bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel cuproptosis-related gene signature for predicting prognosis in cervical cancer
Authors: Lei Lei , Tan Liao , Sui Long 
Published: August 2022

Purpose: Cuproptosis, a form of copper-induced cell death, can be a promising therapeutic target for refractory cancers. Hence, we conducted this research to explore the association between cuproptosis and prognosis in cervical cancer (CC).Methods: For constructing a prognostic signature based on cuproptosis-related genes from TCGA database, the least absolute shrinkage and selection operator Cox regression was utilized. The GSE44001 cohort was utilized for validation.Results: A total of nine cuproptosis-related genes showed distinct expression in CC and normal samples in TCGA-GTEx cohort. Two risk groups were identified based on a seven-gene signature. A significant decrease in overall survival was observed in the high-risk group (p &lt; 0.001). The risk score (HR = 2.77, 95% CI = 1.58–4.86) was an autocephalous predictor with a better predictive ability than the clinical stage. Functional analysis indicated that immune activities were suppressed more in the high-risk group than in the low-risk group. A total of 11 candidate compounds targeting the signature were identified.Conclusion: A total of seven cuproptosis-related gene signatures were constructed to predict prognosis and propose a new therapeutic target for patients with CC.
Incidence of Down Syndrome by maternal age in Chinese population
Authors: Song Yi , Jieping Song , Tianshu Zhou , Zhijun Zhang , Jingxuan Zhang , Bo Wang 
Published: August 2022

Objective: This study aims to estimate the maternal age-related risk of Down syndrome in an Asian population.Methods: We performed a retrospective data analysis including a total of 206,295 pregnant women who presented for second-trimester maternal serum screening for Down syndrome at Hubei Maternal and Child Health Hospital for the years 2008–2017. Cases were assigned to three groups: ≤26 years of age, 27–33 years of age, and ≥34 years of age. The incidence of Down Syndrome was calculated for each age group. The differences between groups were tested using the chi-square (χ2) test.Results: The incidence of Down syndrome in women ≤26 years of age, 27–33 years of age, and ≥34 years of age was 0.67‰, 0.29‰, and 2.07‰ respectively. Statistically significant difference was found between the three age groups (χ2 = 79.748, p &lt; 0.05).Conclusion: Down syndrome rate was significantly higher in women ≥34 years of age. Younger women (≤26 years of age) had a significantly higher risk for Down’s syndrome, compared to women aged 27–33.
Serum cytokine levels are associated with tumor progression during FOLFIRINOX chemotherapy and overall survival in pancreatic cancer patients
Authors: van der Sijde Fleur , Dik Willem A. , Mustafa Dana A. M. , Vietsch Eveline E. , Besselink Marc G. , Debets Reno , Koerkamp Bas Groot , Haberkorn Brigitte C. M. , Homs Marjolein Y. V. , Janssen Quisette P. , Luelmo Saskia A. C. , Mekenkamp Leonie J. M. , Oostvogels Astrid A. M. , Smits-te Nijenhuis Marja A. W. , Wilmink Johanna W. , van Eijck Casper H. J. ,   the Dutch Pancreatic Cancer Group
Published: August 2022

BackgroundBiomarkers predicting treatment response may be used to stratify patients with pancreatic ductal adenocarcinoma (PDAC) for available therapies. The aim of this study was to evaluate the association of circulating cytokines with FOLFIRINOX response and with overall survival (OS).MethodsSerum samples were collected before start and after the first cycle of FOLFIRINOX from patients with PDAC (n=83) of all disease stages. Overall, 34 circulating cytokines were analyzed with a multiplex immunoassay. In addition, changes in peripheral blood immune cell counts were determined by flow cytometry to correlate with differences in cytokine levels. Chemotherapy response was determined by CT scans with the RECIST 1.1 criteria, as disease control (n=64) or progressive disease (n=19) within eight cycles of FOLFIRINOX.ResultsPatients with high serum IL-1RA concentrations after one cycle of chemotherapy were less likely to have tumor progression during FOLFIRINOX (OR 0.25,P=0.040). Increase of circulating IL-1RA concentrations correlated with increase of total, classical (CD14+CD16-), and non-classical monocytes (CD14-CD16+), and dendritic cells. In multivariable cox regression, including the variables chemotherapy response outcome and baseline CA19-9 level, serum concentrations of IL-7 (HR 2.14,P=0.010), IL-18 (HR 2.00,P=0.020), and MIP-1β (HR 0.51,P=0.025) after one cycle of FOLFIRINOX showed correlations with OS.ConclusionsCirculating IL-1RA, IL-7, IL-18, and MIP-1β concentrations are biomarkers associated with FOLFIRINOX response in PDAC patients, suggesting an important role for specific immune cells in chemotherapy response and PDAC progression. Cytokine-based treatment might improve patient outcome and should be evaluated in future studies.
MMKP: A mind mapping knowledgebase prototyping tool for precision medicine
Authors: Liang Siliang , Li Yun , Dong Qingling , Chen Xin 
Published: August 2022

