The effects of probiotics supplementation on Helicobacter pylori standard treatment: an umbrella review of systematic reviews with meta-analyses.

Helicobacter pylori infection, a worldwide health issue, is typically treated with standard antibiotic therapies. However, these treatments often face resistance and non-compliance due to side effects. In this umbrella review, we aimed to comprehensively assess the impact of probiotics supplementation in different preparations on Helicobacter pylori standard treatment. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials in the Cochrane Library from inception to June 1, 2023, to identify systematic reviews with meta-analyses that focused on eradication rates, total side effects and other outcomes of interest. The most comprehensive meta-analysis was selected for data extraction. AMSTAR 2 was used to assess quality of meta-analyses. Overall, 28 unique meta-analyses based on 534 RCTs were included. The results suggests that probiotics supplementation with pooled probiotic strains was significantly associated with improved eradication rates (RR 1.10, 95% CI 1.06-1.14) and reduced risk of total side effects (RR 0.54, 95% CI 0.42-0.70) compared with standard therapy alone. Single-strained or multi-strained preparation of probiotics supplementation showed similar results. Despite Bifidobacterium spp. showing the highest potential for eradication, the study quality was critically low for most meta-analyses, necessitating further high-quality research to explore the optimal probiotic strains or their combinations for Helicobacter pylori treatment.aq_start?>Kindly check and confirm the edit made in article title.

Dual sensitivity-enhanced microring resonance-based integrated microfluidic biosensor for Aß42 detection.

Sensitive, accurate, and straightforward biosensors are pivotal in the battle against Alzheimer's disease, particularly in light of the escalating patient population. These biosensors enable early adjunctive diagnosis, thereby facilitating prompt intervention, alleviating socioeconomic burdens, and preserving individual well-being. In this study, we introduce the development of a highly sensitive add-drop dual-microring resonant microfluidic sensing chip boasting a sensitivity of 188.11 nm/RIU, marking a significant 20.7% enhancement over single microring systems. Leveraging ultra-thin Parylene C for streamlined antibody immobilization and non-destructive removal, this platform facilitates the precise quantification of the Alzheimer's disease biomarker Aß42. Employing an immune sensing strategy that amplifies and captures antigen signals using Au-labeled antibodies, we achieve an exceptional limit of detection of 9.02 pg/mL. The designed microring-based microfluidic biosensor chip exhibits outstanding specificity and sensitivity for Aß42 in serum samples, offering a promising avenue for the early adjunctive diagnosis of Alzheimer's disease.

[Genetic analysis of a fetus with cryptophthalmos due to variants of FREM2 gene].

OBJECTIVE: To explore the genetic etiology of a fetus with cryptophthalmos detected by prenatal ultrasonography. METHODS: A fetus undergoing induced labor at 32nd gestational week due to absence of bilateral eye fissures detected by prenatal ultrasonography in January 2017 was selected as the study subject. Umbilical cord blood sample from the fetus and peripheral blood samples from its parents were collected for the extraction of genomic DNA. Pathogenic variants were screened through whole exome sequencing (WES) and verified by Sanger sequencing. Pathogenicity of candidate variants was verified by bioinformatic analysis and protein structure simulation. Based on the results of genetic testing, prenatal diagnosis was provided to the couple upon their subsequent pregnancy. RESULTS: The couple had four adverse pregnancies previously. The aborted fetus was the fifth, with fused bilateral upper and lower eyelids, poorly developed eyeballs, adhesion of the cornea with the upper eyelid, low-set ears, and abnormal plantar creases, and was diagnosed with cryptophthalmos. WES and Sanger sequencing revealed that the fetus has harbored compound heterozygous variants of the FREM2 gene, namely c.4537G>A (p.D1513N) and c.7292C>T (p.T2431M). Both variants were unreported associated with cryptophthalmos previously. Protein structure simulation showed that they may lead to loss of hydrogen bonds in the protein product. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PM1_Supporting+PM2_Supporting+PM5+PP3+PP4; PM2_Supporting+PM3+PP3+PP4). The mother was performed prenatal diagnosis in her sixth pregnancy based on the variants detected in this family, and delivered a daughter with normal phenotype. CONCLUSION: The FREM2: c.4537G>A and c.7292C>T compound heterozygous variants probably underlay the pathogenesis of cryptophthalmos in this fetus. Above finding has enriched the mutational spectrum of the FREM2 gene.

