bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGF-β Signaling Pathway-Based Model to Predict the Subtype and Prognosis of Head and Neck Squamous Cell Carcinoma
Authors: Zheng Lian , Guan Zhenjie , Xue Miaomiao 
Published: May 2022

Background: Although immunotherapy with immune checkpoint therapy has been used to treat head and neck squamous cell carcinoma (HNSCC), response rates and treatment sensitivity remain limited. Recent studies have indicated that transforming growth factor-β (TGF-β) may be an important target for novel cancer immunotherapies.Materials and methods: We collected genomic profile data from The Cancer Genome Atlas and Gene Expression Omnibus. The least absolute shrinkage and selection operator method and Cox regression were used to establish a prognostic model. Gene set enrichment analysis was applied to explore biological functions. Tracking of indels by decomposition and subclass mapping algorithms were adopted to evaluate immunotherapy efficiency.Result: We established a seven TGF-β pathway-associated gene signature with good prediction efficiency. The high-risk score subgroup mainly showed enrichment in tumor-associated signaling such as hypoxia and epithelial-mesenchymal transition (EMT) pathways; This subgroup was also associated with tumor progression. The low-risk score subgroup was more sensitive to immunotherapy and the high-risk score subgroup to cisplatin, erlotinib, paclitaxel, and crizotinib.Conclusion: The TGF-β pathway signature gene model provides a novel perspective for evaluating effectiveness pre-immunotherapy and may guide further studies of precision immuno-oncology.
Fitness of B-Cell Responses to SARS-CoV-2 WT and Variants Up to One Year After Mild COVID-19 – A Comprehensive Analysis
Authors: Meyer Benjamin , Martinez-Murillo Paola Andrea , Lemaitre Barbara , Blanchard-Rohner Géraldine , Didierlaurent Arnaud M. , Fontannaz Paola , Eugercios Manzanas Chloé , Lambert Paul-Henri , Loevy Natasha , Kaiser Laurent , Sartoretti Julie , Tougne Chantal , Villard Jean , Huttner Angela , Siegrist Claire-Anne , Eberhardt Christiane S. 
Published: May 2022

ObjectiveTo comprehensively evaluate SARS-CoV-2 specific B-cell and antibody responses up to one year after mild COVID-19.MethodsIn 31 mildly symptomatic COVID-19 participants SARS-CoV-2-specific plasmablasts and antigen-specific memory B cells were measured by ELISpot. Binding antibodies directed against the proteins spike (S), domain S1, and nucleocapsid (N) were estimated using rIFA, ELISA, and commercially available assays, and avidity measured using thiocyanate washout. Neutralizing antibodies against variants of concern were measured using a surrogate-neutralization test.ResultsPlasmablast responses were assessed in all participants who gave sequential samples during the first two weeks after infection; they preceded the rise in antibodies and correlated with antibody titers measured at one month. S1 and N protein-specific IgG memory B-cell responses remained stable during the first year, whereas S1-specific IgA memory B-cell responses declined after 6 months. Antibody titers waned over time, whilst potent affinity maturation was observed for anti-RBD antibodies. Neutralizing antibodies against wild-type (WT) and variants decayed during the first 6 months but titers significantly increased for Alpha, Gamma and Delta between 6 months and one year. Therefore, near-similar titers were observed for WT and Alpha after one year, and only slightly lower antibody levels for the Delta variant compared to WT. Anti-RBD antibody responses correlated with the neutralizing antibody titers at all time points, however the predicted titers were 3-fold lower at one year compared to one month.ConclusionIn mild COVID-19, stable levels of SARS-CoV-2 specific memory B cells and antibodies neutralizing current variants of concern are observed up to one year post infection. Care should be taken when predicting neutralizing titers using commercial assays that measure binding antibodies.
eRNAs Identify Immune Microenvironment Patterns and Provide a Novel Prognostic Tool in Acute Myeloid Leukemia
Authors: Jiang Ziming , Long Junyu , Deng Kaige , Zheng Yongchang , Chen Miao 
Published: May 2022

