Combination Of Tests Research Articles

Effect of training method and dairy cow personality traits on adaptation to an automated milking system

Training dairy cows on the automated milking system (AMS) can improve their performance, however, the ideal training method and how their individual personality relates to training is unknown. The objectives of this study were to determine: 1) the effect of AMS training method on adaptation of primiparous cows to an AMS, 2) whether the personality of a cow affects their adaptation to the AMS, and 3) whether certain personality types adapt better based on the type of training they receive. Forty-eight primiparous Holstein dairy cows, who had not previously been milked by an AMS, were enrolled in the study at ∼85 DIM and were assessed for personality traits using a combined arena test comprised of 3 parts: a novel arena test, a novel object test, and a novel human test. Cows were allocated into 1 of 4 AMS training treatments (n = 12): control (CON; no training), environment exposure only (ENV), environment and AMS concentrate provision (PEL), and environment and mechanics exposure (MEC). Cows in the ENV, PEL, and MEC treatments were subjected to training 4 × /d for 4 d, and then cows from all 4 treatments were milked on the AMS in the evening of the 4th training d. Milking activity and production were recorded for the first 14 d on the AMS. PEL cows had fewer visits to the AMS, fewer milkings, and fewer voluntary milkings compared with CON cows across the 14 d. Cows on all experimental treatments had more fetching events than CON cows, while MEC and ENV treatment cows had a higher milk yield compared with those on the CON treatment. Principal component analysis of the behaviors recorded during the personality assessment revealed 2 factors interpreted as personality traits, "explore-active" and "bold." Across all cows, more "explore-active" cows had greater milk yield. Only the performance of ENV cows was associated with personality; ENV cows who scored low for "explore-active" differed from CON cows, through increased visits and voluntary milkings. Overall, the results demonstrate that providing concentrate on its own during AMS training may not be motivating enough to improve adaptation and performance. However, exposing cows to the mechanics (e.g., the robotic arm and sounds of the AMS) before first milking may improve milk yield. Finally, cow personality may influence the performance of cows trained using less complicated training methods, such as only exposing them to the environment of the AMS.

Prevalence of Metallo β-Lactamase Genes Among MDR Pseudomonas <i>Aeruginosa</i> Isolated from Different Sources in Baghdad

Background: Pseudomonas aeruginosa is a gram-negative apportunistic pathogen that has ability to couse different type of infections and charecterised by their high resistance to commonly used antibiotics via different stratiges. Objective: The objective of this study is to detect the prevalence rate of MβL gene among MDR Pseudomonas aeruginosa. Methods: Forty clinical isolates of Pseudomonas aeruginosa were obtained from different hospitials in Baghdad/Iraq. Their identification was confirmed by using 16s rDNA as a housekeeping gene (reference gene). Specific primers were used to detect 3 types of Metallo β-lactamase (MβL) genes vim, spm1, and imp1 genes followed by sequencing the amplified fragment which was analyzed by Geneious software. Antibiotic sensitivity test for 15 antimicrobial agents was done using the Kirby-Bauer disc diffusion method. Results: The revealed resistance pattern was as following: 100% for the combination of Trimethoprim/Sulphamethoxazole and Nitrofurantoin, 95% for Tigecycline, 82.5% for Ciprofloxacin, 67.5% for Cefepime, 60% for Levofloxacin, 57.5% for Carbenicillin, 55% for Piperacillin, 50% for Amikacin, 47.5% for Tobramycin, 45% for both Imipenem and Ceftazidime, 27.5% for piperacillin/tazobactam, 22.5% for Aztreonam and 7.5% for Colistin. More than half (55%) of isolates were positive for MβL enzymes production during phenotypically assessed by combined disc test. The MIC of meropenem ranged from 16µg/ml to 32 µg/ml. The percentage of MβL genes among the total isolates during conventional PCR was as follows: 95% for vim, 25% of the isolates harbored both vim and imp1, while spm 1 are negative in all isolates. The result of the study explained that 10 isolates from the antibiotic susceptibility test were resistant to 10-14 antimicrobial agents that harbored both vim and imp1 genes. Conclusions: MβL gene could be used as a genetic marker to determine the degree of resistance in MDR P. aeruginosa which are more resistant than other isolates that have one gene of MβL responsible for break the β-lactam ring then inactivating the β-lactam antibiotic.

