from four designated hospitals between 27 April 2021 and 30 November 2022, who were interviewed via telephone from 29 January to 1 March 2023. Univariable and multivariable analyses were used to explore risk factors associated with reinfection. A total of 16,558 patients were followed up, during the telephone survey of an average of 310.0 days, 1610 (9.72%) participants self-reported reinfection. The mean time range of reinfection was 257.9 days. The risks for reinfection were analysed using multivariable logistic regression. Patients with severe first infection were at higher risk for reinfection (aORs, 2.50; P

ABSTRACTBackground: Peripheral T-cell lymphomas (PTCL) are an aggressive group of mature T-cell neoplasms, often associated with poor outcomes, in part, due to frequent relapsed/refractory disease. The objective of this study was to assess the prognostic impact of disease progression within 24 months (POD24) on overall survival (OS) for patients diagnosed with PTCL.Methods: A retrospective analysis was conducted on a cohort of patients with newly diagnosed PTCL who underwent chemotherapy at the Affiliated Hospital of Xuzhou Medical University between January 2010 and September 2021. Prognostic assessment was limited to patients who were evaluable for POD24.Results: Records were reviewed for 106 patients with PTCL, of whom 66 patients experienced POD24 (referred to as the POD24 group) and 40 patients did not experience POD24 (referred to as the no POD24 group). Significant differences were observed between the POD24 group and the no POD24 group in regard to clinical stage, Eastern Cooperative Oncology Group (ECOG) performance status (PS), International Prognostic Index (IPI) score, lactate dehydrogenase (LDH) levels, β2-microglobulin (β2-MG) levels, prealbumin and albumin levels. Patients in the POD24 group had a significant shorter median OS compared to the no POD24 group (11.9 months vs not reached, respectively; P

Branched chain α-keto acid dehydrogenase kinase (BCKDK) is a key enzyme involved in the metabolism of branched-chain amino acids (BCAAs). Its potential as a therapeutic target and prognostic factor for a variety of cancers has been widely reported. In this study, we investigated the expression of BCKDK in clinical glioma samples and found that BCKDK was significantly overexpressed in glioblastoma (GBM) and was associated with its poor prognosis. We further found that BCKDK is phosphorylated by tyrosine protein kinase Fyn at Y151, which increases its catalytic activity and stability, and demonstrate through in vivo and in vitro experiments that BCKDK phosphorylation promotes GBM cell proliferation. In addition, we found that the levels of the metabolite N-acetyl-L-alanine (NAAL) in GBM cells with high BCKDK were higher than those in the silencing group, and silencing or inhibition of BCKDK promotes the expression of ACY1, an enzyme that catalyzes the hydrolysis of NAAL into acetic acid and alanine. Exogenous addition of NAAL can activate the ERK signaling pathway and promote the proliferation of GBM cells. Taken together, we identified a novel mechanism of BCKDK activation and found NAAL is a novel oncogenic metabolite. Our study confirms the importance of the Fyn-BCKDK-ACY1-NAAL signalling axis in the development of GBM and suggests that p-BCKDK (Y151) and NAAL can serve as potential predictors of GBM progression and prognosis.

Summary: Methicillin-resistant Staphylococcus aureus (MRSA) infection, a major cause of hospital- and community-acquired pneumonia, still has a high mortality rate. Extracellular vesicles (EVs), as crucial mediators of intercellular communication, have a significant impact on infectious diseases. However, the role of EVs from alveolar macrophages (AMs) in MRSA pneumonia remains unclear. We report that AMs phagocytose MRSA and release more EVs in mice with MRSA pneumonia. EVs from AMs harboring phagocytosed MRSA exhibit significant proinflammatory effects and induce necroptosis by delivering tumor necrosis factor α (TNF-α) and miR-146a-5p. Mechanically, the upregulated miR-146a-5p in these EVs enhances the phosphorylation of RIPK1, RIPK3, and MLKL by targeting TNF receptor-associated factor 6 (TRAF6), thereby promoting TNF-α-induced necroptosis. The combination of a TNF-α antagonist and an miR-146a-5p antagomir effectively improves the outcomes of mice with MRSA pneumonia. Overall, we reveal the pronecrotic effect of EVs from MRSA-infected AMs and provide a promising target for the prevention and treatment of MRSA pneumonia.

