bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exoskeleton gait training on real-world terrain improves spatiotemporal performance in cerebral palsy
Authors: Tagoe Emmanuella A. , Fang Ying , Williams Jack R. , Stone Julie L. , Lerner Zachary F. 
Published: December 2024

IntroductionWalking is essential for daily life but poses a significant challenge for many individuals with neurological conditions like cerebral palsy (CP), which is the leading cause of childhood walking disability. Although lower-limb exoskeletons show promise in improving walking ability in laboratory and controlled overground settings, it remains unknown whether these benefits translate to real-world environments, where they could have the greatest impact.MethodsThis feasibility study evaluated whether an untethered ankle exoskeleton with an adaptable controller can improve spatiotemporal outcomes in eight individuals with CP after low-frequency exoskeleton-assisted gait training on real-world terrain.ResultsComparing post- and pre-assessment, assisted walking speed increased by 11% and cadence by 7% (p = 0.003; p = 0.006), while unassisted walking speed increased by 8% and cadence by 5% (p = 0.009; p = 0.012). In the post-assessment, assisted walking speed increased by 9% and stride length by 8% relative to unassisted walking (p &lt; 0.001; p &lt; 0.001). Improvements in walking speed were more strongly associated with longer strides than higher cadence (R2 = 0.92; R2 = 0.68). Muscle activity outcomes, including co-contraction of the soleus and tibialis anterior, did not significantly change after training.DiscussionThese findings highlight the spatiotemporal benefits of an adaptive ankle exoskeleton for individuals with CP in real-world settings after short-term training. This work paves the way for future randomized controlled trials (RCTs) to evaluate the isolated effects of adaptive ankle exoskeletons on gait performance and neuromuscular outcomes in individuals with CP in real-world environments
MicroRNA-21-5p profile in the alveolar bone following tooth extraction in medication-related osteonecrosis of the jaw rat model
Authors: Morakotsriwan Manta , Chanamuangkon Theerapat , Vacharaksa Anjalee , Limlawan Pirawish 
Published: December 2024

ObjectiveThis study aimed to compare microRNA-21-5p expressions at the extraction wound in the maxillary bones of rats with medication-related osteonecrosis of the jaw (MRONJ) and normal rats at different time points.Materials and methodsIn total, 18 female, 8-week-old Sprague-Dawley rats were randomly assigned to the experimental group (n = 9) and the control group (n = 9). To establish MRONJ in the right maxillary first molar area in the experimental group, zoledronate (66 µg/kg) and dexamethasone (5 mg/kg) were administered intraperitoneally every other day for 2 weeks before tooth extraction. Normal saline was administered in the control group. After tooth extraction, the drugs were continuously administered until the experimental endpoints, namely 1, 14, and 28 days post-tooth extraction. At each endpoint, three rats from each group were euthanized. The maxilla bones at the wound area were harvested. A real-time polymerase chain reaction (RT-PCR) was performed to compare the expression levels of miRNA-21-5p at each time point between the MRONJ group and the control group.ResultsFrom their gross appearance, the rats that received zoledronate and dexamethasone developed MRONJ as demonstrated by non-healing wounds and exposed bone at 14 and 28 days post-extraction in contrast to the controls. The RT-PCR showed that the expression levels of miRNA-21-5p were relatively higher in the MRONJ rats compared to the control rats at day 14 and then the difference was lower at day 28 post-tooth extraction.ConclusionThe findings indicated that the microRNA-21-5p expression levels varied during the socket healing process in the MRONJ rats, reaching a peak at 2 weeks after tooth extraction.
Association between erectile dysfunction and the predicted 10-year risk for atherosclerosis cardiovascular disease among U.S. men: a population-based study from the NHANES 2001-2004
Authors: Mei Yangyang , Chen Yiming , Wang Xiaogang , Xu Renfang , Xu Rui , Feng Xingliang 
Published: December 2024

