bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune checkpoint inhibitors in first-line therapies of metastatic or early triple-negative breast cancer: a systematic review and network meta-analysis
Authors: Liang Xueyan , Chen Xiaoyu , Li Huijuan , Li Yan 
Published: May 2023

BackgroundThe optimal first-line immune checkpoint inhibitor (ICI) treatment strategy for metastatic or early triple-negative breast cancer (TNBC) has not yet been determined as a result of various randomized controlled trials (RCTs). The purpose of this study was to compare the efficacy and safety of ICIs in patients with metastatic or early TNBC.MethodsRCTs comparing the efficacy and safety of ICIs in patients with TNBC were included in the studies. Based on PRISMA guidelines, we estimated pooled hazard ratios (HRs) and odds ratios (ORs) using random-effects models of Bayesian network meta-analysis. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included pathologic complete response rate (pCR), grade ≥ 3 treatment-related adverse events (trAEs), immune-related adverse events (irAEs), and grade ≥ 3 irAEs.ResultsThe criteria for eligibility were met by a total of eight RCTs involving 4,589 patients with TNBC. When ICIs were used in patients without programmed death-ligand 1 (PD-L1) selection, there was a trend toward improved PFS, OS, and pCR, without significant differences. Pembrolizumab plus chemotherapy is superior to other treatment regimens in terms of survival for TNBC patients based on Bayesian ranking profiles. Subgroup analysis by PD-L1 positive population indicated similar results, and atezolizumab plus chemotherapy provided better survival outcomes. Among grade ≥ 3 trAEs and any grade irAEs, there was no statistically significant difference among different ICI agents. The combination of ICIs with chemotherapy was associated with a higher incidence of grade ≥ 3 irAEs. Based on rank probability, the ICI plus chemotherapy group was more likely to be associated with grade ≥ 3 trAEs, any grade irAEs, and grade ≥ 3 irAEs. Hypothyroidism and hyperthyroidism were the most frequent irAEs in patients receiving ICI.ConclusionsICI regimens had relatively greater efficacy and safety profile. Pembrolizumab plus chemotherapy and atezolizumab plus chemotherapy seem to be superior first-line treatments for intention-to-treat and PD-L1-positive TNBC patients, respectively. It may be useful for making clinical decisions to evaluate the efficacy and safety of different ICIs based on our study.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022354643.
Predicting skip metastasis in lateral lymph nodes of papillary thyroid carcinoma based on clinical and ultrasound features
Authors: Zhao Min , Shi Xinyu , Zou Ziran , Wen Runze , Lu Yixing , Li Jihui , Cao Jinming , Zhang Bin 
Published: May 2023

BackgroundSkip metastasis in papillary thyroid cancer (PTC), defined as lateral lymph node metastasis (LLNM) without the involvement of central lymph node metastasis (CLNM), is generally unpredictable. Our study aimed to develop a model to predict skip metastasis by using clinicopathological and ultrasound factors of PTC.MethodsWe retrospectively reviewed the medical records of patients who underwent total thyroidectomy and central lymph node dissection (CLND) plus lateral lymph node dissection (LLND) between January 2019 and December 2021 at the First Affiliated Hospital of Soochow University. Furthermore, univariate and multivariate analyses assessed the clinical and ultrasound risk factors. Receiver operating characteristic (ROC) curves were used to find the optimal cut-off values for age and dominant nodule diameter. Multivariate logistic regression analysis results were used to construct a nomogram and were validated internally.ResultsIn all patients, the skip metastasis rate was 15.4% (41/267). Skip metastasis was more frequently found in patients with a tumour size ≤10 mm (OR 0.439; P = 0.033), upper tumour location (OR 3.050; P=0.006) and fewer CLNDs (OR 0.870; P = 0.005). After analysing the clinical and ultrasound characteristics of the tumour, five factors were ultimately associated with lateral lymph node skip metastasis and were used to construct the model. These factors were an age &gt;40 years, tumour diameter &lt;9.1 mm, upper tumour location, non-smooth margin and extrathyroidal extension. The internally evaluated calibration curves indicated an excellent correlation between the projected and actual skip metastasis probability. The nomogram performed well in discrimination, with a concordance index of 0.797 (95% CI, 0.726 to 0.867).ConclusionsThis study screened for predictors of skip metastasis in PTC and established a nomogram that effectively predicted the risk of potential skip metastasis in patients preoperatively. The method can predict and distinguish skip metastases in PTC in a simple and inexpensive manner, and it may have future therapeutic utility.
Coupled dynamic characteristics of 10 MW semi-submersible offshore wind turbine under typical operation, extreme, and fault conditions
Authors: Li Yu , Han Dongdong , Wang Bin , Wang Wenhua , Li Xin , Su Xiaohui 
Published: May 2023

