bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of ultrasound-guided microwave ablation versus surgical resection for Bethesda category IV thyroid nodules: A retrospective comparative study
Authors: Yang Jingjing , Zhang Ya , Li Xingjia , Zhao Yueting , Han Xue , Chen Guofang , Chu Xiaoqiu , Li Ruiping , Wang Jianhua , Huang Fei , Liu Chao , Xu Shuhang 
Published: September 2022

ObjectiveThe objective of this study was to assess the efficacy and safety of ultrasound-guided microwave ablation (MWA) for Bethesda IV thyroid nodules and to compare the outcomes, complications, and costs of MWA and thyroidectomy.MethodsA total of 130 patients with Bethesda IV nodules were retrospectively reviewed, involving 46 in the MWA group and 84 in the surgery group. The local institutional review board approved this study. Patients in the MWA group were followed up at 1, 3, 6, and 12 months after the intervention. Postoperative complications, treatment time, and cost in the two groups were compared.ResultsAmong 84 patients with 85 Bethesda IV nodules in the surgery group, postoperative pathology was benign lesions, borderline tumors, papillary thyroid carcinoma, follicular variant papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary carcinoma in 44, 4, 27, 6, 3, and 1 cases, respectively. Malignant thyroid nodules were more prone to solid echostructure (86.11% vs. 72.72%), hypoechogenicity (55.56% vs. 13.63%), and irregular margin (47.22% vs. 13.63%) than benign lesions. The nodule volume reduction rate of patients at 12 months after MWA was 85.01% ± 10.86%. Recurrence and lymphatic and distant metastases were not reported during the follow-up period. The incidence of complications, treatment time, hospitalization time, incision length, and cost were significantly lower in the MWA group than in the surgery group (all p &lt; 0.001).ConclusionsMWA significantly reduces the volume of Bethesda IV nodules with high safety and is recommended for those with surgical contraindications or those who refuse surgical resection. Patients with suspicious ultrasound features for malignancy should be actively treated with surgery.
Cross-sectional associations between cardiorespiratory fitness and NMR-derived metabolic biomarkers in children – the PANIC study
Authors: Haapala Eero A. , Leppänen Marja H. , Lehti Maarit , Lintu Niina , Tompuri Tuomo , Viitasalo Anna , Schwab Ursula , Lakka Timo A. 
Published: September 2022

ObjectiveCardiorespiratory fitness has been inversely associated with cardiovascular risk across the lifespan. Some studies in adults suggest that higher cardiorespiratory fitness is associated with cardioprotective metabolite profile, but the evidence in children is lacking. Therefore, we investigated the cross-sectional association of cardiorespiratory fitness with serum nuclear magnetic resonance derived metabolic biomarkers in children.MethodsA population sample of 450 children aged 6–8 years was examined. Cardiorespiratory fitness was assessed by a maximal exercise test on a cycle ergometer and quantified as maximal power output normalised for lean body mass assessed by dual-energy X-ray absorbtiometry. Serum metabolites were assessed using a high throughput nuclear magnetic resonance platform. The data were analysed using linear regression analyses adjusted for age and sex and subsequently for body fat percentage (BF%) assessed by DXA.ResultsCardiorespiratory fitness was directly associated with high density lipoprotein (HDL) cholesterol (β=0.138, 95% CI=0.042 to 0.135, p=0.005), average HDL particle diameter (β=0.102, 95% CI=0.004 to 0.199, p=0.041), and the concentrations of extra-large HDL particles (β=0.103, 95% CI=0.006 to 0.201, p=0.038), large HDL particles (β=0.122, 95% CI=0.025 to 0.220, p=0.014), and medium HDL particles (β=0.143, 95% CI=0.047 to 0.239, p=0.004) after adjustment for age and sex. Higher cardiorespiratory fitness was also associated with higher concentrations of ApoA1 (β=0.145, 95% CI=0.047 to 0.242, p=0.003), glutamine (β=0.161, 95% CI=0.064 to 0.257, p=0.001), and phenylalanine (β=0.187, 95% CI=0.091 to 0.283, p&lt;0.001). However, only the direct associations of cardiorespiratory fitness with the concentrations of HDL cholesterol (β=0.114, 95% CI=0.018 to 0.210, p=0.021), medium HDL particles (β=0.126, 95% CI=0.030 to 0.223, p=0.010), ApoA1 (β=0.126, 95% CI=0.030 to 0.223, p=0.011), glutamine (β=0.147, 95% CI=0.050 to 0.224, p=0.003), and phenylalanine (β=0.217, 95% CI=0.122 to 0.311, p&lt;0.001) remained statistically significant after further adjustment for BF%.ConclusionsHigher cardiorespiratory fitness was associated with a cardioprotective biomarker profile in children. Most associations were independent of BF% suggesting that the differences in serum metabolites between children are driven by cardiorespiratory fitness and not adiposity.
A functional polymorphism of microRNA-143 is associated with the risk of type 2 diabetes mellitus in the northern Chinese Han population
Authors: Kong Dexian , Duan Ya , Wang Jinli , Liu Yabin 
Published: September 2022

