bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal assessment of motor function following the unilateral intrastriatal 6-hydroxydopamine lesion model in mice
Authors: Sun Xiuping , Li Xianglei , Zhang Ling , Zhang Yu , Qi Xiaolong , Wang Siyuan , Qin Chuan 
Published: November 2022

IntroductionDespite the widespread use of the unilateral striatal 6-hydroxydopamine (6-OHDA) lesion model in mice in recent years, the stability of behavioral deficits in the 6-OHDA striatal mouse model over time is not yet clear, raising concerns about using this model to evaluate a compound’s long-term therapeutic effects.Materials and methodsIn the current study, mice were tested at regular intervals in the cylinder test and gait analysis beginning 3 days after 6-OHDA injection of 4 and 8 μg and lasting until 56 days post-lesion. Apomorphine-induced rotational test and rotarod test were also performed on Day 23 and 43 post-lesion, respectively. Immunohistochemistry for dopaminergic neurons stained by tyrosine hydroxylase (TH) was also performed.ResultsOur results showed that both the 4 and 8 μg 6-OHDA lesion groups exhibited forelimb use asymmetry with a preference for the ipsilateral (injection) side on Day 3 and until Day 21 post-lesion, but did not show forelimb asymmetry on Day 28 to 56 post-lesion. The 8 μg 6-OHDA lesion group still exhibited forelimb asymmetry on Day 28 and 42 post-lesion, but not on Day 56. The gait analysis showed that the contralateral front and hind step cycles increased from Day 3 to 42 post-lesion and recovered on Day 56 post-lesion. In addition, our results displayed a dose-dependent reduction in TH+ cells and TH+ fibers, as well as dose-dependent apomorphine-induced rotations. In the rotarod test, the 8 μg 6-OHDA lesion group, but not the 4 μg group, decreased the latency to fall on the rotarod on Day 43 post-lesion.ConclusionIn summary, unilateral striatal 6-OHDA injections of 4 and 8 μg induced spontaneous motor impairment in mice, which partially recovered starting on Day 28 post-lesion. Forced motor deficits were observed in the 8 g 6-OHDA lesion group, which remained stable on Day 43 post-lesion. In addition, the rotarod test and apomorphine-induced rotational test can distinguish between lesions of different extents and are useful tools for the assessment of functional recovery in studies screening novel potential therapies.
Structure and activity alteration in adult highland residents' cerebrum: Voxel-based morphometry and amplitude of low-frequency fluctuation study
Authors: Zhong Minzhi , Zeng Huaqu , Wang Dongye , Li Jiesheng , Duan Xuguang , Li Yong 
Published: November 2022

IntroductionPeople living in highland areas may have factors that allow them to adapt to chronic hypoxia, but these physiological mechanisms remain unclear. This study aimed to investigate the brain mechanism in a cohort of adult residents of Tibet, a well-known plateau section in China, by observing differences in brain structure and function in non-plateau populations.MethodsThe study included 27 Tibetan and 27 non-plateau region residents who were matched in age, sex, and education. All participants underwent high-resolution three-dimensional T1 weighted imaging (3D-T1WI) and resting-state functional magnetic resonance imaging (rs-fMRI) scans on a 1.5 Tesla MR. Gray matter volumes and regional spontaneous neuronal activity (SNA) were calculated and compared between the two groups.ResultsWhen comparing gray matter in people living in high altitudes to those living in the flatlands, the results showed positive activation of gray matter in local brain regions (p &lt; 0.05, false discovery rate (FDR) corrected), in the right postcentral [automated atomic labeling (aal)], left postcentral (aal), and right lingual (aal) regions. Comparing the people of high altitude vs. flat land in the brain function study (p &lt; 0.05, FDR corrected), positive activation was found in the right superior motor area (aal) and left superior frontal (aal), and negative activation was found in the right precuneus (aal).ConclusionIn high-altitude individuals, larger regional gray matter volumes and higher SNA may represent a compensatory mechanism to adapt to chronic hypoxia.
Association between tea consumption and prevention of coronary artery disease: A systematic review and dose-response meta-analysis
Authors: Yang Xin , Dai Haiyun , Deng Ruihang , Zhang Ziang , Quan Yiwen , Giri Mohan , Shen Jian 
Published: November 2022