Background: Enhancer RNAs (eRNAs) play an essential role in tumorigenesis as non-coding RNAs transcribed from enhancer regions. However, the landscape of eRNAs in acute myeloid leukemia (AML) and the potential roles of eRNAs in the tumor microenvironment (TME) remain unclear.Method: Gene expression data collected from The Cancer Genome Atlas (TCGA) project were combined with Histone ChIP-seq so as to reveal the comprehensive landscape of eRNAs. Single-sample gene set enrichment analysis algorithm (ssGSEA) and ESTIMATE were employed to enumerate immune cell infiltration and tumor purity.Results: Most prognostic eRNAs were enriched in immune-related pathways. Two distinct immune microenvironment patterns, the immune-active subtype and the immune-resistant subtype, were identified in AML. We further developed an eRNA-derived score (E-score) that could quantify immune microenvironment patterns and predict the response to immune checkpoint inhibitor (ICI) treatment. Finally, we established a prognostic nomogram combining E-score and other clinical features, which showed great discriminative power in both the training set [Harrell’s concordance index (C index): 0.714 (0.651–0.777), p &lt; 0.0001] and validation set [C index: 0.684 (0.614–0.755), p &lt; 0.0001]. Calibration of the nomogram was also validated independently.Conclusion: In this study, we systematically understood the roles of eRNAs in regulating TME diversity and complexity. Moreover, our E-score model provided the first predictive model for ICI treatment in AML.
Correlation Between Chronic Tinnitus Distress and Symptoms of Depression: A Systematic Review
Authors: Meijers Sebastiaan M. , Rademaker Maaike , Meijers Rutger L. , Stegeman Inge , Smit Adriana L. 
Published: May 2022

ObjectivesIn this systematic review, we aim to evaluate the evidence regarding the correlation between tinnitus distress and the severity of depressive symptoms in patients with chronic tinnitus. Also, the prevalence of clinically relevant depressive symptoms scores in patients with chronic tinnitus was evaluated.MethodsWe performed a systematic review in PubMed, EMBASE, and the Cochrane library in June 2021 using the terms “depression” and “tinnitus,” and their synonyms, following PRISMA guidelines. Studies were selected on relevance and critically appraised regarding risk of bias using the Newcastle–Ottowa Quality Assessment Scale.ResultsA total of 1,912 articles were screened on title and abstract after the removal of the duplicates. Eventually, 33 (1.5%) articles were included for the final analysis. Only cross-sectional cohort studies and case–control studies with a low level of evidence and a high risk of bias due to the study design and patient selection were found. Statistically significant correlations between the experienced tinnitus distress and depressive symptoms were reported in 31 out of 33 studies. Clinically relevant depression scores had a prevalence of 4.6–41.7%.ConclusionsIn this systematic review, in which mostly cross-sectional studies were included, a statistically significant correlation was found between the experienced tinnitus distress and the reported severity of symptoms of depression in patients with chronic tinnitus. A wide range of clinically relevant depression scores were reported in included studies. Due to the high risk of bias of included studies it is not possible to provide a definite answer on the existence of this relationship. Future population-based studies are necessary to provide more clarity.
First Pass Effect and Location of Occlusion in Recanalized MCA M1 Occlusions
Authors: Salahuddin Hisham , Rao Rahul R. , Zaidi Syed F. , Prologo-Richardson Paige , Khalid Fatima , Saju Linda , Taqi Muhammad Asif , Burgess Richard R. , Jumaa Mouhammad A. 
Published: May 2022

BackgroundThe first pass effect has been shown to improve clinical outcomes in patients with middle cerebral artery (MCA) M1 occlusions.ObjectiveTo determine the rates of first pass effect in MCA M1 occlusions and determine if proximal or distal location of occlusion modified clinical outcomes.MethodsPatients with recanalized MCA M1 occlusions who underwent endovascular thrombectomy (EVT) were reviewed to determine the effect of first pass effect (FPE) and location of occlusion on clinical outcomes. MCA occlusions were classified as proximal if they included the first two thirds of the MCA and involved the lenticulostriate vessels, or distal if they did not.ResultsWe included 261 patients of which 27% achieved FPE. Of the cohort, there were 91 (35%) proximal MCA occlusions and 170 (65%) distal MCA occlusions. Baseline demographics and treatment time metrics were comparable across both groups. There was a trend toward good clinical outcome in patients with or without a FPE (60 vs. 46%; p = 0.06), however a higher rate of excellent clinical outcome was noted in patients with FPE (46 vs. 30%; p = 0.02). When compared by location, patients with distal MCA occlusions had a higher rate of excellent clinical outcome (40 vs. 25%; p = 0.02). Multivariable analysis showed that distal MCA occlusion was the strongest predictor of an excellent clinical outcome and first pass effect.ConclusionPatients with MCA M1 occlusions with FPE have a higher rate of excellent clinical outcomes compared to those who did not. Location of MCA occlusion appears to modify rates of first pass effect and excellent clinical outcomes.
Deriving Pulmonary Ventilation Images From Clinical 4D-CBCT Using a Deep Learning-Based Model
Authors: Liu Zhiqiang , Tian Yuan , Miao Junjie , Men Kuo , Wang Wenqing , Wang Xin , Zhang Tao , Bi Nan , Dai Jianrong 
Published: May 2022