Network pharmacology analysis and experimental validation of Xiao-Qing-Long-Tang's therapeutic effects against neutrophilic asthma.

BACKGROUND: Xiao-Qing-Long-Tang (XQLT), a classical Chinese herbal medicine formula, has been extensively used for allergic asthma treatment. However, there is limited research on its anti-inflammatory effects and mechanisms specifically in neutrophilic asthma (NA). PURPOSE: This study aims to investigate the potential therapeutic effects of XQLT against NA using a combination of network pharmacology and experimental validation. STUDY DESIGN: By utilizing traditional Chinese medicine and disease databases, we constructed an XQLT-asthma network to identify potential targets of XQLT for NA. In the experimental phase, we utilized an ovalbumin (OVA)/lipopolysaccharide (LPS)-induced model for neutrophilic asthma and examined the therapeutic effects of XQLT. RESULTS: Our research identified 174 bioactive components within XQLT and obtained 140 target genes of XQLT against asthma. Functional enrichment analysis revealed that these target genes were primarily associated with inflammation and cytokines. In the experimental validation, mice induced with OVA-LPS showcased eosinophilic and neutrophilic cell infiltration in peri-bronchial areas, elevated levels of IL-4 and IL-17 in both serum and lung, increased percentages of Th2 and Th17 cells in the spleen, as well as elevated levels of CD11b+ and CD103+ dendritic cells (DCs) within the lung. Treatment with XQLT effectively reduced IL-4 and IL-17 levels, decreased the percentages of Th2, Th17, CD11b+, and CD103+ DCs, and improved inflammatory cell infiltrations in lung tissues. These findings serve as a foundation for the potential clinical application of XQLT in neutrophilic asthma.

Divergent Geminal Alkynylation-Allylation and Acylation-Allylation of Carbenes: Evolution and Roles of Two Transition-Metal Catalysts.

Cooperative bimetallic catalysis to access novel reactivities is a powerful strategy for reaction development in transition-metal-catalyzed chemistry. Particularly, elucidation of the evolution of two transition-metal catalysts and understanding their roles in dual catalysis are among the most fundamental goals for bimetallic catalysis. Herein, a novel three-component reaction of a terminal alkyne, a diazo ester, and an allylic carbonate was successfully developed via cooperative Cu/Rh catalysis with Xantphos as the ligand, providing a highly efficient strategy to access 1,5-enynes with an all-carbon quaternary center that can be used as immediate synthetic precursors for complex cyclic molecules. Notably, a Meyer-Schuster rearrangement was involved in the reactions using propargylic alcohols, resulting in an unprecedented acylation-allylation of carbenes. Mechanistic studies suggested that in the course of the reaction Cu(I) species might aggregate to some types of Cu clusters and nanoparticles (NPs), while the Rh(II)2 precursor can dissociate to mono-Rh species, wherein Cu NPs are proposed to be responsible for the alkynylation of carbenes and work in cooperation with Xantphos-coordinated dirhodium(II) or Rh(I)-catalyzed allylic alkylation.

Global and regional trends in the incidence and prevalence of uterine fibroids and attributable risk factors at the national level from 2010 to 2019: A worldwide database study.

BACKGROUND: Uterine fibroids (UFs), the most common tumors in women worldwide, may reduce quality of life and daily activities and even lead to adverse fertility and general health events in patients, causing significant societal health and financial burdens. The objective was to evaluate the global burden through epidemiological trends and examine the potential risk factors for UFs at the national level. METHODS: Data on the incidence, prevalence, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized prevalence rates (ASPRs), and age-standardized DALY rates for UFs were collected, and the associations with the Human Development Index (HDI) and fertility were evaluated. The age trends in the average annual percent change (AAPC) of the incidence and prevalence rates of UFs were evaluated by joinpoint regression analysis. The associations between lifestyle, metabolic, and socioeconomic factors and the ASIRs of UFs were examined using multivariable linear regression analysis. RESULTS: The worldwide incidence and prevalence of UFs have been increasing in the past decade, with AAPCs of 0.27% in the incidence rate and 0.078% in the prevalence rate. During 2010-2019, significant increasing trends in UF ASIR were observed in 52 of 88 countries. The age-specific incidence and prevalence of UFs in most age groups showed increasing trends except for 45-54-year-old women which showed no significant trend. Ecological analysis demonstrated no relationship between the incidence of UFs and the HDI but an inverse association with fertility. The incidence of UFs was positively correlated with alcohol intake, hypertension, overweight, and obesity and negatively correlated with smoking. CONCLUSION: With the increasing incidence and prevalence worldwide, effective targeted prevention and control of relevant risk factors at the national level should be encouraged to reduce the disease burden of UFs.

