bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alteration of network connectivity in stroke patients with apraxia of speech after tDCS: A randomized controlled study
Authors: Zhao Jiayi , Li Yuanyuan , Zhang Xu , Yuan Ying , Cheng Yinan , Hou Jun , Duan Guoping , Liu Baohu , Wang Jie , Wu Dongyu 
Published: September 2022

ObjectiveThis study aimed to examine the changes in the functional connectivity of the cortical speech articulation network after anodal transcranial direct current stimulation (A-tDCS) over the left lip region of the primary motor cortex (M1) in subacute post-stroke patients with apraxia of speech (AoS), and the effect of A-tDCS on AoS.MethodsA total of 24 patients with post-stroke AoS were randomized into two groups and received A-tDCS over the left lip region of M1 (tDCS group)/ sham tDCS (control group) as well as speech and language therapy two times per day for 5 days. Before and after the treatment, the AoS assessments and electroencephalogram (EEG) were evaluated. The cortical interconnections were measured using the EEG non-linear index of cross approximate entropy (C-ApEn).ResultsThe analysis of EEG showed that, after the treatment, the activated connectivity was all in the left hemisphere, and not only regions in the speech articulation network but also in the dorsal lateral prefrontal cortex (DLPFC) in the domain-general network were activated in the tDCS group. In contrast, the connectivity was confined to the right hemisphere and between bilateral DLPFC and bilateral inferior frontal gyrus (IFG) in the control group. In AoS assessments, the tDCS group improved significantly more than the control group in four of the five subtests. The results of multivariate linear regression analyses showed that only the group was significantly associated with the improvement of word repetition (P = 0.002).ConclusionA-tDCS over the left lip region of M1 coupled with speech therapy could upregulate the connectivity of both speech-specific and domain-general networks in the left hemisphere. The improved articulation performance in patients with post-stroke AoS might be related to the enhanced connectivity of networks in the left hemisphere induced by tDCS.Clinical trial registrationChiCTR-TRC-14005072.
Endovascular thrombectomy in acute ischemic stroke patients with prestroke disability (mRS ≥2): A systematic review and meta-analysis
Authors: Yang Jin-Cai , Bao Qiang-Ji , Guo Yu , Chen Shu-Jun , Zhang Jin-Tao , Zhang Qiang , Zhou Ping , Yang Ming-Fei 
Published: September 2022

ObjectiveThe effect of endovascular thrombectomy (EVT) in acute ischemic stroke patients with prestroke disability (modified Rankin Scale score, mRS) ≥2) has not been well-studied. This study aimed to assess the safety and benefit of EVT in patients with prestroke disability.MethodsAccording to PRISMA guidelines, literature searching was performed using PubMed, Embase, and Cochrane databases, for a series of acute ischemic stroke patients with prestroke mRS ≥2 treated by EVT. Random-effects meta-analysis was used to pool the rate of return to prestroke mRS and mortality at 3-month follow-up.ResultsIn total, 13 observational studies, with 2,625 patients, were analyzed. The rates of return to prestroke mRS in patients with prestroke mRS of 2–4 were 20% (120/588), 27% (218/827), and 31% (34/108), respectively. Patients with prestroke disability treated by EVT had a higher likelihood of return to prestroke mRS (relative risk, RR, 1.86; 95% CI 1.28–2.70) and a lower likelihood of mortality (RR 0.75; 95%CI 0.58–0.97) compared with patients with standard medical treatment. Successful recanalization (Thrombolysis in Cerebral Infarction grade 2b-3) after EVT gave a higher likelihood of return to prestroke mRS (RR 2.04; 95% CI 1.17–3.55) and lower mortality (RR 0.72; 95% CI 0.62–0.84) compared with unsuccessful reperfusion.ConclusionsAcute ischemic stroke patients with prestroke disability may benefit from EVT. Withholding EVT on the sole ground of prestroke disabilities may not be justified.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/.
Mast cell stabilizer disodium cromoglycate improves long-term cognitive impairment after general anesthesia exposure in neonatal mice
Authors: Zhang Xiaojun , Wu Wensi , Zheng Zhenzhen , Li Liang , Chen Junjun , Zhong Junying , Zhao Le , Chen Jiawei , Wang Zhi , Meng Fanqing 
Published: September 2022

