bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic value of artificial intelligence-assisted endoscopy for chronic atrophic gastritis: a systematic review and meta-analysis
Authors: Shi Yanting , Wei Ning , Wang Kunhong , Tao Tao , Yu Feng , Lv Bing 
Published: May 2023

Background and aimsThe diagnosis of chronic atrophic gastritis (CAG) under normal white-light endoscopy depends on the endoscopist's experience and is not ideal. Artificial intelligence (AI) is increasingly used to diagnose diseases with good results. This review aimed to evaluate the accuracy of AI-assisted diagnosis of CAG through a meta-analysis.MethodsWe conducted a comprehensive literature search of four databases: PubMed, Embase, Web of Science, and the Cochrane Library. Studies published by November 21, 2022, on AI diagnosis CAG with endoscopic images or videos were included. We assessed the diagnostic performance of AI using meta-analysis, explored the sources of heterogeneity through subgroup analysis and meta-regression, and compared the accuracy of AI and endoscopists in diagnosing CAG.ResultsEight studies that included a total of 25,216 patients of interest, 84,678 image training set images, and 10,937 test set images/videos were included. The results of the meta-analysis showed that the sensitivity of AI in identifying CAG was 94% (95% confidence interval [CI]: 0.88–0.97, I2 = 96.2%), the specificity was 96% (95% CI: 0.88–0.98, I2 = 98.04%), and the area under the summary receiver operating characteristic curve was 0.98 (95% CI: 0.96–0.99). The accuracy of AI in diagnosing CAG was significantly higher than that of endoscopists.ConclusionsAI-assisted diagnosis of CAG in endoscopy has high accuracy and clinical diagnostic value.Systematic review registrationhttp://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42023391853.
Whole genome sequence of Lactiplantibacillus plantarum MC5 and comparative analysis of eps gene clusters
Authors: Zhao Xuefang , Liang Qi , Song Xuemei , Zhang Yan 
Published: May 2023

IntroductionProbiotic Lactiplantibacillus plantarum MC5 produces large amounts of exopolysaccharides (EPS), and its use as a compound fermentor can greatly improve the quality of fermented milk.MethodsTo gain insight into the genomic characteristics of probiotic MC5 and reveal the relationship between its EPS biosynthetic phenotype and genotype, we analyzed the carbohydrate metabolic capacity, nucleotide sugar formation pathways, and EPS biosynthesis-related gene clusters of strain MC5 based on its whole genome sequence. Finally, we performed validation tests on the monosaccharides and disaccharides that strain MC5 may metabolize.ResultsGenomic analysis showed that MC5 has seven nucleotide sugar biosynthesis pathways and 11 sugar-specific phosphate transport systems, suggesting that the strain can metabolize mannose, fructose, sucrose, cellobiose, glucose, lactose, and galactose. Validation results showed that strain MC5 can metabolize these seven sugars and produce significant amounts of EPS (&gt; 250 mg/L). In addition, strain MC5 possesses two typical eps biosynthesis gene clusters, which include the conserved genes epsABCDE, wzx, and wzy, six key genes for polysaccharide biosynthesis, and one MC5-specific epsG gene.DiscussionThese insights into the mechanism of EPS-MC5 biosynthesis can be used to promote the production of EPS through genetic engineering.
Development and evaluation of a centrifugal disk system for the rapid detection of multiple pathogens and their antibiotic resistance genes in urinary tract infection
Authors: Chen Nianzhen , Li Gen , Si Yuying , Ye Yangqin , Zhang Tong , Chi Dali , Zhang Wenyan , Pan Lifeng , Qu Guoying , Lu Yun , Zong Ming , Sui Guodong , Fan Lieying 
Published: May 2023