Analysis of hospital and payer costs of care: aggressive warming versus routine warming in abdominal major surgery.

Background: Hypothermia is common and active warming is recommended in major surgery. The potential effect on hospitals and payer costs of aggressive warming to a core temperature target of 37°C is poorly understood. Methods: In this sub-analysis of the PROTECT trial (clinicaltrials.gov, NCT03111875), we included patients who underwent radical procedures of colorectal cancer and were randomly assigned to aggressive warming or routine warming. Perioperative outcomes, operation room (OR) scheduling process, internal cost accounting data from the China Statistical yearbook (2022), and price lists of medical and health institutions in Beijing were examined. A discrete event simulation (DES) model was established to compare OR efficiency using aggressive warming or routine warming in 3 months. We report base-case net costs and sensitivity analyses of intraoperative aggressive warming compared with routine warming. Costs were calculated in 2022 using US dollars (USD). Results: Data from 309 patients were analyzed. The aggressive warming group comprised 161 patients and the routine warming group comprised 148 patients. Compared to routine warming, there were no differences in the incidence of postoperative complications and total hospitalization costs of patients with aggressive warming. The potential benefit of aggressive warming was in the reduced extubation time (7.96 ± 4.33 min vs. 10.33 ± 5.87 min, p < 0.001), lower incidence of prolonged extubation (5.6% vs. 13.9%, p = 0.017), and decreased staff costs. In the DES model, there is no add-on or cancelation of operations performed within 3 months. The net hospital costs related to aggressive warming were higher than those related to routine warming in one operation (138.11 USD vs. 72.34 USD). Aggressive warming will have an economic benefit when the OR staff cost is higher than 2.37 USD/min/person, or the cost of disposable forced-air warming (FAW) is less than 12.88 USD/piece. Conclusion: Despite improving OR efficiency, the economic benefits of aggressive warming are influenced by staff costs and the cost of FAW, which vary from different regions and countries. Clinical trial registration: clinicaltrials.gov, identifier (NCT03111875).

Correction to " Application of Terahertz Nondestructive Testing Technology in the Detection of Polyethylene Pipe Defects".

[This corrects the article DOI: 10.1021/acsomega.3c02701.].

Identification of 13 Novel Loci in a Genome-Wide Association Study on Taiwanese with Hepatocellular Carcinoma.

Liver cancer is caused by complex interactions among genetic factors, viral infection, alcohol abuse, and metabolic diseases. We conducted a genome-wide association study and polygenic risk score (PRS) model in Taiwan, employing a nonspecific etiology approach, to identify genetic risk factors for hepatocellular carcinoma (HCC). Our analysis of 2836 HCC cases and 134,549 controls revealed 13 novel associated loci such as the FAM66C gene, noncoding genes, liver-fibrosis-related genes, metabolism-related genes, and HCC-related pathway genes. We incorporated the results from the UK Biobank and Japanese database into our study for meta-analysis to validate our findings. We also identified specific subtypes of the major histocompatibility complex that influence both viral infection and HCC progression. Using this data, we developed a PRS to predict HCC risk in the general population, patients with HCC, and HCC-affected families. The PRS demonstrated higher risk scores in families with multiple HCCs and other cancer cases. This study presents a novel approach to HCC risk analysis, identifies seven new genes associated with HCC development, and introduces a reproducible PRS model for risk assessment.

Application of Terahertz Nondestructive Testing Technology in the Detection of Polyethylene Pipe Defects.