High-order harmonic generation is a nonlinear optical frequency conversion process that occurs during intense ultrafast laser-matter interaction. At the Advanced Laser Light Source laboratory, we use ultrafast laser pulses having diverse wavelengths, spanning visible, near- and mid-infrared ranges, to generate high-order harmonics from laser-ablated plumes in the extreme ultraviolet or soft X-ray region of the electromagnetic spectrum. The Advanced Laser Light Source Laboratory is situated within the Énergie Matériaux Télécommunications Center of the Institut national de la recherche scientifique in Montréal, Quebec, Canada. We focus on generating bright and broadband harmonics by exploiting various types of ultrafast resonances in different species within the laser-ablated plume, and use them for applications in ultrafast spectroscopy, imaging, and AMO science. We are also actively exploring previously unknown physics governing the harmonic generation from different resonances. In this review article, we provide an overview of the recent advancements made in these directions.

Background: The utility of bronchoscopy in the treatment of patients with ventilator-associated pneumonia (VAP) has been proposed, although prior research has yielded inconclusive findings. This systematic review and meta-analysis were conducted to examine the impact of bronchoscopy on mortality rates, duration of mechanical ventilation (MV), and length of stay in the intensive care unit (ICU) among patients with VAP. Methods: Relevant randomized controlled trials (RCTs) and cohort studies were acquired by conducting a comprehensive search in the PubMed, Embase, and Cochrane Library databases. To account for the potential heterogeneity, a random-effects model was utilized to combine the findings and incorporate its potential influence. Results: Eight RCTs and three cohort studies, including 3907 patients with highly suspected or clinically diagnosed VAP, were included. Compared to the controls, bronchoscopy use was not associated with a significant effect on all-cause mortality (relative risk [RR]: 0.81, 95 % confidence interval [CI]: 0.62 to 1.05, p = 0.12; I2 = 57 %). Subgroup analysis showed that bronchoscopy used for the microbiological diagnosis of VAP was not associated with reduced mortality (RR: 0.92, 95 % CI: 0.75 to 1.13), while therapeutic bronchoscopy use was associated with significantly reduced mortality (RR: 0.53, 95 % CI: 0.35 to 0.81). The duration of MV or length of ICU stay was not significantly different between groups. Conclusions: Bronchoscopy use for the purpose of the microbiological diagnosis of VAP did not reduce short-term mortality compared to diagnosis without bronchoscopy use, while therapeutic bronchoscopy use was associated with reduced mortality in these patients.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL), also known as MALT lymphoma, is an extranodal multiorgan-invasive proliferative lymphoma composed of small B cells with variable morphology. It most commonly occurs in the digestive tract, with a high prevalence in the stomach, but EMZL originating in the small intestine is rare and lacks specificity in clinical manifestations, which makes it easy to be misdiagnosed. Herein, we report a rare case of small intestinal EMZL presentation as intussusception in a 32-year-old man. A colonoscopy performed at the local hospital revealed a pedicled polyp about 5 cm × 5 cm in size with a rough surface, and hyperemia was seen in the ileocecal region. He was admitted to our hospital for a polypectomy. A contrast-enhanced computed tomographic (CT) scan suggested ileocolic intussusception, which was subsequently confirmed by a colonoscopy in our hospital. Adult intussusception is relatively rare, with 90% of cases having a known causative mechanism and 40% of cases caused by primary or secondary malignancies. Therefore, we performed a laparoscopic-assisted right hemicolectomy for the patient. The resected specimen showed that the terminal ileum was intussuscepted into the ascending colon, and the intussusception was hyperemia and edema. A 2.5 cm × 2.5 cm × 1.5 cm mass was seen at the end of the intussusception. Postoperative pathology revealed that the mass was EMZL, partially transformed into a large B-cell lymphoma. The patient was transferred to the hematology department and completed a PET-CT showing postoperative manifestations of primary intestinal lymphoma, Lugano staging IE2. Although EMZL was an indolent lymphoma and the patient was in the early stages, the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen was given in view of the histological transformation. The patient is in regular follow-up. This was a rare case of small intestinal mass due to EMZL presented as intussusception in adults, which highlighted laparoscopic-assisted enterectomy as a potential therapeutic approach in the multidisciplinary collaborative therapy of small intestine EMZL.