BackgroundWith significant advancements in the area of precision medicine, the breadth and complexity of the relevant knowledge in the field has increased significantly. However, the difficulty associated with dynamic modelling and the disorganization of such knowledge hinders its rapid development potential.ResultsTo overcome the difficulty in using the relational database model for dynamic modelling, and to aid in the organization of precision medicine knowledge, we developed the Mind Mapping Knowledgebase Prototyping (MMKP) tool. The MMKP implements a novel design that we call a “polymorphic foreign key”, which allows the establishment of a logical linkage between a single table field and a record from any table. This design has advantages in supporting dynamic changes to the structural relationships in precision medicine knowledge. Knowledge stored in MMKP is presented as a mind map to facilitate human interaction. When using this tool, medical experts may curate the structure and content of the precision knowledge in a flow that is similar to the human thinking process.ConclusionsThe design of polymorphic foreign keys natively supports knowledge modelling in the form of mind mapping, which avoids the hard-coding of medical logic into a rigid database schema and significantly reduces the workload that is required for adapting a relational data model to future changes to the medical logic. The MMKP tool provides a graphical user interface for both data management and knowledgebase prototyping. It supports the flexible customization of the data field constraints and annotations. MMKP is available as open-source code on GitHub: https://github.com/ZjuLiangsl/mmkp.
Identification and validation of an anoikis-associated gene signature to predict clinical character, stemness, IDH mutation, and immune filtration in glioblastoma
Authors: Sun Zhongzheng , Zhao Yongquan , Wei Yan , Ding Xuan , Tan Chenyang , Wang Chengwei 
Published: August 2022

BackgroundGlioblastoma (GBM) is the most prominent and aggressive primary brain tumor in adults. Anoikis is a specific form of programmed cell death that plays a key role in tumor invasion and metastasis. The presence of anti-anoikis factors is associated with tumor aggressiveness and drug resistance.MethodsThe non-negative matrix factorization algorithm was used for effective dimension reduction for integrated datasets. Differences in the tumor microenvironment (TME), stemness indices, and clinical characteristics between the two clusters were analyzed. Difference analysis, weighted gene coexpression network analysis (WGCNA), univariate Cox regression, and least absolute shrinkage and selection operator regression were leveraged to screen prognosis-related genes and construct a risk score model. Immunohistochemistry was performed to evaluate the expression of representative genes in clinical specimens. The relationship between the risk score and the TME, stemness, clinical traits, and immunotherapy response was assessed in GBM and pancancer.ResultsTwo definite clusters were identified on the basis of anoikis-related gene expression. Patients with GBM assigned to C1 were characterized by shortened overall survival, higher suppressive immune infiltration levels, and lower stemness indices. We further constructed a risk scoring model to quantify the regulatory patterns of anoikis-related genes. The higher risk score group was characterized by a poor prognosis, the infiltration of suppressive immune cells and a differentiated phenotype, whereas the lower risk score group exhibited the opposite effects. In addition, patients in the lower risk score group exhibited a higher frequency of isocitrate dehydrogenase (IDH) mutations and a more sensitive response to immunotherapy. Drug sensitivity analysis was performed, revealing that the higher risk group may benefit more from drugs targeting the PI3K/mTOR signaling pathway.ConclusionWe revealed potential relationships between anoikis-related genes and clinical features, TME, stemness, IDH mutation, and immunotherapy and elucidated their therapeutic value.
Mucosal immune and stress responses of Neoparamoeba perurans-infected Atlantic salmon (Salmo salar) treated with peracetic acid shed light on the host-parasite-oxidant interactions
Authors: Lazado Carlo C. , Strand David A. , Breiland Mette W. , Furtado Francisco , Timmerhaus Gerrit , Gjessing Mona C. , Hytterød Sigurd , Merkin Grigory V. , Pedersen Lars-Flemming , Pittman Karin A. , Krasnov Aleksei 
Published: August 2022