BackgroundUrinary tract infections (UTIs) are some of the most common bacterial infections in the world. Nevertheless, as uncomplicated UTIs are treated empirically without culturing the urine, adequate knowledge of the resistance pattern of uropathogens is essential. Conventional urine culture and identification take at least 2 days. Here, we developed a platform based on LAMP and centrifugal disk system (LCD) to simultaneously detect the main pathogens and antibiotic resistant genes (ARGs) of urgent concern multidrug-resistant among UTIs.MethodsWe designed specific primers to detect the target genes above and evaluated their sensitivity and specificity. We also assessed the result of our preload LCD platform on 645 urine specimens with a conventional culturing method and Sanger sequencing.ResultsThe results obtained with the 645 clinical samples indicated that the platform has high specificity (0.988–1) and sensitivity (0.904–1) for the studied pathogens and ARGs. Moreover, the kappa value of all pathogens was more than 0.75, revealing an excellent agreement between the LCD and culture method. Compared to phenotypic tests, the LCD platform is a practical and fast detection approach for methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococci, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Acinetobacter, carbapenem-resistant Pseudomonas aeruginosa (kappa value of all &gt;0.75), and non-extended-spectrum β-lactamase producers.ConclusionWe developed a detection platform that has high accuracy and that meets the need for rapid diagnosis, which can be completed within 1.5 h from specimen collection. It may be a powerful tool for evidence-based UTIs diagnosis, which has essential support for the rational use of antibiotics. More high-quality clinical studies are required to prove the effectiveness of our platform.
In silico analysis of the profilaggrin sequence indicates alterations in the stability, degradation route, and intracellular protein fate in filaggrin null mutation carriers
Authors: Paul Argho Aninda , Szulc Natalia A. , Kobiela Adrian , Brown Sara J. , Pokrzywa Wojciech , Gutowska-Owsiak Danuta 
Published: May 2023

Background: Loss of function mutation in FLG is the major genetic risk factor for atopic dermatitis (AD) and other allergic manifestations. Presently, little is known about the cellular turnover and stability of profilaggrin, the protein encoded by FLG. Since ubiquitination directly regulates the cellular fate of numerous proteins, their degradation and trafficking, this process could influence the concentration of filaggrin in the skin.Objective: To determine the elements mediating the interaction of profilaggrin with the ubiquitin-proteasome system (i.e., degron motifs and ubiquitination sites), the features responsible for its stability, and the effect of nonsense and frameshift mutations on profilaggrin turnover.Methods: The effect of inhibition of proteasome and deubiquitinases on the level and modifications of profilaggrin and processed products was assessed by immunoblotting. Wild-type profilaggrin sequence and its mutated variants were analysed in silico using the DEGRONOPEDIA and Clustal Omega tool.Results: Inhibition of proteasome and deubiquitinases stabilizes profilaggrin and its high molecular weight of presumably ubiquitinated derivatives. In silico analysis of the sequence determined that profilaggrin contains 18 known degron motifs as well as multiple canonical and non-canonical ubiquitination-prone residues. FLG mutations generate products with increased stability scores, altered usage of the ubiquitination marks, and the frequent appearance of novel degrons, including those promoting C-terminus-mediated degradation routes.Conclusion: The proteasome is involved in the turnover of profilaggrin, which contains multiple degrons and ubiquitination-prone residues. FLG mutations alter those key elements, affecting the degradation routes and the mutated products’ stability.
An economic evaluation of a primary care-based technology-enabled intervention for stroke secondary prevention and management in rural China: a study protocol
Authors: Gong Enying , Yang Bolu , Chen Xingxing , Li Yuhan , Li Zixiao , Bettger Janet Prvu , Oldenburg Brian , Dong Dejin , Si Lei , Yan Lijing L. 
Published: May 2023

IntroductionSecondary prevention of stroke is a leading challenge globally and only a few strategies have been tested to be effective in supporting stroke survivors. The system-integrated and technology-enabled model of care (SINEMA) intervention, a primary care-based and technology-enabled model of care, has been proven effective in strengthening the secondary prevention of stroke in rural China. The aim of this protocol is to outline the methods for the cost-effectiveness evaluation of the SINEMA intervention to better understand its potential economic benefits.MethodsThe economic evaluation will be a nested study based on the SINEMA trial; a cluster-randomized controlled trial implemented in 50 villages in rural China. The effectiveness of the intervention will be estimated using quality-adjusted life years for the cost-utility analysis and reduction in systolic blood pressure for the cost-effectiveness analysis. Health resource and service use and program costs will be identified, measured, and valued at the individual level based on medication use, hospital visits, and inpatients' records. The economic evaluation will be conducted from the perspective of the healthcare system.ConclusionThe economic evaluation will be used to establish the value of the SINEMA intervention in the Chinese rural setting, which has great potential to be adapted and implemented in other resource-limited settings.
Compliance with a high-protein and energy-dense oral nutritional supplement in patients with disease-related malnutrition: a randomized open-label crossover trial
Authors: Leon-Sanz Miguel , Linares Francisca , Gonzalo Montserrat , Tapia María José , Maiz-Jimenez María , Ruiz Aguado Marta , Lizán Luis , Olveira Gabriel 
Published: May 2023