The Technical University of Denmark (DTU) 10 MW wind turbine is selected as the object of this study. The braceless semi-submersible platform for the National Renewable Energy Laboratory 5 MW wind turbine is upscaled to support the DTU 10 MW wind turbine. The servo control system of the 10 MW semi-submersible wind turbine is redesigned. Furthermore, torque control is performed below the rated wind speed to achieve maximum power capture, and the gain scheduling proportional integral (GSPI) control method is performed above the rated wind speed to realize the design of the variable propeller control system. This ensures the safe operation of the floating wind turbine above the rated wind speed. The reliability of the designed servo control system is verified by a full coupling dynamic response analysis with the designed servo control system, aerodynamics, and hydrodynamics under the combined action of wind and waves. The coupled dynamic characteristics of the 10 MW semi-submersible wind turbine under different conditions are analyzed, including operational, extreme, and fault situations. The results show that the servo control system effectively controls the motion response of a 10 MW floating offshore wind turbine (FOWT). Turbulent wind has an obvious excitation effect on the surge and pitch of the FOWT, whereas the heave motion is primarily excited by wave loads. Different fault conditions can cause different motion and structural responses. Furthermore, the tower top bending moment is greatly affected by the imbalance of aerodynamic load, and the surge, pitch motion, tower base bending moment, and mooring tension of the FOWT are affected by different fault conditions to varying degrees. In addition, the heave motion is generally barely affected by the fault conditions.
A novel multilayer composite structure based battery thermal management system
Authors: Kang Chuanzhi , Yang Jiaming , Yuan Xiaolu , Qiu Chenghui , Cai Yufei 
Published: May 2023

The battery thermal management system (BTMS) utilizing phase change materials (PCM) has shown promising performance in high heat flux heat dissipation. However, conventional PCM systems do not fully exploit the latent thermal properties of paraffin wax to enhance battery cooling efficiency. To address this issue, this paper proposes a novel multilayer composite material for BTMS, aiming to improve the thermal performance of the battery and overcome the low thermal conductivity of paraffin wax. The preparation process involves positioning the battery at the center of a triangular container, melting paraffin wax and pouring it into a 100 mm high container to form a 20 mm paraffin layer, placing copper foils and graphite layers on the paraffin surface, and repeating this step once. Finally, pour the 40 mm paraffin wax into the container, resulting in a sandwich-like structure with two layers of graphite. The cooling performance of the multilayer composite structure was experimentally tested at different ambient temperatures (15°C and 20°C) and discharge rates, and compared with a conventional BTMS based on pure paraffin wax. The results demonstrate that the multilayer composite structure exhibits superior heat dissipation compared to the pure paraffin structure, significantly reducing battery temperature rise, particularly at higher discharge rates. At an ambient temperature of 20°C and a discharge rate of 5°C, the battery temperature rise is only 14.97°C, with a remarkable cooling effect of 32.6%. Moreover, optimization of the number and thickness of graphite layers in the composite structure reveals that the 6-layer graphite structure outperforms the 2-layer, 4-layer, 8-layer, and 10-layer graphite structures. Additionally, a relatively lower battery surface temperature is observed with a graphite thickness of 0.5 mm on the basis of the 6-layer graphite structure. These findings indicate that the proposed novel layout structure exhibits excellent thermal performance, effectively addressing the low thermal conductivity limitation of traditional paraffin cooling systems, and providing a new approach for thermal management of lithium batteries.
Phenomic and genomic prediction of yield on multiple locations in winter wheat
Authors: Jackson Robert , Buntjer Jaap B. , Bentley Alison R. , Lage Jacob , Byrne Ed , Burt Chris , Jack Peter , Berry Simon , Flatman Edward , Poupard Bruno , Smith Stephen , Hayes Charlotte , Barber Tobias , Love Bethany , Gaynor R. Chris , Gorjanc Gregor , Howell Phil , Mackay Ian J. , Hickey John M. , Ober Eric S. 
Published: May 2023

