bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hourglass-shaped grafts are superior to conventional grafts for restoring knee stability and graft force at knee flexion angle of 30° following anterior cruciate ligament reconstruction: A finite element analysis
Authors: Wang Huizhi , Fang Chaohua , Tao Mingzhu , Shi Qinyi , He Kaixin , Cheng Cheng-Kung 
Published: December 2022

Background: Anterior cruciate ligament reconstruction (ACLR) using a generally columnar graft is considered the gold standard for treating anterior cruciate ligament ruptures, but such grafts cannot replicate the geometry and mechanical properties of the native anterior cruciate ligament.Purpose: To evaluate the effectiveness of an innovative hourglass-shaped graft versus a traditional columnar graft for restoring joint stability and graft force, while avoiding notch impingement following anterior cruciate ligament reconstruction.Methods: Finite element models of a human knee were developed to simulate ① An intact state, ② anterior cruciate ligament reconstruction using columnar grafts with different diameters (7.5–12 mm in 0.5 mm increments), ③ anterior cruciate ligament reconstruction using columnar grafts with different Young’s moduli (129.4, 168.0 and 362.2 MPa) and ④ anterior cruciate ligament reconstruction using hourglass-shaped grafts with different Young’s moduli. The knee model was flexed to 30° and loaded with an anterior tibial load of 103 N, internal tibial moment of 7.5 Nm, and valgus tibial moment of 6.9 Nm. The risk of notch impingement, knee stability and graft forces were compared among the different groups.Results: This study found that columnar grafts could not simultaneously restore knee stability in different degree of freedoms (DOFs) and graft force to a level similar to that of the intact knee. The anterior tibial translation and graft force were restored to a near-normal condition when the internal tibial rotation was over-restrained and valgus tibial rotation was lax. A graft diameter of at least 10 mm was needed to restore knee stability and graft force to physiological levels, but such large grafts were found to be at high risk of notch impingement. In contrast, the hourglass-shaped graft was able to simultaneously restore both knee stability and graft force at knee flexion of 30° while also having a much lower risk of impingement.Conclusion: Under knee flexion angle of 30°, an hourglass-shaped graft was better able to restore joint stability and graft force to a near-physiological level than columnar grafts, while also reducing the risk of notch impingement.
Development and validation of a nomogram for predicting significant coronary artery stenosis in suspected non-ST-segment elevation acute coronary artery syndrome with low-to-intermediate risk stratification
Authors: Chen Meixiang , Li Pengfei , Huang Yuekang , Li Shuang , Ruan Zheng , Qin Changyu , Huang Jianyu , Wang Ruixin , Lin Zhongqiu , Liu Peng , Xu Lin 
Published: December 2022

BackgroundPatients with non-ST-segment coronary artery syndrome (NSTE-ACS) have significant heterogeneity in their coronary arteries. A better assessment of significant coronary artery stenosis (SCAS) in low-to-intermediate risk NSTE-ACS patients would help identify who might benefit from invasive coronary angiography (ICA). Our study aimed to develop a multivariable-based model for pretesting SCAS in suspected NSTE-ACS with low-to-intermediate risk.MethodsThis prediction nomogram was constructed retrospectively in 469 suspected NSTE-ACS patients with low-to-intermediate risk. Patients were divided into a development group (n = 331, patients admitted to hospital before 1 May 2021) and a temporal validation group (n = 138, patients admitted to hospital since 1 May 2021). The outcome was existing SCAS, including left main artery stenosis ≥50% or any subepicardial coronary artery stenosis ≥70%, all confirmed by invasive coronary angiography. Pretest predictors were selected using Least Absolute Shrinkage and Selection Operator (LASSO) and stepwise logistic regression.ResultsDerivation analyses from the development group (n = 331, admitted before 1 May 2021) generated the 7 strongest predictors out of 25 candidate variables comprising smoker, diabetes, heart rate, cardiac troponin T, N-terminal pro-B-type natriuretic peptide, high-density lipoprotein cholesterol, and left atrial diameter. This nomogram model showed excellent discrimination ability with an area under the receiver operating characteristic curve (AUC) of 0.83 in the development set and 0.79 in the validation dataset. Good calibration was generally displayed, although it slightly overestimated patients’ SCAS risk in the validation group. Decision curve analysis demonstrated the clinical benefit of this model, indicating its value in clinical practice. Furthermore, an optimal cut-off of prediction probability was assigned as 0.61 according to the Youden index.ConclusionA prediction nomogram consisting of seven readily available clinical parameters was established to pretest the probability of SCAS in suspected NSTE-ACS patients with low-to-intermediate risk, which may serve as a cost-effective risk stratification tool and thus assist in initial decision making.
CYP2C19 metabolizer phenotypes may affect the efficacy of statins on lowering small dense low-density lipoprotein cholesterol of patients with coronary artery disease
Authors: Dai Ruozhu , Zhao Xiaoyu , Zhuo Huilin , Wang Wei , Xu Yue , Hu Zixin , Zhang Tiexu , Zhao Jiangman 
Published: December 2022