IntroductionPatient compliance with oral nutritional supplements (ONS) is not optimal for meeting energy and nutritional requirements in a high proportion of patients with disease-related malnutrition (DRM). Energy density or prescribed volume of ONS may impact compliance.MethodsA randomized, open-label crossover trial was conducted in outpatients with DRM to compare compliance with a high energy-dense ONS (edONS, 2.4 kcal/mL) and a reference ONS (heONS, 2.0 kcal/mL; NCT05609006). Patients were randomly assigned to two 8-week treatment sequences of four-weeks periods: edONS + heONS (sequence A) or heONS + edONS (sequence B). Patients daily reported the amount of product left over gastrointestinal tolerance and satisfaction with ONS. A non-inferiority analysis was performed to compare the compliance rate (percentage of consumed energy over the prescribed) for each period and sequence.ResultsFifty-three patients were assigned to sequence A and 50 to sequence B (55.7 ± 13.9 years, 37.0% female, 67.1% oncology patients). In sequence A, the compliance rates were 88.6% ± 14.3% vs. 84.1 ± 21.8% (p = 0.183), while in sequence B, they were 78.9% ± 23.8% vs. 84.4% ± 21.4% (p &lt; 0.01). In both sequences, the lower range of the confidence interval for compliance with edONS was greater than the non-inferiority threshold (for sequence A ΔCompA was 4.5% [95% CI, −2.0% to 10.0%], and for sequence, B ΔCompB was 5.6% [95% CI, −3.0% to 14.0%]). The total discarded cost for each ONS was higher for heONS than edONS, being the difference statistically significant in sequence B. BMI increased slightly and not significantly in both sequences, and the percentage of patients with severe malnutrition was reduced. The frequency of gastrointestinal symptoms was low for both sequences, and satisfaction with ONS was slightly higher for edONS.ConclusionOur findings highlight that edONS was non-inferior to heONS in terms of consumed energy over the prescribed, with a lower amount of edONS discarded, which suggests a higher efficiency of edONS.
Correlation between pathologic complete response, event-free survival/disease-free survival and overall survival in neoadjuvant and/or adjuvant HR+/HER2-breast cancer
Authors: Gogate Anagha , Ranjan Sandip , Kumar Amit , Bhandari Hitesh , Papademetriou Eros , Kim Inkyu , Potluri Ravi 
Published: May 2023

PurposeThe study’s purpose was to evaluate the correlation between overall survival (OS) and its potential surrogate endpoints: pathologic complete response (pCR) and event-free survival (EFS)/disease-free survival (DFS) in neoadjuvant and/or adjuvant HR+/HER2- breast cancer.MethodsSystematic search was performed in MEDLINE, EMBASE, Cochrane Library databases and other relevant sources to identify literature that have reported outcomes of interest in the target setting. The strength of correlation of EFS/DFS with OS, pCR with OS, and pCR with EFS/DFS was measured using Pearson’s correlation coefficient (r) based on weighted regression analysis. For Surrogate Endpoint-True Endpoint pairs where correlation was found to be moderate, surrogate threshold effect (STE) was estimated using a mixed-effects model. Sensitivity analyses were conducted on the scale and weights used and removing outlier data.ResultsModerate correlation was observed of relative measures [log(HR)] of EFS/DFS and OS (r = 0.91; 95% CI: 0.83, 0.96, p &lt; 0.0001). STE for HREFS/DFS was estimated to be 0.73. Association between EFS/DFS at 1, 2 and 3 years with OS at 4- and 5-year landmarks was moderate. Relative treatment effects of pCR and EFS/DFS were not strongly associated (r: 0.24; 95% CI: -0.63, 0.84, p = 0.6028). Correlation between pCR and OS was either not evaluated due to inadequate sample size (relative outcomes) or weak (absolute outcomes). Results obtained in the sensitivity analyses were similar to base scenario.ConclusionEFS/DFS were moderately correlated with OS in this trial-level analysis. They may be considered as valid surrogates for OS in HR+/HER2- breast cancer.
CD25 targeting with the afucosylated human IgG1 antibody RG6292 eliminates regulatory T cells and CD25+ blasts in acute myeloid leukemia
Authors: Pousse Laurène , Korfi Koorosh , Medeiros Bruno C. , Berrera Marco , Kumpesa Nadine , Eckmann Jan , Hutter Idil Karakoc , Griesser Vera , Karanikas Vaios , Klein Christian , Amann Maria 
Published: May 2023