Genomic selection has recently become an established part of breeding strategies in cereals. However, a limitation of linear genomic prediction models for complex traits such as yield is that these are unable to accommodate Genotype by Environment effects, which are commonly observed over trials on multiple locations. In this study, we investigated how this environmental variation can be captured by the collection of a large number of phenomic markers using high-throughput field phenotyping and whether it can increase GS prediction accuracy. For this purpose, 44 winter wheat (Triticum aestivum L.) elite populations, comprising 2,994 lines, were grown on two sites over 2 years, to approximate the size of trials in a practical breeding programme. At various growth stages, remote sensing data from multi- and hyperspectral cameras, as well as traditional ground-based visual crop assessment scores, were collected with approximately 100 different data variables collected per plot. The predictive power for grain yield was tested for the various data types, with or without genome-wide marker data sets. Models using phenomic traits alone had a greater predictive value (R2 = 0.39–0.47) than genomic data (approximately R2 = 0.1). The average improvement in predictive power by combining trait and marker data was 6%–12% over the best phenomic-only model, and performed best when data from one full location was used to predict the yield on an entire second location. The results suggest that genetic gain in breeding programmes can be increased by utilisation of large numbers of phenotypic variables using remote sensing in field trials, although at what stage of the breeding cycle phenomic selection could be most profitably applied remains to be answered.
Influenza A viruses in gulls in landfills and freshwater habitats in Minnesota, United States
Authors: Rasmussen Elizabeth A. , Czaja Agata , Cuthbert Francesca J. , Tan Gene S. , Lemey Philippe , Nelson Martha I. , Culhane Marie R. 
Published: May 2023

Introduction: The unpredictable evolution of avian influenza viruses (AIVs) presents an ongoing threat to agricultural production and public and wildlife health. Severe outbreaks of highly pathogenic H5N1 viruses in US poultry and wild birds since 2022 highlight the urgent need to understand the changing ecology of AIV. Surveillance of gulls in marine coastal environments has intensified in recent years to learn how their long-range pelagic movements potentially facilitate inter-hemispheric AIV movements. In contrast, little is known about inland gulls and their role in AIV spillover, maintenance, and long-range dissemination.Methods: To address this gap, we conducted active AIV surveillance in ring-billed gulls (Larus delawarensis) and Franklin's gulls (Leucophaeus pipixcan) in Minnesota's natural freshwater lakes during the summer breeding season and in landfills during fall migration (1,686 samples).Results: Whole-genome AIV sequences obtained from 40 individuals revealed three-lineage reassortants with a mix of genome segments from the avian Americas lineage, avian Eurasian lineage, and a global “Gull” lineage that diverged more than 50 years ago from the rest of the AIV global gene pool. No poultry viruses contained gull-adapted H13, NP, or NS genes, pointing to limited spillover. Geolocators traced gull migration routes across multiple North American flyways, explaining how inland gulls imported diverse AIV lineages from distant locations. Migration patterns were highly varied and deviated far from assumed “textbook” routes.Discussion: Viruses circulating in Minnesota gulls during the summer breeding season in freshwater environments reappeared in autumn landfills, evidence of AIV persistence in gulls between seasons and transmission between habitats. Going forward, wider adoption of technological advances in animal tracking devices and genetic sequencing is needed to expand AIV surveillance in understudied hosts and habitats.
Population genomics of American mink using genotype data
Authors: Hu Guoyu , Do Duy Ngoc , Manafiazar Ghader , Kelvin Alyson A. , Sargolzaei Mehdi , Plastow Graham , Wang Zhiquan , Miar Younes 
Published: May 2023

Understanding the genetic structure of the target population is critically important to develop an efficient genomic selection program in domestic animals. In this study, 2,973 American mink of six color types from two farms (Canadian Centre for Fur Animal Research (CCFAR), Truro, NS and Millbank Fur Farm (MFF), Rockwood, ON) were genotyped with the Affymetrix Mink 70K panel to compute their linkage disequilibrium (LD) patterns, effective population size (Ne), genetic diversity, genetic distances, and population differentiation and structure. The LD pattern represented by average r2, decreased to &lt;0.2 when the inter-marker interval reached larger than 350 kb and 650 kb for CCFAR and MFF, respectively, and suggested at least 7,700 and 4,200 single nucleotide polymorphisms (SNPs) be used to obtain adequate accuracy for genomic selection programs in CCFAR and MFF respectively. The Ne for five generations ago was estimated to be 76 and 91 respectively. Our results from genetic distance and diversity analyses showed that American mink of the various color types had a close genetic relationship and low genetic diversity, with most of the genetic variation occurring within rather than between color types. Three ancestral genetic groups was considered the most appropriate number to delineate the genetic structure of these populations. Black (in both CCFAR and MFF) and pastel color types had their own ancestral clusters, while demi, mahogany, and stardust color types were admixed with the three ancestral genetic groups. This study provided essential information to utilize the first medium-density SNP panel for American mink in their genomic studies.
Biological activity of human IgE monoclonal antibodies targeting Der p 2, Fel d 1, Ara h 2 in basophil mediator release assays
Authors: Pena-Castellanos Glorismer , Smith Bryan R. E. , Pomés Anna , Smith Scott A. , Stigler Maria A. , Widauer Hannah L. , Versteeg Serge A. , van Ree Ronald , Chapman Martin D. , Aglas Lorenz 
Published: May 2023

