bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune-Related Biomarkers Improve Performance of Risk Prediction Models for Survival in Patients With Hepatocellular Carcinoma
Authors: Wan Haifeng , Lu Shan , Xu Lin , Yuan Kefei , Xiao Yang , Xie Kunlin , Wu Hong 
Published: July 2022

ObjectThe prediction of hepatocellular carcinoma (HCC) prognosis faced great challenge due to tumor heterogeneity. The purpose of this study was to explore the correlation between the immune infiltrate and prognosis. Moreover, we aimed to establish a risk prediction model for survival in HCC patients based on clinicopathological and immune indicators.MethodsIn this study, 316 patients with HCC who underwent radical resection in West China Hospital from 2009 to 2014 were included. Clinicopathological data and pathological specimens were collected. H&amp;E staining and immunohistochemical staining were performed on the pathological tissue sections. The evaluation of tumor-infiltrating lymphocyte (TIL) density was based on H&amp;E slices, and the assessment of the expressions of CD8, CD68, Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin domain and mucin domain-3 (TIM-3), Programmed Cell Death Protein 1 (PD-1), Programmed Cell Death Ligand 1 (PD-L1), OX40, CD66b, and Tryptase. was performed on the immunohistochemical slices. A risk prediction model for survival in HCC patients was established by integrating immune-related biomarkers and clinicopathological indicators.ResultsThe Barcelona Clinic Liver Cancer (BCLC) stage; the microvascular invasion status; the density of TILs; the expressing levels of CD66b, OX40, and PD-L1 in the immune cell; CD68; and CD8 were the predictors of patients’ overall survival (OS). The BCLC stage; the density of TILs; and the expressions of OX40, CD68, and CD8 were associated with disease-free survival (DFS). The expressions of CD66b, CD68, OX40, and CD8 had a cumulative effect on prognosis. The area under the curve of the prediction model for OS based on clinicopathological features was improved from 0.62 to 0.74 by adding to CD8, OX40, CD68, CD66b, and TILs, whereas it was improved from 0.59 to 0.73 for the DFS prediction model.ConclusionOur results, if confirmed, indicated that immune-related biomarkers should be taken into account or stratified in survival analysis for HCC.
Erring Characteristics of Deformable Image Registration-Based Auto-Propagation for Internal Target Volume in Radiotherapy of Locally Advanced Non-Small Cell Lung Cancer
Authors: Rich Benjamin J. , Spieler Benjamin O. , Yang Yidong , Young Lori , Amestoy William , Monterroso Maria , Wang Lora , Dal Pra Alan , Yang Fei 
Published: July 2022

PurposeRespiratory motion of locally advanced non-small cell lung cancer (LA-NSCLC) adds to the challenge of targeting the disease with radiotherapy (RT). One technique used frequently to alleviate this challenge is an internal gross tumor volume (IGTV) generated from manual contours on a single respiratory phase of the 4DCT via the aid of deformable image registration (DIR)-based auto-propagation. Through assessing the accuracy of DIR-based auto-propagation for generating IGTVs, this study aimed to identify erring characteristics associated with the process to enhance RT targeting in LA-NSCLC.Methods4DCTs of 19 patients with LA-NSCLC were acquired using retrospective gating with 10 respiratory phases (RPs). Ground-truth IGTVs (GT-IGTVs) were obtained through manual segmentation and union of gross tumor volumes (GTVs) in all 10 phases. IGTV auto-propagation was carried out using two distinct DIR algorithms for the manually contoured GTV from each of the 10 phases, resulting in 10 separate IGTVs for each patient per each algorithm. Differences between the auto-propagated IGTVs (AP-IGTVs) and their corresponding GT-IGTVs were assessed using Dice coefficient (DICE), maximum symmetric surface distance (MSSD), average symmetric surface distance (ASSD), and percent volume difference (PVD) and further examined in relation to anatomical tumor location, RP, and deformation index (DI) that measures the degree of deformation during auto-propagation. Furthermore, dosimetric implications due to the analyzed differences between the AP-IGTVs and GT-IGTVs were assessed.ResultsFindings were largely consistent between the two algorithms: DICE, MSSD, ASSD, and PVD showed no significant differences between the 10 RPs used for propagation (Kruskal–Wallis test, ps &gt; 0.90); MSSD and ASSD differed significantly by tumor location in the central–peripheral and superior–inferior dimensions (ps &lt; 0.0001) while only in the central–peripheral dimension for PVD (p &lt; 0.001); DICE, MSSD, and ASSD significantly correlated with the DI (Spearman’s rank correlation test, ps &lt; 0.0001). Dosimetric assessment demonstrated that 79% of the radiotherapy plans created by targeting planning target volumes (PTVs) derived from the AP-IGTVs failed prescription constraints for their corresponding ground-truth PTVs.ConclusionIn LA-NSCLC, errors in DIR-based IGTV propagation present to varying degrees and manifest dependences on DI and anatomical tumor location, indicating the need for personalized consideration in designing RT internal target volume.
Sex differences of language abilities of preschool children with autism spectrum disorder and their anatomical correlation with Broca and Wernicke areas
Authors: Zhang Yun , Qin Bin , Wang Longlun , Chen Jie , Cai Jinhua , Li Tingyu 
Published: July 2022