BackgroundAcute Myeloid leukemia is a heterogeneous disease that requires novel targeted treatment options tailored to the patients’ specific microenvironment and blast phenotype.MethodsWe characterized bone marrow and/or blood samples of 37 AML patients and healthy donors by high dimensional flow cytometry and RNA sequencing using computational analysis. In addition, we performed ex vivo ADCC assays using allogeneic NK cells isolated from healthy donors and AML patient material to test the cytotoxic potential of CD25 Mab (also referred to as RG6292 and RO7296682) or isotype control antibody on regulatory T cells and CD25+ AML cells.ResultsBone marrow composition, in particular the abundance of regulatory T cells and CD25 expressing AML cells, correlated strongly with that of the blood in patients with time-matched samples. In addition, we observed a strong enrichment in the prevalence of CD25 expressing AML cells in patients bearing a FLT3-ITD mutation or treated with a hypomethylating agent in combination with venetoclax. We adopted a patient-centric approach to study AML clusters with CD25 expression and found it most highly expressed on immature phenotypes. Ex vivo treatment of primary AML patient samples with CD25 Mab, a human CD25 specific glycoengineered IgG1 antibody led to the specific killing of two different cell types, CD25+ AML cells and regulatory T cells, by allogeneic Natural Killer cells.ConclusionThe in-depth characterization of patient samples by proteomic and genomic analyses supported the identification of a patient population that may benefit most by harnessing CD25 Mab’s dual mode of action. In this pre-selected patient population, CD25 Mab could lead to the specific depletion of regulatory T cells, in addition to leukemic stem cells and progenitor-like AML cells that are responsible for disease progression or relapse.
Interventions to improve neurocognitive late-effects in pediatric and adolescent CNS tumor patients and survivors - a systematic review
Authors: Kasteler Rahel , Fuchs Philipp , Otth Maria , Scheinemann Katrin 
Published: May 2023

IntroductionSurvival of children and adolescents diagnosed with central nervous system (CNS) tumors massively improved over the last decades due to better diagnostics, treatment, and supportive care. However, morbidity is still the highest of all cancer entities in this age group with neurocognitive late-effects being one of the most severe.AimWith this systematic review, we aim to summarize interventions designed to prevent or improve neurocognitive late-effects in CNS tumor patients.MethodWe searched PubMed on August 16th 2022 and included publications studying interventions for neurocognitive late-effects in pediatric and adolescent patients and survivors diagnosed with a CNS tumor. We included any form of neurocognitive intervention during treatment or following treatment completion. We considered all types of studies except for expert opinions and case reports.ResultsThe literature search resulted in 735 publications. We included 43 publications in the full text screening and 14 met our inclusion criteria. Of those, two assessed the impact of pharmacological interventions, three of exercise interventions, five of online cognitive training, and four assessed behavioral interventions. Different neuropsychological test batteries and imaging were used to measure the impact of the respective interventions. Most studies showed a positive impact of the interventions in single to several of the subtests used.ConclusionWe found several intervention studies indicating improvement of neurocognitive problems in children and adolescent CNS tumor survivors. In this population exercise interventions or online cognitive training might mitigate or improve neurocognitive late-effects.
Identification of novel molecular subtypes and a signature to predict prognosis and therapeutic response based on cuproptosis-related genes in prostate cancer
Authors: Zhang Jili , Jiang Shaoqin , Gu Di , Zhang Wenhui , Shen Xianqi , Qu Min , Yang Chenghua , Wang Yan , Gao Xu 
Published: May 2023