ObjectiveTo explore the association between two polymorphisms of microRNA-143 (miR-143) and the risk of type 2 diabetes mellitus (T2DM) in the northern Chinese Han population.Study DesignThis case–control study involved 326 patients with T2DM and 342 healthy controls. Two genetic variants (rs4705342 and rs353292) of miR-143 were genotyped by the polymerase chain reaction/ligase detection reaction (PCR-LDR) method. The levels of miR-143 in the serum from 52 T2DM patients and 55 healthy subjects were investigated by quantitative real-time PCR (qRT–PCR).ResultsThe CC genotype frequency of rs4705342 was significantly higher in the T2DM patients than in the healthy controls (P = 0.012). After adjusting for sex, age, and body mass index, the rs4705342 CC genotype was also related to a significantly increased risk of T2DM compared with the TT genotype (adjusted OR: 1.87; 95% CI = 1.09-3.19; P = 0.022). Stratified analyses demonstrated that T2DM patients with the rs4705342 CC genotype had significantly higher levels of low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), and glycated haemoglobin (HbA1C) than those carrying the rs4705342 TT genotype. The qRT–PCR results showed that the expression levels of miR-143 were significantly higher in the serum of cases than in the serum of controls (P &lt; 0.001). Furthermore, the levels of miR-143 were significantly higher in the serum of T2DM patients carrying the rs4705342 CC genotype than in those carrying the TC and TT genotypes of rs4705342 (P = 0.005 and 0.003, respectively).ConclusionThe CC genotype of rs4705342 might be a risk factor for developing T2DM by increasing the expression of miRNA-143 in the northern Chinese Han population.
Breaking the reproductive barrier of divergent species to explore the genomic landscape
Authors: Gilles A. , Thevenin Y. , Dione F. , Martin J.-F. , Barascud B. , Chappaz R. , Pech N. 
Published: September 2022

Background: Climate change will have significant consequences for species. Species range shifts induce the emergence of new hybrid zones or the spatial displacement of pre-existing ones. These hybrid zones may become more porous as alleles are passed from one species to another. Currently, hybridization between highly divergent species living in sympatry seems extremely limited. Indeed, this phenomenon involves breaking two barriers. The first is the pre-mating barrier, related to the reproductive phenology of the two species. The second is the post-zygotic barrier, related to the genetic divergence between these species. Here, we were interested in identifying new hybridization patterns and potential implications, especially in the context of environmental modifications.Methods: We sampled Telestes souffia and Parachondrostoma toxostoma wild specimens from different locations across France and genotyped them for SNP markers. We identified discriminant loci using F1-hybrid specimens and parental species and performed principal component analysis and Bayesian model-based clustering to analyze phylogenetic information. Furthermore, we assessed deviation in allele frequency from F1 to F2 and for Hardy–Weinberg equilibrium for F2 and assessed gene function associated with two F2 cohorts.Results: We demonstrate that by breaking the ecological barrier, massive introgressive hybridization is possible between two endemic lineages of Cyprinidae belonging to two distinct genera. For both cohorts studied (=2 cm and &gt;2 cm), a large majority of loci (&gt;88%) presented no deviation in allele frequency and no departure from the Hardy–Weinberg equilibrium. For individuals beyond the 2 cm stage, two phenomena were observed. The first was an allelic imbalance in favor of P. toxostoma, for some genomic regions, with genes involved in developmental regulatory processes, cytoskeletal organization, and chromosome organization. The second was an excess of heterozygous loci coupled with an equilibrium of allelic frequencies for genes involved in immune response and kidney/liver development. Moreover, the 2 cm-sized specimens with high mortality yielded a particular genomic signature.Conclusion: Our study displayed important results for understanding the early stages of hybridization between divergent lineages and predicting the emergence of future hybrid zones in the wild. Moreover, this hybridization generates a wide spectrum of hybrids that are a potential source of important evolutionary novelties.
A novel mutation in RS1 and clinical manifestations in a Chinese twin family with congenital retinoschisis
Authors: Wang Xiao-Fang , Chen Fei-Fei , Zhou Xin , Cheng Xin-Xuan , Xie Zheng-Gao 
Published: September 2022