MR elastography vs a combination of common non-invasive tests for estimation of severe liver fibrosis in patients with hepatobiliary tumors.

To evaluate the accuracy of combined imaging and blood test indices related to liver fibrosis (LF) compared to magnetic resonance elastography (MRE) for estimating severe LF (F3-4) in preoperative patients. This retrospective study included patients who underwent MRE, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI, and dynamic CT before liver resection. Liver stiffness measurement (LSM) using MRE, liver-to-spleen signal intensity ratio (LSR) using Gd-EOB-DTPA-enhanced MRI, and spleen volume normalized to body surface area (SV/BSA) using CT volumetry were measured. Laboratory parameters, including levels of type IV collagen 7S and hyaluronic acid, were also measured. Logistic regression and receiver operating characteristic analyses were performed to identify parameters that could estimate severe LF more accurately than LSM alone. A total of 81 patients (mean age, 67 years ± 9.9 [SD]; 58 men) were enrolled. Multivariable logistic regression analysis indicated that LSR (odds ratio [OR]: 0.14, 95% confidence interval [CI]: 0.05-0.37, p < 0.001), SV/BSA (OR: 1.25, 95% CI: 1.02-1.52, p = 0.03) and type IV collagen 7S (OR: 1.84, 95% CI: 1.12-3.00, p = 0.02) were associated with severe LF. Receiver operating characteristic analysis showed that for estimating severe LF, the area under the curve was significantly larger for the combination of LSR, SV/BSA, and type IV collagen 7S than for LSM alone (0.95 vs 0.85, p = 0.04). The combined evaluation of LSR, SV/BSA, and type IV collagen 7S obtained by clinically common preoperative examinations was more accurate than MRE alone for estimating severe LF in preoperative patients. Question What indicators among the imaging and blood tests commonly performed preoperatively can provide a more accurate estimate of severe LF compared to MRE? Findings The combination of LSR, SV/BSA, and type IV collagen 7S was more accurate thanan LSM alone for estimating severe LF. Clinical relevance A combination of commonly performed non-invasive preoperative tests provides a more accurate estimation of severe LF than MR elastography, an examination with relatively limited.

Evaluation of the Expression of SIM and NDM Genes in Pseudomonas Aeruginosa Isolated from Clinical Sources

Pseudomonas aeruginosa has recently been labeled a major threat to public health due to its resistance to almost all commonly used antibiotics. Many factors have been suggested for P. aeruginosa's antibiotic resistance. The goal of this study is to find out what role SIM and NDM, which are related to carbapenem resistance, play in P. aeruginosa isolates from local clinical sources. In this study, out of 110 different clinical specimens, 50 were identified as P. aeruginosa from hospitalized patients. All of the isolates were characterized based on the biochemical test and confirmed using the VitekII compact system. P. aeruginosa isolates were tested for antibiotic susceptibility using 8 antibiotics, including: amikacin, tobramycin, ciprofloxacin, levofloxacin, imipenem, meropenem, piperacillin/tazobactam, ticarcillin, and clavulanate. Susceptibility testing results revealed that every isolate was highly resistant to Piperacillin/Tazobactam, with lower resistance to Ticarcillin/clavulanate (TCC). Using the broth dilution method, the minimum inhibitory concentration (MIC) of P. aeruginosa isolates resistant to meropenem ranged from 32µg/100µl to 128 µg/100µl. The EDTA combined disc test was used to detect the ability of P. aeruginosa isolates to produce carbapenemase, and the results showed that all isolates were carbapenemase producers. Additionally, conventional PCR confirmed the identification of P. aeruginosa using 16S. Real-time PCR was adopted to assess the expression of the NDM and SIM genes in 25 of the identified P. aeruginosa isolates. The mean of gene expression results for NDM showed increased expression compared to the control sample of 1.74, while the SIM gene showed expression of 0.95. These genes, SIM and NDM in class B (which are important for resistance in Pseudomonas aeruginosa), result from chromosomal changes that mutate the membrane permeability flow pump, causing excessive expression.

Array Comparative Genomic Hybridization (aCGH) Results among Patients Referred to Invasive Prenatal Testing after First-Trimester Screening: A Comprehensive Cohort Study.