BackgroundErectile dysfunction (ED) is considered the tip of the iceberg for cardiovascular disease (CVD). However, there is still conflicting evidence regarding their relationship. Recently, a validated tool for the Atherosclerotic Cardiovascular Disease (ASCVD) risk score has provided a key opportunity to delve deeper into the relationship between ED and CVD. Therefore, we intended to assess the relationship between ED and 10-year ASCVD risk scoreMethodsComplete data of 1207 participants from the 2001-2004 National Health and Nutrition Examination Survey (NHANES) were used in the study. Various weighted logistic and linear regression models were employed to investigate the effect of the presence of ED on the higher 10-Year ASCVD risk score or high risk of 10-Year ASCVD. Conversely, logistic regression models were repeated to explore the effect of continuous or categorical ASCVD risk score on the prevalence of ED. Sensitivity analyses were also conducted, focusing on severe ED with a more stringent definition. Additionally, we supplemented our study with subgroup analyses, restricted cubic spline (RCS) analysis, and receiver operating characteristic (ROC) analysis to enhance the robustness of our results.ResultsParticipants with ED had higher ASCVD risk scores and a higher risk of ASCVD, which corresponded to a greater prevalence of ED or severe ED. When considering the presence of ED as the exposure, our results indicated that the presence of ED increased the ASCVD risk score (Model 3: β [95%CI]: 2.09 [1.12, 3.06]) in Model 3, as well as the high risk of ASCVD (OR [95%CI]: 2.27 [1.13, 4.59]). Conversely, a continuous increase in the ASCVD risk score was also associated with an increased prevalence of ED (OR [95%CI]: 1.04 [1.02,1.06]). Additionally, those in the borderline ASCVD risk group (OR [95% CI]: 2.95 [1.60, 5.44]), intermediate ASCVD risk group (OR [95% CI]: 4.53 [2.35, 8.73]), and high ASCVD risk group (OR [95% CI]: 7.62 [3.19, 18.19]) exhibited progressively increasing ED risk when compared to the low-risk group. Furthermore, the RCS analysis demonstrated a linear relationship between ED prevalence and the continuous ASCVD risk score, with the latter showing high efficacy in predicting ED (AUC [95%CI]: 0.794 [0.768, 0.821]).ConclusionsThe presence of ED may precede the onset of ASCVD by some years. Consequently, timely and dynamic evaluation of the cardiovascular status provides an earlier opportunity to identify and implement effective prevention strategies to promote cardiovascular health for ED patients.
Medium- and long-term recurrence after radioiodine therapy for differentiated thyroid carcinoma with recombinant human thyrotropin: a meta-analysis
Authors: Yao Qixian , Song Lili , Xu Jun , Wu Zhongliang 
Published: December 2024

IntroductionRadioactive iodine (RAI) is commonly used in the management of differentiated thyroid cancers (DTCs). However, the long-term efficacy and the risk of tumor recurrence associated with it remain unclear. In particular, the comparison between recombinant human thyrotropin (rhTSH) and thyroid hormone withdrawal (THW) in terms of medium- and long-term recurrence rate in DTC patients has not been fully elucidated.MethodsA systematic search was carried out to identify articles comparing medium- and long-term outcomes (&gt; 2 years) based on treatment with either rhTSH or THW. Ten studies, consisting of six randomized controlled trials (RCTs) and four retrospective studies with a total of 2,833 patients, were included in the analysis.ResultsThere was no significant difference in the medium- and long-term recurrence rates between the rhTSH group and the THW group. This was also the case in subgroup analyses of only RCTs or only retrospective studies. The structural incomplete response (SIR) rate was slightly higher in the rhTSH group, but a subgroup analysis of RCTs alone showed no significant difference in SIR between the two groups.DiscussionrhTSH is comparable to THW in achieving successful ablation of residual disease and maintaining low recurrence rates. However, further RCTs are required to investigate whether rhTSH can increase the risk of SIR.
Correlations of the triglyceride−glucose index and modified indices with arterial stiffness in overweight or obese adults
Authors: Tang Yuchen , Li Li , Li Jialin 
Published: December 2024

