bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single vaccination of nucleoside-modified Rabies mRNA vaccine induces prolonged highly protective immune responses in mice
Authors: Bai Shimeng , Yang Tianhan , Zhu Cuisong , Feng Meiqi , Zhang Li , Zhang Ziling , Wang Xiang , Yu Rui , Pan Xinghao , Zhao Chen , Xu Jianqing , Zhang Xiaoyan 
Published: January 2023

BackgroundRabies is a lethal zoonotic disease that kills approximately 60,000 people each year. Although inactivated rabies vaccines are available, multiple-dose regimensare recommended for pre-exposure prophylaxis or post-exposure prophylaxis,which cuts down the cost- and time-effectiveness, especially in low- and middle incomecountries.MethodsWe developed a nucleoside-modified Rabies mRNA-lipid nanoparticle vaccine (RABV-G mRNA-LNP) encoding codon-optimized viral glycoprotein and assessed the immunogenicity and protective efficacy of this vaccine in mice comparing to a commercially available inactivated vaccine.ResultsWe first showed that, when evaluated in mice, a single vaccination of RABV-G mRNA with a moderate or high dose induces more potent humoral and T-cell immune responses than that elicited by three inoculations of the inactivated vaccine. Importantly, mice receiving a single immunization of RABV-G mRNA, even at low doses, showed full protection against the lethal rabies challenge. We further demonstrated that the humoral immune response induced by single RABV-G mRNA vaccination in mice could last for at least 25 weeks, while a two-dose strategy could extend the duration of the highly protective response to one year or even longer. In contrast, the three-dose regimen of inactivated vaccine failed to do so.ConclusionOur study confirmed that it is worth developing a single-dose nucleoside-modified Rabies mRNA-LNP vaccine, which could confer much prolonged and more effective protection.
Exploring the pathogenesis and immune infiltration in dilated cardiomyopathy complicated with atrial fibrillation by bioinformatics analysis
Authors: Gan Ting , Hu Jing , Aledan Anwer Khalid Okab , Liu Wenhu , Li Cui , Lu Shuai , Wang Ya , Xu Qian , Wang Yan , Wang Zhaohui 
Published: January 2023

BackgroundAtrial fibrillation (AF) is a serious complication of dilated cardiomyopathy (DCM), which increases the risk of thromboembolic events and sudden death in DCM patients. However, the common mechanism of DCM combined with AF remains unclear. This study aims to explore the molecular mechanism and analyze immune infiltration in DCM complicated with AF through comprehensive bioinformatics analysis.MethodsThe gene expression datasets of DCM (GSE141910) and AF (GSE41177 and GSE79768) were obtained from the Gene Expression Omnibus database. Gene enrichment analyses were performed after screening the common differentially expressed genes (DEGs) of DCM and AF. Protein-protein interaction network was constructed in the STRING database and visualized in Cytoscape software, which helped to further screen the central functional modules of DEGs and hub genes. In addition, ImmuCellAI algorithm was performed to estimate immune infiltration patterns, and Spearman correlation was conducted to investigate the correlation between the abundance of multiple immune cells and the expression levels of hub immune-related genes after obtaining hub immune-related genes from the ImmPort database. The hub immune-related genes expression and immune infiltration patterns were additionally verified in the validation datasets (GSE57338, GSE115574, and GSE31821). The diagnostic effectiveness of hub immune-related genes was evaluated through Receiver Operator Characteristic Curve analysis.ResultsA total of 184 common DEGs in DCM and AF were identified for subsequent analyses. The functions of hub genes were significantly associated with immune responses. We identified 7 hub immune-related genes (HLA-DRA, LCK, ITK, CD48, CD247, CD3D, and IL2RG) and a spectrum of immune cell subsets including Monocyte, Neutrophil, and follicular helper T (Tfh) cells were found to be concurrently dysregulated in both DCM and AF. 7 hub immune-related genes were predominantly favorably correlated with Tfh cells and were primarily negatively correlated with Neutrophil infiltrations in DCM and AF. CD48+CD3D were verified to diagnose DCM and AF with excellent sensitivity and specificity, showing favorable diagnostic value.ConclusionsOur study reveals that immune cells (Tfh cells) disorders caused by hub immune-related genes (CD48 and CD3D) may be the common pathogenesis of DCM combined with AF, which lays a foundation for further immune mechanism research.
Safety and feasibility of toripalimab plus lenvatinib with or without radiotherapy in advanced BTC
Authors: Wang Yunchao , Zhang Nan , Xue Jingnan , Zhu Chengpei , Wang Yanyu , Zhang Longhao , Yang Xu , Wang Hao , Wang Shanshan , Chao Jiashuo , Yang Xiaobo , Zhao Haitao 
Published: January 2023