Introduction: Invasive prenatal testing with chromosomal microarray analysis after first-trimester screening is a relevant option but there is still debate regarding the indications. Therefore, we evaluated the prevalence of numerical chromosomal aberrations detected by classic karyotype and clinically relevant copy number variants (CNVs) in prenatal samples using array comparative genomic hybridization (aCGH) stratified to NT thickness: <the 95th percentile, the 95th percentile-2.9 mm, 3.0-3.4 mm, 3.5-3.9 mm, 4.0-4.5 mm, and >4.5 mm, and by the presence/absence of associated structural anomalies detected by ultrasonography. Materials and Methods: Retrospective cohort study carried out at two tertiary Polish centers for prenatal diagnosis (national healthcare system) in central and south regions from January 2018 to December 2021. A total of 1746 prenatal samples were received. Indications for invasive prenatal testing included high risk of Down syndrome in the first-trimester combined test (n = 1484) and advanced maternal age (n = 69), and, in 193 cases, other reasons, such as parental request, family history of congenital defects, and genetic mutation carrier, were given. DNA was extracted directly from amniotic fluid (n = 1582) cells and chorionic villus samples (n = 164), and examined with classic karyotype and aCGH. Results: Of the entire cohort of 1746 fetuses, classical karyotype revealed numerical chromosomal aberrations in 334 fetuses (19.1%), and aCGH detected CNV in 5% (n = 87). The frequency of numerical chromosomal aberrations increased with NT thickness from 5.9% for fetuses with NT < p95th to 43.3% for those with NT > 4.5 mm. The highest rate of numerical aberrations was observed in fetuses with NT > 4.5 mm having at least one structural anomaly (50.2%). CNVs stratified by NT thickness were detected in 2.9%, 2.9%, 3.5%, 4.3%, 12.2%, and 9.0% of fetuses with NT < 95th percentile, 95th percentile-2.9 mm, 3.0-3.4 mm, 3.5-3.9 mm, 4.0-4.5 mm, and >4.5 mm, respectively. After exclusion of fetuses with structural anomalies and numerical aberrations, aCGH revealed CNVs in 2.0% of fetuses with NT < 95th percentile, 1.5% with NTp95-2.9 mm, 1.3% with NT 3.0-3.4 mm, 5.4% with NT 3.5-3.9 mm, 19.0% with NT 4.0-4.5 mm, and 14.8% with NT > 4.5 mm. Conclusions: In conclusion, our study indicates that performing aCGH in samples referred to invasive prenatal testing after first-trimester screening provides additional clinically valuable information over conventional karyotyping, even in cases with normal NT and anatomy.

Predicting malignant potential of solitary pulmonary nodules in patients with COVID-19 infection: a comprehensive analysis of CT imaging and tumor markers

ObjectiveTo analyze the value of combining computed tomography (CT) with serum tumor markers in the differential diagnosis of benign and malignant solitary pulmonary nodules (SPNs).MethodsThe case data of 267 patients diagnosed with SPNs in the First Affiliated Hospital of Zhengzhou University from March 2020 to January 2023 were retrospectively analyzed. All individuals diagnosed with coronavirus disease 2019 (COVID-19) were confirmed via respiratory specimen viral nucleic acid testing. The included cases underwent CT, serum tumor marker testing and pathological examination. The diagnostic efficacy and clinical significance of CT, serum tumor marker testing and a combined test in identifying benign and malignant SPNs were analyzed using pathological histological findings as the gold standard. Finally, a nomogram mathematical model was established to predict the malignant probability of SPNs.ResultsOf the 267 patients with SPNs, 91 patients were not afflicted with COVID-19, 36 exhibited malignant characteristics, whereas 55 demonstrated benign features. Conversely, within the cohort of 176 COVID-19 patients presenting with SPNs, 62 were identified as having malignant SPNs, and the remaining 114 were diagnosed with benign SPNs. CT scans revealed statistically significant differences between the benign and malignant SPNs groups in terms of CT values (P<0.001), maximum nodule diameter (P<0.001), vascular convergence sign (P<0.001), vacuole sign (P = 0.0007), air bronchogram sign (P = 0.0005), and lobulation sign (P = 0.0005). Malignant SPNs were associated with significantly higher levels of carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) compared to benign SPNs (P < 0.05), while no significant difference was found in carbohydrate antigen 125 (CA125) levels (P = 0.054 for non-COVID-19; P = 0.072 for COVID-19). The sensitivity (95.83%), specificity (95.32%), and accuracy (95.51%) of the comprehensive diagnosis combining serum tumor markers and CT were significantly higher than those of CT alone (70.45%, 79.89%, 76.78%) or serum tumor marker testing alone (56.52%, 73.71%, 67.79%) (P < 0.05). A visual nomogram predictive model for malignant pulmonary nodules was constructed.ConclusionCombining CT with testing for CEA, CA125, and NSE levels offers high diagnostic accuracy and sensitivity, enables precise differentiation between benign and malignant nodules, particularly in the context of COVID-19, thereby reducing the risk of unnecessary surgical interventions.

