bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Pathogenesis of COVID-19 Myocardial Injury: An Immunohistochemical Study of Postmortem Biopsies
Authors: Hartmann Camila , Miggiolaro Anna Flavia Ribeiro dos Santos , Motta Jarbas da Silva , Baena Carstens Lucas , Busatta Vaz De Paula Caroline , Fagundes Grobe Sarah , Hermann de Souza Nunes Larissa , Lenci Marques Gustavo , Libby Peter , Zytynski Moura Lidia , de Noronha Lucia , Pellegrino Baena Cristina 
Published: November 2021

RationaleMyocardial injury associates significantly and independently with mortality in COVID-19 patients. However, the pathogenesis of myocardial injury in COVID-19 remains unclear, and cardiac involvement by SARS-CoV-2 presents a major challenge worldwide.ObjectiveThis histological and immunohistochemical study sought to clarify the pathogenesis and propose a mechanism with pathways involved in COVID-19 myocardial injury.Methods and ResultsPostmortem minimally invasive autopsies were performed in six patients who died from COVID-19, and the myocardium samples were compared to a control group (n=11). Histological analysis was performed using hematoxylin-eosin and toluidine blue staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: caspase-1, caspase-9, gasdermin-d, ICAM-1, IL-1β, IL-4, IL-6, CD163, TNF-α, TGF-β, MMP-9, type 1 and type 3 collagen. The samples were also assessed for apoptotic cells by TUNEL. Histological analysis showed severe pericardiocyte interstitial edema and higher mast cells counts per high-power field in all COVID-19 myocardium samples. The IHC analysis showed increased expression of caspase-1, ICAM-1, IL-1β, IL-6, MMP-9, TNF-α, and other markers in the hearts of COVID-19 patients. Expression of caspase-9 did not differ from the controls, while gasdermin-d expression was less. The TUNEL assay was positive in all the COVID-19 samples supporting endothelial apoptosis.ConclusionsThe pathogenesis of COVID-19 myocardial injury does not seem to relate to primary myocardiocyte involvement but to local inflammation with associated interstitial edema. We found heightened TGF-β and interstitial collagen expression in COVID-affected hearts, a potential harbinger of chronic myocardial fibrosis. These results suggest a need for continued clinical surveillance of patients for myocardial dysfunction and arrythmias after recovery from the acute phase of COVID-19.
Salmonella Infantis Delays the Death of Infected Epithelial Cells to Aggravate Bacterial Load by Intermittent Phosphorylation of Akt With SopB
Authors: Chu Bing-Xin , Li Ya-Nan , Liu Ning- , Yuan Lan-Xin , Chen Shi-Yan , Zhu Yao-Hong , Wang Jiu-Feng 
Published: November 2021

Salmonella Infantis has emerged as a major clinical pathogen causing gastroenteritis worldwide in recent years. As an intracellular pathogen, Salmonella has evolved to manipulate and benefit from the cell death signaling pathway. In this study, we discovered that S. Infantis inhibited apoptosis of infected Caco-2 cells by phosphorylating Akt. Notably, Akt phosphorylation was observed in a discontinuous manner: immediately 0.5 h after the invasion, then before peak cytosolic replication. Single-cell analysis revealed that the second phase was only induced by cytosolic hyper-replicating bacteria at 3–4 hpi. Next, Akt-mediated apoptosis inhibition was found to be initiated by Salmonella SopB. Furthermore, Akt phosphorylation increased mitochondrial localization of Bcl-2 to prevent Bax oligomerization on the mitochondrial membrane, maintaining the mitochondrial network homeostasis to resist apoptosis. In addition, S. Infantis induced pyroptosis, as evidenced by increased caspase-1 (p10) and GSDMS-N levels. In contrast, cells infected with the ΔSopB strain displayed faster but less severe pyroptosis and had less bacterial load. The results indicated that S. Infantis SopB–mediated Akt phosphorylation delayed pyroptosis, but aggravated its severity. The wild-type strain also caused more severe diarrhea and intestinal inflammatory damage than the ΔSopB strain in mice. These findings revealed that S. Infantis delayed the cells’ death by intermittent activation of Akt, allowing sufficient time for replication, thereby causing more severe inflammation.
The Ki-67 Proliferation Index-Related Nomogram to Predict the Response of First-Line Tyrosine Kinase Inhibitors or Chemotherapy in Non-small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor-Mutant Status
Authors: Gu Weiguo , Hu Mingbin , Xu Linlin , Ren Yuanhui , Mei Jinhong , Wang Weijia , Wang Chunliang 
Published: November 2021