BackgroundToripalimab shows antitumor efficacy in cholangiocarcinoma. Radiotherapy (RT) may enhance systemic responses of PD-1 inhibitors and lenvatinib. This study was designed to assess the safety and feasibility of toripalimab plus lenvatinib with or without RT in advanced BTC.MethodsThis study involved 88 patients with advanced BTC receiving toripalimab plus lenvatinib with or without RT from the clinical trials (NCT03892577). Propensity score matching (PSM) (1:1) analysis was used to balance potential bias. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) were evaluated.ResultsAfter PSM, the final analysis included 40 patients: 20 receiving toripalimab plus lenvatinib without RT (NRT); 20 receiving toripalimab plus lenvatinib with RT. The AEs were more frequent in the RT group than in the NRT group without treatment-associated mortality. The addition of RT did not cause specific AEs. The median PFS was significantly longer with RT (10.8 versus 4.6 months, p&lt;0.001). The median OS was 13.7 months with RT versus 9.2 months in the NRT group (p=0.008). The ORR was 35% (95% CI: 12.1-57.9) in the RT group versus 20% (95% CI: 0.8-39.2) in the NRT group.ConclusionsThe addition of RT may enhance the efficacy of toripalimab plus lenvatinib. Toripalimab plus lenvatinib with RT have a good safety profile without an increase in specific toxicities in advanced BTC patients.
Distinct patterns of fasting plasma glucose and lipid profile levels over time in adults tested positive for HIV on HAART in Shanghai, China, revealed using growth mixture models
Authors: Lang Jingjing , Xin Xin , Chen Panpan , Ning Zhen , Xiao Shaotan 
Published: January 2023

ObjectivesThis study sought to identify potential change patterns and predictors of fasting plasma glucose (FPG) and lipid levels after initiating highly active antiretroviral therapy (HAART).MethodsA retrospective cohort study was conducted on 1,572 patients tested positive for HIV who initiated HAART between January 2010 and October 2020 in Shanghai, China. The growth mixture models (GMM) were used for capturing subgroups of FPG trajectories as well as triglyceride (TG) and total cholesterol (TC) dual-trajectories. Multinomial logistic regression models identified correlates of given trajectories.ResultsThe median follow-up time was 2.0 years (IQR 1.0–4.7). Three FPG trajectory subgroups were identified as FPG low-stable (62.3%), medium-stable (30.5%), and high-increasing (7.2%). Furthermore, three subgroups of TG and TC dual-trajectories were identified as TG and TC high-slight increasing (13.7%), low-rapid increasing (27.6%), and a subgroup of medium-stable TC and slight-decreasing TG (58.7%). Older age, high TG, FPG, BMI, CD4 count of &lt;200 at baseline, and initial use of zidovudine (AZT) and protease inhibitors (PIs) helped to identify the class with increasing glucose or lipid metabolism trajectories.ConclusionThe change patterns of plasma glucose and lipid in patients tested positive for HIV were heterogeneous and tailored interventions should be considered in specific subgroups.
Post-COVID-19 interstitial lung disease: Insights from a machine learning radiographic model
Authors: Karampitsakos Theodoros , Sotiropoulou Vasilina , Katsaras Matthaios , Tsiri Panagiota , Georgakopoulou Vasiliki E. , Papanikolaou Ilias C. , Bibaki Eleni , Tomos Ioannis , Lambiri Irini , Papaioannou Ourania , Zarkadi Eirini , Antonakis Emmanouil , Pandi Aggeliki , Malakounidou Elli , Sampsonas Fotios , Makrodimitri Sotiria , Chrysikos Serafeim , Hillas Georgios , Dimakou Katerina , Tzanakis Nikolaos , Sipsas Nikolaos V. , Antoniou Katerina , Tzouvelekis Argyris 
Published: January 2023