Reversible protonic ceramic electrochemical cells (R-PCECs) demonstrate great feasibility for efficient energy storage and conversion. One critical challenge for the development of R-PCECs is the design of novel air electrodes with the characteristics of high catalytic activity and acceptable durability. Here, we report a donor doping of Hf into the B-site of a cobalt-based double perovskite with a nominal formula of PrBa0.8Ca0.2Co1.9Hf0.1O5+δ (PBCCHf0.1), which is naturally reconfigured to a double perovskite PrBa0.8-xCa0.2Co1.9Hf0.1-xO5+δ (PBCCHf0.1-x) backbone and nano-sized BaHfO3 (BHO) on the surface of PBCCHf0.1−x. The air electrode demonstrates enhanced catalytic activity and durability (a stable polarization resistance of 0.269 ​Ω ​cm2 for ∼100 ​h at 600 ​°C), due likely to the fast surface exchange process and bulk diffusion process. When employed as an air electrode of R-PCECs, a cell with PBCCHf0.1 air electrode demonstrates encouraging performances in modes of the fuel cell (FC) and electrolysis (EL) at 600 ​°C: a peak power density of 0.998 ​W ​cm−2 and a current density of −1.613 ​A ​cm−2 ​at 1.3 ​V (with acceptable Faradaic efficiencies). More importantly, the single-cell with PBCCHf0.1 air electrode demonstrates good cycling stability, switching back and forth from FC mode to EL mode ±0.5 ​A ​cm−2 for 200 ​h and 50 cycles.

Abstract Resistance training is an exercise against resistance designed to train the endurance and strength of muscle. To observe the effect of intervention of periodic resistance training on obese patients with type 2 diabetic nephropathy. A total of 60 obese patients with type 2 diabetic nephropathy were randomized into resistance training group and aerobic exercise group (30 patients each group) for observing the changes of blood glucose, body weight, blood lipid, insulin resistance, serum creatinine (Scr), urinary microalbumin, urinary albumin excretion rate (UAER) calculated by urinary creatinine, and glomerular filtration rate (GFR) after 12 weeks of intervention, and relevant significance as well. The number of patients with hypoglycemia during the intervention was also recorded. After 12 weeks of intervention, the weight, Body mass index (BMI), Waist, Triglyceride (TG), Cholesterol (TC), Low-density lipoprotein cholesterol (LDL), Fasting glucose (FBG), Fasting insulin (FINS), Glycosylated hemoglobin (HbA1c) and urine Albumin–Creatinine Ratio (uACR) were decreased and GFR was increased in both groups (P 0.05). Periodic resistance training can not only control the weight, blood sugar and blood lipid of obese patients with type 2 diabetic nephropathy, but also improve the urinary albumin excretion rate and glomerular filtration rate of early obese patients with type 2 diabetic nephropathy, and delay the progression of diabetic nephropathy. It is an effective non-drug intervention.

Abstract Endocrine-disrupting chemicals (EDCs) pose a significant threat to human well-being and the ecosystem. However, in managing the many thousands of uncharacterized chemical entities, the high-throughput screening of EDCs using relevant biological endpoints remains challenging. Three-dimensional (3D) culture technology enables the development of more physiologically relevant systems in more realistic biochemical microenvironments. The high-content and quantitative imaging techniques enable quantifying endpoints associated with cell morphology, cell–cell interaction, and microtissue organization. In the present study, 3D microtissues formed by MCF-7 breast cancer cells were exposed to the model EDCs estradiol (E2) and propyl pyrazole triol (PPT). A 3D imaging and image analysis pipeline was established to extract quantitative image features from estrogen-exposed microtissues. Moreover, a machine-learning classification model was built using estrogenic-associated differential imaging features. Based on 140 common differential image features found between the E2 and PPT group, the classification model predicted E2 and PPT exposure with AUC-ROC at 0.9528 and 0.9513, respectively. Deep learning-assisted analysis software was developed to characterize microtissue gland lumen formation. The fully automated tool can accurately characterize the number of identified lumens and the total luminal volume of each microtissue. Overall, the current study established an integrated approach by combining non-supervised image feature profiling and supervised luminal volume characterization, which reflected the complexity of functional ER signaling and highlighted a promising conceptual framework for estrogenic EDC risk assessment.