ObjectivePeople with autism spectrum disorder (ASD) often have language difficulties. This study focuses on whether there are sex differences in language ability in children with ASD and aims to analyze whether such differences may arise from developmental imbalances in the anatomical structures of Broca and Wernicke areas.MethodsThe language development quotient (DQ) scores of Gesell Developmental Scale (GDS) and the scores of language communication of Childhood Autism Rating Scale (CARS) were used to judge the language ability, and the FREESURFER software extracted the anatomical structures of Broca and Wernicke areas on 3DT1 sequences. We analyzed the correlation between the anatomical structure of Broca/Wernicke areas and language abilities assessments.ResultsThe study initially included 44 cases of ASD, with 36 males (81.8 %) and 8 females (18.2%), and the age range was 24–72 months. Males have better language abilities than females. Specifically, the GDS verbal DQ of males was significantly higher than that of females (56.50 ± 18.02 vs. 29.23 ± 6.67, p &lt; 0.001). Broca thickness-L was positively correlated with verbal DQ scores in GDS (r = 0.382, p = 0.011) and lower than grade 2 and 3 on the CARS verbal communication grade 4 (5.76 ± 0.17 vs. 6.21 ± 0.30 and 6.11 ± 0.35), with statistically significant differences between groups (p &lt; 0.05).ConclusionThere were sex differences in the language abilities of preschoolers with ASD, which may be due to an imbalance development of certain structures in Broca and Wernicke areas, especially Broca area.
Should we give antibiotics to neonates with mild non-progressive symptoms? A comparison of serial clinical observation and the neonatal sepsis risk calculator
Authors: Berardi Alberto , Zinani Isotta , Bedetti Luca , Vaccina Eleonora , Toschi Alessandra , Toni Greta , Lecis Marco , Leone Federica , Monari Francesca , Cozzolino Michela , Zini Tommaso , Boncompagni Alessandra , Iughetti Lorenzo , Miselli Francesca , Lugli Licia 
Published: July 2022