IntroductionPost-acute sequelae of COVID-19 seem to be an emerging global crisis. Machine learning radiographic models have great potential for meticulous evaluation of post-COVID-19 interstitial lung disease (ILD).MethodsIn this multicenter, retrospective study, we included consecutive patients that had been evaluated 3 months following severe acute respiratory syndrome coronavirus 2 infection between 01/02/2021 and 12/5/2022. High-resolution computed tomography was evaluated through Imbio Lung Texture Analysis 2.1.ResultsTwo hundred thirty-two (n = 232) patients were analyzed. FVC% predicted was ≥80, between 60 and 79 and &lt;60 in 74.2% (n = 172), 21.1% (n = 49), and 4.7% (n = 11) of the cohort, respectively. DLCO% predicted was ≥80, between 60 and 79 and &lt;60 in 69.4% (n = 161), 15.5% (n = 36), and 15.1% (n = 35), respectively. Extent of ground glass opacities was ≥30% in 4.3% of patients (n = 10), between 5 and 29% in 48.7% of patients (n = 113) and &lt;5% in 47.0% of patients (n = 109). The extent of reticulation was ≥30%, 5–29% and &lt;5% in 1.3% (n = 3), 24.1% (n = 56), and 74.6% (n = 173) of the cohort, respectively. Patients (n = 13, 5.6%) with fibrotic lung disease and persistent functional impairment at the 6-month follow-up received antifibrotics and presented with an absolute change of +10.3 (p = 0.01) and +14.6 (p = 0.01) in FVC% predicted at 3 and 6 months after the initiation of antifibrotic.ConclusionPost-COVID-19-ILD represents an emerging entity. A substantial minority of patients presents with fibrotic lung disease and might experience benefit from antifibrotic initiation at the time point that fibrotic-like changes are “immature.” Machine learning radiographic models could be of major significance for accurate radiographic evaluation and subsequently for the guidance of therapeutic approaches.
Amyloid beta accumulations and enhanced neuronal differentiation in cerebral organoids of Dutch-type cerebral amyloid angiopathy patients
Authors: Daoutsali Elena , Pepers Barry A. , Stamatakis Stavros , van der Graaf Linda M. , Terwindt Gisela M. , Parfitt David A. , Buijsen Ronald A. M. , van Roon-Mom Willeke M. C. 
Published: January 2023

IntroductionADutch-type cerebral amyloid angiopathy (D-CAA) is a hereditary brain disorder caused by a point mutation in the amyloid precursor protein (APP) gene. The mutation is located within the amyloid beta (Aβ) domain of APP and leads to Aβ peptide accumulation in and around the cerebral vasculature. There lack of disease models to study the cellular and molecular pathological mechanisms of D-CAA together with the absence of a disease phenotype in vitro in overexpression cell models, as well as the limited availability of D-CAA animal models indicates the need for a D-CAA patient-derived model.MethodsWe generated cerebral organoids from four D-CAA patients and four controls, cultured them up to 110 days and performed immunofluorescent and targeted gene expression analyses at two time points (D52 and D110).ResultsD-CAA cerebral organoids exhibited Aβ accumulations, showed enhanced neuronal and astrocytic gene expression and TGFβ pathway de-regulation.ConclusionsThese results illustrate the potential of cerebral organoids as in vitro disease model of D-CAA that can be used to understand disease mechanisms of D-CAA and can serve as therapeutic intervention platform for various Aβ-related disorders.
Definitive intensity modulated proton re-irradiation for lung cancer in the immunotherapy era
Authors: Janopaul-Naylor James R. , Cao Yichun , McCall Neal S. , Switchenko Jeffrey M. , Tian Sibo , Chen Haijian , Stokes William A. , Kesarwala Aparna H. , McDonald Mark W. , Shelton Joseph W. , Bradley Jeffrey D. , Higgins Kristin A. 
Published: January 2023