At present, polyethylene pipeline is widely used in urban gas projects, but a relatively mature and reliable nondestructive testing technology has not been formed. Therefore, it is urgent to develop a new nondestructive testing technology to meet the increasing demand for inspection of non-metallic pipes. The terahertz testing technology and related equipment have played an increasingly important role in the nondestructive testing of many nonmetallic structures, but they have not been applied to polyethylene (PE) pipes. In this work, terahertz time-domain spectroscopy was used to detect prefabricated defects inside the PE pipe specimens. The results show that the terahertz nondestructive testing technology can be used to detect common defects in nonblack PE pipes with a detection error of less than 10%. Higher-power terahertz devices can detect defects in black PE pipe, while lower-power terahertz devices cannot. Because the black PE pipe contains carbon and has a strong absorption of terahertz waves. The penetration of lower-power terahertz devices to the black PE pipe is not enough, resulting in a low resolution of the imaging. The results of this work may promote the progress of the nondestructive testing technology of nonmetallic pipelines.

Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas.

BACKGROUND: Comprehensive and integrative analysis of hepatocellular carcinoma (HCC) is important. In this study, we explored Taiwanese HCCs using multi-omics analyses. METHODS: We analyzed 254 HCCs by whole genome sequencing and total RNA sequencing, and then used bioinformatic tools to analyze genomic and transcriptomic alterations in coding and non-coding sequences to explore the clinical importance of each sequence. RESULTS: The frequencies of the five most commonly mutated cancer-related genes were TERT, TP53, CTNNB1, RB1, and ARID1A. Genetic alteration frequencies influenced the etiology of HCC; some alterations were also correlated with clinicopathological conditions. Many cancer-related genes had copy number alterations (CNAs) and structure variants (SVs) that changed according to etiology and exhibited potential associations with survival. We also identified several alterations in histone-related genes, HCC-related long non-coding RNAs, and non-coding driver genes that may contribute to the onset and progression of HCC. Transcriptomic analysis revealed that 229 differentially expressed and 148 novel alternative splicing (AS) genes, as well as the presence of fusion genes, were associated with patient survival. Moreover, somatic mutations, CNAs, and SVs were associated with immune checkpoint gene expression and tumor microenvironment. Finally, we identified relationships among AS, immune checkpoint gene expression and tumor microenvironment. CONCLUSIONS: This study shows that genomic alterations are associated with survival, including DNA-based and RNA-based data. Moreover, genomic alterations and their associations with immune checkpoint genes and the tumor microenvironment may provide novel insights for the diagnosis and treatment of HCC.

Comprehensive Analysis and Drug Modulation of Human Endogenous Retrovirus in Hepatocellular Carcinomas.

BACKGROUND: Human endogenous retroviruses (HERVs) play an important role in the development of cancer and many diseases. Here, we comprehensively explored the impact of HERVs on hepatocellular carcinomas (HCCs). METHODS: We employed Telescope to identify HERVs and quantify their expression in the total RNA sequencing data obtained from 254 HCC samples, comprising 254 tumor tissues and 34 matched normal tissues. RESULTS: In total, 3357 locus-specific activations of HERVs were differentially expressed, and 180 were correlated with patient survival. Using these 180 HERVs for classification, we found four subgroups with survival correlation. Higher expression levels of the 180 HERVs were correlated with poorer survival, while age, AFP, some mutations, and copy and structural variants differed among subgroups. The differential expression of host genes in high expression of these 180 HERVs primarily involved the activation of pathways related to immunity and infection, lipid and atherosclerosis, MAPK and NF-kB signaling, and cytokine-cytokine receptor interactions. Conversely, there was a suppression of pathways associated with RNA processing, including nucleocytoplasmic transport, surveillance and ribosome biogenesis, and transcriptional misregulation in cancer pathways. Almost all genes involved in HERV activation restriction, KRAB zinc finger proteins, RNA nucleocytoplasmic transport, stemness, HLA and antigen processing and presentation, and immune checkpoints were overexpressed in cancerous tissues, and many over-expressed HERV-related nearby genes were correlated with high HERV activation and poor survival. Twenty-three immune and stromal cells showed higher expression in non-cancerous than cancerous tissues, and seven were correlated with HERV activation. Small-molecule modulation of alternative splicing (AS) altered the expression of survival-related HERVs and their activation-related genes, as well as nearby genes. CONCLUSION: Comprehensive and integrated approaches for evaluating HERV expression and their correlation with specific pathways have the potential to provide new companion diagnostics and therapeutic strategies for HCC.