Treatment development for parasitic infestation is often limited to disease resolution as an endpoint response, and physiological and immunological consequences are not thoroughly considered. Here, we report the impact of exposing Atlantic salmon affected with amoebic gill disease (AGD) to peracetic acid (PAA), an oxidative chemotherapeutic. AGD-affected fish were treated with PAA either by exposing them to 5 ppm for 30 min or 10 ppm for 15 min. Unexposed fish from both infected and uninfected groups were also included. Samples for molecular, biochemical, and histological evaluations were collected at 24 h, 2 weeks, and 4 weeks post-treatment. Behavioral changes were observed during PAA exposure, and post-treatment mortality was higher in the infected and PAA treated groups, especially in 10 ppm for 15 min. Plasma indicators showed that liver health was affected by AGD, though PAA treatment did not exacerbate the infection-related changes. Transcriptome profiling in the gills showed significant changes, triggered by AGD and PAA treatments, and the effects of PAA were more notable 24 h after treatment. Genes related to immune pathways of B- and T- cells and protein synthesis and metabolism were downregulated, where the magnitude was more remarkable in 10 ppm for 15 min group. Even though treatment did not fully resolve the pathologies associated with AGD, 5 ppm for 30 min group showed lower parasite load at 4 weeks post-treatment. Mucous cell parameters (i.e., size and density) increased within 24 h post-treatment and were significantly higher at termination, especially in AGD-affected fish, with some treatment effects influenced by the dose of PAA. Infection and treatments resulted in oxidative stress—in the early phase in the gill mucosa, while systemic reactive oxygen species (ROS) dysregulation was evident at the later stage. Infected fish responded to elevated circulating ROS by increasing antioxidant production. Exposing the fish to a crowding stress revealed the interference in the post-stress responses. Lower cortisol response was displayed by AGD-affected groups. Collectively, the study established that PAA, within the evaluated treatment protocols, could not provide a convincing treatment resolution and, thus, requires further optimization. Nonetheless, PAA treatment altered the mucosal immune and stress responses of AGD-affected Atlantic salmon, shedding light on the host-parasite-treatment interactions.
Comprehensive analysis of a novel signature incorporating lipid metabolism and immune-related genes for assessing prognosis and immune landscape in lung adenocarcinoma
Authors: Wang Yuli , Xu Jing , Fang Yuan , Gu Jiefei , Zhao Fanchen , Tang Yu , Xu Rongzhong , Zhang Bo , Wu Jianchun , Fang Zhihong , Li Yan 
Published: August 2022

BackgroundAs the crosstalk between metabolism and antitumor immunity continues to be unraveled, we aim to develop a prognostic gene signature that integrates lipid metabolism and immune features for patients with lung adenocarcinoma (LUAD).MethodsFirst, differentially expressed genes (DEGs) related to lipid metabolism in LUAD were detected, and subgroups of LUAD patients were identified via the unsupervised clustering method. Based on lipid metabolism and immune-related DEGs, variables were determined by the univariate Cox and LASSO regression, and a prognostic signature was established. The prognostic value of the signature was evaluated by the Kaplan–Meier method, time-dependent ROC, and univariate and multivariate analyses. Five independent GEO datasets were employed for external validation. Gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and immune infiltration analysis were performed to investigate the underlying mechanisms. The sensitivity to common chemotherapeutic drugs was estimated based on the GDSC database. Finally, we selected PSMC1 involved in the signature, which has not been reported in LUAD, for further experimental validation.ResultsLUAD patients with different lipid metabolism patterns exhibited significant differences in overall survival and immune infiltration levels. The prognostic signature incorporated 10 genes and stratified patients into high- and low-risk groups by median value splitting. The areas under the ROC curves were 0.69 (1-year), 0.72 (3-year), 0.74 (5-year), and 0.74 (10-year). The Kaplan–Meier survival analysis revealed a significantly poorer overall survival in the high-risk group in the TCGA cohort (p &lt; 0.001). In addition, both univariate and multivariate Cox regression analyses indicated that the prognostic model was the individual factor affecting the overall survival of LUAD patients. Through GSEA and GSVA, we found that tumor progression and inflammatory and immune-related pathways were enriched in the high-risk group. Additionally, patients with high-risk scores showed higher sensitivity to chemotherapeutic drugs. The in vitro experiments further confirmed that PSMC1 could promote the proliferation and migration of LUAD cells.ConclusionsWe developed and validated a novel signature incorporating both lipid metabolism and immune-related genes for all-stage LUAD patients. This signature can be applied not only for survival prediction but also for guiding personalized chemotherapy and immunotherapy regimens.
Effect of atorvastatin on skeletal muscles of patients with knee osteoarthritis: Post-hoc analysis of a randomised controlled trial
Authors: Lim Yuan Z. , Cicuttini Flavia M. , Wluka Anita E. , Jones Graeme , Hill Catherine L. , Forbes Andrew B. , Tonkin Andrew , Berezovskaya Sofia , Tan Lynn , Ding Changhai , Wang Yuanyuan 
Published: August 2022