BackgroundEvidence from previous studies reporting on the relationship between tea consumption and its preventive effect on coronary artery disease (CAD) has conflicting outcomes. With the accumulation of new clinical evidence, we conducted this meta-analysis to assess tea consumption and CAD risk.MethodsWe searched PubMed, EMBASE, Cochrane Library, and Medline databases for published observational studies from their inception to May 2022. A random-effects model was used to calculate risk ratios with 95% confidence intervals. We also conducted linear and non-linear dose-response meta-analyses to analyze the association. We regarded that one cup equals 237 mL. Subgroup analyses and univariate meta-regression were conducted to explore the source of heterogeneity.ResultsA total of 35 studies, including 24 on green tea and 11 on black tea consumption, were included in this meta-analysis. An inverse association for the risk of CAD was observed for black tea (RR: 0.85; 95% CI: 0.76, 0.96) and green tea (RR: 0.93; 95% CI: 0.88, 0.99). The dose-response meta-analysis showed that drinking less than four cups of black tea daily may effectively prevent CAD, while more than 4–6 cups/d will promote disease risk. Furthermore, the dose-response relationship between green tea consumption and the prevention of CAD showed that the risk of CAD gradually decreased as green tea consumption increased. We also demonstrated that the more cups of green tea consumed, the lower the risk of CAD. In the subgroup analysis by continent, a significant negative correlation between CAD risk and green tea consumption was observed in the Asian population (RR: 0.92; 95% CI: 0.85, 0.99) but not in the western population [North America (RR: 0.97; 95% CI: 0.92, 1.03), Europe/Oceana (RR: 0.91; 95% CI: 0.78, 1.07)].ConclusionsHigher green tea consumption was associated with reduced CAD risk, but drinking more than 4–6 cups of black tea per day may increase the risk. This study offers new insight into the relationship between tea consumption and its preventive effect on CAD. However, further large prospective cohort studies are needed to validate these findings.Systematic review registrationThe protocol of this systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) system (CRD42022348069).
Association between triglyceride-glucose index and worsening renal function in the elderly
Authors: Lei Li , Liang Hongbin , Qu Yali , Zhong Qianhong , Zhang Qiuxia , Dai Lei , Lu Junyan , Xiao Min , Zhao Zhimeng , Zhou Fengyun , Li Yun , Hu Guifang , Xiu Jiancheng , Zhang Xinlu 
Published: November 2022

BackgroundTriglyceride-glucose (TyG) index is a simple marker of insulin resistance. However, insufficient data is available on whether the TyG index is associated with worsening renal function (WRF) in the elderly. Therefore, this study was designed to explore the association between the TyG index and WRF based on a community elderly cohort.MethodsIn this study, 7,822 elderly (aged ≥ 65 years) adults from southern China were enrolled and divided into four groups according to the TyG index quartiles. The primary endpoint was incident chronic kidney disease (CKD), defined as incident estimated glomerular filtration rate (eGFR) &lt; 60 mL/min/1.73 m2. Additional endpoints included a decline in eGFR of 30% and 40% during the follow-up period.ResultsDuring the median 2.04 year follow-up period, 1,541 (19.7%) participants developed CKD. After adjusting for confounding factors, multivariable Cox regression models revealed significant associations between TyG index and incident CKD (HR per SD increase, 1.21; 95% CI: 1.14–1.29), a decline in eGFR of 30% (HR per SD increase, 1.38; 95% CI: 1.26–1.50), and decline in eGFR of 40% (HR per SD increase, 1.42; 95% CI: 1.24–1.63). Furthermore, compared with those in Q1, participants in Q4 demonstrated a higher risk of developing CKD (HR, 1.59; 95% CI: 1.35–1.88). These positive associations remained consistent across different subgroup populations.ConclusionOur study suggests a positive and independent association between the TyG index and WRF in the elderly.
Skin cancer outcomes and risk factors in renal transplant recipients: Analysis of organ procurement and transplantation network data from 2000 to 2021
Authors: Hao Xiaowei , Lai Wenhui , Xia Xinze , Xu Junnan , Wu Yangyang , Lv Chao , Meng Qingyang , Lv Kaikai , Huang Shuai , Luo Zhenjun , Dong Jun , Yuan Qing 
Published: November 2022