Background: The correlation between Ki-67 and epidermal growth factor receptor (EGFR)- or Kristen rat sarcoma viral oncogene homolog (KRAS)-mutant status in advanced or postoperative-recurrent non-small cell lung cancer (NSCLC) has fewer studies reported, and the prognostic role of Ki-67 with first-line EGFR-tyrosine kinase inhibitors (TKIs) or chemotherapy remains controversial.Methods: A total of 295 patients were tested for EGFR-mutant status in advanced or postoperative-recurrent NSCLC and received first-line EGFR-TKIs or chemotherapy for treatment. Ki-67 expression was retrospectively analyzed by immunohistochemistry. The Kaplan-Meier method was used to calculate survival rates. The multivariate Cox proportional hazards model was used to generate a nomogram. The established nomogram was validated using the calibration plots.Results: The expression levels of Ki-67 were divided into low (&lt;60%, n = 186) and high (≥60%, n = 109) groups, based on the receiver operating characteristic curve. The expression levels of Ki-67 were found to be higher in patients with KRAS mutations when compared to KRAS wildtype, and EGFR wildtype was higher than EGFR mutations. The median overall survival (OS) of the low Ki-67 expression group was significantly longer than that of the high Ki-67 group, no matter in all NSCLC, EGFR mutations, EGFR wildtype, KRAS-mutant status, EGFR-TKIs, or chemotherapy of patients (P &lt; 0.05). Subgroup analysis showed that the KRAS wildtype or EGFR mutations combine with low Ki-67 expression group had the longest median OS than KRAS mutations or EGFR wildtype combine with Ki-67 high expression group (P &lt; 0.05). In the training cohort, the multivariate Cox analysis identified age, serum lactate dehydrogenase (LDH), serum Cyfra211, EGFR mutations, and Ki-67 as independent prognostic factors, and a nomogram was developed based on these covariates. The calibration curve for predicting the 12-, 24-, and 30-month OS showed an optimal agreement between the predicted and actual observed outcomes.Conclusions: The Ki-67 expression-based nomogram can well predict the efficacy of first-line therapy in NSCLC patients with EGFR- or KRAS-mutant status, high expression levels of Ki-67 correlated with a poor prognosis.
Association Between Sleep and Motoric Cognitive Risk Syndrome Among Community-Dwelling Older Adults: Results From the China Health and Retirement Longitudinal Study
Authors: Xu Weihao , Bai Anying , Huang Xin , Gao Yinghui , Liu Lin 
Published: November 2021

Background: Sleep is increasingly recognized as an important lifestyle contributor to health; however, its relationship with Motoric cognitive risk syndrome (MCR) is still unclear. The present study aimed to examine the associations between sleep duration, sleep quality, and MCR among community-dwelling Chinese older adults.Methods: We recruited 5,387 participants aged ≥60 years from the China Health and Retirement Longitudinal Study (CHARLS). Sleep-related variables including night sleep duration and sleep quality were assessed via self-reported questionnaires. MCR syndrome was defined as cognitive complaints and slow gait speed without dementia or impaired mobility. Multivariate logistic regression analysis was performed to explore the associations between sleep-related variables and MCR after controlling for all potential confounders including demographic characteristics, lifestyle factors, and comorbidities.Results: We found that sleep duration was significantly associated with MCR, and the multivariate-adjusted odds ratios (OR) were highest for those with the shortest (&lt;6 h OR = 1.55, 95% CI = 1.18–2.04) and longest (≥10 h OR = 1.73, 95% CI = 1.03–2.91) sleep durations. Moreover, an increasing frequency of self-perceived poor sleep quality was significantly associated with MCR in the adjusted model (3–4 days OR = 1.58, 95% CI = 1.16–2.17; 5–7 days OR = 1.81, 95% CI = 1.37–2.40).Conclusions: Our study indicated an inverted U-shaped association between night sleep duration and MCR. Poor sleep quality was also associated with higher odds of MCR in community-dwelling Chinese elders. Longitudinal studies with a larger population size are needed to establish causality in the future and further explore potential action mechanisms.
The Differences Between Motor Attempt and Motor Imagery in Brain-Computer Interface Accuracy and Event-Related Desynchronization of Patients With Hemiplegia
Authors: Chen Shugeng , Shu Xiaokang , Wang Hewei , Ding Li , Fu Jianghong , Jia Jie 
Published: November 2021