Purpose: We aim to analyze the clinical and genetic features in a Chinese family with congenital retinoschisis by whole-exome sequencing and comprehensive clinical examination.Methods: Six members were recruited from a Chinese family. Three of them were diagnosed as congenital retinoschisis, including two twin siblings. All subjects received a full eye examination. Whole-exome sequencing (WES) and Sanger sequencing were performed on two twin probands and all participants, respectively.Results: A novel splice site mutation RS1.c.53-1G&gt;A was identified in a Chinese congenital retinoschisis family. The mean onset age was 16.7 ± 2.4 years old. The average BCVA in patients was 0.37 ± 0.05. A typical spoke-wheel pattern was observed in all affected eyes. OCT examination results showed fovea schisis and schisis cavities were located in the inner nuclear layer in 100% eyes (6/6). ERG b/a ratio was decreased markedly, but was still more than 1 in the four eyes that were available.Conclusion: The present study discovered a new pathogenic splice cite variant of RS1 in congenital retinoschisis, which expands the mutational spectrum. In contrast to previous research, the phenotype of patients with the same mutation within one family was highly similar. Early molecular testing is crucial for early diagnosis, clinical management, and genetic counseling of patients with congenital retinoschisis.
An EMT-based risk score thoroughly predicts the clinical prognosis, tumor immune microenvironment and molecular subtypes of bladder cancer
Authors: Xiao Zicheng , Cai Zhiyong , Deng Dingshan , Tong Shiyu , Zu Xiongbing 
Published: September 2022

BackgroundEpithelial mesenchymal transition (EMT) is closely related to the occurrence, development, metastasis and antitumor immunity of tumors. However, comprehensive studies correlating EMT and prognosis, tumor microenvironment (TME) and molecular subtypes of bladder cancer (BLCA) are lacking.MethodsTCGA-BLCA was chosen as our training cohort, while Xiangya cohort, GSE13507, GSE48075 were selected as our validation cohorts. Prognostic genes were screened out using univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. Then we developed an EMT risk score based on these prognostic genes and systematically correlated the risk score with prognosis, TME and molecular subtypes of BLCA.ResultsBased on EMT related genes, we developed two different EMT patterns, named EMT cluster 1 and cluster 2, and found that cluster 2 showed a worse prognosis and an inflammatory TME phenotype. For personalized prognosis and TME phenotypes predicting, we developed and validated an EMT-based risk score by 7 candidate genes (ANXA10, CNTN1, FAM180A, FN1, IGFL2, KANK4 and TOX3). Patients with high EMT risk scores had lower overall survival (OS) with high predictive accuracy both in the training cohort and validation cohort. In addition, we comprehensively correlated the EMT risk score with TME and molecular subtype, and found that high EMT risk score suggested higher levels of immune cell infiltration and more inclined to present the basal molecular subtype. It was noteworthy that the same results also appeared in the validation of Xiangya cohort.ConclusionsEMT related genes play an important role in tumor progression and immunity in BLCA. Our EMT risk score could accurately predict prognosis and immunophenotype of a single patient, which could guide more effective precision medical strategies.
Lymphomas in cartilage-hair hypoplasia – A case series of 16 patients reveals advanced stage DLBCL as the most common form
Authors: Kukkola Hanna-Leena , Utriainen Pauliina , Huttunen Pasi , Taskinen Mervi , Mäkitie Outi , Vakkilainen Svetlana 
Published: September 2022