PurposePosttransplant skin cancer is the most common malignancy after patients have undergone renal transplantation. Through comprehensive observation with a large sample size nationwide, understanding the risk factors and outcome of posttransplant skin cancer will help to develop appropriate patient surveillance and disease prevention strategies.Materials and methodsThis retrospective population-based cohort study was based on Organ Procurement and Transplantation Network data released in March 2021. Characteristics and outcomes, including patient survival and graft survival of recipients, were compared. Risk factors for posttransplant skin cancer, cancer onset momentum, and mortality were determined.ResultsA total of 199,564 renal transplant recipients were included. After renal transplantation, 7,334 (3.68%), 6,093 (3.05%), and 936 (0.47%) were diagnosed with squamous cell carcinoma, basal cell carcinoma, and melanoma, respectively. Skin cancer was the major cause of death (squamous cell carcinoma: 23.8%, basal cell carcinoma: 18%, and melanoma: 41.6%). Five-year survival rates ranked from best to worst were as follows: basal cell carcinoma (96.7 [95% confidence interval: 96.3–97.2]%), squamous cell carcinoma (94.1 [93.5–94.6]%), melanoma (89.7 [87.7–91.6]%), and cancer-free (87.4 [87.2–87.5]%) (p &lt; 0.001 for all except melanoma vs. cancer-free, p = 0.534). Regarding graft survival, death-censored graft survival, posttransplant skin cancer, and melanoma were significantly better than the cancer-free group (p &lt; 0.001). Independent risk factors for developing posttransplant skin cancer included older age, male sex, Caucasian race, pretransplant malignancy, polycystic kidney disease-induced end-stage renal disease (ESRD), retransplantation, private health insurance, T-cell depletion induction, and tacrolimus/mycophenolic acid use. Caucasian race and pretransplant malignancy were independent risk factors for posttransplant skin cancer onset momentum. Male sex, Caucasian race, pretransplant malignancy, hypertension- or diabetes-induced ESRD, retransplantation, diabetes history, deceased donor, cyclosporin, and mTOR inhibitor use were independent risk factors for posttransplant skin cancer mortality.ConclusionAlthough posttransplant skin cancer is a major cause of recipient death, information regarding its impact on patient and graft survival is limited. Given the differences regarding risk factors for posttransplant skin cancer incidence, onset momentum, and mortality, personalized approaches to screening may be appropriate to address the complex issues encountered by kidney transplant recipients.
Prognostic analysis of pT1-T2aN0M0 cervical adenocarcinoma based on random survival forest analysis and the generation of a predictive nomogram
Authors: Ouyang Dong , Shi Mengting , Wang Yiman , Luo Limin , Huang Luzhong 
Published: November 2022

BackgroundThe efficacy of adjuvant radiotherapy for postoperative patients with early-stage cervical adenocarcinoma who are lymph node-negative is still inconclusive. Establishing a nomogram to predict the prognosis of such patients could facilitate clinical decision-making.MethodsWe recruited 4636 eligible patients with pT1-T2aN0M0 cervical adenocarcinoma between 2004 and 2016 from the Surveillance, Epidemiology and End Results (SEER) database. Random survival forest (RSF) and conditional survival forest (CSF) model was used to assess the prognostic importance of each clinical characteristic variable. We identified independent prognostic factors associated with overall survival (OS) by univariate and multivariate Cox regression risk methods and then constructed a nomogram. We stratified patients based on nomogram risk scores and evaluated the survival benefit of different adjuvant therapies. To reduce confounding bias, we also used propensity score matching (PSM) to match the cohorts before performing survival analyses.ResultsThe RSF and CSF model identified several important variables that are associated with prognosis, including grade, age, radiotherapy and tumor size. Patients were randomly divided into training and validation groups at a ratio of 7:3. Multivariate cox analysis revealed that age, grade, tumor size, race, radiotherapy and histology were independent prognostic factors for overall survival. Using these variables, we then constructed a predictive nomogram. The C-index value for evaluating the prognostic nomogram fluctuated between 0.75 and 0.91. Patients were divided into three subgroups based on risk scores, and Kaplan-Meier (K-M) survival analysis revealed that in the low-risk group, postoperative chemotherapy alone was associated with a significantly worse OS than surgery alone. Following PSM, survival analysis showed that compared with surgery alone, radiotherapy was associated with a worse OS in the training group although there was no significant difference in the validation group.ConclusionsFor patients with pT1-T2aN0M0 cervical adenocarcinoma, adjuvant treatments such as postoperative radiotherapy or chemotherapy, compared with surgery alone, are of no benefit with regards to patient survival. Our prognostic nomogram exhibits high accuracy for predicting the survival of patients with early-stage postoperative cervical adenocarcinoma.
Repeated trans-arterial treatments of LDL-DHA nanoparticles induce multiple pathways of tumor cell death in hepatocellular carcinoma bearing rats
Authors: Wang Yuzhu , Li Junjie , Vale Goncalo Dias do , Chaudhary Jaideep , Anwar Arnida , McDonald Jeffrey G. , Qin Tao , Zhang Hongwei , Corbin Ian R. 
Published: November 2022