ObjectivePopulations with knee osteoarthritis (KOA) are at increased risk of cardiovascular disease, due to higher prevalence of risk factors including dyslipidaemia, where statins are commonly prescribed. However, the effect of statins on muscles and symptoms in this population is unknown. Thus, this study examined the effect of atorvastatin on muscle properties in patients with symptomatic KOA.DesignPost-hoc analysis of a 2-year multicentre randomised, double-blind, placebo-controlled trial.SettingAustralian community.ParticipantsParticipants aged 40–70 years (mean age 55.7 years, 55.6% female) with KOA who met the American College of Rheumatology clinical criteria received atorvastatin 40 mg daily (n = 151) or placebo (n = 153).Main outcome measuresLevels of creatinine kinase (CK), aspartate transaminase (AST), and alanine transaminase (ALT) at 1, 6, 12, and 24 months; muscle strength (by dynamometry) at 12 and 24 months; vastus medialis cross-sectional area (CSA) on magnetic resonance imaging at 24 months; and self-reported myalgia.ResultsThere were no significant between-group differences in CK and AST at all timespoints. The atorvastatin group had higher ALT than placebo group at 1 (median 26 vs. 21, p = 0.004) and 6 (25 vs. 22, p = 0.007) months without significant between-group differences at 12 and 24 months. Muscle strength increased in both groups at 24 months without between-group differences [mean 8.2 (95% CI 3.5, 12.9) vs. 5.9 (1.3, 10.4), p = 0.49]. Change in vastus medialis CSA at 24 months favoured the atorvastatin group [0.11 (−0.10, 0.31) vs. −0.23 (−0.43, −0.03), p = 0.02] but of uncertain clinical significance. There was a trend for more myalgia in the atorvastatin group (8/151 vs. 2/153, p = 0.06) over 2 years, mostly occurring within 6 months (7/151 vs. 1/153, p = 0.04).ConclusionsIn those with symptomatic KOA, despite a trend for more myalgia, there was no clear evidence of an adverse effect of atorvastatin on muscles, including those most relevant to knee joint health.
COL17A1 editing via homology-directed repair in junctional epidermolysis bullosa
Authors: Petković Igor , Bischof Johannes , Kocher Thomas , March Oliver Patrick , Liemberger Bernadette , Hainzl Stefan , Strunk Dirk , Raninger Anna Maria , Binder Heide-Marie , Reichelt Julia , Guttmann-Gruber Christina , Wally Verena , Piñón Hofbauer Josefina , Bauer Johann Wolfgang , Koller Ulrich 
Published: August 2022

