bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Rogue” [DEspR+CD11b+] neutrophil subset correlates with severity in spontaneous intracerebral hemorrhage
Authors: Herrera Victoria L. M. , Takahashi Courtney E. , Nguyen Mai Q. , Mosaddeghi Julie Z. , Denis Ridiane , Greer David M. , Ruiz-Opazo Nelson 
Published: July 2022

ObjectiveCumulative clinical, cellular, and molecular evidence reinforces the role of neutrophils in secondary brain injury in spontaneous intracerebral hemorrhage (sICH). However, since generalized neutrophil inhibition is detrimental, identification of targetable “rogue” neutrophil subsets associated with sICH severity is key.MethodsIn a pilot prospective observational study of consented patients with sICH, we immunotyped whole blood to assess circulating neutrophil markers (~day 3 after ICH symptoms onset): (a) DEspR±CD11b± neutrophils by flow cytometry, (b) DEspR±CD11b± neutrophil extracellular trap (NET)-forming neutrophils by immunofluorescence cytology, and (c) neutrophil-lymphocyte ratio (NLR). Using Spearman rank correlation (r) with Bonferroni correction, we assessed the association of neutrophil markers with same-day clinical and neuroimaging parameters of sICH severity, index ICH score, 90-day modified Rankin Scale (mRS) score, and potential interrelationships. As comparators, we assessed same-day plasma biomarkers elevated in sICH: interleukin-6/IL-6, myeloperoxidase/MPO, soluble-terminal complement complex/sC5b-9, endothelin-1/ET-1, and mitochondrial/nuclear DNA ratio (mt/nDNA ratio).ResultsWe detected strong correlations [r(n = 13) &gt; 0.71, power &gt; 0.8, Bonferroni corrected pB &lt; 0.05] for all three neutrophil markers with 90-day mRS score, differentially for DEspR+CD11b+ neutrophil counts, and NLR with perihematomal edema (PHE) volume and for DEspR+CD11b+ NET-forming neutrophil counts with intraparenchymal hemorrhage (IPH)-volume. Only DEspR+CD11b+ neutrophil counts show a strong correlation with index ICH score, same-day Glasgow Coma Scale (GCS) score, and NLR and NET-forming neutrophil counts. The sum of the ICH score and three neutrophil markers exhibited the highest correlation: [r(n = 13) 0.94, pB = 10−5]. In contrast, plasma biomarkers tested were elevated except for MPO but exhibited no correlations in this pilot study.ConclusionStrong correlation with multiple sICH severity measures, NET formation, and NLR identifies DEspR+CD11b+ neutrophils as a putative “rogue” neutrophil subset in sICH. The even stronger correlation of the sum of three neutrophil markers and the index ICH score with 90-day mRS outcome reinforces early neutrophil-mediated secondary brain injury as a key determinant of outcome in patients with sICH. Altogether, data provide a basis for the formal study of the DEspR+CD11b+ neutrophil subset as a potential actionable biomarker for neutrophil-driven secondary brain injury in sICH. Data also show ex vivo analysis of patients with sICH neutrophils as a translational milestone to refine hypotheses between preclinical and clinical studies.
A preliminary trial of botulinum toxin type A in patients with vestibular migraine: A longitudinal fMRI study
Authors: Oh Sun-Young , Kang Jin-Ju , Kim Sohui , Lee Jong-Min , Kim Ji-Soo , Dieterich Marianne 
Published: July 2022

ObjectiveThis study aims to investigate the efficacy of botulinum toxin type A (BTX-A) in the prophylactic management of vestibular migraine (VM) and to determine whether this treatment modulates intrinsic functional brain network.MethodsVestibular migraine patients (n = 20, mean age 45.4 years) who were resistant to conventional prophylactic therapies had BTX-A injection and rs-fMRI before and 2 months after the injection. We also measured the changes in the frequency of vertigo and migraine attacks, symptomatic functional disability scores, and neuropsychiatric inventories.ResultsAfter BTX-A injection, the mean monthly frequencies of migraine and vertigo episodes decreased significantly compared with the baseline (p &lt; 0.01, paired t-test). The Headache Impact Test-6 score and the Migraine Disability Assessment, and the vertigo parameters, measured by the Dizziness Handicap Inventory and the Vertigo Symptom Scale, showed an improvement, as did the anxiety and depression scores 2 months after BTX-A treatment. The low-frequency fluctuation analysis of the rs-fMRI data found significant changes in the functional connectivity of the right superior temporal gyrus. Adoption of this cluster as the seed region increased the functional connectivity with the left post-central gyrus, right supramarginal gyrus, and right middle temporal gyrus after BTX-A treatment.ConclusionThis prospective study suggests that BTX-A treatment is effective at ameliorating migraine and vertigo symptoms in VM patients who were resistant to conventional therapies. Along with symptomatic improvements, changes in the functional connectivity within the multisensory vestibular and pain networks suggest a dysmodulation of multimodal sensory integration and abnormal cortical processing of the vestibular and pain signals in VM patients.
Cold Cognition as Predictor of Treatment Response to rTMS; A Retrospective Study on Patients With Unipolar and Bipolar Depression
Authors: Rostami Reza , Kazemi Reza , Nasiri Zahra , Ataei Somayeh , Hadipour Abed L. , Jaafari Nematollah 
Published: July 2022