BackgroundInsulin resistance (IR) contributes substantially to the development of cardiovascular disease (CVD) and metabolic disorders, particularly obesity. The homeostatic model assessment of IR is a prevalent IR indicator, but insulin measurement is quite impractical for widely use. Given its convenience and accessibility, the triglyceride−glucose (TyG) index, along with modified indices such as the triglyceride−glucose−waist circumference (TyG−WC) and triglyceride−glucose−waist−height ratio (TyG−WHtR), are gaining recognition as practical tools for assessing IR. This study aimed to investigate the specific correlation between the TyG index and its modified indices with arterial stiffness in an overweight or obese population and to explore novel, self-defined modified TyG indices for identifying individuals at elevated risk for such conditions.MethodsThis retrospective study included 1,143 overweight or obese individuals from 2021 to 2023. Medical data, including brachial-ankle pulse wave velocity (baPWV), were collected. Two novel modified TyG indices, TyG-1h and TyG-2h, were defined by substituting the fasting glucose level in the TyG formula with 1-hour and 2-hour post-load plasma glucose levels, respectively. Multivariate logistic regression analyses were conducted to identify parameters that demonstrated a statistically significant correlation with arterial stiffness, defined as a baPWV threshold of ≥ 1400 cm/s. Additionally, restricted cubic spline (RCS) modelling was employed to further explore these relationships in a visually interpretable manner. To evaluate and compare the diagnostic accuracy of the conventional TyG index and its novel modified versions, receiver operating characteristic (ROC) curve analyses were performed.ResultsOur findings revealed that individuals with arterial stiffness presented significantly elevated TyG index and all its modified versions (P&lt; 0.05). By utilizing a binary logistic regression model and adjusting for potential confounders, we determined that all TyG-related parameters independently correlated with an increased risk of developing arterial stiffness. Moreover, TyG-WHtR displayed the best correlation (OR 3.071, 95% CI 1.496-6.303) when stratified by quartiles, followed by TyG-1h (OR 2.298, 95% CI 1.248-4.234) and TyG-2h (OR 2.115, 95% CI 1.175-3.807). ROC curves suggested that TyG-1h and TyG-2h demonstrated superior diagnostic performance compared to TyG, with AUCs of 0.685, 0.679 and 0.673, respectively.ConclusionsThe modified TyG indices exhibited strong effectiveness in identifying arterial stiffness in Chinese overweight or obese individuals.
Identification and validation of the nicotine metabolism-related signature of bladder cancer by bioinformatics and machine learning
Authors: Zhan Yating , Weng Min , Guo Yangyang , Lv Dingfeng , Zhao Feng , Yan Zejun , Jiang Junhui , Xiao Yanyi , Yao Lili 
Published: December 2024

BackgroundSeveral studies indicate that smoking is one of the major risk factors for bladder cancer. Nicotine and its metabolites, the main components of tobacco, have been found to be strongly linked to the occurrence and progression of bladder cancer. However, the function of nicotine metabolism-related genes (NRGs) in bladder urothelial carcinoma (BLCA) are still unclear.MethodsNRGs were collected from MSigDB to identify the clusters associated with nicotine metabolism. Prognostic differentially expressed genes (DEGs) were filtered via differentially expression analysis and univariate Cox regression analysis. Integrative machine learning combination based on 10 machine learning algorithms was used for the construction of robust signature. Subsequently, the clinical application of signature in terms of prognosis, tumor microenvironment (TME) as well as immunotherapy was comprehensively evaluated. Finally, the biology function of the signature gene was further verified via CCK-8, transwell migration and colony formation.ResultsThree clusters associated with nicotine metabolism were discovered with distinct prognosis and immunological patterns. A four gene-signature was developed by random survival forest (RSF) method with highest average Harrell’s concordance index (C-index) of 0.763. The signature exhibited a reliable and accurate performance in prognostic prediction across TCGA-train, TCGA-test and GSE32894 cohorts. Furthermore, the signature showed highly correlation with clinical characteristics, TME and immunotherapy responses. Suppression of MKRN1 was found to reduce the migration and proliferation of bladder cancer cell. In addition, enhanced migration and proliferation caused by nicotine was blocked down by loss of MKRN1.ConclusionsThe novel nicotine metabolism-related signature may provide valuable insights into clinical prognosis and potential benefits of immunotherapy in bladder cancer patients.
Machine learning-based selection of immune cell markers in osteosarcoma: prognostic determination and validation of CLK1 in disease progression
Authors: Zhang Nan , Haizhen Zhou , Zhang Runqi , Li Xiaoju 
Published: December 2024