BackgroundDyslipidemia is a major cause of arteriosclerotic cardiovascular disease (ASCVD), and low-density lipoprotein cholesterol (LDL-C) is the profile to be reduced to prevent disease progression. Small dense low-density lipoprotein cholesterol (sdLDL-C) has been proven to be a more effective biomarker than LDL-C for ASCVD primary and secondary prevention. CYP2C19 is an important drug metabolism gene. This study aimed to investigate the relationship between sdLDL-C and coronary artery disease (CAD) risk factors and explore the influence of CYP2C19 metabolizer phenotypes on the sdLDL-C lowering efficacy of statins.MethodsThis study recruited 182 patients with CAD and 200 non-CAD controls. Baseline laboratory indices of fasting blood were detected, including blood lipids, glucose, and creatinine. In addition, LDL-C subfractions were separated and quantified. Gene polymorphisms of SLCO1B1 and CYP2C19 were detected in patients with CAD. The LDL-C subfractions levels of patients with CAD were followed up after statin drug treatment.ResultsTotal cholesterol, LDL-C, LDLC-2, LDLC-3, LDLC-4, LDLC-5, LDLC-6, LDLC-7, and sdLDL-C levels of patients with CAD were significantly higher than those in non-CAD controls. Meanwhile, sdLDL-C (AUC = 0.838) and LDLC-4 (AUC = 0.835) performed outstandingly in distinguishing patients with CAD from controls. Based on CYP2C19 metabolizer phenotypes, 113 patients with CAD were divided into the extensive metabolizer (EM, n = 49), intermediate metabolizer (IM, n = 52), and poor metabolizer (PM, n = 12) groups. The patients with IM and PM metabolizer phenotypes had better sdLDL-C lowering efficacy after taking statin drugs than patients with EM phenotype (P = 0.0268, FDR = 0.0536). The SLCO1B1 genotype had no significant impact on the efficacy of statins (P = 0.1611, FDR = 0.1611).ConclusionsdLDL-C and LDLC-4 outperformed other blood lipids such as LDL-C for CAD risk screening. CYP2C19 metabolizer phenotypes had the potential to predict the efficacy of statins in lowering sdLDL-C.
Assessment of aortic valve area on cardiac computed tomography in symptomatic bicuspid aortic stenosis: Utility and differences from Doppler echocardiography
Authors: Kim Kyu , Lee Soo Ji , Seo Jiwon , Suh Young Joo , Cho Iksung , Hong Geu-Ru , Ha Jong-Won , Kim Young Jin , Shim Chi Young 
Published: December 2022

BackgroundIn this study, we investigate the utility of geometric orifice area (GOA) on cardiac computed tomography (CT) and differences from effective orifice area (EOA) on Doppler echocardiography in patients with bicuspid aortic stenosis (AS).MethodsA total of 163 patients (age 64 ± 10 years, 56.4% men) with symptomatic bicuspid AS who were referred for surgery and underwent both cardiac CT and echocardiography within 3 months were studied. To calculate the aortic valve area, GOACT was measured by multiplanar CT planimetry, and EOAEcho was calculated by the continuity equation with Doppler echocardiography. The relationships between GOACT and EOAEcho and patient symptom scale, biomarkers, and left ventricular (LV) functional variables were analyzed.ResultsThere was a significant but modest correlation between EOAEcho and GOACT (r = 0.604, p &lt; 0.001). Both EOAEcho and GOACT revealed significant correlations with mean pressure gradient and peak transaortic velocity, and the coefficients were higher in EOAEcho than in GOACT. EOAEcho of 1.05 cm2 and GOACT of 1.25 cm2 corresponds to hemodynamic cutoff values for diagnosing severe AS. EOAEcho was well correlated with the patient symptom scale and log NT-pro BNP, but GOACT was not. In addition, EOAEcho had a higher correlation coefficient with estimated LV filling pressure and LV global longitudinal strain than GOACT.ConclusionGOACT can be used to evaluate the severity of bicuspid AS. The threshold for GOACT for diagnosing severe AS should be higher than that for EOAEcho. However, EOAEcho is still the method of choice because EOAEcho showed better correlations with clinical and functional variables than GOACT.
Effects of follicular output rate on cumulative clinical pregnancy rate and cumulative live birth rate in PCOS patients with different characteristics
Authors: Jiang Rulan , Cao Mingya , Hao Haomeng , Jia Rui , Chen Peipei , Liu Yuanyuan , Zhao Zhiming 
Published: December 2022