BackgroundCognitive impairments are prevalent in patients with unipolar and bipolar depressive disorder (UDD and BDD, respectively). Considering the fact assessing cognitive functions is increasingly feasible for clinicians and researchers, targeting these problems in treatment and using them at baseline as predictors of response to treatment can be very informative.MethodIn a naturalistic, retrospective study, data from 120 patients (Mean age: 33.58) with UDD (n = 56) and BDD (n = 64) were analyzed. Patients received 20 sessions of bilateral rTMS (10 Hz over LDLPFC and 1 HZ over RDLPFC) and were assessed regarding their depressive symptoms, sustained attention, working memory, and executive functions, using the Beck Depression Inventory (BDI-II) and Neuropsychological Test Automated Battery Cambridge, at baseline and after the end of rTMS treatment course. Generalized estimating equations (GEE) and logistic regression were used as the main statistical methods to test the hypotheses.ResultsFifty-three percentage of all patients (n = 64) responded to treatment. In particular, 53.1% of UDD patients (n = 34) and 46.9% of BDD patients (n = 30) responded to treatment. Bilateral rTMS improved all cognitive functions (attention, working memory, and executive function) except for visual memory and resulted in more modulations in the working memory of UDD compared to BDD patients. More improvements in working memory were observed in responded patients and visual memory, age, and sex were determined as treatment response predictors. Working memory, visual memory, and age were identified as treatment response predictors in BDD and UDD patients, respectively.ConclusionBilateral rTMS improved cold cognition and depressive symptoms in UDD and BDD patients, possibly by altering cognitive control mechanisms (top-down), and processing negative emotional bias.
Effect of fermented oyster (Crassostrea gigas) extracts and regular walking on muscle strength and mass in older adults with relatively low muscle mass: A randomized controlled trial
Authors: Lee Ye Li , Lee Sang Yeoup 
Published: July 2022

IntroductionOysters possess an excellent nutritional profile containing γ-aminobutyric acid (GABA). Previous data suggest that GABA is a potent bioactive compound for improving muscle health. Lactic acid fermentation is thought to increase GABA content. However, the effect of oral supplementation of fermented oyster extracts (FO) on human muscle strength and mass is unclear. Therefore, we tested the effects and safety of consumption of FO combined with regular walking for 12 weeks on muscle strength and mass in older adults with relatively low muscle mass.Materials and methodsA randomized controlled trial was conducted on 54 adults between 50 and 78 years of age. Participants were randomized to receive either placebo or 1,200 mg FO daily for 12 weeks. By fermentation with Lactobacillus brevis BJ20, FO was prepared from Crassostrea gigas. At baseline and at 12 weeks after treatment, the following parameters of the participants were examined: knee strengths, handgrip strengths, body composition, blood tests, and 24-h dietary recall. All participants were required to walk for 30–60 min/day for &gt;3 days/week during the trial period. Physical activity was assessed using an exercise log during the study.ResultsOf the 54 participants, 49 completed the trial without reporting adverse effects. FO supplementation over 12 weeks did not cause any increase in knee or grip strength compared to the control group. Also, no differences were observed in the muscle mass, growth hormone, muscle biomarkers, anti-inflammatory markers, and antioxidative markers between the two groups. None of the participants experienced adverse events. Application of FO was well tolerated, and no notable adverse effect was reported in both groups.DiscussionFO supplementation with regular walking did not improve remarkably muscle function compared to regular walking alone in adults with relatively low muscle mass.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT04109911].
Anemia and Bone Marrow Suppression After Intra-Arterial Chemotherapy in Children With Retinoblastoma: A Retrospective Analysis
Authors: Zeng Changjuan , Han Minglei , Fan Jiayan , He Xiaoyu , Jia Renbing , Li Li , Wen Xuyang , Song Xuefei , Hou Lili 
Published: July 2022