IntroductionOsteosarcoma (OS) is a malignancy of the bone that mainly afflicts younger individuals. Despite existing treatment approaches, patients with metastatic or recurrent disease generally face poor prognoses. A greater understanding of the tumor microenvironment (TME) is critical for enhancing outcomes in OS patients.MethodsThe clinical and RNA expression data of OS patients were extracted from the TARGET database. The single-cell RNA sequencing (scRNA-seq) data of 11 OS samples was retrieved from the GEO database, and analyzed using the Seurat package of R software. Copy number variation (CNV) was analyzed using the InferCNV software. The potential interactions between the different cells in the TME was analyzed with the CellChat package. A multi-algorithm-based computing framework was used to calculate the tumor-infiltrating immune cell (TIIC) scores. A prognostic model was constructed using 20 machine learning algorithms. Maftools R package was used to characterize the genomic variation landscapes in the patient groups stratified by TIIC score. The human OS cell lines MG63 and U2OS were used for the functional assays. Cell proliferation and migration were analyzed by the EdU assay and Transwell assay respectively. CLK1 protein expression was measured by immunoblotting.ResultsWe observed higher CNV in the OS cells compared to endothelial cells. In addition, there was distinct transcriptional heterogeneity across the OS cells, and cluster 1 was identified as the terminal differentiation state. S100A1, TMSB4X, and SLPI were the three most significantly altered genes along with the pseudo-time trajectory. Cell communication analysis revealed an intricate network between S100A1+ tumor cells and other TME cells. Cluster 1 exhibited significantly higher aggressiveness features, which correlated with worse clinical outcomes. A prognostic model was developed based on TIIC-related genes that were screened using machine learning algorithms, and validated in multiple datasets. Higher TIIC signature score was associated with lower cytotoxic immune cell infiltration and generally inferior immune response and survival rate. Moreover, TIIC signature score was further validated in the datasets of other cancers. CLK1 was identified as a potential oncogene that promotes the proliferation and migration OS cells.ConclusionA TIIC-based gene signature was developed that effectively predicted the prognosis of OS patients, and was significantly associated with immune infiltration and immune response. Moreover, CLK1 was identified as an oncogene and potential therapeutic target for OS.
PAQR6 as a prognostic biomarker and potential therapeutic target in kidney renal clear cell carcinoma
Authors: Zou Tao , Jia Zongming , Wu Jixiang , Liu Xuxu , Deng Minghao , Zhang Xuefeng , Lin Yuxin , Ping Jigen 
Published: December 2024

BackgroundProgestin And AdipoQ Receptor Family Member VI (PAQR6) plays a significant role in the non-genomic effects of rapid steroid responses and is abnormally expressed in various tumors. However, its biological function in kidney renal clear cell carcinoma (KIRC) and its potential as a therapeutic target remain underexplored.MethodsIn this study, PAQR6 was identified as a critical oncogene by WGCNA algorithm and differential gene expression analysis using TCGA - KIRC and GSE15641 data. The differences in PAQR6 expression and its association with KIRC survival outcomes were investigated, and transcriptomic data were used to further elucidate PAQR6’s biological functions. Moreover, XCELL and single - cell analysis assessed the correlation between PAQR6 expression and immune infiltration. TIDE algorithm was used to assess how well various patient cohorts responded to immune checkpoint therapy. Finally, the role of PAQR6 in the development of KIRC was verified through EdU, scratch assays, and Transwell assays.ResultsOur findings suggest that elevated expression of PAQR6 is linked to a poor prognosis for KIRC patients. Functional enrichment analysis demonstrated that PAQR6 is primarily involved in angiogenesis and pluripotent stem cell differentiation, which are crucial in mediating the development of KIRC. Additionally, we established a ceRNA network that is directly related to overall prognosis, further supporting the role of PAQR6 as a prognostic biomarker for KIRC.ConclusionUsing both computational and experimental methods, this study leads the charge in discovering and verifying PAQR6 as a prognostic biomarker and possible therapeutic target for KIRC. In the future, to determine its molecular mechanism in KIRC carcinogenesis, more in vivo research will be carried out.
Haptoglobin 2-2 genotype is associated with increased risk of cardiovascular disease in patients with rheumatoid arthritis: a matched case-control study
Authors: Xu Chuanhui , Khin Lay Wai , Tam Hui Zhen , Goh Liuh Ling , Koh Ee Tzun , Dalan Rinkoo , Leong Khai Pang 
Published: December 2024