BackgroundProlonged exposure to general anesthesia (GA) results in long-lasting cognitive impairment, especially during critical stages of brain development. An exaggerated neuroinflammation induced by anesthesia is generally considered to be a key cause of cognitive impairment.Materials and methodsPostnatal day 7 (PND 7) mice were exposed to GA by isoflurane inhalation for 6 h or mock anesthesia. Disodium cromoglycate (DSCG) was intraperitoneally injected daily for 2 weeks, beginning from 30 min before anesthesia. The post-anesthesia evaluation included behavioral tests, toluidine blue staining, immunofluorescence and western blot.ResultsOur results demonstrated the long-term cognition were impaired after 6 h GA exposure in neonatal mice. DSCG treatment ameliorated early mast cells (MCs) degranulation and mast cell tryptase (MCT) expression, which helps to attenuate subsequent neuroinflammation, activation of microglia and astrocytes, and damage to oligodendrocytes and synapses to improve cognitive impairment.ConclusionDisodium cromoglycate could effectively improve long-term cognitive impairment after GA exposure in neonatal mice.
Association of myosteatosis with various body composition abnormalities and longer length of hospitalization in patients with decompensated cirrhosis
Authors: Wang Xiaoyu , Sun Mingyu , Li Yifan , Guo Gaoyue , Yang Wanting , Mao Lihong , Yu Zihan , Hui Yangyang , Fan Xiaofei , Cui Binxin , Jiang Kui , Sun Chao 
Published: September 2022

BackgroundMyosteatosis is linked to dismal outcomes in the context of cirrhosis. However, the association of myosteatosis with various body composition abnormalities remains enigmatic. We aimed to clarify the determinants of myosteatosis and its relationship with other body composition profiles and length of hospitalization (LOH).MethodsWe retrospectively analyzed the data of 473 consecutive patients with cirrhosis hospitalized for decompensation. Computed tomography-based segmentation of the cross-sectional area at the third lumbar vertebra was used to evaluate body composition abnormalities. The categories of myosteatosis were built according to our previously outcome-based cutoffs for each gender.ResultsTotally, 83 patients (17.55%) were stratified as myosteatosis, of whom 85.54% had concomitant high visceral adiposity indicative of increased visceral adipose tissue index (VATI). The prevalence of sarcopenia showed no significant difference between the groups with and without myosteatosis. Multivariate analysis showed that advanced age [odds ratio (OR) = 1.097, p &lt; 0.001], higher visceral to subcutaneous ratio of adipose tissue area (VSR; OR = 1.574, p = 0.032), and higher VATI (OR = 1.026, p &lt; 0.001) are independently associated with myosteatosis. Correlation analyses revealed a positive relationship between intramuscular adipose tissue content (IMAC) and VATI (ρ = 0.48, p &lt; 0.001), subcutaneous adipose tissue index (SATI) (ρ = 0.36, p &lt; 0.001), and age (ρ = 0.36, p &lt; 0.001). None of the skeletal muscle or adipose tissue indicators were significantly related to longer LOH.ConclusionHigher VSR, higher VATI, and advanced age are associated with myosteatosis among patients with cirrhosis at the decompensation phase. It is tempting to target divergent adipose tissue depots aimed at timely intervention/prevention of myosteatosis.
Expanding the phenotypic spectrum of non-alcoholic fatty liver disease and hypertriglyceridemia
Authors: Meroni Marica , Longo Miriam , Paolini Erika , Tria Giada , Ripolone Michela , Napoli Laura , Moggio Maurizio , Fracanzani Anna Ludovica , Dongiovanni Paola 
Published: September 2022