ObjectiveTo compare two strategies [the neonatal sepsis risk calculator (NSC) and the updated serial clinical observation approach (SCO)] for the management of asymptomatic neonates at risk of early-onset sepsis (EOS) and neonates with mild non-progressive symptoms in the first hours of life.MethodsThis was a single-center, retrospective cohort study conducted over 15 months (01/01/2019–31/03/2020). All live births at ≥34 weeks of gestation were included. Infants were managed using SCO and decisions were compared with those retrospectively projected by the NSC. The proportion of infants recommended for antibiotics or laboratory testing was compared in both strategies. McNemar's non-parametric test was used to assess significant differences in matched proportions.ResultsAmong the 3,445 neonates (late-preterm, n = 178; full-term, n = 3,267) 262 (7.6%) presented with symptoms of suspected EOS. There were no cases of culture-proven EOS. Only 1.9% of the neonates were treated with antibiotics (median antibiotic treatment, 2 days) and 4.0% were evaluated. According to NSC, antibiotics would have been administered in 5.4% of infants (absolute difference between SCO and NSC, 3.51%; 95% CI, 3.14–3.71%; p &lt;0.0001) and 5.6% of infants would have undergone “rule out sepsis” (absolute difference between SCO and NSC, 1.63%, 95% CI 1.10–2.05; p &lt;0.0001).ConclusionSCO minimizes laboratory testing and unnecessary antibiotics in infants at risk of EOS or with mild non-progressive symptoms, without the risk of a worse neonatal outcome. The NSC recommends almost three times more antibiotics than the SCO without improving neonatal outcomes.
Thyroid cancer in children: A multicenter international study highlighting clinical features and surgical outcomes of primary and secondary tumors
Authors: Martucci Cristina , Crocoli Alessandro , De Pasquale Maria Debora , Spinelli Claudio , Strambi Silvia , Brazzarola Paolo , Morelli Eleonora , Cassiani Jessica , Mancera Juliana , Luengas Juan Pablo , Lobos Pablo , Liberto Daniel , Astori Estefanìa , Sarnacki Sabine , Couloigner Vincent , Simon François , Lambert Cassandre , Abib Simone de Campos Vieira , Cervantes Onivaldo , Caran Eliana , Delgado Lindman Diana , Jones Matthew O. , Shukla Rajeev , Losty Paul D. , Inserra Alessandro 
Published: July 2022

Background:Thyroid gland malignancies are rare in pediatric patients (0.7% of tumors); only 1.8% are observed in patients aged &lt;20 years, with a higher prevalence recorded in women and adolescents. Risk factors include genetic syndromes, MEN disorders, autoimmune diseases, and exposure to ionizing radiation. Radiotherapy is also associated with an increased risk of secondary thyroid cancer. This study describes the clinical features and surgical outcomes of primary and secondary thyroid tumors in pediatric patients.MethodsInstitutional data were collected from eight international surgical oncology centers for pediatric patients with thyroid cancer between 2000 and 2020. Statistical analyses were performed using the GraphPad Prism software.ResultsAmong 255 total cases of thyroid cancer, only 13 (5.1%) were secondary tumors. Primary thyroid malignancies were more likely to be multifocal in origin (odds ratio [OR] 1.993, 95% confidence interval [CI].7466–5.132, p = 0.2323), have bilateral glandular location (OR 2.847, 95% CI.6835–12.68, p = 0.2648), and be metastatic at first diagnosis (OR 1.259, 95% CI.3267–5.696, p &gt; 0.999). Secondary tumors showed a higher incidence of disease relapse (OR 1.556, 95% CI.4579-5.57, p = 0.4525) and surgical complications (OR 2.042, 95% CI 0.7917–5.221, p = 0.1614), including hypoparathyroidism and recurrent laryngeal nerve injury. The overall survival (OS) was 99% at 1 year and 97% after 10 years. No EFS differences were evident between the primary and secondary tumors (chi-square 0.7307, p = 0.39026).ConclusionsThis multicenter study demonstrated excellent survival in pediatric thyroid malignancies. Secondary tumors exhibited greater disease relapse (15.8 vs. 10.5%) and a higher incidence of surgical complications (36.8 vs. 22.2%).
Effect of Acid Suppressants on Non–Helicobacter pylori Helicobacters Within Parietal Cells
Authors: Nakamura Masahiko , Murasato Futa , Øverby Anders , Kodama Yosuke , Michimae Hirofumi , Sasaki Kazuki , Flahou Bram , Haesebrouck Freddy , Murayama Somay Y. , Takahashi Shinichi , Uchida Masayuki , Suzuki Hidekazu , Matsui Hidenori 
Published: July 2022