BackgroundRetinoblastoma (Rb) is a common ocular malignant tumor in children. Intra-arterial chemotherapy (IAC) has been widely used in children with Rb and has achieved an ideal therapeutic effect. However, IAC has side effects, including anemia and bone marrow suppression, for which explicit evidence on the risk factors is lacking. This study aimed to evaluate the covariates that may affect the occurrence of anemia and bone marrow suppression in children with Rb after IAC.MethodsChildren with Rb admitted between May 2019 and January 2021 were included into the study. The differences in the number of children with anemia and bone marrow suppression before and after IAC according to different covariates were recorded. All potential impact factors were included into the univariate and multivariate regression models to identify the related covariates of post-IAC anemia and bone marrow suppression.ResultsData of 282 children with Rb were retrospectively collected. After IAC, children with Rb had increased severities of anemia (p &lt;0.0001, chi-square test) and bone marrow suppression (p = 0.001, chi-square test). Moreover, the number of children with Rb who had an increased cross-level change in the severity of anemia and degree of bone marrow suppression was 80 (41.24%) and 64 (32.49%), respectively. The univariate regression analysis showed that numerous factors (such as pre-IAC intravenous chemotherapy, results of pre-IAC routine blood tests, and some serological indicators for liver and kidney function) affected the anemia severity and degree of bone marrow suppression in children with Rb after IAC. Additionally, the predictive model of the multivariate regression could predict anemia and bone marrow suppression.ConclusionChildren with Rb may have an increased risk of anemia and bone marrow suppression after IAC, but this is temporary and can be influenced by several factors. Therefore, IAC should be maintained as the standard of care. We generated predictive equations for predicting anemia severity and degree of bone marrow suppression, which can guide the prediction and timely control of anemia and bone marrow suppression after IAC.
A distinct lipid metabolism signature of acute myeloid leukemia with prognostic value
Authors: Li Ding , Liang Jiaming , Yang Wei , Guo Wenbin , Song Wenping , Zhang Wenzhou , Wu Xuan , He Baoxia 
Published: July 2022

BackgroundAcute myeloid leukemia (AML) is a highly aggressive hematological malignancy characterized by extensive genetic abnormalities that might affect the prognosis and provide potential drug targets for treatment. Reprogramming of lipid metabolism plays important roles in tumorigenesis and progression and has been newly recognized a new hallmark of malignancy, and some related molecules in the signal pathways could be prognostic biomarkers and potential therapeutic targets for cancer treatment. However, the clinical value of lipid metabolism reprogramming in AML has not been systematically explored. In this study, we aim to explore the clinical value of lipid metabolism reprogramming and develop a prognostic risk signature for AML.MethodsWe implemented univariate Cox regression analysis to identify the prognosis-related lipid metabolism genes, and then performed LASSO analysis to develop the risk signature with six lipid metabolism-related genes (LDLRAP1, PNPLA6, DGKA, PLA2G4A, CBR1, and EBP). The risk scores of samples were calculated and divided into low- and high-risk groups by the median risk score.ResultsSurvival analysis showed the high-risk group hold the significantly poorer outcomes than the low-risk group. The signature was validated in the GEO datasets and displayed a robust prognostic value in the stratification analysis. Multivariate analysis revealed the signature was an independent prognostic factor for AML patients and could serve as a potential prognostic biomarker in clinical evaluation. Furthermore, the risk signature was also found to be closely related to immune landscape and immunotherapy response in AML.ConclusionsOverall, we conducted a comprehensive analysis of lipid metabolism in AML and constructed a risk signature with six genes related to lipid metabolism for the malignancy, prognosis, and immune landscape of AML, and our study might contribute to better understanding in the use of metabolites and metabolic pathways as the potential prognostic biomarkers and therapeutic targets for AML.
Prognostic Role of Combined EGFR and Tumor-Infiltrating Lymphocytes in Oral Squamous Cell Carcinoma
Authors: Wongpattaraworakul Wattawan , Gibson-Corley Katherine N. , Choi Allen , Buchakjian Marisa R. , Lanzel Emily A. , Rajan KD Anand , Simons Andrean L. 
Published: July 2022