A urine-based liquid biopsy for detection of upper tract urothelial carcinoma: a self-matched study

BackgroundTo establish the pathological diagnosis of UTUC before treatment is profitable. At present, the conventional pathological diagnostic methods have certain problems. Besides, the urine-based DNA methylation test have been already utilized to detect bladder cancer.ObjectiveTo evaluate the sensitivity and specificity of DNA methylation plus 17 genes mutation test and compare the combined test with cytology.Materials and methodsWe included 45 patients from April 2019 to May 2022, all of whom underwent radical nephroureterectomy (RNU), nephrectomy, diagnostic ureteroscopy or tissue biopsy. Before surgery, the urine samples were collected for DNA methylation plus 17 genes mutation test and cytology. The test performance was calculated, and comparative ROC curves were drawn.ResultsThe median age of the patients was 67 years. The Kappa value of the DNA methylation plus 17 genes mutation test and tissue pathology was 0.59 (p<0.001). The sensitivity/specificity/PPV/NPV of DNA methylation plus 17 genes mutation test was 86/80/94/62% compared with 29/100/100/29% for cytology. The AUC of DNA methylation plus 17 genes mutation test was 0.829 (p<0.001).The mutated gene proportion of UTUC patients was 51.43% for TERT and 25.71% for TP53.ConclusionThe test performance of DNA methylation plus 17 genes mutation test was satisfactory, which may replace cytology in the future. Further multicenter studies with larger samples are needed to confirm the clinical value of this promising method.Novelty & impact statementsWe evaluated the diagnostic efficacy of a urine-based liquid biopsy for the detection of UTUC and compared the combined test with cytology. We found satisfactory results and concluded that the test could partly replace cytology. Further studies are needed.

Development and validation of an explainable machine learning model for predicting multidimensional frailty in hospitalized patients with cirrhosis.

We sought to develop and validate a machine learning (ML) model for predicting multidimensional frailty based on clinical and laboratory data. Moreover, an explainable ML model utilizing SHapley Additive exPlanations (SHAP) was constructed. This study enrolled 622 patients hospitalized due to decompensating episodes at a tertiary hospital. The cohort data were randomly divided into training and test sets. External validation was carried out using 131 patients from other tertiary hospitals. The frail phenotype was defined according to a self-reported questionnaire (Frailty Index). The area under the receiver operating characteristics curve was adopted to compare the performance of five ML models. The importance of the features and interpretation of the ML models were determined using the SHAP method. The proportions of cirrhotic patients with nonfrail and frail phenotypes in combined training and test sets were 87.8% and 12.2%, respectively, while they were 88.5% and 11.5% in the external validation dataset. Five ML algorithms were used, and the random forest (RF) model exhibited substantially predictive performance. Regarding the external validation, the RF algorithm outperformed other ML models. Moreover, the SHAP method demonstrated that neutrophil-to-lymphocyte ratio, age, lymphocyte-to-monocyte ratio, ascites, and albumin served as the most important predictors for frailty. At the patient level, the SHAP force plot and decision plot exhibited a clinically meaningful explanation of the RF algorithm. We constructed an ML model (RF) providing accurate prediction of frail phenotype in decompensated cirrhosis. The explainability and generalizability may foster clinicians to understand contributors to this physiologically vulnerable situation and tailor interventions.