Background and aimsHypertriglyceridemia is a common feature of metabolic syndrome (MetS), as well as of non-alcoholic fatty liver disease (NAFLD), which is considered the hepatic manifestation of MetS. Fat accumulation in hepatocytes may alter mitochondrial homeostasis predisposing to advanced liver disease. Here, we report a case of a 40-year-old woman with early aggressive NAFLD due to severe hypertriglyceridemia that ensued from a combination of genetic variants and additional metabolic risk factors.MethodsGenetic screening was performed by using whole-exome sequencing (WES), and mitochondrial structures were evaluated by TEM.ResultsAt presentation, the patient is reported to have hepatomegaly, hypertriglyceridemia, and raised transaminases. Genetic analysis revealed that the patient beard heritable alterations in genes implicated in lipid handling, among which APOB, APOE, CETP, and HSPG2, accompanied by missense mutations in genes involved in mitochondrial function, i.e., AK2, ALG6, ASPA, NDUFAF1, POLG, and TMEM70. Abdominal ultrasound (US) and transient elastography were suggestive of severe hepatic steatosis and fibrosis. A liver biopsy confirmed the diagnosis of non-alcoholic steatohepatitis (NASH)-related fibrosis. Thus, to better outline whether mutations involved in lipid remodeling and mitochondrial function may also affect organelles’ morphology, we exploited TEM. Along with multifaceted abnormalities of mitochondrial architecture that have been already observed in patients with NAFLD, astonishing ultrastructural defects, such as mitochondrial vacuolization, sub-compartmentalization, and onion-like mitochondria, were identified.ConclusionThe anomalies reported may expand the phenotypic spectrum of mitochondrial abnormalities observed in patients with NAFLD, which may contribute to the switching toward a progressive disease.
Real-world eligibility for platinum doublet plus immune checkpoint inhibitors in extensive-stage small-cell lung cancer
Authors: Rittberg Rebekah , Leung Bonnie , Al-Hashami Zamzam , Ho Cheryl 
Published: September 2022

IntroductionSmall cell lung cancer (SCLC) is a rapidly progressing aggressive malignancy. Durvalumab in CASPIAN and atezolizumab in IMPower133 were found to improve overall survival (OS) for extensive-stage SCLC. Here we evaluate the proportion of real-world ES SCLC patients who may be eligible for first-line immune checkpoint inhibitor (ICI) with platinum doublet.MethodsA retrospective cohort analysis was conducted of referred ES SCLC between 2015 and 2017 in British Columbia, Canada. Patient demographics, staging, treatment, and survival data were collected through the Cancer Registry. Retrospective chart review was completed to extract past medical history and missing variables. CASPIAN/IMPower133 excluded patients with autoimmune diseases, active infection, and performance status (PS) ≥2.ResultsBetween 2015 and 2017, 349 patients were diagnosed with ES SCLC. In patients who received platinum-doublet chemotherapy (n=227), 15 had medical contraindication to ICI: inflammatory bowel disease (n=4), rheumatoid arthritis (n=4), idiopathic pulmonary fibrosis (n=3), lupus (n=1), Sjogren’s (n=1), Takayasu arteritis (n=1), and active tuberculosis (n=1). ECOG PS was 0–1 in 96 (45%), PS was 2 in 61 (29%), and ≥3 in 51 (10%). Prior to cycle 1, 82 (36%) patients were eligible for ICI in addition to platinum doublet, 23% of the entire ES population. After cycles 1 and 2, additional 15 (7%) and 8 (4%) patients became PS 0–1, respectively. mOS for ES SCLC who received first-line platinum doublet, non-platinum chemotherapy, and best supportive care was 8.4 1.9 and 1.5 months (p&lt;0.001).DiscussionBy CASPIAN/IMpower133 trial eligibility, only 36% of our real-world platinum-treated patients would have been eligible for the addition of ICI, which is 23% of the entire ES population in one Canadian province. After one or two cycles of chemotherapy, an additional 11% of patients showed PS improvement to 0–1. While the results of CASPIAN/IMpower133 are practice-changing, the majority of the patients will not meet clinical trial eligibility and clinical trials including patients with poor PS are necessary.
Radiosensitization effect by HDAC inhibition improves NKG2D-dependent natural killer cytotoxicity in hepatocellular carcinoma
Authors: Liu Yu-Fan , Chiang Yun , Hsu Feng-Ming , Tsai Chiao-Ling , Cheng Jason Chia-Hsien 
Published: September 2022

BackgroundHepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Radiotherapy (RT) controls HCC unsatisfactorily and temporarily. Histone deacetylase inhibitor (HDACi) is a heterogeneous group of epigenetic therapeutics with promising anticancer effects and synergism in combination with RT. HDACi modulates natural killer (NK) cell ligand expression on tumor cells, and leads to immune evasion of cancer cells. Expressions of NK group 2D (NKG2D) ligands on cancer cells determine the cytotoxic effect by interacting with NKG2D receptor on NK cells. However, the role of NKG2D signaling in HCC upon combined RT and HDACi remains unclear.MethodIn vitro co-culture system with NK cells was tested for human and murine HCC cell lines. Pan-HDACi (panobinostat) and specific HDAC4 knockdown (HDAC4-KD) were used for HDAC inhibition. Clonogenic assay and flow cytometry examined HCC cell survival and NKG2D ligand expression, respectively. Syngeneic mouse model was used to validate the radiosensitizing effect in vivo.ResultsCombined RT and HDACi/HDAC4-KD significantly enhanced NK cell-related cytotoxicity and increased NKG2D ligands, MICA/MICB expressions in human and RAE-1/H60 expressions in murine HCC cells. Delayed tumor growth in vivo by the combinational treatment of RT and HDACi/HDAC4-KD was shown with the associated NKG2D ligand expressions. However, NKG2D receptor did not significantly change among tumors.ConclusionRadiosensitizing effect with combined RT and HDAC inhibition increased the expression of NKG2D ligands in HCC cells and enhanced their susceptibility to NK cell-mediated cytotoxicity. These findings imply the potential use of combined RT/HDACi and NK cell-directed immunotherapy.
A computed tomography-based preoperative risk scoring system to distinguish lymphoepithelioma-like gastric carcinoma from non-lymphoepithelioma-like gastric carcinoma
Authors: Li Liming , Huang Wenpeng , Hou Ping , Li Weiwei , Feng Menyun , Liu Yiyang , Gao Jianbo 
Published: September 2022

PurposeThe aim of this study was to develop a preoperative risk scoring model for distinguishing lymphoepithelioma-like gastric carcinoma (LELGC) from non-LELGC based on contrast-enhanced computed tomography (CT) images.MethodsClinicopathological features and CT findings of patients with LELGC and non-LELGC in our hospital from January 2016 to July 2022 were retrospectively analyzed and compared. A preoperative risk stratification model and a risk scoring system were developed using logistic regression.ResultsTwenty patients with LELGC and 40 patients with non-LELGC were included in the training cohort. Significant differences were observed in Epstein–Barr virus (EBV) infection and vascular invasion between the two groups (p &lt; 0.05). Significant differences were observed in the distribution of location, enhancement pattern, homogeneous enhancement, CT-defined lymph node status, and attenuations in the non-contrast, arterial, and venous phases (all p &lt; 0.05). Enhancement pattern, CT-defined lymph node status, and attenuation in venous phase were independent predictors of LELGC. The optimal cutoff score of distinguishing LELGC from non-LELGC was 3.5. The area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy of risk identification model in the training cohort were 0.904, 87.5%, 80.0%, and 85.0%, respectively. The area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy of risk identification model in the validation cohort were 0.705 (95% CI 0.434–0.957), 75.0%, 63.6%, and 66.7%, respectively.ConclusionA preoperative risk identification model based on CT imaging data could be helpful for distinguishing LELGC from non-LELGC.
Relative T2-FLAIR signal intensity surrounding residual cavity is associated with survival prognosis in patients with lower-grade gliomas
Authors: Yuan Tao , Gao Zhen , Wang Fei , Ren Jia-Liang , Wang Tianda , Zhong Hongbo , Gao Guodong , Quan Guanmin 
Published: September 2022

AimsTo investigate whether the relative signal intensity surrounding the residual cavity on T2-fluid-attenuated inversion recovery (rFLAIR) can improve the survival prediction of lower-grade glioma (LGG) patients.MethodsClinical and pathological data and the follow-up MR imaging of 144 patients with LGG were analyzed. We calculated rFLAIR with Image J software. Logistic analysis was used to explore the significant impact factors on progression-free survival (PFS) and overall survival (OS). Several models were set up to predict the survival prognosis of LGG.ResultsA higher rFLAIR [1.81 (0.83)] [median (IQR)] of non-enhancing regions surrounding the residual cavity was detected in the progressed group (n=77) than that [1.55 (0.33)] [median (IQR)] of the not-progressed group (n = 67) (P&lt;0.001). Multivariate analysis showed that lower KPS (≤75), and higher rFLAIR (&gt;1.622) were independent predictors for poor PFS (P&lt;0.05), whereas lower KPS (≤75) and thick-linear and nodular enhancement were the independent predictors for poor OS (P&lt;0.05). The cutoff rFLAIR value of 1.622 could be used to predict poor PFS (HR = 0.31, 95%CI 0.20–0.48) (P&lt;0.001) and OS (HR = 0.27, 95%CI 0.14–0.51) (P=0.002). Both the areas under the ROC curve (AUCs) for predicting poor PFS (AUC, 0.771) and OS (AUC, 0.831) with a combined model that contained rFLAIR were higher than those of any other models.ConclusionHigher rFALIR (&gt;1.622) in non-enhancing regions surrounding the residual cavity can be used as a biomarker of the poor survival of LGG. rFLAIR is helpful to improve the survival prediction of posttreatment LGG patients.
Prediction of lymph node metastasis in patients with breast invasive micropapillary carcinoma based on machine learning and SHapley Additive exPlanations framework
Authors: Jiang Cong , Xiu Yuting , Qiao Kun , Yu Xiao , Zhang Shiyuan , Huang Yuanxi 
Published: September 2022