We investigated the effect of increased pH induced by acid suppressants on the viability of non–Helicobacter pylori helicobacters (NHPHs) within parietal cell intracellular canaliculi and fundic glandular lumina by immunohistochemistry, electron microscopy, quantitative PCR, urea breath tests, and using a bilayer culture system. Three months before the experiment, mice were infected with the NHPH H. suis and then treated with famotidine (2 mg/kg body weight [BW], once daily), lansoprazole (30 mg/kg BW, once daily), or vonoprazan (20 mg/kg BW, once daily) for 3 days. Immunohistochemical studies using the TUNEL method, quantitative PCR analysis, and urea breath tests were performed. PCR analysis showed a decrease in the NHPH quantity after vonoprazan treatment. Urea breath tests revealed a significant decrease in the NHPH urease activity after vonoprazan, lansoprazole, and famotidine treatments for 3 days; however, 4 days after the treatment, urease activity reversed to the pretreatment level for each treatment group. Electron microscopy revealed an increase in the damaged NHPH after vonoprazan treatment. The TUNEL method revealed apoptotic NHPH within parietal cells after vonoprazan treatment. The bilayer culture results demonstrated that NHPH moved more quickly at a pH of 4.0 than at a pH of 3.0, 5.0, and 6.5, and electron microscopy revealed a change from the spiral form to the coccoid form under near-neutral pH conditions. We thus proposed that acid suppressants, especially vonoprazan, induce NHPH damage by altering pH.
A Phase Ib Study of the Simmitecan Single Agent and in Combination With 5-Fluorouracil/Leucovorin or Thalidomide in Patients With Advanced Solid Tumor
Authors: Zhang Qi , Deng Ting , Yang Fen , Guo Weijian , Liu Dan , Yuan Jiajia , Qi Changsong , Cao Yanshuo , Yu Qiuqiong , Cai Huiming , Peng Zhi , Wang Xicheng , Zhou Jun , Lu Ming , Gong Jifang , Li Jian , Ba Yi , Shen Lin 
Published: July 2022

Background: Simmitecan is a potent inhibitor of topoisomerase I with anti-tumor activity. This phase Ib trial was conducted to investigate the safety and anti-tumor effect of simmitecan alone or in combination with other drugs.Methods: Eligible patients with advanced solid tumor had no further standard treatment options. Patients were allocated to receive simmitecan alone, simmitecan in combination with 5-fluorouracil (5-FU)/leucovorin (LV), or simmitecan in combination with thalidomide, 14 days a cycle, until disease progression or unacceptable toxicity occurred.Results: A total of 41 patients were enrolled, with a median age of 55 (range 29–69) years. Among them, 13 patients received simmitecan monotherapy, 10 received simmitecan + 5-FU/LV, and 18 received simmitecan + thalidomide. No dose-limiting toxicity occurred. Overall, the most common grade 3/4 adverse event (AE) was neutropenia (46.2, 70.0, and 88.9%, respectively, in simmitecan, simmitecan + 5-FU/LV, and simmitecan + thalidomide cohorts), and treatment-related severe AEs included anemia and febrile neutropenia (7.7% each in simmitecan cohort), diarrhea (10% in simmitecan +5-FU/LV cohort), and febrile neutropenia (5.6% in simmitecan + thalidomide cohort). The majority of patients (24/41, 58.3%) had progressed on prior irinotecan; nevertheless, partial response was achieved in one colorectal cancer patients treated with simmitecan + thalidomide. The disease control rates of simmitecan, simmitecan + 5-FU/LV, and simmitecan + thalidomide cohorts were 46.2, 80.0, and 61.1%, respectively.Conclusion: This study demonstrated a manageable safety profile of simmitecan as a single agent or as part of a combination therapy. There have not been any safety concerns with simmitecan in combination when compared to simmitecan alone. Simmitecan + 5-FU/LV regimen seemed to have a better efficacy. Nonetheless, the efficacy of this regimen needs to be further explored in the subsequent study.
The common regulatory pathway of COVID-19 and multiple inflammatory diseases and the molecular mechanism of cepharanthine in the treatment of COVID-19
Authors: Jiang Ping , Ye Jingyao , Jia Menglong , Li Xiaopeng , Wei Shujun , Li Nianhu 
Published: July 2022