Abstract Protein function annotation has been one of the longstanding issues in biological sciences, and various computational methods have been developed. However, the existing methods suffer from a serious long-tail problem, with a large number of GO families containing few annotated proteins. Herein, an innovative strategy named AnnoPRO was therefore constructed by enabling sequence-based multi-scale protein representation, dual-path protein encoding using pre-training, and function annotation by long short-term memory-based decoding. A variety of case studies based on different benchmarks were conducted, which confirmed the superior performance of AnnoPRO among available methods. Source code and models have been made freely available at: https://github.com/idrblab/AnnoPRO and https://zenodo.org/records/10012272

Abstract Objective To identify gut microbiome features associated with MRI lesion burden in persons with pediatric‐onset multiple sclerosis (symptom onset 0.08). At the phylum level, high Tenericutes (relative abundance) was associated with higher T1 and T2 volumes (β coefficient = 0.25, 0.37) and high Firmicutes, Patescibacteria or Actinobacteria with lower lesion volumes (β coefficient = −0.30 to −0.07). At the genus level, high Ruminiclostridium, whereas low Coprococcus 3 and low Erysipelatoclostridium were associated with higher lesion volumes. Interpretation Our study characterized the gut microbiota features associated with MRI lesion burden in pediatric‐onset MS, shedding light onto possible pathophysiological mechanisms.

Human monitoring using radar systems operating in the GHz regime has generated significant interest as a result of the increasing availability of commercial radar systems. These sensors offer all weather performance, the ability to measure range and velocity, and the protection of anonymity. However, visually inferring activities present in radar data is often challenging without prior knowledge. Here, we address this by implementing a radar-to-pose system that converts the raw radar data into human poses, such that human forms can be identified and activities monitored. In comparison to prior works, we place our radar in an elevated position, more in line with the placement of existing real world monitoring systems e.g. cameras, or emerging systems, e.g. quadcopters. We present an ensemble predictor network and apply it to a number of human poses of increasing complexity, reporting accuracies in excess of 90%, and verify the generalizable nature of our approach with unseen validation data. We perform an in depth explainability analysis, exploiting the unique mappings created by our radar placement and network structure to confirm that the network is making rational predictions based on the true location of limbs.

The micropulse multibeam photon-counting laser altimeter significantly improves the sampling density along the orbit while introducing abundant noise. Therefore, noise removal is crucial for the subsequent applications of the photon-counting laser altimeter. This study proposes a new multidimensional statistics algorithm based on the Gaussian mixture model for photon noise removal. The method can simultaneously utilize multiple point cloud statistics and avoid manually selecting denoising thresholds, dividing signals and noise adaptively. To evaluate the performance of the algorithm, it is applied to both simulated ICESat-2 data and real ICESat-2 data, and evaluation indicators including recall, precision, and the harmonic means of recall and precision are used for analysis. Experimental results indicate that compared to denoising using a single statistic, denoising with multidimensional statistics (specifically, the sum of the distance of k-nearest neighbors, the photon density, and the standard deviation of the height difference within an elliptic neighborhood of the target photon) generally yields better results. Multidimensional statistics can influence and constrain each other, leading to improved decision-making outcomes. After comparing the algorithm with mainstream DBSCAN and KNN methods, the results indicate that the GMM method achieves the best denoising results, with average F-values 5.22% and 7.26% higher than those of DBSCAN and KNN methods, respectively, across all datasets. In conclusion, this algorithm can comprehensively assess and make decisions based on different statistical measures, demonstrating robustness and adaptability in extracting signal photons, and is worth promoting in the photon denoising applications.

Abstract Infection by Helicobacter pylori, a prevalent global pathogen, currently requires antibiotic-based treatments, which often lead to antimicrobial resistance and gut microbiota dysbiosis. Here, we develop a non-antibiotic approach using sonodynamic therapy mediated by a lecithin bilayer-coated poly(lactic-co-glycolic) nanoparticle preloaded with verteporfin, Ver-PLGA@Lecithin, in conjunction with localized ultrasound exposure of a dosage permissible for ultrasound medical devices. This study reveals dual functionality of Ver-PLGA@Lecithin. It effectively neutralizes vacuolating cytotoxin A, a key virulence factor secreted by H. pylori, even in the absence of ultrasound. When coupled with ultrasound exposure, it inactivates H. pylori by generating reactive oxygen species, offering a potential solution to overcome antimicrobial resistance. In female mouse models bearing H. pylori infection, this sonodynamic therapy performs comparably to the standard triple therapy in reducing gastric infection. Significantly, unlike the antibiotic treatments, the sonodynamic therapy does not negatively disrupt gut microbiota, with the only major impact being upregulation of Lactobacillus, which is a bacterium widely used in yogurt products and probiotics. This study presents a promising alternative to the current antibiotic-based therapies for H. pylori infection, offering a reduced risk of antimicrobial resistance and minimal disturbance to the gut microbiota.