Disrupted Balance of Gray Matter Volume and Directed Functional Connectivity in Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: Alterations in functional connectivity have been demonstrated in Alzheimer's disease (AD), an age-progressive neurodegenerative disorder that affects cognitive function; however, directional information flow has never been analyzed. OBJECTIVE: This study aimed to determine changes in resting-state directional functional connectivity measured using a novel approach, granger causality density (GCD), in patients with AD, and mild cognitive impairment (MCI) and explore novel neuroimaging biomarkers for cognitive decline detection. METHODS: In this study, structural MRI, resting-state functional magnetic resonance imaging, and neuropsychological data of 48 Alzheimer's Disease Neuroimaging Initiative participants were analyzed, comprising 16 patients with AD, 16 with MCI, and 16 normal controls. Volume-based morphometry (VBM) and GCD were used to calculate the voxel-based gray matter (GM) volumes and directed functional connectivity of the brain. We made full use of voxel-based between-group comparisons of VBM and GCD values to identify specific regions with significant alterations. In addition, Pearson's correlation analysis was conducted between directed functional connectivity and several clinical variables. Furthermore, receiver operating characteristic (ROC) analysis related to classification was performed in combination with VBM and GCD. RESULTS: In patients with cognitive decline, abnormal VBM and GCD (involving inflow and outflow of GCD) were noted in default mode network (DMN)-related areas and the cerebellum. GCD in the DMN midline core system, hippocampus, and cerebellum was closely correlated with the Mini- Mental State Examination and Functional Activities Questionnaire scores. In the ROC analysis combining VBM with GCD, the neuroimaging biomarker in the cerebellum was optimal for the early detection of MCI, whereas the precuneus was the best in predicting cognitive decline progression and AD diagnosis. CONCLUSION: Changes in GM volume and directed functional connectivity may reflect the mechanism of cognitive decline. This discovery could improve our understanding of the pathology of AD and MCI and provide available neuroimaging markers for the early detection, progression, and diagnosis of AD and MCI.

Efficacy and safety of modified fasting therapy for weight loss in 2054 hospitalized patients.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of modified fasting therapy, and a retrospective study was conducted to analyze changes in clinical indicators of hospitalized fasting patients. METHODS: A total of 2054 hospitalized fasting patients were enrolled in this observational study. All participants underwent 7 days of modified fasting therapy. The clinical efficacy biomarkers, safety indicators, and body composition were measured before and after fasting. RESULTS: The modified fasting therapy reduced body weight, BMI, abdominal circumference, systolic blood pressure, and diastolic blood pressure significantly. Blood glucose and indicators of body composition were improved to various extents (all p < 0.05). There was a small increase in liver function, kidney function, uric acid, electrolytes, blood count, coagulation, and uric biomarkers. Subgroup analysis results showed that cardiovascular diseases benefited from modified fasting therapy. CONCLUSIONS: At present this study is the largest retrospective population-based study about modified fasting therapy. The results from 2054 patients showed that the modified fasting therapy lasting 7 days was efficient and safe. It led to improvements in physical health and body weight-associated indicators, as well as body composition and relevant cardiovascular risk factors.

Investigation on the Influence of Fiber Bundle Undulating Architecture on Tensile Behavior of Filament Wound Composite Laminates.

In filament wound composites, fiber bundles cross each other and form an undulating architecture, which may significantly affect the mechanical behavior of composites. In this study, the tensile mechanical behavior of filament wound laminates was studied experimentally and numerically, and the influences of the bundle thickness and winding angle on the mechanical behavior of the filament wound plates were also explored. In the experiments, tensile tests were carried out on filament wound plates and laminated plates. It was found that, compared to laminated plates, filament wound plates had lower stiffness, greater failure displacement, similar failure loads, and more obvious strain concentration areas. In numerical analysis, mesoscale finite element models, which take into account the fiber bundles' undulating morphology, were created. The numerical predictions correlated well with the experimental ones. Further numerical studies have shown that the stiffness reduction coefficient of filament wound plates with a winding angle of ±55° decreased from 0.78 to 0.74 as the bundle thickness increased from 0.4 mm to 0.8 mm. The stiffness reduction coefficients of filament wound plates with wound angles of ±15°, ±25°, and ±45° were 0.86, 0.83, and 0.8, respectively.