Evaluation of a Cytology-Molecular Co-Test in Liquid-Based Cytology-Processed Urine for Defining Indeterminate Categories of the Paris System

Introduction: Urine cytology using the Paris system (TPS) classification is useful for the detection and monitoring of bladder urothelial carcinoma (UC). However, the categories “atypical urothelial cells” (AUCs) and “suspicious for high-grade urothelial carcinoma” (SHGUC) do not establish a clear diagnosis. This pilot study aimed to investigate whether the presence of mutations in fibroblast growth factor receptor 3 (FGFR3) and telomerase reverse transcriptase (TERT) genes, in urine processed with liquid-based cytology (LBC) could enhance the diagnostic performance of cytology, particularly in defining the indeterminate categories of AUC and SHGUC. Methods: Urine samples from 82 UC patients with primary tumors or under surveillance and 10 healthy individuals were examined. The ThinPrep method was used for cytology followed by DNA isolation from urine sediments. Targeted molecular analysis was achieved in 70 cases (63 patients and 7 controls) for exons 7 and 10 of the FGFR3 gene and the TERT gene promoter (pTERT), using PCR and Sanger sequencing. Molecular results were correlated with TPS cytology categories and validated by histopathological findings following cystoscopy. Results: In healthy subjects, cytology was negative for high-grade urothelial carcinoma (NHGUC) and no mutations were found. No mutations were found in patients with NHGUC cytology, except for one case with equivocal cystoscopy that carried a pTERT mutation. In high-grade urothelial carcinoma cytology (HGUC) (15/20, 75%) of the cases with histologically confirmed UC, molecular analysis revealed the presence of pTERT without FGFR3 mutations. In SHGUC and AUC cytology, FGFR3 and/or pTERT mutations were detected in 3/4 (75%) and 4/4 (100%) histologically confirmed UC cases, respectively. Cytology sensitivity was 85.7% increasing to 100% with the combined cytology-molecular test, whereas specificity remained unchanged at 86.3%. Conclusions: This pilot study suggests that the incorporation of FGFR3/pTERT molecular testing in urine LBC could enhance the diagnostic value of cytology by diagnosing bladder urothelial carcinoma in indeterminate cytology categories.

High voltage pulsed electric field: A novel method for killing parasitic eggs on the surface of raisins

Aiming to address the issue of stored grain pests easily breeding during the process of dried fruits in Xinjiang, this study proposes a method and a device for killing raisin parasitic eggs based on a high-voltage pulsed electric field. A one-way test and a Box-Behnken central combination test were conducted to investigate the effects of high-voltage pulsed electric field strength and frequency on the unhatched rate and larval survival rate of Plodia interpunctella eggs on raisin surfaces. The experimental results were qualitatively and quantitatively analyzed using biooptical microscope observation and incubation at constant temperature and humidity post-treatment. The findings revealed that with an output voltage of 22.8 kV, the delivery speed of 0.024 m/s, and the electric field frequency of 3.8 Hz, the unhatched rate of the eggs was 68.14 % while the survival rate of the larvae was 20.36 %. These results can provide new insights for both theoretical development and system implementation regarding the use of high voltage pulsed electric fields for eliminating raisin surface eggs, as well as providing valuable academic references for field crop diseases and pests control strategies.

Serum exosomal miR-200c is a potential diagnostic biomarker for breast cancer

Background Breast cancer (BC) is one of the most common malignancies in women. Exosomes are widely found in body fluids and carry microRNAs (miRNAs) that reflect the biological properties of the parental cells. Our study aimed to investigate the differential expression of miR-200c in BC serum exosomes and its diagnostic value. Methodology miRNA profiles in culture supernatant exosomes of normal mammary epithelial cells MCF-10A and BC cells (MCF-7, MDA-MB-231, MCF-7 Taxol) were examined by miRNA deep sequencing to screen for significantly differentially expressed miRNAs; Transmission electron microscopy (TEM), Nanoparticle tracking analysis (NTA), and Western blot were used to identify exosomes; qPCR was used to detect the expression level of miR-200c in cellular exosomes and serum exosomes; The efficacy of individual and combined tests of each indicator to diagnose BC was evaluated using receiver operating characteristic (ROC) curves. Results We identified typical exosome features by TEM, NTA and Western blot, indicating successful exosome extraction. Then our miRNA sequencing results and qRT-PCR experiments showed that miR-200c was significantly down-regulated in BC cell exosomes. In addition, we divided the clinical serum samples into two cohorts according to region, and in independent cohort I, the serum exosomal miR-200c levels of BC patients were significantly lower than those of healthy controls. In cohort II, serum exosomal miR-200c expression was significantly lower in the BC group than in the control and benign breast disease (BBD) groups, whereas miR-200c expression in the BBD group was not statistically different from that in the control group. ROC analyses in both independent cohorts confirmed that serum exosomal miR-200c could differentiate between patients with and without BC disease and could be used as an early diagnostic marker for BC disease. Conclusion Serum exosome miR-200c can be used as a potential biomarker for the diagnosis of BC, and combined with conventional serum diagnostic markers AFP, CA125 and CA153 can help to improve diagnostic efficiency.