Background Abnormal glucose metabolism is a risk factor for colorectal cancer (CRC). However, association of glycosylated hemoglobin (HbA1c) with CRC risk remains under-reported. We examined the association between glycemic indicators (HbA1c, fasting plasma glucose, fasting insulin, 2-hour glucose, 2-hour insulin, and homeostasis model of risk assessment-insulin resistance index) and CRC risk using prospective analysis and meta-analysis. Methods Participants (n=1,915) from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy were included. CRC events were identified through record linkage. Cox regression was used to assess the associations of glycemic indicators with CRC risk. A meta-analysis was performed to investigate the association between HbA1c and CRC risk. Results During an average of 12.9 years follow-up (standard deviation, 2.8), 42 incident CRC cases occurred. After adjusting for potential confounders, the hazard ratio (95% confidence interval [CI]) of CRC for per % increment in HbA1c was 1.28 (95% CI, 1.01 to 1.63) in overall population, 1.51 (95% CI, 1.13 to 2.02) in women and 1.06 (95% CI, 0.68 to 1.68) in men. No significant association of other measures of glycemic indicators and baseline diabetes with CRC risk was found. Meta-analyses of 523,857 participants including our results showed that per % increment of HbA1c was associated with 13% higher risk of CRC, with the pooled risk ratio being 1.13 (95% CI, 1.01 to 1.27). Subgroupanalyses found stronger associations in women, colon cancer, Asians, and case-control studies. Conclusion Higher HbA1c was a significant predictor of CRC in the general population. Our findings shed light on the pathology of glucose metabolism and CRC, which warrants more in-depth investigation.

Abstract Objective The relationship between multiple sclerosis and the gut microbiome has been supported by animal models in which commensal microbes are required for the development of experimental autoimmune encephalomyelitis. However, observational study findings in humans have only occasionally converged when comparing multiple sclerosis cases and controls which may in part reflect confounding by comorbidities and disease duration. The study of microbiome in pediatric‐onset multiple sclerosis offers unique opportunities as it is closer to biological disease onset and minimizes confounding by comorbidities and environmental exposures. Methods A multicenter case–control study in which 35 pediatric‐onset multiple sclerosis cases were 1:1 matched to healthy controls on age, sex, self‐reported race, ethnicity, and recruiting site. Linear mixed effects models, weighted correlation network analyses, and PICRUSt2 were used to identify microbial co‐occurrence networks and for predicting functional abundances based on marker gene sequences. Results Two microbial co‐occurrence networks (one reaching significance after adjustment for multiple comparisons; q

Abstract Objective To investigate gastrointestinal (GI)‐related physician visits and drug dispensations in the 5 years preceding a first recorded demyelinating event or multiple sclerosis (MS) onset. Methods Using linked administrative and clinical data from British Columbia (1996–2013), Canada, we identified an administrative cohort via a validated algorithm (n = 6863), a clinical cohort diagnosed at a MS clinic (n = 966), and matched controls (administrative cohort: n = 31,865; clinical cohort: n = 4534). In each cohort, the 5 years before a first demyelinating event or MS symptom onset (i.e., index date) were examined. We compared rates of GI‐related physician visits and risk of ≥1 GI‐related dispensation between MS cases and controls using negative binomial and robust Poisson models. Sex differences were tested using interaction terms. Results The administrative cohort MS cases had higher rates of physician visits related to gastritis and duodenitis (adjusted rate/risk ratio (aRR):1.42, 95% CI: 1.10–1.83) and diseases of the esophagus (aRR: 1.46, 95% CI: 1.06–2.02) prior to the index date. MS cases also had greater risk of at least one dispensation for several drug classes, including constipation‐related (aRR: 1.82, 95% CI: 1.50–2.22), antiemetics/antinauseants (aRR: 1.64, 95% CI: 1.43–1.89), and propulsives (promotility drugs; aRR: 1.62, 95% CI: 1.47–1.79). Men had a disproportionally higher relative risk for propulsives than women (aRR: men = 2.32, 95% CI: 1.79–3.00; women = 1.54, 95% CI: 1.36–1.72). Several findings were similar in the smaller clinical cohort though none reached statistical significance. Interpretation GI‐related physician visits and drug dispensations were more common in the 5 years before the first demyelinating event versus matched controls. GI symptoms are a measurable feature of the prodromal or early phase of MS, with a sex difference evident.