BackgroundPatients with cartilage-hair hypoplasia (CHH) have an increased risk of malignancy, particularly non-Hodgkin lymphoma and basal cell carcinoma. The characteristics, clinical course, response to therapy and outcome of lymphomas in CHH remains unexplored.MethodsWe assessed clinical features of lymphoma cases among Finnish patients with CHH. Data were collected from the Finnish Cancer Registry, hospital records, the National Medical Databases and Cause-of-Death Registry of Statistics Finland.ResultsAmong the 160 CHH patients, 16 (6 men, 10 women) were diagnosed with lymphoma during 1953-2016. Lymphoma was diagnosed in young adulthood (median age 26.4 years, range from 6.4 to 69.5 years), mostly in advanced stage. The most common lymphoma type was diffuse large cell B-cell lymphoma (DLBCL) (6/16, 38%). Eight patients received chemotherapy (8/16, 50%), and two of them survived. Standard lymphoma chemotherapy regimens were administered in the majority of cases. Altogether, eleven CHH patients died due to lymphomas (11/16, 69%). In almost all surviving lymphoma patients, the diagnosis was made either during routine follow-up or after evaluation for non-specific mild symptoms. Search for CHH-related clinical predictors demonstrated higher prevalence of recurrent respiratory infections, in particular otitis media, and Hirschsprung disease in patients with lymphoma. However, three patients had no clinical signs of immunodeficiency prior to lymphoma diagnosis.ConclusionDLBCL is the most common type of lymphoma in CHH. The outcome is poor probably due to advanced stage of lymphoma at the time of diagnosis. Other CHH-related manifestations poorly predicted lymphoma development, implying that all CHH patients should be regularly screened for malignancy.
Immunogenicity and safety of the booster BNT162b2 vaccine in patients with axial spondyloarthritis treated with biological disease-modifying drugs
Authors: Smetanova Jitka , Milota Tomas , Rataj Michal , Hurnakova Jana , Zelena Hana , Sediva Anna , Horvath Rudolf 
Published: September 2022

BackgroundVaccination confers relatively short-term protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), indicating the need for booster doses. Immunocompromised individuals, including those with immune-mediated inflammatory diseases (IMIDs), may have pronounced immune response waning. Vaccine-boosted humoral and T-cell responses minimize poor coronavirus disease 19 (COVID-19) outcome without increasing adverse events (AE). There is limited evidence of third-dose vaccination in axial spondyloarthritis (AxSpA) patients. We investigated immune-response persistence after primary vaccination and immunogenicity and safety after the BNT162b2 booster vaccination.MethodsThis prospective observational study enrolled an AxSpA cohort treated with interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNFα) inhibitors. Serum SARS-CoV-2-specific and virus-neutralizing antibodies for humoral response and flow cytometric detection of intracellular cytokines following SARS-CoV-2-specific peptide-based stimulation for T-cell immune responses were assessed, and safety was evaluated via a clinical questionnaire.ResultsFifteen male AxSpA patients treated with TNFα (73·3%) or IL-17 (26·7%) inhibitors were enrolled and had humoral response persistence at 6 months: 905·6 ( ± 186·1 SD) and 409·1 ( ± 335·7) U/mL. Specific antibody concentrations further increased after booster vaccination to 989·7 ( ± 12·62) and 1000 U/mL and T-cell responders from 53·3% to 80%, with no differences between AxSpA (including “vaccination only” and “hybrid immunity” subgroups) and healthy control (HC) cohorts. No severe AE occurred; the AE spectrum was comparable to that of the general population.ConclusionImmune-response persistence after primary vaccination and immunogenicity after booster vaccination were unaffected by anti-IL17 or anti-TNFα therapy with similar AE as in the general population.
Causes of death and conditional survival estimates of long-term lung cancer survivors
Authors: Zhang Qun , Dai Yuan , Liu Hongda , Sun Wenkui , Huang Yuming , Gong Zheng , Dai Shanlin , Kong Hui , Xie Weiping 
Published: September 2022