BackgroundHuman Immunoglobulin E monoclonal antibodies (hIgE mAb) are unique tools for investigating IgE responses. Here, the biological activity of hIgE mAb, derived from immortalized B cells harvested from the blood of allergic donors, targeting three allergens (Der p 2, Fel d 1 and Ara h 2) was investigated.MethodsThree Der p 2-, three Fel d 1- and five Ara h 2-specific hIgE mAb produced by human B cell hybridomas, were combined in pairs and used to passively sensitize humanized rat basophilic leukemia cells and compared with sensitization using serum pools. Sensitized cells were stimulated with corresponding allergens (recombinant or purified), allergen extracts or structural homologs, having 40-88% sequence similarity, and compared for mediator (β-hexosaminidase) release.ResultsOne, two and eight pairs of Der p 2-, Fel d 1- and Ara h 2-specific hIgE mAb, respectively, produced significant mediator release (&gt;50%). A minimum hIgE mAb concentration of 15-30 kU/L and a minimum antigen concentration between 0.01-0.1 µg/mL were sufficient to induce a pronounced mediator release. Individual sensitization with one Ara h 2-specific hIgE mAb was able to induce crosslinking independently of a second specific hIgE mAb. Der p 2- and Ara h 2-specific mAb showed a high allergen specificity when compared to homologs. Mediator release from cells sensitized with hIgE mAb was comparable to serum sensitization.ConclusionThe biological activity of hIgE mAb reported here provides the foundation for novel methods of standardization and quality control of allergen products and for mechanistic studies of IgE-mediated allergic diseases, using hIgE mAb.
Intermittent fasting protects against food allergy in a murine model via regulating gut microbiota
Authors: Ma Ru-xue , Hu Jia-qian , Fu Wei , Zhong Jian , Cao Can , Wang Chang-chang , Qi Shi-quan , Zhang Xiao-Lian , Liu Guang-hui , Gao Ya-dong 
Published: May 2023

BackgroundThe prevalence of food allergy (FA) is increasing. Decreases in the diversity of gut microbiota may contribute to the pathogenesis of FA by regulating IgE production of B cells. Intermittent fasting (IF) is a popular diet with the potential to regulate glucose metabolism, boosting immune memory and optimizing gut microbiota. The potential effect of long-term IF on the prevention and treatment of FA is still unknown.MethodsTwo IF protocols (16 h fasting/8 h feeding and 24 h fasting/24 h feeding) were conducted on mice for 56 days, while the control mice were free to intake food (free diet group, FrD). To construct the FA model, all mice were sensitized and intragastrical challenged with ovalbumin (OVA) during the second half of IF (day 28 to day 56). Rectal temperature reduction and diarrhea were recorded to evaluate the symptoms of FA. Levels of serum IgE, IgG1, Th1/Th2 cytokines, mRNA expression of spleen T cell related transcriptional factors, and cytokines were examined. H&amp;E, immunofluorescence, and toluidine blue staining were used to assess the structural changes of ileum villi. The composition and abundance of gut microbiota were analyzed by 16srRNA sequencing in cecum feces.ResultsThe diarrhea score and rectal temperature reduction were lower in the two fasting groups compared to the FrD groups. Fasting was associated with lower levels of serum OVA-sIgE, OVA-sIgG1, interleukin (IL)-4 and IL-5, and mRNA expression of IL-4, IL-5, and IL-10 in the spleen. While no significant association was observed in interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6, IL-2 levels. Less mast cell infiltration in ileum was observed in the 16h/8h fasting group compared to the FrD group. ZO-1 expression in the ileum of the two fasting groups was higher in IF mice. The 24h/24h fasting reshaped the gut microbiota, with a higher abundance of Alistipes and Rikenellaceae strains compared to the other groups.ConclusionIn an OVA-induced mice FA model, long-term IF may attenuate FA by reducing Th2 inflammation, maintaining the integrity of the intestinal epithelial barrier, and preventing gut dysbiosis.
Association between inflammatory bowel disease and interleukins, chemokines: a two-sample bidirectional mendelian randomization study
Authors: Fang Guojiu , Kong Fanzhi , Zhang Haiqing , Huang Bin , Zhang Jifa , Zhang Xueli 
Published: May 2023