ObjectiveWe aim to explore the effects of follicular output rate (FORT) on cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR) in polycystic ovary syndrome (PCOS) patients with different characteristics undergoing in vitro fertilization (IVF) treatment.MethodsThis retrospective study analyzed 454 patients with PCOS undergoing their first IVF cycle at our center from January 2016 to December 2020. FORT was calculated as pre-ovulatory follicle count (PFC) × 100/antral follicle count (AFC). Multivariate regression analyses were conducted to explore the relationships between FORT and CCPR and CLBR. Curve fitting and threshold effect analyses were established to find nonlinear relationships. Effect modification in different subgroups were examined by stratification analyses.ResultsBased on the FORT values, individuals were classified into the following three groups: low-FORT group, middle-FORT group and high-FORT group. Multivariate regression analyses revealed that FORT was an independent factor affecting the CCPR and CLBR significantly (OR = 1.015, 95% CI: 1.001, 1.030 and OR = 1.010, 95% CI:1.001, 1.020). Curve fitting and threshold effect analyses showed that the CCPR and CLBR had a positive correlation with FORT when the FORT was less than 70% (OR = 1.039, 95% CI: 1.013, 1.065 and OR = 1.024, 95% CI: 1.004, 1.044). Stratification analyses showed that the CLBR increased by 1.3% with each additional unit of FORT for patients with hyperandrogenic manifestations (OR = 1.013, 95% CI: 1.001, 1.025). Compared with the low-FORT group, in the high-FORT group, CCPR increased 1.251 times for patients with polycystic ovarian morphology, while CCPR and CLBR increased 1.891 times and 0.99 times for those with ovulation disorder, respectively (OR = 2.251, 95% CI: 1.008, 5.028 and OR = 2.891, 95% CI: 1.332, 6.323 and OR = 1.990, 95% CI: 1.133, 3.494).ConclusionIn patients with PCOS, cumulative IVF outcomes have a positive correlation with FORT when the FORT is less than 70%. For PCOS patients with polycystic ovarian morphology, ovulation disorder or hyperandrogenic manifestations, a high FORT could be conductive to achieving better pregnancy outcomes.
CCNB1 and AURKA are critical genes for prostate cancer progression and castration-resistant prostate cancer resistant to vinblastine
Authors: Chen Xi , Ma Junjie , Wang Xin’an , Zi Tong , Qian Duocheng , Li Chao , Xu Chengdang 
Published: December 2022

BackgroundProstate cancer (PCa) is a common malignancy occurring in men. As both an endocrine and gonadal organ, prostate is closely correlated with androgen. So, androgen deprivation therapy (ADT) is effective for treating PCa. However, patients will develop castration-resistant prostate cancer (CRPC) stage after ADT. Many other treatments for CRPC exist, including chemotherapy. Vinblastine, a chemotherapeutic drug, is used to treat CRPC. However, patients will develop resistance to vinblastine. Genetic alterations have been speculated to play a critical role in CRPC resistance to vinblastine; however, its mechanism remains unclear.MethodsVarious databases, such as Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Chinese Prostate Cancer Genome and Epigenome Atlas (CPGEA), were used to collect the RNA-sequence data of PCa and CRPC patients and vinblastine-resistant PCa cells. Using online tools, Metascape and TIMER, the pathways and immune infiltration associated with vinblastine resistance-related genes in PCa were analyzed. The function of these genes was verified in clinical samples and CRPC cells.ResultsUsing GSE81277 dataset, we collected the RNA-sequence data of vinblastine sensitive and resistant LNCaP cells and found nine genes (CDC20, LRRFIP1, CCNB1, GPSM2, AURKA, EBLN2, CCDC150, CENPA and TROAP) that correlated with vinblastine resistance. Furthermore, CCNB1, GPSM2 and AURKA were differently expressed between normal prostate and PCa tissues, even influencing PCa progression. The GSE35988 dataset revealed that CCNB1 and AURKA were upregulated in PCa and CRPC samples. Various genes were also found to affect the survival status of PCa patients based on TCGA. These genes were also related to immune cell infiltration. Finally, we verified the function of CCNB1 and AURKA and observed that they were upregulated in PCa and CRPC clinical samples and increased the sensitivity of CRPC cells to vinblastine.ConclusionCCNB1 and AURKA are central to CRPC resistance to vinblastine and affect PCa progression.
The harmful intestinal microbial community accumulates during DKD exacerbation and microbiome–metabolome combined validation in a mouse model
Authors: Shang Jin , Cui Wen , Guo Ruixue , Zhang Yiding , Wang Peipei , Yu Wei , Zheng Xuejun , Wang Ting , Dong Yijun , Zhao Jing , Ding Suying , Xiao Jing , Ren Zhigang , Zhao Zhanzheng 
Published: December 2022