IntroductionAs immunotherapy has improved distant metastasis-free survival (DMFS) in Non-Small Cell Lung Cancer (NSCLC), isolated locoregional recurrences have increased. However, management of locoregional recurrences can be challenging. We report our institutional experience with definitive intent re-irradiation using Intensity Modulated Proton Therapy (IMPT).MethodRetrospective cohort study of recurrent or second primary NSCLC or LS-SCLC treated with IMPT. Kaplan-Meier method and log-rank test were used for time-to-event analyses.Results22 patients were treated from 2019 to 2021. After first course of radiation (median 60 Gy, range 45-70 Gy), 45% received adjuvant immunotherapy. IMPT re-irradiation began a median of 28.2 months (8.8-172.9 months) after initial radiotherapy. The median IMPT dose was 60 GyE (44-60 GyE). 36% received concurrent chemotherapy with IMPT and 18% received immunotherapy after IMPT. The median patient’s IMPT lung mean dose was 5.3 GyE (0.9-13.9 GyE) and 5 patients had cumulative esophagus max dose &gt;100 GyE with 1-year overall survival (OS) 68%, 1-year local control 80%, 1-year progression free survival 45%, and 1-year DMFS 60%. Higher IMPT (HR 1.4; 95% CI 1.1-1.7, p=0.01) and initial radiotherapy mean lung doses (HR 1.3; 95% CI 1.0-1.6, p=0.04) were associated with worse OS. Two patients developed Grade 3 pneumonitis or dermatitis, one patient developed Grade 2 pneumonitis, and seven patients developed Grade 1 toxicity. There were no Grade 4 or 5 toxicities.DiscussionDefinitive IMPT re-irradiation for lung cancer can prolong disease control with limited toxicity, particularly in the immunotherapy era.
Efficacy of modified thoraco-laparoscopic Ivor-Lewis versus traditional thoraco-laparoscopic Ivor-Lewis for esophageal cancer: Propensity score-matched analysis
Authors: Hong Ziqiang , Gou Wenxi , Lu Yingjie , Wu Xusheng , Sheng Yannan , Cui Baiqiang , Bai Xiangdou , Jin Dacheng , Gou Yunjiu 
Published: January 2023