In-plane density gradation of shoe midsoles for optimal energy absorption performance

Midsoles are important components in footwear as they provide shock absorption and stability, thereby improving comfort and effectively preventing certain foot injuries. A strategically engineered midsole designed to mitigate plantar pressure can enhance athletic performance and comfort levels. Despite the importance of midsole design, the potential of using in-plane density gradation (deliberate variation of material density across the horizontal plane) in midsoles has been rarely explored. The present work investigated the effectiveness of in-plane density gradation in shoe midsoles using novel polyurea foams as the material candidate. Different polyurea foam densities, ranging from 95 to 350 kg/m2 were examined and tested to construct density-dependent correlative mathematical relations required for optimizing the midsole design for enhanced cushioning and reduced weight. This study combined mechanical testing and plantar pressure measurements to validate the efficacy of density-graded midsoles. The methodology introduced here is relevant to realistic walking conditions, ensured by biomechanical tests supplemented by digital image correlation analyses. An optimization framework was then created to allocate foam densities at certain plantar zones based on the required cushioning performance constrained by the local pressure. The optimization algorithm was specifically tailored to accommodate varying local pressures experienced by different areas of the foot. The optimization strategy in this study aimed at reducing the overall weight of the midsole while ensuring there were no compromises in cushioning efficacy or distribution of plantar pressure. The approach presented herein has the potential to be applied to a wide range of gait speeds and user-specific plantar pressure patterns.

Characterizing carbapenemase production in Enterobacterales through combined disk test and genetic profiling

Objectives: Carbapenem-resistant Enterobacterales (CRE) are a major organism among the critical group of drug-resistant bacteria and are associated with high morbidity and mortality. With limited treatment options, the detection and characterization of carbapenemase are important for appropriate management. This study aims to characterize carbapenemase produced by Enterobacterales using a combined disk test and molecular profiling. Materials and Methods: All CRE isolated from various clinical samples were included in the study. Carbapenemase production was characterized by observing synergy on combining meropenem disk with beta-lactamase inhibitors such as phenylboronic acid, ethylenediaminetetraacetic acid, and cloxacillin, following which genetic profiling was done using multiplex polymerase chain reaction. Statistical analysis: Statistical analyses were done using the Statistical Package for the Social Sciences Statistics and Microsoft Excel. The data were presented in tables, charts, and graphs to elucidate the findings comprehensively. Results: Out of 445 Enterobacterales isolated, 104 (23.4%) were carbapenem-resistant. The most common CRE isolated was Klebsiella pneumoniae (62 out of 104), followed by Escherichia coli (40 out of 104), and two out of 104 CRE isolates were Enterobacter species. Coproduction of NDM and OXA-48-like enzymes (39.4%) was the most common mechanism, followed by NDM alone (19.2%) and OXA-48 alone (16.3%). NDM was the most common gene detected overall, with 72 out of 104 CRE (69.2%) isolates showing its presence, followed by OXA-48 present in 63 of 104 (60.6%) isolates. Conclusions: Metallo-beta-lactamases (NDM) were the predominant type of carbapenemase gene detected among the Enterobacterales isolates, with the coproduction of NDM and OXA-48 enzymes being the most common mechanism of resistance.