IntroductionRepeated hepatic arterial delivery of therapeutic agents to the liver by percutaneously implanted port-catheter systems has been widely used to treat unresectable liver cancer. This approach is applied to assess the therapeutic efficacy of repeated low-density lipoprotein-docosahexaenoic acid (LDL-DHA) nanoparticle treatments in a rat model of hepatocellular carcinoma.MethodsN1S1 hepatoma bearing rats underwent placement of a percutaneously implanted hepatic artery port-catheter system and were allocated to untreated, control LDL-triolein (LDL-TO) or LDL-DHA nanoparticle infusions groups. Treatments were performed every three days over a nine day study period. MRI was performed at baseline and throughout the study. At the end of the study tissue samples were collected for analyses.Results and DiscussionImplantation of the port catheters was successful in all rats. MRI showed that repeated infusions of LDL-DHA nanoparticles significantly impaired the growth of the rat hepatomas eventually leading to tumor regression. The tumors in the LDL-TO treated group showed delayed growth, while the untreated tumors grew steadily throughout the study. Histopathology and MRI support these findings demonstrating extensive tumor necrosis in LDL-DHA treated groups while the control groups displayed minor necrosis. Molecular and biochemical analyses also revealed that LDL-DHA treated tumors had increased levels of nuclear factor-kappa B and lipid peroxidation and depletion of glutathione peroxidase 4 relative to the control groups. Evidence of both ferroptosis and apoptosis tumor cell death was observed following LDL-DHA treatments. In conclusion repeated transarterial infusions of LDL-DHA nanoparticles provides sustained repression of tumor growth in a rat hepatoma model.
PET/CT radiomics for prediction of hyperprogression in metastatic melanoma patients treated with immune checkpoint inhibitors
Authors: Gabryś H. S. , Basler L. , Burgermeister S. , Hogan S. , Ahmadsei M. , Pavic M. , Bogowicz M. , Vuong D. , Tanadini-Lang S. , Förster R. , Kudura K. , Huellner M. , Dummer R. , Levesque M. P. , Guckenberger M. 
Published: November 2022

PurposeThis study evaluated pretreatment 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET/CT-based radiomic signatures for prediction of hyperprogression in metastatic melanoma patients treated with immune checkpoint inhibition (ICI).Material and methodFifty-six consecutive metastatic melanoma patients treated with ICI and available imaging were included in the study and 330 metastatic lesions were individually, fully segmented on pre-treatment CT and FDG-PET imaging. Lesion hyperprogression (HPL) was defined as lesion progression according to RECIST 1.1 and doubling of tumor growth rate. Patient hyperprogression (PD-HPD) was defined as progressive disease (PD) according to RECIST 1.1 and presence of at least one HPL. Patient survival was evaluated with Kaplan-Meier curves. Mortality risk of PD-HPD status was assessed by estimation of hazard ratio (HR). Furthermore, we assessed with Fisher test and Mann-Whitney U test if demographic or treatment parameters were different between PD-HPD and the remaining patients. Pre-treatment PET/CT-based radiomic signatures were used to build models predicting HPL at three months after start of treatment. The models were internally validated with nested cross-validation. The performance metric was the area under receiver operating characteristic curve (AUC).ResultsPD-HPD patients constituted 57.1% of all PD patients. PD-HPD was negatively related to patient overall survival with HR=8.52 (95%CI 3.47-20.94). Sixty-nine lesions (20.9%) were identified as progressing at 3 months. Twenty-nine of these lesions were classified as hyperprogressive, thereby showing a HPL rate of 8.8%. CT-based, PET-based, and PET/CT-based models predicting HPL at three months after the start of treatment achieved testing AUC of 0.703 +/- 0.054, 0.516 +/- 0.061, and 0.704 +/- 0.070, respectively. The best performing models relied mostly on CT-based histogram features.ConclusionsFDG-PET/CT-based radiomic signatures yield potential for pretreatment prediction of lesion hyperprogression, which may contribute to reducing the risk of delayed treatment adaptation in metastatic melanoma patients treated with ICI.
Epithelioid glioblastoma exhibits a heterogeneous molecular feature: A targeted next-generation sequencing study
Authors: Pan Rui , Wang Xiaotong , Fang Ru , Xia Qiuyuan , Wu Nan , Rao Qiu 
Published: November 2022