PurposeThe current algorithms for measuring ventilation images from 4D cone-beam computed tomography (CBCT) are affected by the accuracy of deformable image registration (DIR). This study proposes a new deep learning (DL) method that does not rely on DIR to derive ventilation images from 4D-CBCT (CBCT-VI), which was validated with the gold-standard single-photon emission-computed tomography ventilation image (SPECT-VI).Materials and MethodsThis study consists of 4D-CBCT and 99mTc-Technegas SPECT/CT scans of 28 esophagus or lung cancer patients. The scans were rigidly registered for each patient. Using these data, CBCT-VI was derived using a deep learning-based model. Two types of model input data are studied, namely, (a) 10 phases of 4D-CBCT and (b) two phases of peak-exhalation and peak-inhalation of 4D-CBCT. A sevenfold cross-validation was applied to train and evaluate the model. The DIR-dependent methods (density-change-based and Jacobian-based methods) were used to measure the CBCT-VIs for comparison. The correlation was calculated between each CBCT-VI and SPECT-VI using voxel-wise Spearman’s correlation. The ventilation images were divided into high, medium, and low functional lung regions. The similarity of different functional lung regions between SPECT-VI and each CBCT-VI was evaluated using the dice similarity coefficient (DSC). One-factor ANONA model was used for statistical analysis of the averaged DSC for the different methods of generating ventilation images.ResultsThe correlation values were 0.02 ± 0.10, 0.02 ± 0.09, and 0.65 ± 0.13/0.65 ± 0.15, and the averaged DSC values were 0.34 ± 0.04, 0.34 ± 0.03, and 0.59 ± 0.08/0.58 ± 0.09 for the density change, Jacobian, and deep learning methods, respectively. The strongest correlation and the highest similarity with SPECT-VI were observed for the deep learning method compared to the density change and Jacobian methods.ConclusionThe results showed that the deep learning method improved the accuracy of correlation and similarity significantly, and the derived CBCT-VIs have the potential to monitor the lung function dynamic changes during radiotherapy.
Plasma Drug Concentration of Propranolol and Genetic Study in Chinese Han Patients With Infantile Haemangioma
Authors: Li Li , Yu Lu , He Huan , Wei Li , Xu Zigang , Zhao Libo , Sun Yujuan , Zhang Bin , Liu Yuanxiang , He Rui , Wang Xiaoling , Ma Lin 
Published: May 2022

Background and PurposeThis study was conducted to explore the plasma drug concentration of propranolol in Chinese Han patients with infantile haemangioma (IH) and the influencing factors, as well as the relationship among plasma drug concentrations of propranolol, β1-AR mutation and CYP2D6 188C&gt;T, efficacy, and safety.Experimental ApproachFrom January 2018 to April 2019, 140 patients with IH who were admitted to the hospital for oral propranolol and agreed to have their plasma concentration of propranolol tested, including 112 patients with β1-AR and CYP2D6 gene tested.Key Results and Conclusions and ImplicationsThe mean peak blood levels of propranolol, 4-hydroxypropranolol (4-OH-P), and N-deisopropylpropranolol (NDP) were 60.35 ± 37.90, 1.90 ± 2.37, and 0.24 ± 0.18 ng/ml, respectively. The mean trough blood levels of propranolol, 4-OH-P, and NDP were 24.98 ± 17.68, 0.45 ± 0.52, and 0.05±0.05 ng/ml, respectively. The higher the dose of propranolol, the higher the plasma concentration of propranolol (p = 0.031). The plasma concentration of propranolol was not related to the treatment efficacy.
Metabolic Profiling Analysis of the Effect and Mechanism of Gushiling Capsule in Rabbits With Glucocorticoid-Induced Osteonecrosis of the Femoral Head
Authors: Mei Runhong , Chen Dan , Zhong Duming , Li Guoyong , Lin Shaobai , Zhang Guangquan , Chen Kaiyun , Yu Xuefeng 
Published: May 2022