IntroductionLung cancer ranks the leading cause of cancer-related death worldwide. This retrospective cohort study was designed to determine time-dependent death hazards of diverse causes and conditional survival of lung cancer.MethodsWe collected 816,436 lung cancer cases during 2000-2015 in the SEER database, after exclusion, 612,100 cases were enrolled for data analyses. Cancer-specific survival, overall survival and dynamic death hazard were assessed in this study. Additionally, based on the FDA approval time of Nivolumab in 2015, we evaluated the effect of immunotherapy on metastatic patients’ survival by comparing cases in 2016-2018 (immunotherapy era, n=7135) and those in 2013-2016 (non-immunotherapy era, n=42061).ResultsOf the 612,100 patients, 285,705 were women, the mean (SD) age was 68.3 (11.0) years old. 252,558 patients were characterized as lung adenocarcinoma, 133,302 cases were lung squamous cell carcinoma, and only 78,700 cases were small cell lung carcinomas. TNM stage was I in 140,518 cases, II in 38,225 cases, III in 159,095 cases, and IV in 274,262 patients. 164,394 cases underwent surgical intervention. The 5-y overall survival and cancer-specific survival were 54.2% and 73.8%, respectively. The 5-y conditional survival rate of cancer-specific survival is improved in a time-dependent pattern, while conditional overall survival tends to be steady after 5-y follow-up. Except from age, hazard disparities of other risk factors (such as stage and surgery) diminished over time according to the conditional survival curves. After 8 years since diagnosis, mortality hazard from other causes became higher than that from lung cancer. This critical time point was earlier in elder patients while was postponed in patients with advanced stages. Moreover, both cancer-specific survival and overall survival of metastatic patients in immunotherapy era were significantly better than those in non-immunotherapy era (P&lt;0.001), indicating that immunotherapeutic intervention indeed bring remarkable benefits to advanced lung cancer patients.ConclusionsOur findings expand on previous studies by demonstrating that non-lung-cancer related death risk becomes more and more predominant over the course of follow-up, and we establish a personalized web-based calculator to determine this critical time point for long-term survivors. We also confirmed the survival benefit of advanced lung cancer patients in immunotherapy era.
Neutrophil Extracellular Traps (NETs) Promote Non-Small Cell Lung Cancer Metastasis by Suppressing lncRNA MIR503HG to Activate the NF-κB/NLRP3 Inflammasome Pathway
Authors: Wang Yong , Liu Fen , Chen Lin , Fang Chen , Li Shuangyan , Yuan Shangkun , Qian Xiaoying , Yin Yan , Yu Biao , Fu Biqi , Zhang Xinwei , Li Yong 
Published: September 2022

Neutrophil extracellular traps (NETs) that are produced in the tumour microenvironment (TME) have been suggested to play an essential role in the dissemination of metastatic cancer under multiple infectious and inflammatory conditions. However, the functions of NETs in promoting non-small cell lung cancer (NSCLC) metastasis and the underlying mechanisms remain incompletely understood. Here, we found that NETs promoted NSCLC cell invasion and migration by inducing epithelial to mesenchymal transition (EMT). To explore how NETs contribute to NSCLC metastasis, microarrays were performed to identify substantial numbers of long noncoding RNAs (lncRNAs) and mRNAs that were differentially expressed in NSCLC cells after stimulation with NETs. Interestingly, we observed that the expression of lncRNA MIR503HG was downregulated after NETs stimulation, and ectopic MIR503HG expression reversed the metastasis-promoting effect of NETs in vitro and in vivo. Notably, bioinformatics analysis revealed that differentially expressed genes were involved in the NOD-like receptor and NF-κB signalling pathways that are associated with inflammation. NETs facilitated EMT and thereby contributed to NSCLC metastasis by activating the NF-κB/NOD-like receptor protein 3 (NLRP3) signalling pathway. Further studies revealed that MIR503HG inhibited NETs-triggered NSCLC cell metastasis in an NF-κB/NLRP3-dependent manner, as overexpression of NF-κB or NLRP3 impaired the suppressive effect of MIR503HG on NETs-induced cancer cell metastasis. Together, these results show that NETs activate the NF-κB/NLRP3 pathway by downregulating MIR503HG expression to promote EMT and NSCLC metastasis. Targeting the formation of NETs may be a novel therapeutic strategy for treating NSCLC metastasis.