Modelling the joint accuracy of two diagnostic tests using evidence synthesis methods incorporating linked electronic health records

Background and ObjectivesTo compare the accuracy of different diagnostic pathways comprising of multiple diagnostic tests, statistical methods that evaluate combined or sequential test accuracy are required. This can only be achieved through joint synthesis of diagnostic accuracy data on all tests of interest, using models that account for dependencies between multiple tests. The aim of this research is to develop joint models to assess the diagnostic accuracy of two tests, using real-world evidence to inform within-study dependencies between tests. ApproachUsing a case study in Alzheimer’s disease dementia (ADD), we will develop Bayesian meta-analysis models to evaluate the combined diagnostic accuracy of two tests. A novel application of trivariate copulas will be used to capture within-study dependencies between two tests assessed in the same patients. Individual participant data from Dementias Platform UK (DPUK) Data Portal – a repository of linked electronic health record data optimised for dementia research – will be used to estimate dependencies between diagnostic tests for ADD. ResultsThe DPUK Data Portal includes records of over 3 million people from 51 long-term cohort studies, including individual-level test results for ADD verified against confirmed diagnoses. Analysis will focus on modelling the diagnostic accuracy of different testing strategies for ADD, combining cognitive function, imaging, and biomarker tests. Conclusions and ImplicationsResults of this study have the potential to inform healthcare decision-making regarding optimal diagnostic pathways by enabling the comparison of different testing strategies. The incorporation of real-world data from the DPUK Data Portal makes better use of the available evidence.

Exploring Bio-Based Polyurethane Adhesives for Eco-Friendly Structural Applications: An Experimental and Numerical Study.

In response to heightened environmental awareness, various industries, including the civil and automotive sector, are contemplating a shift towards the utilization of more sustainable materials. For adhesive bonding, this necessitates the exploration of materials derived from renewable sources, commonly denoted as bio-adhesives. This study focuses on a bio-adhesive L-joint, which is a commonly employed configuration in the automotive sector for creating bonded structural components with significant bending stiffness. In this investigation, the behavior of joints composed of pine wood and bio-based adhesives was studied. Two distinct configurations were studied, differing solely in the fiber orientation of the wood. The research combined experimental testing and finite element modeling to analyze the strength of the joints and determine their failure mode when subjected to tensile loading conditions. The findings indicate that the configuration of the joint plays a crucial role in its overall performance, with one of the solutions demonstrating higher strength. Additionally, a good degree of agreement was observed between the experimental and numerical analyses for one of the configurations, while the consideration of the maximum principal stress failure predictor (MPSFP) proved to accurately predict the location for crack propagation in both configurations.

High-throughput screening identification of apigenin that reverses the colistin resistance of mcr-1-positive pathogens.

The plasmid-mediated gene mcr-1 that makes bacteria resistant to the antibiotic colistin is spreading quickly, which means that colistin is no longer working well to treat Gram-negative bacterial infections. Herein, we utilized a computer-aided high-throughput screening drugs method to identify the natural product apigenin, a potential mcr-protein inhibitor, which effectively enhanced the antimicrobial activity of colistin. Several assays, including a checkerboard minimum inhibitory concentration assay, a time-kill assay, the combined disk test, molecular simulation dynamics, and animal infection models assay, were conducted to verify whether apigenin enhanced the ability of colistin to fight Gram-negative bacterial infections. The results showed that apigenin improved the antimicrobial activity of colistin against multidrug-resistant Enterobacteriaceae infection. Moreover, apigenin not only did not increase the toxic effect of colistin but also had the ability to effectively inhibit the frequency of bacterial resistance mutations to colistin. Studies clearly elucidated that apigenin could interfere with the thermal stability of the protein by binding to the mcr-1 protein. Additionally, the combination of apigenin and colistin could exert multiple effects, including disrupting bacterial membranes, the generation of bacterial nitric oxide and reactive oxygen species, as well as inhibiting bacterial adenosine triphosphate production. Furthermore, the addition of apigenin was able to significantly inhibit colistin-stimulated high expression levels of the bacterial mcr-1 gene. Finally, apigenin exhibited a characteristic anti-inflammatory effect while enhancing the antimicrobial activity of colistin against mcr-1-positive Escherichia coli (E. coli) infected animals. In conclusion, as a potential lead compound, apigenin is promising in combination with colistin in the future treatment of mcr-1-positive E. coli infections.IMPORTANCEThis study found that apigenin was able to inhibit the activity of the mcr-1 protein using a high-throughput virtual screening method. Apigenin effectively enhanced the antimicrobial activity of colistin against multidrug-resistant Enterobacteriaceae, including mcr-1-positive strains, in vitro and in vivo. This study will provide new options and strategies for the future treatment of multidrug-resistant pathogen infections.