Background: Motor attempt and motor imagery (MI) are two common motor tasks used in brain-computer interface (BCI). They are widely researched for motor rehabilitation in patients with hemiplegia. The differences between the motor attempt (MA) and MI tasks of patients with hemiplegia can be used to promote BCI application. This study aimed to explore the accuracy of BCI and event-related desynchronization (ERD) between the two tasks.Materials and Methods: We recruited 13 patients with stroke and 3 patients with traumatic brain injury, to perform MA and MI tasks in a self-control design. The BCI accuracies from the bilateral, ipsilesional, and contralesional hemispheres were analyzed and compared between different tasks. The cortical activation patterns were evaluated with ERD and laterality index (LI).Results: The study showed that the BCI accuracies of MA were significantly (p &lt; 0.05) higher than MI in the bilateral, ipsilesional, and contralesional hemispheres in the alpha-beta (8–30 Hz) frequency bands. There was no significant difference in ERD and LI between the MA and MI tasks in the 8–30 Hz frequency bands. However, in the MA task, there was a negative correlation between the ERD values in the channel CP1 and ipsilesional hemispheric BCI accuracies (r = −0.552, p = 0.041, n = 14) and a negative correlation between the ERD values in channel CP2 and bilateral hemispheric BCI accuracies (r = −0.543, p = 0.045, n = 14). While in the MI task, there were negative correlations between the ERD values in channel C4 and bilateral hemispheric BCI accuracies (r = −0.582, p = 0.029, n = 14) as well as the contralesional hemispheric BCI accuracies (r = −0.657, p = 0.011, n = 14). As for motor dysfunction, there was a significant positive correlation between the ipsilesional BCI accuracies and FMA scores of the hand part in 8–13 Hz (r = 0.565, p = 0.035, n = 14) in the MA task and a significant positive correlation between the ipsilesional BCI accuracies and FMA scores of the hand part in 13–30 Hz (r = 0.558, p = 0.038, n = 14) in the MI task.Conclusion: The MA task may achieve better BCI accuracy but have similar cortical activations with the MI task. Cortical activation (ERD) may influence the BCI accuracy, which should be carefully considered in the BCI motor rehabilitation of patients with hemiplegia.
Abnormal Network Homogeneity in the Right Superior Medial Frontal Gyrus in Cervical Dystonia
Authors: Wei Shubao , Chen Xiuqiong , Xiao Yousheng , Jiang Wenyan , Yin Qiong , Lu Chunhui , Yang Lu , Wei Jing , Liu Yang , Li Wenmei , Tang Jingqun , Guo Wenbin , Luo Shuguang 
Published: November 2021

Background: Increasing evidence from modern neuroimaging has confirmed that cervical dystonia (CD) is caused by network abnormalities. Specific brain networks are known to be crucial in patients suffering from CD. However, changes in network homogeneity (NH) in CD patients have not been characterized. Therefore, the purpose of this study was to investigate the NH of patients with CD.Methods: An automated NH method was used to analyze resting-state functional magnetic resonance (fMRI) data from 19 patients with CD and 21 gender- and age-matched healthy controls (HC). Correlation analysis were conducted between NH, illness duration and symptom severity measured by the Tsui scale.Results: Compared with the HC group, CD patients showed a lower NH in the right superior medial frontal gyrus. No significant correlations were found between abnormal NH values and illness duration or symptom severity.Conclusion: Our findings suggest the existence of abnormal NH in the default mode network (DMN) of CD patients, and thereby highlight the importance of the DMN in the pathophysiology of CD.
Prospective Quantitative Neuroimaging Analysis of Putative Temporal Lobe Epilepsy
Authors: Elisevich Kost , Davoodi-Bojd Esmaeil , Heredia John G. , Soltanian-Zadeh Hamid 
Published: November 2021