BackgroundEpidermal growth factor receptor (EGFR) is well known as a general prognostic biomarker for head and neck tumors, however the specific prognostic value of EGFR in oral squamous cell carcinoma (OSCC) is controversial. Recently, the presence of tumor-infiltrating T cells has been associated with significant survival advantages in a variety of disease sites. The present study will determine if the inclusion of T cell specific markers (CD3, CD4 and CD8) would enhance the prognostic value of EGFR in OSCCs.MethodsTissue microarrays containing 146 OSCC cases were analyzed for EGFR, CD3, CD4 and CD8 expression using immunohistochemical staining. EGFR and T cell expression scores were correlated with clinicopathological parameters and survival outcomes.ResultsResults showed that EGFR expression had no impact on overall survival (OS), but EGFR-positive (EGFR+) OSCC patients demonstrated significantly worse progression free survival (PFS) compared to EGFR-negative (EGFR-) patients. Patients with CD3, CD4 and CD8-positive tumors had significantly better OS compared to CD3, CD4 and CD8-negative patients respectively, but no impact on PFS. Combined EGFR+/CD3+ expression was associated with cases with no nodal involvement and significantly more favorable OS compared to EGFR+/CD3- expression. CD3 expression had no impact on OS or PFS in EGFR- patients. Combinations of EGFR/CD8 and EGFR/CD4 expression showed no significant differences in OS or PFS among the expression groups.ConclusionAltogether these results suggest that the expression of CD3+ tumor-infiltrating T cells can enhance the prognostic value of EGFR expression and warrants further investigation as prognostic biomarkers for OSCC.
Risk of human papillomavirus infection and cervical intraepithelial lesions in Chinese renal transplant recipients
Authors: Chen Ming , Cui Qiulin , Chen Meilian , Xia Meng , Liu Duo , Chen Peisong , Wang Changxi , He Mian 
Published: July 2022

ObjectiveWhile human papillomavirus (HPV) infection in women is associated with cervical intraepithelial neoplasia and cervical cancer, HPV testing is not often performed in routine practice for renal transplantation patients. The genotype-specific prevalence of HPV and risk factors for HPV infection are still unclear.MethodsFrom 2010 to 2020, patients receiving renal transplantation surgery (referred to as RTRs), who had been screened for HPV infection one year after transplantation were enrolled. A comparison cohort of four age- and marital status-matched healthy individuals was selected for RTRs. The clinical characteristics and cervical screening results of RTRs were analyzed.ResultsOur study included 196 female renal transplant recipients (RTRs), none of whom had been vaccinated against HPV. Overall high-risk HPV (hrHPV) infection and abnormal cytology rates in the RTR group were 23.5% and 20.9%, respectively. The odds ratios of hrHPV infection and cervical intraepithelial neoplasia grade 2+ in RTRs vs. non-RTRs were 3.033 (95% CI, 2.013-4.568) and 3.628 (95% CI, 1.863-7.067), respectively. The prevalence of HPV16 in RTRs was much higher (30.4% vs. 8.3%, P=0.002). The multi-infection rate was much higher in HPV-infected RTRs (23.9% vs. 1.14%, P&lt;0.001). The only risk factor for hrHPV infection was the duration of immunosuppression, which increased with time.ConclusionRTRs had significantly higher HPV infection rates and increased risks of HPV-related cervical premalignancies and cancers due to the immunosuppressed state. The duration of immunosuppression is a risk factor for transplant recipients. Female RTRs may benefit from more frequent cervical cancer screening after renal transplantation than healthy women. Prospective research on HPV infection dynamics in RTRs and optimal screening methods should be further explored in the future.
A machine learning model based on ultrasound image features to assess the risk of sentinel lymph node metastasis in breast cancer patients: Applications of scikit-learn and SHAP
Authors: Zhang Gaosen , Shi Yan , Yin Peipei , Liu Feifei , Fang Yi , Li Xiang , Zhang Qingyu , Zhang Zhen 
Published: July 2022