ObjectiveTo compare the clinical results of the modified Ivor-Lewis procedure, which preserves the azygous vein, thoracic duct and surrounding tissues, with the traditional Ivor-Lewis procedure, which removes these tissues, for treating esophageal squamous cell carcinoma, and evaluating whether the azygous vein, thoracic duct and surrounding tissues are required to be removed for the surgery of esophageal cancer.MethodsTo retrospectively analyze the clinical data of patients suffering from esophageal cancer treated by thoracic-laparoscopic Ivor-Lewis procedure admitted to the Department of Thoracic Surgery of Gansu Provincial People’s Hospital from September 2017 to September 2019. According to the surgical method, they were divided into the modified thoracolaparoscopic Ivor-Lewis (modified group) and the traditional thoracolaparoscopic Ivor-Lewis (traditional group). Propensity score matching analysis (PSM) was applied to reduce the selection bias of confounding factors.ResultsA total of 245 patients who suffered from esophageal cancer and underwent thoracic-laparoscopic Ivor-Lewis were enrolled in the study. There were 124 cases in the modified group and 121 cases in the traditional group. The discrepancies in the age and T-stage among patients in the traditional and modified groups were statistically significant. After PSM, the above-mentioned factors became statistically insignificant. There were 86 patients in each group after PSM. Compared with the traditional group, the modified group has shorter operative time (p=0.007), less intraoperative bleeding (p=0.003) and less postoperative 3 days chest drainage(p=0.001), with a statistically significant difference. No significant difference in local recurrence (p=0.721) and distant metastasis (p=0.742) after surgery were found in the two groups, and the difference was not statistically significant. There was also no statistically significant difference in the 3-year postoperative survival rate (44.2% vs. 41.9%, p=0.605) between the modified and traditional groups.ConclusionThe modified Ivor-Lewis procedure, which preserves the azygous vein, thoracic duct, and surrounding tissue, reduces surgical trauma in esophageal cancer, has not increased postoperative recurrent metastases, while achieved the same long-term outcomes as expanded surgery.
Ten interleukins and risk of prostate cancer
Authors: Li Bing-Hui , Yan Si-Yu , Luo Li-Sha , Zeng Xian-Tao , Wang Yong-Bo , Wang Xing-Huan 
Published: January 2023

BackgroundInterleukins (ILs) have been reported to be related to prostate cancer. The aims of this study were to estimate the levels for several key interleukins in prostate cancer and the causal effects between them.MethodsWe conducted a bi-directional two-sample Mendelian randomization (MR) study to assess the causal associations between ILs and prostate cancer. Genetic instruments and summary-level data for 10 ILs were obtained from three genome-wide association meta-analyses. Prostate cancer related data were obtained from the PRACTICAL (79,148 cases and 61,106 controls), UK Biobank (7,691 cases and 169,762 controls) and FinnGen consortium (10,414 cases and 124,994 controls), respectively.ResultsThe odds ratio of prostate cancer was 0.92 (95% confidence interval (CI), 0.89, 0.96; P=1.58×10-05) and 1.12 (95% CI, 1.07, 1.17; P=6.61×10-07) for one standard deviation increase in genetically predicted IL-1ra and IL-6 levels, respectively. Genetically predicted levels of IL-1ß, IL-2a, IL-6ra, IL-8, IL-16, IL-17, IL-18, and IL-27 were not associated with the risk of prostate cancer. Reverse MR analysis did not find the associations between genetic liability to prostate cancer and higher levels of IL-1ra (β, -0.005; 95% CI, -0.010, 0.001; P=0.111) and IL-6 (β, 0.002; 95% CI, -0.011, 0.014; P=0.755).ConclusionThis MR study suggests that long-term IL-6 may increase the risk of prostate cancer and IL-1ra may reduce it.
Protein-energy malnutrition and worse outcomes after major cancer surgery: A nationwide analysis
Authors: Jin Jiewen , Zhu Xianying , Deng Zhantao , Zhang Pengyuan , Xiao Ying , Han Hedong , Li Yanbing , Li Hai 
Published: January 2023