BackgroundEpidermolysis bullosa (EB), a severe genetic disorder characterized by blister formation in skin, is caused by mutations in genes encoding dermal-epidermal junction proteins that function to hold the skin layers together. CRISPR/Cas9-induced homology-directed repair (HDR) represents a promising tool for editing causal mutations in COL17A1 in the treatment of junctional epidermolysis bullosa (JEB).MethodsIn this study, we treated primary type XVII collagen (C17)-deficient JEB keratinocytes with either Cas9 nuclease or nickase (Cas9n) ribonucleoproteins (RNP) and a single-stranded oligonucleotide (ssODN) HDR template in order to correct a causal pathogenic frameshift mutation within the COL17A1 gene.ResultsAs analyzed by next-generation sequencing of RNP-nucleofected keratinocytes, we observed an HDR efficiency of ∼38% when cells were treated with the high-fidelity Cas9 nuclease, a mutation-specific sgRNA, and an ssODN template. The combined induction of end-joining repair and HDR-mediated pathways resulted in a C17 restoration efficiency of up to 60% as assessed by flow cytometry. Furthermore, corrected JEB keratinocytes showed a significantly increased adhesive strength to laminin-332 and an accurate deposition of C17 along the basement membrane zone (BMZ) upon differentiation into skin equivalents.ConclusionHere we present a gene editing approach capable of reducing end joining-generated repair products while increasing the level of seamless HDR-mediated gene repair outcomes, thereby providing a promising CRISPR/Cas9-based gene editing approach for JEB.
Natural, longitudinal recovery of adults with COVID-19 using standardized rehabilitation measures
Authors: Ciro Carrie A. , James Shirley A. , McGuire Hillary , Lepak Vince , Dresser Susan , Costner-Lark Amy , Robinson Wanda , Fritz Terrie 
Published: August 2022

BackgroundWhile studies recommend rehabilitation following post-hospitalization recovery from COVID-19, few implement standardized tools to assess continued needs. The aim of this study was to identify post-hospitalization recommendations using an interdisciplinary needs assessment with standardized rehabilitation measures. A secondary aim was to use these tools to measure recovery over a 30-day period.Materials and methodsUsing a 30-day longitudinal design, we completed weekly rapid needs assessments in this convenience sample of 20 people diagnosed with COVID-19 discharged from the hospital to home. We computed summary statistics and used the Wilcoxon Signed Rank Test to assess change over the 4-week course of the study with alpha level = 0.05.ResultsOur sample (65% male, 47% over 50 years of age, 35% White, 37% with a confirmed diagnosis of diabetes, and 47% obese) included no patients who had required mechanical ventilation. Initial assessments demonstrated the majority of our participants were at an increased risk of falls, had disability in activities of daily living (ADL) and instrumental activities of daily living (IADL), mild cognitive impairment, and dyspnea. At the 30-day follow-up, most were independent in mobility and basic ADLs, with continued disability in IADLs and cognitive function.DiscussionIn this sample of patients who were not mechanically-ventilated, early and individualized rehabilitation was necessary. The results of this study suggest patients would benefit from a multi-disciplinary team needs assessment after medical stabilization to minimize fall risk and disability, and to prevent secondary complications resulting from post-hospital deconditioning due to COVID-19.
The application value of CT radiomics features in predicting pressure amplitude correlation index in patients with severe traumatic brain injury
Authors: Liu Jiaqi , Shan Yingchi , Gao Guoyi 
Published: August 2022

PurposeTo explore the application value of a machine learning model based on CT radiomics features in predicting the pressure amplitude correlation index (RAP) in patients with severe traumatic brain injury (sTBI).MethodsRetrospectively analyzed the clinical and imaging data in 36 patients with sTBI. All patients underwent surgical treatment, continuous ICP monitoring, and invasive arterial pressure monitoring. The pressure amplitude correlation index (RAP) was collected within 1 h after surgery. Three volume of interest (VOI) was selected from the craniocerebral CT images of patients 1 h after surgery, and a total of 93 radiomics features were extracted from each VOI. Three models were established to be used to evaluate the patients' RAP levels. The accuracy, precision, recall rate, F1 score, receiver operating characteristic (ROC) curve, and area under the curve (AUC) were used to evaluate the predictive performance of each model.ResultsThe optimal number of features for three predicting models of RAP was five, respectively. The accuracy of predicting the model of the hippocampus was 77.78%, precision was 88.24%, recall rate was 60%, the F1 score was 0.6, and AUC was 0.88. The accuracy of predicting the model of the brainstem was 63.64%, precision was 58.33%, the recall rate was 60%, the F1 score was 0.54, and AUC was 0.82. The accuracy of predicting the model of the thalamus was 81.82%, precision was 88.89%, recall rate was 75%, the F1 score was 0.77, and AUC was 0.96.ConclusionsCT radiomics can predict RAP levels in patients with sTBI, which has the potential to establish a method of non-invasive intracranial pressure (NI-ICP) monitoring.