Abstract Background Regional anesthesia with ultrasound-guided brachial plexus block is widely used for patients undergoing shoulder and upper limb surgery, but needle misplacement can result in complications. The purpose of this study was to develop and validate a convolutional neural network (CNN) model for segmentation of the brachial plexus at the interscalene level. Methods This prospective study included patients who underwent ultrasound-guided brachial plexus block in the Anesthesiology Department of Beijing Jishuitan Hospital between October 2019 and June 2022. A Unet semantic segmentation model was developed to train the CNN to identify the brachial plexus features in the ultrasound images. The degree of overlap between the predicted segmentation and ground truth segmentation (manually drawn by experienced clinicians) was evaluated by calculation of the Dice index and Jaccard index. Results The final analysis included 502 images from 127 patients aged 41 ± 14 years-old (72 men, 56.7%). The mean Dice index was 0.748 ± 0.190, which was extremely close to the threshold level of 0.75 for good overlap between the predicted and ground truth segregations. The Jaccard index was 0.630 ± 0.213, which exceeded the threshold value of 0.5 for a good overlap. Conclusion The CNN performed well at segregating the brachial plexus at the interscalene level. Further development could allow the CNN to be used to facilitate real-time identification of the brachial plexus during interscalene block administration. Clinical trial registration The trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry (ChiCTR2200055591), the site url is https://www.chictr.org.cn/ . The date of trial registration and patient enrollment is 14/01/2022.

Abstract Little is known about disease-modifying drug (DMD) initiation by immigrants with multiple sclerosis (MS) in countries with universal health coverage. We assessed the association between immigration status and DMD use within 5-years after the first MS-related healthcare encounter. Using health administrative data, we identified MS cases in British Columbia (BC), Canada. The index date was the first MS-related healthcare encounter (MS/demyelinating disease-related diagnosis or DMD prescription filled), and ranged from 01/January/1996 to 31/December/2012. Those included were ≥ 18 years old, BC residents for ≥ 1-year pre- and ≥ 5-years post-index date. Persons becoming permanent residents 1985–2012 were defined as immigrants, all others were long-term residents. The association between immigration status and any DMD prescription filled within 5-years post-index date (with the latest study end date being 31/December/2017) was assessed using logistic regression, reported as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). We identified 8762 MS cases (522 were immigrants). Among immigrants of lower SES, odds of filling any DMD prescription were reduced, whereas they did not differ between immigrants and long-term residents across SES quintiles (aOR 0.96; 95%CI 0.78–1.19). Overall use (odds) of a first DMD within 5 years after the first MS-related encounter was associated with immigration status.

Abstract Background Poor sleep quality has been linked to depression in older adults, but results of the association between daytime napping and depression remains limited and conflicting. Moreover, whether the association of daytime napping with depression varies by nighttime sleep quality is unclear. Hence, we examined the associations of daytime napping and nighttime sleep quality with depressive symptoms in older Chinese. Methods A total of 16,786 participants aged ≥50 from the Guangzhou Biobank Cohort Study second-round examination (2008–2012) were included in this cross-sectional study. Geriatric Depression Scale (GDS-15), Pittsburgh Sleep Quality Index (PSQI), napping and demographic data were collected by face-to-face interview using a computerized questionnaire. Logistic regression was used to calculate odds ratio (OR) of depressive symptoms for napping and sleep quality. Results The prevalence of depressive symptoms (GDS score > 5) and poor global sleep quality (PSQI score ≥ 6) was 5.3 and 31.9%, respectively. Compared to non-nappers, nappers showed significantly higher odds of depressive symptoms, with OR (95% confidence interval (CI)) being 1.28 (1.11–1.49). The odds of depressive symptoms for daytime napping varied by nighttime sleep quality (P for interaction = 0.04). In good-quality sleepers, compared to non-nappers, nappers had significantly higher odds of depressive symptoms, with OR (95% CI) being 1.57 (1.23–2.01), whereas no association was found in poor-quality sleepers (OR = 1.13, 0.94–1.36). Conclusion Napping was associated with higher odds of depressive symptoms in older people, and the association was stronger in good-quality sleepers.