IntroductionTraditional risk factors do not fully explain the increased risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). The Haptoglobin (Hp) 2-2 genotype confers a lower anti-oxidant and higher inflammatory effect on the vasculature compared to the non-Hp 2-2 genotype. This study investigates the association of the Hp genotype with CVD in patients with RA.MethodsData from 69 RA patients with CVD and 207 sex- and ethnicity-matched RA patients without CVD, collected from 1 January 2000 to 31 December 2020, were retrieved from the Tan Tock Seng Hospital RA Registry. CVD was examined against demographics, clinical and laboratory variables in univariate models. Associations between the Hp genotypes and CVD were analyzed using conditional logistic regression.ResultsWe studied 276 patients (65.2% female, 82.6% Chinese, median age 60.9 years). Most participants were in low disease activity or remission (79.3%). The Hp 2-2 genotype was present in 49.6% (137/276). In the group with CVD, the prevalence of the Hp 2-2 genotype was 50.9% (29/57) in the Chinese, 100% (5/5) in the Indians, and 28.6% (2/7) in the Malays. In the non-CVD group, the respective prevalence was 46.8% (80/171), 66.7% (10/15), and 52.4% (11/21). In univariate analysis, the matched odds ratio (OR) of the Hp 2-2 genotype for CVD in RA was 1.34 [95% confidence interval (CI): 1.22–1.47; p &lt; 0.001]. The Hp 2-2 genotype was significantly associated with CVD (adjusted matched OR: 1.13; 95% CI: 1.01–1.27; p = 0.033) in the multivariate logistic regression model after adjusting the confounding factors, including age, smoking, diabetes, hypertension, hyperlipidemia, anti-CCP autoantibodies, and disease activity.ConclusionThe Hp 2-2 genotype is associated with an increased risk of CVD in patients with RA in this multi-ethnic cohort.
Electrolyte imbalance and liver function test abnormalities among pregnant women with hyperemesis gravidarum at Wag-himra zone public hospitals, Northeast Ethiopia, 2023: a comparative cross-sectional study
Authors: Worede Abebaw , Deress Teshiwal , Wondifraw Habtamu , Fetene Getnet , Berie Alemseged 
Published: December 2024

BackgroundHyperemesis gravidarum affects about 4.8% of pregnant women. It can lead to electrolyte imbalances and liver function disturbances, which may result in pregnancy complications. Despite its prevalence, data on these abnormalities in the study area is scarce. Therefore, the current study investigated these health concerns among HG-affected pregnant women in this region from June to October 2023.MethodA comparative cross-sectional study was conducted on 123 study participants. Socio-demographic, clinical, and anthropometric data were collected using structured questionnaires. Blood samples were taken to determine liver function tests and electrolyte levels. Statistical analysis was performed using a one-way ANOVA with a Tuckey post hoc test, Kruskal-Wallis with a Mann–Whitney U test, and binary logistic regression analysis. A p-value of &lt;0.05 with 95% confidence intervals was considered statistically significant.ResultsThe results showed that pregnant women with hyperemesis gravidarum had significantly higher levels of AST and ALT and lower levels of Na+ and K+ compared to normal pregnant women and non-pregnant women. The abnormalities observed were elevated AST (48.8%), ALT (46.3%), and decreased Na+ (51.2%) and K+ (41.5%). Hyperemesis gravidarum was associated with both electrolyte imbalances and liver function test abnormalities.ConclusionPregnant women with hyperemesis gravidarum experience electrolyte imbalances and liver function test abnormalities. Given the marked increase in liver enzymes and decrease in electrolyte levels, the authors recommend routine laboratory testing of liver function and electrolyte parameters for pregnant women with hyperemesis gravidarum is recommended.