Purpose: A prospective study of individual and combined quantitative imaging applications for lateralizing epileptogenicity was performed in a cohort of consecutive patients with a putative diagnosis of mesial temporal lobe epilepsy (mTLE).Methods: Quantitative metrics were applied to MRI and nuclear medicine imaging studies as part of a comprehensive presurgical investigation. The neuroimaging analytics were conducted remotely to remove bias. All quantitative lateralizing tools were trained using a separate dataset. Outcomes were determined after 2 years. Of those treated, some underwent resection, and others were implanted with a responsive neurostimulation (RNS) device.Results: Forty-eight consecutive cases underwent evaluation using nine attributes of individual or combinations of neuroimaging modalities: 1) hippocampal volume, 2) FLAIR signal, 3) PET profile, 4) multistructural analysis (MSA), 5) multimodal model analysis (MMM), 6) DTI uncertainty analysis, 7) DTI connectivity, and 9) fMRI connectivity. Of the 24 patients undergoing resection, MSA, MMM, and PET proved most effective in predicting an Engel class 1 outcome (&gt;80% accuracy). Both hippocampal volume and FLAIR signal analysis showed 76% and 69% concordance with an Engel class 1 outcome, respectively.Conclusion: Quantitative multimodal neuroimaging in the context of a putative mTLE aids in declaring laterality. The degree to which there is disagreement among the various quantitative neuroimaging metrics will judge whether epileptogenicity can be confined sufficiently to a particular temporal lobe to warrant further study and choice of therapy. Prediction models will improve with continued exploration of combined optimal neuroimaging metrics.
Imaging Features of Hepatocellular Carcinoma With Bile Duct Tumor Thrombus: A Multicenter Study
Authors: Wu Jun-Yi , Huang Li-Ming , Bai Yan-Nan , Wu Jia-Yi , Wei Yong-Gang , Zhang Zhi-Bo , Yan Mao-Lin 
Published: November 2021

ObjectivesThere are still challenging problems in diagnosis of hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) before operation. This study aimed to analyze the imaging features of HCC with B1–B3 BDTT.Materials and MethodsThe clinicopathological data and imaging findings of 30 HCC patients with B1–B3 BDTT from three high-volume institutions were retrospectively reviewed. A total of 631 patients without BDTT who were randomly collected from each of the enrolled centers were recorded as the control group to analyze the differences in clinicopathological characteristics and imaging features between the two groups. A total of 453 HCC patients who underwent surgical treatment in the three institutions from January 2020 to December 2020 were collected for a blinded reading test as the validation group.ResultsHCC patients with B1–B3 BDTT had more advanced tumor stages and adverse clinicopathological features. HCC lesions were detected in all patients, and intrahepatic bile duct dilation was observed in 28 (93.3%) patients with B1–B3 BDTT and 9 (1.43%) patients in HCC without BDTT. The intrahepatic bile duct dilation showed no enhancement at hepatic arterial phase (HAP) and no progressively delayed enhancement at portal venous phase (PVP), but it was more obvious at PVP on CT. In the reports of the 30 HCC patients with B1–B3 BDTT generated for the image when the scan was done, BDTT was observed in all 13 B3 patients and 3 of 12 B2 patients, but none of the 5 B1 patients. Fourteen patients were misdiagnosed before surgery. However, when using intrahepatic bile duct dilation in HCC patients as a potential biomarker for BDTT diagnosis, the sensitivity and specificity for BDTT diagnosis were 93.33% and 98.57%, respectively. The blinded reading test showed that intrahepatic bile duct dilation in CT and MRI scans could be for separating HCC patients with B1–B3 BDTT from HCC patients without BDTT.ConclusionsThe HCC lesions and intrahepatic bile duct dilation on CT or MRI scans are imaging features of HCC with BDTT, which might facilitate the early diagnosis of B1–B3 BDTT.
Clinical Value of Machine Learning-Based Ultrasomics in Preoperative Differentiation Between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: A Multicenter Study
Authors: Ren Shanshan , Li Qian , Liu Shunhua , Qi Qinghua , Duan Shaobo , Mao Bing , Li Xin , Wu Yuejin , Zhang Lianzhong 
Published: November 2021

ObjectiveThis study aims to explore the clinical value of machine learning-based ultrasomics in the preoperative noninvasive differentiation between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).MethodsThe clinical data and ultrasonic images of 226 patients from three hospitals were retrospectively collected and divided into training set (n = 149), test set (n = 38), and independent validation set (n = 39). Manual segmentation of tumor lesion was performed with ITK-SNAP, the ultrasomics features were extracted by the pyradiomics, and ultrasomics signatures were generated using variance filtering and lasso regression. The prediction models for preoperative differentiation between HCC and ICC were established by using support vector machine (SVM). The performance of the three models was evaluated by the area under curve (AUC), sensitivity, specificity, and accuracy.ResultsThe ultrasomics signatures extracted from the grayscale ultrasound images could successfully differentiate between HCC and ICC (p &lt; 0.05). The combined model had a better performance than either the clinical model or the ultrasomics model. In addition to stability, the combined model also had a stronger generalization ability (p &lt; 0.05). The AUC (along with 95% CI), sensitivity, specificity, and accuracy of the combined model on the test set and the independent validation set were 0.936 (0.806–0.989), 0.900, 0.857, 0.868, and 0.874 (0.733–0.961), 0.889, 0.867, and 0.872, respectively.ConclusionThe ultrasomics signatures could facilitate the preoperative noninvasive differentiation between HCC and ICC. The combined model integrating ultrasomics signatures and clinical features had a higher clinical value and a stronger generalization ability.
Effect and Management of Excess Weight in the Context of Fertility-Sparing Treatments in Patients With Atypical Endometrial Hyperplasia and Endometrial Cancer: Eight-Year Experience of 227 Cases
Authors: Shan Ying , Qin Meng , Yin Jie , Cai Yan , Li Yan , Gu Yu , Wang Wei , Wang Yong-xue , Chen Jia-yu , Jin Ying , Pan Ling-ya 
Published: November 2021