BackgroundProstate cancer (PCa) is the most common malignant tumor of the male urinary system. Cuproptosis, as a novel regulated cell death, remains unclear in PCa. This study aimed to investigate the role of cuproptosis-related genes (CRGs) in molecular stratification, prognostic prediction, and clinical decision-making in PCa. MethodsCuproptosis-related molecular subtypes were identified by consensus clustering analysis. A prognostic signature was constructed with LASSO cox regression analyses with 10-fold cross-validation. It was further validated in the internal validation cohort and eight external validation cohorts. The tumor microenvironment between the two risk groups was compared using the ssGSEA and ESTIMATE algorithms. Finally, qRT-PCR was used to explore the expression and regulation of these model genes at the cellular level. Furthermore, 4D Label-Free LC-MS/MS and RNAseq were used to investigate the changes in CRGs at protein and RNA levels after the knockdown of the key model gene B4GALNT4.ResultsTwo cuproptosis-related molecular subtypes with significant differences in prognoses, clinical features, and the immune microenvironment were identified. Immunosuppressive microenvironments were associated with poor prognosis. A prognostic signature comprised of five genes (B4GALNT4, FAM83D, COL1A, CHRM3, and MYBPC1) was constructed. The performance and generalizability of the signature were validated in eight completely independent datasets from multiple centers. Patients in the high-risk group had a poorer prognosis, more immune cell infiltration, more active immune-related functions, higher expression of human leukocyte antigen and immune checkpoint molecules, and higher immune scores. In addition, anti-PDL-1 immunotherapy prediction, somatic mutation, chemotherapy response prediction, and potential drug prediction were also analyzed based on the risk signature. The validation of five model genes' expression and regulation in qPCR was consistent with the results of bioinformatics analysis. Transcriptomics and proteomics analyses revealed that the key model gene B4GALNT4 might regulate CRGs through protein modification after transcription.ConclusionThe cuproptosis-related molecular subtypes and the prognostic signature identified in this study could be used to predict the prognosis and contribute to the clinical decision-making of PCa. Furthermore, we identified a potential cuproptosis-related oncogene B4GALNT4 in PCa, which could be used as a target to treat PCa in combination with cuproptosis.
A multiplexed assay for quantifying immunomodulatory proteins supports correlative studies in immunotherapy clinical trials
Authors: Whiteaker Jeffrey R. , Zhao Lei , Schoenherr Regine M. , Huang Dongqing , Lundeen Rachel A. , Voytovich Ulianna , Kennedy Jacob J. , Ivey Richard G. , Lin Chenwei , Murillo Oscar D. , Lorentzen Travis D. , Colantonio Simona , Caceres Tessa W. , Roberts Rhonda R. , Knotts Joseph G. , Reading Joshua J. , Perry Candice D. , Richardson Christopher W. , Garcia-Buntley Sandra S. , Bocik William , Hewitt Stephen M. , Chowdhury Shrabanti , Vandermeer Jackie , Smith Stephen D. , Gopal Ajay K. , Ramchurren Nirasha , Fling Steven P. , Wang Pei , Paulovich Amanda G. 
Published: May 2023

IntroductionImmunotherapy is an effective treatment for a subset of cancer patients, and expanding the benefits of immunotherapy to all cancer patients will require predictive biomarkers of response and immune-related adverse events (irAEs). To support correlative studies in immunotherapy clinical trials, we are developing highly validated assays for quantifying immunomodulatory proteins in human biospecimens.MethodsHere, we developed a panel of novel monoclonal antibodies and incorporated them into a novel, multiplexed, immuno-multiple reaction monitoring mass spectrometry (MRM-MS)-based proteomic assay targeting 49 proteotypic peptides representing 43 immunomodulatory proteins.Results and discussionThe multiplex assay was validated in human tissue and plasma matrices, where the linearity of quantification was &gt;3 orders of magnitude with median interday CVs of 8.7% (tissue) and 10.1% (plasma). Proof-of-principle demonstration of the assay was conducted in plasma samples collected in clinical trials from lymphoma patients receiving an immune checkpoint inhibitor. We provide the assays and novel monoclonal antibodies as a publicly available resource for the biomedical community.