ObjectiveDiabetic kidney disease (DKD) is one of the most prevalent complications of diabetes mellitus (DM) and is associated with gut microbial dysbiosis. We aim to build a diagnostic model to aid clinical practice and uncover a crucial harmful microbial community that contributes to DKD pathogenesis and exacerbation.DesignA total of 528 fecal samples from 180 DKD patients and 348 non-DKD populations (138 DM and 210 healthy volunteers) from the First Affiliated Hospital of Zhengzhou University were recruited and randomly divided into a discovery phase and a validation phase. The gut microbial composition was compared using 16S rRNA sequencing. Then, the 180 DKD patients were stratified into four groups based on clinical stages and underwent gut microbiota analysis. We established DKD mouse models and a healthy fecal microbiota transplantation (FMT) model to validate the effects of gut microbiota on DKD and select the potential harmful microbial community. Untargeted metabolome–microbiome combined analysis of mouse models helps decipher the pathogenetic mechanism from a metabolic perspective.ResultsThe diversity of the gut microbiome was significantly decreased in DKD patients when compared with that of the non-DKD population and was increased in the patients with more advanced DKD stages. The DKD severity in mice was relieved after healthy gut microbiota reconstruction. The common harmful microbial community was accumulated in the subjects with more severe DKD phenotypes (i.e., DKD and DKD5 patients and DKD mice). The harmful microbial community was positively associated with the serum injurious metabolites (e.g., cholic acid and hippuric acid).ConclusionThe fecal microbial community was altered markedly in DKD. Combining the fecal analysis of both human and animal models selected the accumulated harmful pathogens. Partially recovering healthy gut microbiota can relieve DKD phenotypes via influencing pathogens’ effect on DKD mice’s metabolism.
Macrophages and γδ T cells interplay during SARS-CoV-2 variants infection
Authors: Atmeh Perla Abou , Gay Laetitia , Levasseur Anthony , La Scola Bernard , Olive Daniel , Mezouar Soraya , Gorvel Jean-Pierre , Mege Jean-Louis 
Published: December 2022

IntroductionThe emergence of several SARS-CoV-2 variants during the COVID pandemic has revealed the impact of variant diversity on viral infectivity and host immune responses. While antibodies and CD8 T cells are essential to clear viral infection, the protective role of innate immunity including macrophages has been recognized. The aims of our study were to compare the infectivity of different SARS-CoV-2 variants in monocyte-derived macrophages (MDM) and to assess their activation profiles and the role of ACE2 (Angiotensin-converting enzyme 2), the main SARS-CoV-2 receptor. We also studied the ability of macrophages infected to affect other immune cells such as γδ2 T cells, another partner of innate immune response to viral infections.ResultsWe showed that the SARS-CoV-2 variants α-B.1.1.7 (United Kingdom), β-B.1.351 (South Africa), γ-P.1 (Brazil), δ-B.1.617 (India) and B.1.1.529 (Omicron), infected MDM without replication, the γ-Brazil variant exhibiting increased infectivity for MDM. No clear polarization profile of SARS-CoV-2 variants-infected MDM was observed. The β-B.1.351 (South Africa) variant induced macrophage activation while B.1.1.529 (Omicron) was rather inhibitory. We observed that SARS-CoV-2 variants modulated ACE2 expression in MDM. In particular, the β-B.1.351 (South Africa) variant induced a higher expression of ACE2, related to MDM activation. Finally, all variants were able to activate γδ2 cells among which γ-P.1 (Brazil) and β-B.1.351 (South Africa) variants were the most efficient.ConclusionOur data show that SARS-CoV-2 variants can infect MDM and modulate their activation, which was correlated with the ACE2 expression. They also affect γδ2 T cell activation. The macrophage response to SARS-CoV-2 variants was stereotypical.
Systematic analysis of virus nucleic acid sensor DDX58 in malignant tumor
Authors: Huang Zhijian , Yi Limu , Jin Liangzi , Chen Jian , Han Yuanyuan , Zhang Yan , Shi Libin 
Published: December 2022