AbstractBackground and purpose: Machine learning (ML) is applied for outcome prediction and treatment support. This study aims to develop different ML models to predict risk of axillary lymph node metastasis (LNM) in breast invasive micropapillary carcinoma (IMPC) and to explore the risk factors of LNM.MethodsFrom the Surveillance, Epidemiology, and End Results (SEER) database and the records of our hospital, a total of 1547 patients diagnosed with breast IMPC were incorporated in this study. The ML model is built and the external validation is carried out. SHapley Additive exPlanations (SHAP) framework was applied to explain the optimal model; multivariable analysis was performed with logistic regression (LR); and nomograms were constructed according to the results of LR analysis.ResultsAge and tumor size were correlated with LNM in both cohorts. The luminal subtype is the most common in patients, with the tumor size &lt;=20mm. Compared to other models, Xgboost was the best ML model with the biggest AUC of 0.813 (95% CI: 0.7994 - 0.8262) and the smallest Brier score of 0.186 (95% CI: 0.799-0.826). SHAP plots demonstrated that tumor size was the most vital risk factor for LNM. In both training and test sets, Xgboost had better AUC (0.761 vs 0.745; 0.813 vs 0.775; respectively), and it also achieved a smaller Brier score (0.202 vs 0.204; 0.186 vs 0.191; 0.220 vs 0.221; respectively) than the nomogram model based on LR in those three different sets. After adjusting for five most influential variables (tumor size, age, ER, HER-2, and PR), prediction score based on the Xgboost model was still correlated with LNM (adjusted OR:2.73, 95% CI: 1.30-5.71, P=0.008).ConclusionsThe Xgboost model outperforms the traditional LR-based nomogram model in predicting the LNM of IMPC patients. Combined with SHAP, it can more intuitively reflect the influence of different variables on the LNM. The tumor size was the most important risk factor of LNM for breast IMPC patients. The prediction score obtained by the Xgboost model could be a good indicator for LNM.
Typing characteristics of metabolism-related genes in osteoporosis
Authors: Guo Jiandong , Huang Qinghua , Zhou Yundong , Xu Yining , Zong Chenyu , Shen Panyang , Ma Yan , Zhang Jinxi , Cui Yongfeng , Yu Liuqian , Gao Jiawei , Liu Gang , Huang Kangmao , Xu Wenbin 
Published: September 2022

Objective: Osteoporosis is a common musculoskeletal disease. Fractures caused by osteoporosis place a huge burden on global healthcare. At present, the mechanism of metabolic-related etiological heterogeneity of osteoporosis has not been explored, and no research has been conducted to analyze the metabolic-related phenotype of osteoporosis. This study aimed to identify different types of osteoporosis metabolic correlates associated with underlying pathogenesis by machine learning.Methods: In this study, the gene expression profiles GSE56814 and GSE56815 of osteoporosis patients were downloaded from the GEO database, and unsupervised clustering analysis was used to identify osteoporosis metabolic gene subtypes and machine learning to screen osteoporosis metabolism-related characteristic genes. Meanwhile, multi-omics enrichment was performed using the online Proteomaps tool, and the results were validated using external datasets GSE35959 and GSE7429. Finally, the immune and stromal cell types of the signature genes were inferred by the xCell method.Results: Based on unsupervised cluster analysis, osteoporosis metabolic genotyping can be divided into three distinct subtypes: lipid and steroid metabolism subtypes, glycolysis-related subtypes, and polysaccharide subtypes. In addition, machine learning SVM identified 10 potentially metabolically related genes, GPR31, GATM, DDB2, ARMCX1, RPS6, BTBD3, ADAMTSL4, COQ6, B3GNT2, and CD9.Conclusion: Based on the clustering analysis of gene expression in patients with osteoporosis and machine learning, we identified different metabolism-related subtypes and characteristic genes of osteoporosis, which will help to provide new ideas for the metabolism-related pathogenesis of osteoporosis and provide a new direction for follow-up research.