An Improved YOLOv5-Based Underwater Object-Detection Framework.

To date, general-purpose object-detection methods have achieved a great deal. However, challenges such as degraded image quality, complex backgrounds, and the detection of marine organisms at different scales arise when identifying underwater organisms. To solve such problems and further improve the accuracy of relevant models, this study proposes a marine biological object-detection architecture based on an improved YOLOv5 framework. First, the backbone framework of Real-Time Models for object Detection (RTMDet) is introduced. The core module, Cross-Stage Partial Layer (CSPLayer), includes a large convolution kernel, which allows the detection network to precisely capture contextual information more comprehensively. Furthermore, a common convolution layer is added to the stem layer, to extract more valuable information from the images efficiently. Then, the BoT3 module with the multi-head self-attention (MHSA) mechanism is added into the neck module of YOLOv5, such that the detection network has a better effect in scenes with dense targets and the detection accuracy is further improved. The introduction of the BoT3 module represents a key innovation of this paper. Finally, union dataset augmentation (UDA) is performed on the training set using the Minimal Color Loss and Locally Adaptive Contrast Enhancement (MLLE) image augmentation method, and the result is used as the input to the improved YOLOv5 framework. Experiments on the underwater datasets URPC2019 and URPC2020 show that the proposed framework not only alleviates the interference of underwater image degradation, but also makes the mAP@0.5 reach 79.8% and 79.4% and improves the mAP@0.5 by 3.8% and 1.1%, respectively, when compared with the original YOLOv8 on URPC2019 and URPC2020, demonstrating that the proposed framework presents superior performance for the high-precision detection of marine organisms.

A Self-Rectifying Synaptic Memristor Array with Ultrahigh Weight Potentiation Linearity for a Self-Organizing-Map Neural Network.

Two-terminal self-rectifying (SR)-synaptic memristors are preeminent candidates for high-density and efficient neuromorphic computing, especially for future three-dimensional integrated systems, which can self-suppress the sneak path current in crossbar arrays. However, SR-synaptic memristors face the critical challenges of nonlinear weight potentiation and steep depression, hindering their application in conventional artificial neural networks (ANNs). Here, a SR-synaptic memristor (Pt/NiOx/WO3-x:Ti/W) and cross-point array with sneak path current suppression features and ultrahigh-weight potentiation linearity up to 0.9997 are introduced. The image contrast enhancement and background filtering are demonstrated on the basis of the device array. Moreover, an unsupervised self-organizing map (SOM) neural network is first developed for orientation recognition with high recognition accuracy (0.98) and training efficiency and high resilience toward both noises and steep synaptic depression. These results solve the challenges of SR memristors in the conventional ANN, extending the possibilities of large-scale oxide SR-synaptic arrays for high-density, efficient, and accurate neuromorphic computing.

Sensitivity-enhanced nanoplasmonic biosensor using direct immobilization of two engineered nanobodies for SARS-CoV-2 spike receptor-binding domain detection.

Sensitive, rapid, and easy-to-implement biosensors are critical in responding to highly contagious and fast-spreading severe acute respiratory syndrome coronavirus (SARS-CoV-2) mutations, enabling early infection screening for appropriate isolation and treatment measures to prevent the spread of the virus. Based on the sensing principle of localized surface plasmon resonance (LSPR) and nanobody immunological techniques, an enhanced sensitivity nanoplasmonic biosensor was developed to quantify the SARS-CoV-2 spike receptor-binding domain (RBD) in serum within 30 min. The lowest concentration in the linear range can be detected down to 0.01 ng/mL by direct immobilization of two engineered nanobodies. Both the sensor fabrication process and immune strategy are facile and inexpensive, with the potential for large-scale application. The designed nanoplasmonic biosensor achieved excellent specificity and sensitivity for SARS-CoV-2 spike RBD, providing a potential option for accurate early screening of the novel coronavirus disease 2019 (COVID-19).