ObjectiveTo investigate the oncologic and reproductive outcomes of fertility-sparing treatments (FSTs) in atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) patients with excess weight (EW).MethodsThis retrospective study comprised patients with AEH or EC who achieved a complete response (CR) after FST from 2010 to 2018. The clinical characteristics, oncological and reproductive outcomes were compared between the excess weight (EW) group (body mass index (BMI)≥25 kg/m2) and normal weight (NW) group (BMI&lt;25 kg/m2). The risk factors associated with recurrence and unsuccessful pregnancy in patients with EW were analyzed.ResultsOverall, 227 patients were enrolled, including 139 (61.2%) in EW group and 88 (38.8%) in NW group. In patients with EW, the pregnancy rate, the live birth rate and the relapse rate were 29.8%, 23.4%, and 30.9%, respectively. In patients with NW, these rates were 61.1%, 47.2%, and 31.8%, respectively. No significant differences were observed in the time to remission (P=0.865) and disease-free survival (DFS) (P=0.750). Patients in NW group achieved a better pregnancy rate than patients in the EW group (P=0.034). The patients with EW using ovulation induction to increase fertility tended to have a shorter time to pregnancy (P=0.042). However, no significant risk factors associated with unsuccessful pregnancy were identified after the multivariate analysis. In terms of DFS, the combination of gonadotropin-releasing hormone agonist (GnRH-a) and LNG-IUD was better for patients with EW than GnRH-a or oral progestin therapy alone (P=0.044, adjusted hazard ratio (HR)=0.432, 95% confidence interval (CI): 0.152-1.229), especially for patients with EW diagnosed with EC (P=0.032).ConclusionFSTs for overweight and obese patients should be more individualized. GnRH-a and/or LNG-IUD may be options prior to FSTs in patients with EW. Further prospective studies are needed.
Immunogenomic Landscape and Immune-Related Gene-Based Prognostic Signature in Asian Gastric Cancer
Authors: Mao Chenchen , Ma Liangliang , Huang Yingpeng , Yang Xinxin , Huang He , Cai Wentao , Sitrakiniaina Andriamifehimanjaka , Gu Ruihong , Xue Xiangyang , Shen Xian 
Published: November 2021

BackgroundAsians have the highest incidence of gastric cancer (GC), and the prognosis of Asian GC is poor. Furthermore, the therapeutics for Asian GC is limited because of genetic heterogeneity and screening difficulty at the early stage. This study aimed to develop an immune-related gene (IRG)-based prognostic signature and to explore prognosis-related regulatory mechanism and therapeutic target for Asian GC.MethodsTo elucidate the prognostic value of IRGs in Asian GC, a comprehensive analysis of IRG expression profiles and overall survival times in 364 Asian GC patients from the Asian Cancer Research Group (ACRG) and The Cancer Genome Atlas (TCGA) databases was performed, and a novel prognostic index was established. To further explore regulatory prognosis mechanisms and therapeutic targets, a tumor immunogenomic landscape analysis, including stromal and immune subcomponents, cell types, panimmune gene sets, and immunomodulatory genes, was performed.ResultOur analysis allowed the creation of an optimal risk assessment model, the Asian-specific IRG-based prognostic index (ASIRGPI), which showed a high accuracy in predicting survival in Asian GC. We also developed an ASIRGPI-based nomogram to predict the 3- and 5-year overall survival (OS) of Asian GC patients. The impact of the ASIRGPI on the worse prognosis of Asian GC was possibly related to the stromal component remodeling. Specifically, TGFβ gene sets were significantly associated with the ASIRGPI and worse prognosis. Immunomodulatory gene analysis further revealed that TGFβ1 and EDNRB may be the novel potential therapeutic targets for Asian GC.ConclusionsAs a tumor microenvironment-relevant gene set-based prognostic signature, the ASIRGPI model provides an effective approach for evaluating the prognosis of Asian GC and may even prolong OS by enabling the selection of individualized therapy with the novel targets.