BackgroundMendelian randomization (MR) was used to evaluate the bidirectional causal relationship between inflammatory bowel disease (IBD) and interleukins (ILs), chemokines.MethodsGenetic instruments and summary data of five ILs and six chemokines were obtained from a genome-wide association study database, and instrumental variables related to IBD were obtained from the FinnGen Consortium. Inverse variance weighting (IVW) was used as the main MR analysis method, and several other MR methods including MR-Egger and weighted median were used to confirm the reliability of the results. Sensitivity analyses such as heterogeneity and pleiotropy were also performed.ResultsThe IVW method provided evidence to support that genetically predicted IL-16, IL-18, and CXCL10 significantly positively correlated with IBD, while IL-12p70 and CCL23 significantly negatively correlated with IBD. IL-16 and IL-18 had a suggestive association with an increased risk of ulcerative colitis (UC), and CXCL10 had a suggestive association with an increased risk of Crohn’s disease (CD). However, there was no evidence to support that IBD and two main subtypes (UC and CD) are associated with changes in the levels of ILs and chemokines. The results of the sensitivity analyses were robust and no evidence of heterogeneity and horizontal pleiotropy was observed.ConclusionsThe present study showed that some ILs and chemokines affect IBD, but IBD and its main subtypes (UC and CD) have no effect on the level changes of ILs and chemokines.
Seroprevalence and durability of antibody responses to AstraZeneca vaccination in Ugandans with prior mild or asymptomatic COVID-19: implications for vaccine policy
Authors: Serwanga Jennifer , Baine Claire , Mugaba Susan , Ankunda Violet , Auma Betty Oliver , Oluka Gerald Kevin , Kato Laban , Kitabye Isaac , Sembera Jackson , Odoch Geoffrey , Ejou Peter , Nalumansi Amina , Gombe Ben , Musenero Monica , Kaleebu Pontiano ,   the COVID-19 Immunoprofiling Team
Published: May 2023

IntroductionThe duration and timing of immunity conferred by COVID-19 vaccination in sub-Saharan Africa are crucial for guiding pandemic policy interventions, but systematic data for this region is scarce. This study investigated the antibody response after AstraZeneca vaccination in COVID-19 convalescent Ugandans.MethodsWe recruited 86 participants with a previous rt-PCR-confirmed mild or asymptomatic COVID-19 infection and measured the prevalence and levels of spike-directed IgG, IgM, and IgA antibodies at baseline, 14 and 28 days after the first dose (priming), 14 days after the second dose (boosting), and at six- and nine-months post-priming. We also measured the prevalence and levels of nucleoprotein-directed antibodies to assess breakthrough infections.ResultsWithin two weeks of priming, vaccination substantially increased the prevalence and concentrations of spike-directed antibodies (p &lt; 0.0001, Wilcoxon signed rank test), with 97.0% and 66% of vaccinated individuals possessing S-IgG and S-IgA antibodies before administering the booster dose. S-IgM prevalence changed marginally after the initial vaccination and barely after the booster, consistent with an already primed immune system. However, we also observed a rise in nucleoprotein seroprevalence, indicative of breakthroughs six months after the initial vaccination.DiscussionOur results suggest that vaccination of COVID-19 convalescent individuals with the AstraZeneca vaccine induces a robust and differential spike-directed antibody response. The data highlights the value of vaccination as an effective method for inducing immunity in previously infected individuals and the importance of administering two doses to maintain protective immunity. Monitoring anti-spike IgG and IgA when assessing vaccine-induced antibody responses is suggested for this population; assessing S-IgM will underestimate the response. The AstraZeneca vaccine is a valuable tool in the fight against COVID-19. Further research is needed to determine the durability of vaccine-induced immunity and the potential need for booster doses.