Gushiling capsule (GSLC) is an effective traditional Chinese medicine for the treatment of glucocorticoid-induced osteonecrosis of the femoral head (GIONFH). This study established the serum metabolite profiles of GSLC in rabbits and explored the metabolic mechanism and effect of GSLC on GIONFH. Seventy-five Japanese white rabbits were randomly divided into the control, model, and GSLC groups. The rabbits in the model group and the GSLC group received injection of prednisolone acetate. Meanwhile, rabbits in the GSLC group were treated by gavage at a therapeutic dose of GSLC once a day. The control group and the model group received the same volume of normal saline gavage. Three groups of serum samples were collected at different time points, and the changes in the metabolic spectrum were analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The resulting data set was analyzed using multivariate statistical analysis to identify potential biomarkers related to GSLC treatment. The metabolic pathway was analyzed by MetaboAnalyst 4.0 and a heatmap was constructed using the HEML1.0.3.7 software package. In addition, histopathological and radiography studies were carried out to verify the anti-GIONFH effects of GSLC. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) score plots revealed a significant separation trend between the control group and the model group and the GSLC group (1–3 weeks), but there were no significant differences in the GSLC group (4–6 weeks). Orthogonal PLS-DA (OPLS-DA) score plots also revealed an obvious difference between the model and the GSLC groups (4–6 weeks). Ten potential metabolite biomarkers, mainly phospholipids, were identified in rabbit serum samples and demonstrated to be associated with GIONFH. Hematoxylin and eosin staining and magnetic resonance imaging indicated that the pathological changes in femoral head necrosis in the GSLC group were less than in the model group, which was consistent with the improved serum metabolite spectrum. GSLC regulated the metabolic disorder of endogenous lipid components in GIONFH rabbits. GSLC may prevent and treat GIONFH mainly by regulating phospholipid metabolism in vivo.
Behavior and Immune Response of Conventional and Slow-Growing Broilers to Salmonella Typhimurium
Authors: Snyder Ashlyn M. , Riley Sean P. , Robison Cara I. , Karcher Darrin M. , Wickware Carmen L. , Johnson Timothy A. , Weimer Shawna L. 
Published: May 2022

Fast growth rate in broiler chickens comes with welfare concerns and the contribution of growth rate to pathogen resistance and sickness behavior is relatively unknown. The objective of this study was to evaluate physiological and behavioral responses of conventional (CONV) and slow-growing (SG) male broilers challenged with Salmonella Typhimurium. CONV (n = 156) and SG (n = 156) chicks were raised in a pen with wood litter shavings until day 7 of age, when birds were transferred to 24 isolators (n = 11 chicks/isolator). On day 14 of age, half of the birds (n = 12 isolators) were challenged with S. Typhimurium (ST) and the other half (n = 12 isolators) received a control (C). On days 7, 13, 17, 21, and 24, body weight was recorded, and blood, jejunum and ileum sections were collected from 2 birds/isolator (n = 48 birds/sampling) to measure plasma IgA and IgG and intestinal histomorphology, respectively. On days 12, 16, 21, and 23, video was recorded to evaluate bird postures (sitting, standing, or locomoting) and behaviors (eating, drinking, preening, stretching, sham foraging, allopreening, and aggression). CONV birds were 70 g heavier (p = 0.03) on day 21 and 140 g heavier (p = 0.007) on day 24 than SG. On day 7, CONV jejunum villus height and crypt depth were 22 and 7 μm greater (p ≤ 0.001), respectively, than SG. On day 24, ST ileum villus height was 95 μm shorter (p = 0.009) than C. IgA increased after day 17 for all birds and at day 21, CONV IgA was greater (p = 0.01) than SG. Although SG IgG was 344 μg/ml greater (p = 0.05) than CONV on day 7, CONV IgG increased with age (p &lt; 0.0001) to greater (p ≤ 0.03) concentrations than SG on day 21 and day 24 by 689 μg/ml and 1,474 μg/ml, respectively, while SG IgG remained at similar concentrations after day 13. Generally, a greater proportion of birds sham foraged as they aged (p &lt; 0.0001). A greater proportion of CONV tended to sit (p = 0.09) and fewer locomoted (p &lt; 0.0001) than SG as they aged. The results illustrate conventional and slow-growing broilers differ in their behavior, immunity, and response to Salmonella.
The Feminine Condition and Women's Sexual and Reproductive Health in Brazil and France
Authors: Silva Simone Santana da , Fortuna Cinira Magali , Monceau Gilles , Soulière Marguerite , Pilotti Anne 
Published: May 2022