BackgroundThis study aimed to determine an optimal machine learning (ML) model for evaluating the preoperative diagnostic value of ultrasound signs of breast cancer lesions for sentinel lymph node (SLN) status.MethodThis study retrospectively analyzed the ultrasound images and postoperative pathological findings of lesions in 952 breast cancer patients. Firstly, the univariate analysis of the relationship between the ultrasonographic features of breast cancer morphological features and SLN metastasis. Then, based on the ultrasound signs of breast cancer lesions, we screened ten ML models: support vector machine (SVM), extreme gradient boosting (XGBoost), random forest (RF), linear discriminant analysis (LDA), logistic regression (LR), naive bayesian model (NB), k-nearest neighbors (KNN), multilayer perceptron (MLP), long short-term memory (LSTM), and convolutional neural network (CNN). The diagnostic performance of the model was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), Kappa value, accuracy, F1-score, sensitivity, and specificity. Then we constructed a clinical prediction model which was based on the ML algorithm with the best diagnostic performance. Finally, we used SHapley Additive exPlanation (SHAP) to visualize and analyze the diagnostic process of the ML model.ResultsOf 952 patients with breast cancer, 394 (41.4%) had SLN metastasis, and 558 (58.6%) had no metastasis. Univariate analysis found that the shape, orientation, margin, posterior features, calculations, architectural distortion, duct changes and suspicious lymph node of breast cancer lesions in ultrasound signs were associated with SLN metastasis. Among the 10 ML algorithms, XGBoost had the best comprehensive diagnostic performance for SLN metastasis, with Average-AUC of 0.952, Average-Kappa of 0.763, and Average-Accuracy of 0.891. The AUC of the XGBoost model in the validation cohort was 0.916, the accuracy was 0.846, the sensitivity was 0.870, the specificity was 0.862, and the F1-score was 0.826. The diagnostic performance of the XGBoost model was significantly higher than that of experienced radiologists in some cases (P&lt;0.001). Using SHAP to visualize the interpretation of the ML model screen, it was found that the ultrasonic detection of suspicious lymph nodes, microcalcifications in the primary tumor, burrs on the edge of the primary tumor, and distortion of the tissue structure around the lesion contributed greatly to the diagnostic performance of the XGBoost model.ConclusionsThe XGBoost model based on the ultrasound signs of the primary breast tumor and its surrounding tissues and lymph nodes has a high diagnostic performance for predicting SLN metastasis. Visual explanation using SHAP made it an effective tool for guiding clinical courses preoperatively.
A Mouse Model of Damp-Heat Syndrome in Traditional Chinese Medicine and Its Impact on Pancreatic Tumor Growth
Authors: Jiao Juying , Cheng Chien-shan , Xu Panling , Yang Peiwen , Ruan Linjie , Chen Zhen 
Published: July 2022

BackgroundDamp-heat syndrome is one of the most important syndrome types in the traditional Chinese medicine (TCM) syndrome differentiation and treatment system, as well as the core pathogenesis of pancreatic cancer (PC) which remains a challenge to medical researchers due to its insidious onset and poor prognosis. Great attention has been given to the impact of damp-heat syndrome on tumorigenesis and progression, but less attention has been given to damp-heat modeling per se. Studying PC in a proper damp-heat syndrome animal model can recapitulate the actual pathological process and contribute to treatment strategy improvement.MethodsHere, an optimized damp-heat syndrome mouse model was established based on our prior experience. The Fibonacci method was applied to determine the maximum tolerated dosage of alcohol for mice. Damp-heat syndrome modeling with the old and new methods was performed in parallel of comparative study about general appearance, food intake, water consumption and survival. Major organs, including the liver, kidneys, lungs, pancreas, spleen, intestines and testes, were collected for histological evaluation. Complete blood counts and biochemical tests were conducted to characterize changes in blood circulation. PC cells were subcutaneously inoculated into mice with damp-heat syndrome to explore the impact of damp-heat syndrome on PC growth. Hematoxylin-eosin staining, Masson staining and immunohistochemistry were performed for pathological evaluation. A chemokine microarray was applied to screen the cytokines mediating the proliferation-promoting effects of damp-heat syndrome, and quantitative polymerase chain reaction and Western blotting were conducted for results validation.ResultsThe new modeling method has the advantages of mouse-friendly features, easily accessible materials, simple operation, and good stability. More importantly, a set of systematic indicators was proposed for model evaluation. The new modeling method verified the pancreatic tumor-promoting role of damp-heat syndrome. Damp-heat syndrome induced the proliferation of cancer-associated fibroblasts and promoted desmoplasia. In addition, circulating and tumor-located chemokine levels were altered by damp-heat syndrome, characterized by tumor promotion and immune suppression.ConclusionsThis study established a stable and reproducible murine model of damp-heat syndrome in TCM with systematic evaluation methods. Cancer associated fibroblast-mediated desmoplasia and chemokine production contribute to the tumor-promoting effect of damp-heat syndrome on PC.