IntroductionEpithelioid glioblastoma (eGBM) is one of the rare glioblastoma (GBM) variants in the current World Health Organization (WHO) categorization of central nervous system (CNS) tumours. However, the diagnostic basis and molecular features of eGBM have not been clearly defined to date. In this study, we aimed to molecularly characterize these tumours.MethodsThe clinicopathological, molecular, and immunohistochemical characteristics of 12 cases of eGBM were investigated.ResultsThe tumours were found to be made up of epithelioid and rhabdoid cells when examined under a microscope. Six cases (50%) harboured the BRAF V600E mutation, and NF1 mutation was detected in 2 eGBM cases (16.7%). CDKN2A/B homozygous deletion was seen in 5 cases (41.7%). TP53 mutation was recognized in 2 instances (16.7%), and TERT promoter mutation was recognized in 5 cases (41.7%).DiscussioneGBM is characterized by high molecular heterogeneity and has molecular overlaps between low-grade gliomas. Moreover, rather than being a variant or entity, the biological significance of the "epithelioid" appearance may be reduced to a simply morphological pattern. In order to target the proper treatment to suitable patients, molecular stratification via genome-wide molecular profiling will be crucial.
Association of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and De Ritis ratio with mortality in renal cell carcinoma: A multicenter analysis
Authors: Keiner Cathrine , Meagher Margaret , Patil Dattatraya , Saito Kazutaka , Walia Arman , Liu Franklin , Dutt Raksha , Miller Nathan , Dhanji Sohail , Saidian Ava , Wan Fang , Yasuda Yosuke , Fujii Yasuhisa , Tanaka Hajime , Master Viraj , Derweesh Ithaar 
Published: November 2022

BackgroundSeveral markers of inflammation have been associated with oncologic outcomes. Prognostic markers are not well-defined for renal cell carcinoma (RCC). We sought to investigate the association of preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and De Ritis ratio with mortality in RCC.MethodsMulti-center retrospective analysis of patients undergoing surgery for RCC. Primary outcome of interest was all-cause mortality (ACM). Secondary outcomes were non-cancer mortality (NCM) and cancer-specific mortality (CSM). Elevated NLR was defined as ≥2.27, elevated PLR as ≥165, and elevated De Ritis ratio as ≥ 2.72. Multivariable cox regression analysis (MVA) was conducted to elucidate risk factors for primary and secondary outcomes, and Kaplan-Meier analysis (KMA) was used to evaluate survival outcomes comparing elevated and non-elevated NLR, PLR, and De Ritis ratio.Results2656 patients were analyzed (874 patients had elevated NLR; 480 patients had elevated PLR and 932 patients had elevated De Ritis). Elevated NLR was a significant predictor of ACM (HR 1.32, 95% CI: 1.07-1.64, p=0.003) and NCM (HR 1.79, 95% CI: 1.30-2.46, p&lt;0.001) in MVA. Elevated De Ritis was a significant predictor of ACM (HR 2.04, 95% CI: 1.65-2.52), NCM (HR 1.84, 95% CI: 1.33-2.55, p&lt;0.001), and CSM (HR 1.97, 95% CI:1.48-2.63, p&lt;0.001). KMA revealed significant difference in 5-year overall survival (OS) (48% vs. 68%, p&lt;0.001), non-cancer survival (NCS) (69% vs. 87%, p&lt;0.001), and cancer-specific survival (CSS) (60% vs. 73%, p&lt;0.001) for elevated versus non-elevated NLR. For PLR, there was a difference in 5-year OS (51% vs. 61%, p&lt;0.001) and CSS (60% vs. 73%, p&lt;0.001) with KMA.ConclusionsElevated NLR was independently associated with worse ACM and NCM, while elevated De Ritis was predictive for CSM in addition to ACM and NCM. These differences may be useful in refining risk stratification with respect to cancer-related and non-cancer mortality in RCC patients and deserve further investigation.