BackgroundProtein-energy malnutrition (PEM) has been recognized as a poor prognostic factor in many clinical issues. However, nationwide population studies concerning the impact of PEM on outcomes after major cancer surgery (MCS) are lacking. We aimed to evaluate the postoperative outcomes associated with PEM following MCS.MethodsBy using the Nationwide Inpatient Sample database, data of patients undergoing MCS including colectomy, cystectomy, esophagectomy, gastrectomy, hysterectomy, lung resection, pancreatectomy, or prostatectomy were analyzed retrospectively from 2009 to 2015, resulting in a weighted estimate of 1,335,681 patients. The prevalence trend of PEM, as well as mortality and major complications after MCS were calculated. Multivariable regression analysis was applied to estimate the impact of PEM on postoperative outcomes after MCS.ResultsPEM showed an estimated annual percentage increase of 7.17% (95% confidence interval (CI): 4-10.44%) from 2009 to 2015, which contrasts with a 4.52% (95% CI: -6.58–2.41%) and 1.21% (95% CI: -1.85–0.56%) annual decrease in mortality and major complications in patients with PEM after MCS. PEM was associated with increased risk of mortality (odds ratio (OR)=2.26; 95% CI: 2.08-2.44; P &lt; 0.0001), major complications (OR=2.46; 95% CI: 2.36-2.56; P &lt; 0.0001), higher total cost ($35814 [$22292, $59579] vs. $16825 [$11393, $24164], P &lt; 0.0001), and longer length of stay (14 [9-21] days vs. 4 [2-7] days, P &lt; 0.0001), especially in patients underwent prostatectomy, hysterectomy and lung resection.ConclusionsPEM was associated with increased worse outcomes after major cancer surgery. Early identification and timely medical treatment of PEM for patients with cancer are crucial for improving postoperative outcomes.
Ultrathin high-temperature ferromagnetic rare-earth films: GdScGe and GdScSi monolayers
Authors: Wang Rui , Hou Lipeng , Shi Puyuan , Cheng Qianshuai , Zhang Yungeng 
Published: January 2023

Two-dimensional (2D) ferromagnetism with robust room-temperature ferromagnetism has sparked intense interest for future miniature information storage devices. However, most 2D ferromagnetic materials have a low Curie temperature. Here, by using density functional theory, two rare-earth monolayers, the GdScSi monolayer and the GdScGe monolayer, were predicted, in which these two monolayers exhibit ferromagnetic orders with large magnetic moments of approximately 7 μB/Gd. Monte Carlo simulations predict Curie temperatures of approximately 470 K and 495 K for the 2D GdScSi monolayer and the GdScGe monolayer, respectively. The spin band calculations show that they are metal. In addition, these two monolayers exhibit dynamical, mechanical, and thermal stabilities. The combination of these novel magnetic properties makes these 2D ferromagnetic crystals promising candidates for high-efficiency spintronic applications.
Predictive utility of commercial grade technologies for assessing musculoskeletal injury risk in US Marine Corps Officer candidates
Authors: Bird Matthew B. , Koltun Kristen J. , Mi Qi , Lovalekar Mita , Martin Brian J. , Doyle Tim L. A. , Nindl Bradley C. 
Published: January 2023

Recently, commercial grade technologies have provided black box algorithms potentially relating to musculoskeletal injury (MSKI) risk and functional movement deficits, in which may add value to a high-performance model. Thus, the purpose of this manuscript was to evaluate composite and component scores from commercial grade technologies associations to MSKI risk in Marine Officer Candidates. 689 candidates (Male candidates = 566, Female candidates = 123) performed counter movement jumps on SPARTA™ force plates and functional movements (squats, jumps, lunges) in DARI™ markerless motion capture at the start of Officer Candidates School (OCS). De-identified MSKI data was acquired from internal OCS reports for those who presented to the Physical Therapy department for MSKI treatment during the 10 weeks of training. Logistic regression analyses were conducted to validate the utility of the composite scores and supervised machine learning algorithms were deployed to create a population specific model on the normalized component variables in SPARTA™ and DARI™. Common MSKI risk factors (cMSKI) such as older age, slower run times, and females were associated with greater MSKI risk. Composite scores were significantly associated with MSKI, although the area under the curve (AUC) demonstrated poor discrimination (AUC = .55–.57). When supervised machine learning algorithms were trained on the normalized component variables and cMSKI variables, the overall training models performed well, but when the training models were tested on the testing data the models classified MSKI “by chance” (testing AUC avg = .55–.57) across all models. Composite scores and component population specific models were poor predictors of MSKI in candidates. While cMSKI, SPARTA™, and DARI™ models performed similarly, this study does not dismiss the use of commercial technologies but questions the utility of a singular screening task to predict MSKI over 10 weeks. Further investigations should evaluate occupation specific screening, serial measurements, and/or load exposure for creating MSKI risk models.