花生清选筛台架的设计与试验

In order to address the high impurity and loss rates in the cleaning process of existing peanut combine harvesters, the design basis of the cleaning sieve was explored. Tests were conducted to determine the composition of the peanut picking fruit and the characteristics of the material suspension mixture. Additionally, the mechanical relationship between the fruit and miscellaneous mixtures and the cleaning sieve was investigated. The wind speed ranged from 8 m/s to 10 m/s, the vibration frequency ranged from 6 Hz to 8 Hz, and the inclination angle of the sieve ranged from 5° to 9°. The scavenger sieve platform was constructed and tested using Box-Behnken’s central combination test method. The optimal combination of fan wind speed (9 m/s), sieve surface inclination angle (8°), and sieve vibration frequency (7 Hz) resulted in a pod impurity rate of 1.16% and a loss rate of 1.4%. The device significantly reduces impurity content and loss rate during peanut harvesting. The study's results can serve as a reference for improving the design of the peanut combine harvester cleaning mechanism and optimizing operating parameters.

A general consonance principle for closure tests based on -values.

The closure principle is a powerful approach to constructing efficient testing procedures controlling the familywise error rate in the strong sense. For small numbers of hypotheses and the setting of independent elementary -values we consider closed tests where each intersection hypothesis is tested with a -value combination test. Examples of such combination tests are the Fisher combination test, the Stouffer test, the Omnibus test, the truncated test, or the Wilson test. Some of these tests, such as the Fisher combination, the Stouffer, or the Omnibus test, are not consonant and rejection of the global null hypothesis does not always lead to rejection of at least one elementary null hypothesis. We develop a general principle to uniformly improve closed tests based on -value combination tests by modifying the rejection regions such that the new procedure becomes consonant. For the Fisher combination test and the Stouffer test, we show by simulations that this improvement can lead to a substantial increase in power.

Evaluation of the mechanical properties of stiffened composite panels under consideration of water load

Abstract To meet the strength evaluation requirements of a typical stiffened composite panel of the lower fuselage of a new generation amphibious aircraft underwater load, the experimental testing technique and finite element analysis method were investigated. Firstly, according to the loading and support requirements of the typical stiffened composite lower fuselage panel, a testing device for combined axial and pneumatic loading was designed and developed. Then, a finite element model of the stiffened composite plate and the combined load testing device were created. Based on the experiments and finite element analysis, the static strength of the stiffened composite plate was verified to meet the load-bearing capacity requirements, and the strain behavior during loading was determined. Compared with the experimental results, the maximum strain error at the skin is 6.16%, and the maximum strain error at the stiffener is -11.6%. This confirms the effectiveness of the finite element model and also confirms that the test technique and equipment can accurately simulate in-plane axial loading and out-of-plane water loading. Finally, based on the validated finite element model, the load-bearing capacity of the stiffened composite panel under combined loads was predicted.

Targeting RAC1 reactivates pyroptosis to reverse paclitaxel resistance in ovarian cancer by suppressing P21-activated kinase 4.

Pyroptosis may play an important role in the resistance of ovarian cancer (OC) to chemotherapy. However, the mechanism by which pyroptosis modulation can attenuate chemotherapy resistance has not been comprehensively studied in OC. Here, we demonstrated that RAS-associated C3 botulinum toxin substrate 1 (RAC1) is highly expressed in OC and is negatively correlated with patient outcomes. Through cell function tests and in vivo tumor formation tests, we found that RAC1 can promote tumor growth by mediating paclitaxel (PTX) resistance. RAC1 can mediate OC progression by inhibiting pyroptosis, as evidenced by high-throughput automated confocal imaging, the release of lactate dehydrogenase (LDH), the expression of the inflammatory cytokines IL-1β/IL-18 and the nucleotide oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Mechanically, RNA-seq, gene set enrichment analysis (GSEA), coimmunoprecipitation (Co-IP), mass spectrometry (MS), and ubiquitination tests further confirmed that RAC1 inhibits caspase-1/gasdermin D (GSDMD)-mediated canonical pyroptosis through the P21-activated kinase 4 (PAK4)/mitogen-activated protein kinase (MAPK) pathway, thereby promoting PTX resistance in OC cells. Finally, the whole molecular pathway was verified by the results of in vivo drug combination tests, clinical specimen detection and the prognosis. In summary, our results suggest that the combination of RAC1 inhibitors with PTX can reverse PTX resistance by inducing pyroptosis through the PAK4/MAPK pathway.