IntroductionIn December 2019, a novel epidemic of coronavirus pneumonia (COVID-19) was reported，and population-based studies had shown that cancer was a risk factor for death from COVID-19 infection. However, the molecular mechanism between COVID-19 and cancer remains indistinct. In this paper, we analyzed the nucleic acid sensor (DDX58) of SARS-CoV-2 virus, which is a significant gene related to virus infection. For purpose of clarifying the characteristics of DDX58 expression in malignant tumors, this study began to systematically analyze the DDX58 expression profile in the entire cancer type spectrum.MethodsUsing TCGA pan-cancer database and related data resources, we analyzed the expression, survival analysis, methylation expression, mutation status, microsatellite instability (MSI), immune related microenvironment, gene related network, function and drug sensitivity of DDX58.ResultsThe expression level of DDX58 mRNA in most cancers was higher than the expression level in normal tissues. Through TIMER algorithm mining, we found that DDX58 expression was closely related to various levels of immune infiltration in pan-cancer. The promoter methylation level of DDX58 was significantly increased in multiple cancers. In addition, abnormal expression of DDX58 was related to MSI and TMB in multiple cancers, and the most common type of genomic mutation was “mutation.” In the protein–protein interaction (PPI) network, we found that type I interferon, phagocytosis, ubiquitinase, and tumor pathways were significantly enriched. Finally, according to the expression of DDX58 indicated potential sensitive drugs such as Cediranib, VE−821, Itraconazole, JNJ−42756493, IWR−1, and Linsitinib.DiscussionIn conclusion, we had gained new insights into how DDX58 might contribute to tumor development, and DDX58 could be used as an immune-related biomarker and as a potential immunotherapeutic target for COVID-19 infected cancer patients.
Acanthamoeba spp. aggregate and encyst on contact lens material increasing resistance to disinfection
Authors: Campolo Allison , Pifer Reed , Walters Rhonda , Thomas Megan , Miller Elise , Harris Valerie , King Jamie , Rice Christopher A. , Shannon Paul , Patterson Brian , Crary Monica 
Published: December 2022

IntroductionAcanthamoeba keratitis is often caused when Acanthamoeba contaminate contact lenses and infect the cornea. Acanthamoeba is pervasive in the environment as a motile, foraging trophozoite or biocide-resistant and persistent cyst. As contact lens contamination is a potential first step in infection, we studied Acanthamoeba’s behavior and interactions on different contact lens materials. We hypothesized that contact lenses may induce aggregation, which is a precursor to encystment, and that aggregated encystment would be more difficult to disinfect than motile trophozoites.MethodsSix clinically and/or scientifically relevant strains of Acanthamoeba (ATCC 30010, ATCC 30461, ATCC 50370, ATCC 50702, ATCC 50703, and ATCC PRA-115) were investigated on seven different common silicone hydrogel contact lenses, and a no-lens control, for aggregation and encystment for 72 h. Cell count and size were used to determine aggregation, and fluorescent staining was used to understand encystment. RNA seq was performed to describe the genome of Acanthamoeba which was individually motile or aggregated on different lens materials. Disinfection efficacy using three common multi-purpose solutions was calculated to describe the potential disinfection resistance of trophozoites, individual cysts, or spheroids.ResultsAcanthamoeba trophozoites of all strains examined demonstrated significantly more aggregation on specific contact lens materials than others, or the no-lens control. Fluorescent staining demonstrated encystment in as little as 4 hours on contact lens materials, which is substantially faster than previously reported in natural or laboratory settings. Gene expression profiles corroborated encystment, with significantly differentially expressed pathways involving actin arrangement and membrane complexes. High disinfection resistance of cysts and spheroids with multi-purpose solutions was observed.DiscussionAggregation/encystment is a protective mechanism which may enable Acanthamoeba to be more disinfection resistant than individual trophozoites. This study demonstrates that some contact lens materials promote Acanthamoeba aggregation and encystment, and Acanthamoeba spheroids obstruct multi-purpose solutions from disinfecting Acanthamoeba.