IntroductionElements mark the reality of reading the female body in symbolic constructions and social symbols in the exercise of their reproductive health. The study aims to identify elements that characterize the female condition while analyzing the reproductive health of Brazilian and French women.Materials and MethodsA qualitative, multicenter, international study was conducted in Brazil and in France between 2016 and 2019. Data were produced through the use of semi-structured scripts. Focus group discussions and individual interviews were conducted with women who gave birth, hetero-female couples who lived the experience of gestation and birth of a baby, and professionals of maternal and childcare services or members of the associations concerned with the health of mothers and babies. It was guided by the theoretical-methodological framework of institutional analysis in line with the French Institutional Socioclinics.ResultsSexual and reproductive health in the realities researched in Brazil and France are sometimes close and sometimes far apart. In what involves the Brazilian health system, abortion is criminalized and often performed illegally. Furthermore, pregnancy, childbirth, and the postpartum period are highly medicalized. In addition, childbirth is not assured as an experience for a woman and her family. This aspect is confirmed by high numbers of cesarean sections performed or by maternal and infant mortality indicators. The French health system prioritizes vaginal deliveries and seems to assure more autonomy to women, but at the same time, it is worn out by the logic of profit, the efficiency of actions, and the rationalization of practices. In association with these, there are other intrinsic elements in the functioning of the institution that delineates the format of each country: notion of women's rights, violence against women, and discussion regarding the oppression markers of race, gender, sexuality, and social class.ConclusionsBoth countries reveal aspects related to the social role of women's bodies. The established logic reflects in the decision to have children, motherhood, women's autonomy over their own bodies, and in the core values linked to the termination of pregnancy and the professional practices developed in prenatal care, childbirth, and postpartum.
Cognitive Function Mediates the Anti-suicide Effect of Repeated Intravenous Ketamine in Adult Patients With Suicidal Ideation
Authors: Zhou Yanling , Wang Chengyu , Lan Xiaofeng , Li Weicheng , Chao Ziyuan , Wu Kai , McIntyre Roger S. , Ning Yuping 
Published: May 2022

ObjectivePrior research has shown that ketamine has anti-suicide effects. Additional evidence also suggests that ketamine may offer pro-cognitive effects. Herein, we propose that the anti-suicide effects of ketamine are partially mediated via pro-cognitive effects. We aimed to determine whether improvement in cognitive function mediated change in suicidal ideation was associated with ketamine treatment.MethodsUnipolar or bipolar depressive patients (n = 86) with suicidal ideation received six infusions of ketamine (0.5 mg/kg) over 2 weeks. The current severity of suicidal ideation and depression symptoms were assessed with the Beck Scale for Suicide Ideation (SSI) and the Montgomery–Asberg Depression Rating Scale (MADRS), respectively, at baseline, days 13 and 26. Cognitive domains, including processing speed, working memory, visual learning, and verbal learning were measured with the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery at the same time points.ResultsMediation analysis showed a significant total effect of ketamine treatment on SSI score (coef = –1.853, 95%CI [–2.2, –1.5]). The direct and total indirect (MADRS total score and any of cognitive domains) effects of ketamine on suicidal ideation both were statistically significant (direct: coef = –1.064 to –1.352; total indirect: coef = –0.501 to –0.788). MADRS total score and processing speed (but not other cognitive domains) were significant partial mediators of the association between ketamine treatment and improvements in suicidal ideation.ConclusionDepressive symptoms severity and processing speed performance partially mediated improvements in suicidal ideation after repeated ketamine infusions in persons with unipolar or bipolar depressive disorder.