Background: Similar pathogenesis makes Corona Virus Disease 2019 (COVID-19) associated with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and gouty arthritis (GA), and it is possible to introduce common drugs for the treatment of RA, AS and GA into the treatment of COVID-19. That is, “homotherapy for heteropathy”, especially cytokine inhibitors. But little is known about the specific link between the diseases. In addition, “new use of old drugs” is an important short-term strategy for the treatment of COVID-19. Cepharanthine (CEP), a monomer component of traditional Chinese medicine (TCM), is mainly used in the treatment of leukopenia and has recently been proved to have a good therapeutic effect on COVID-19, but its specific molecular mechanism has not been clearly explained. The purpose of this work is to explore the common targets and signaling pathways among COVID-19, RA, AS, and GA by means of network pharmacology (NP), and to infer the potential mechanism of CEP in the treatment of COVID-19.Methods: Firstly, SwissTargetPrediction was used to predict the targets of CEP, and the pathogenic targets of COVID-19, RA, AS and GA were searched in GeneCards, OMIM, TTD, PharmGKB database and literature, respectively. Then, the protein interaction network of CEP and COVID-19 cross targets and the common targets of COVID-19, RA, AS and GA was constructed. Cytosscape 3.7.2 software was used to construct CEP-common targets-signaling pathways-COVID-19 network, module function analysis, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG). Finally, the molecular docking of hub targets and CEP was carried out by AutoDock software.Results: The results showed that the common targets of the four diseases were tumor necrosis factor (TNF), interleukin (IL)-6 and IL-1β, and involved Coronavirus disease, IL-17 signaling pathway and TNF signaling pathway. CEP has a good binding force with AKT Serine/Threonine Kinase 1 (AKT1), phosphatidylinositol 3-kinase (PIK3) CA, PIK3CD and Angiotensin-converting enzyme 2 (ACE2), and plays a role in the treatment of COVID-19 by regulating PI3K-Akt signaling pathway, Relaxin signaling pathway, VEGF signaling pathway and HIF-1 signaling pathway.Conclusion: Therefore, this study not only confirmed the potential mechanism of CEP in the treatment of COVID-19 at the molecular level, but also found that TNF and IL-17 inhibitors, which are commonly used in the treatment of RA, AS and GA, may also affect the treatment of COVID-19, which provides new clues and theoretical basis for the rapid discovery of effective therapeutic drugs for COVID-19.
The Effects of Airway Pressure Release Ventilation on Pulmonary Permeability in Severe Acute Respiratory Distress Syndrome Pig Models
Authors: Cheng Jiangli , Yang Jing , Ma Aijia , Dong Meiling , Yang Jie , Wang Peng , Xue Yang , Zhou Yongfang , Kang Yan 
Published: July 2022

Objective: The aim of the study was to compare the effects of APRV and LTV ventilation on pulmonary permeability in severe ARDS.Methods: Mini Bama adult pigs were randomized into the APRV group (n = 5) and LTV group (n = 5). A severe ARDS animal model was induced by the whole lung saline lavage. Pigs were ventilated and monitored continuously for 48 h.Results: Compared with the LTV group, CStat was significantly better (p &lt; 0.05), and the PaO2/FiO2 ratio showed a trend to be higher throughout the period of the experiment in the APRV group. The extravascular lung water index and pulmonary vascular permeability index showed a trend to be lower in the APRV group. APRV also significantly mitigates lung histopathologic injury determined by the lung histopathological injury score (p &lt; 0.05) and gross pathological changes of lung tissues. The protein contents of occludin (p &lt; 0.05), claudin-5 (p &lt; 0.05), E-cadherin (p &lt; 0.05), and VE-cadherin (p &lt; 0.05) in the middle lobe of the right lung were higher in the APRV group than in the LTV group; among them, the contents of occludin (p &lt; 0.05) and E-cadherin (p &lt; 0.05) of the whole lung were higher in the APRV group. Transmission electron microscopy showed that alveolar–capillary barrier damage was more severe in the middle lobe of lungs in the LTV group.Conclusion: In comparison with LTV, APRV could preserve the alveolar–capillary barrier architecture, mitigate lung histopathologic injury, increase the expression of cell junction protein, improve respiratory system compliance, and showed a trend to reduce extravascular lung water and improve oxygenation. These findings indicated that APRV might lead to more profound beneficial effects on the integrity of the alveolar–capillary barrier architecture and on the expression of biomarkers related to pulmonary permeability.
Abnormal regional signal in the left cerebellum as a potential neuroimaging biomarker of sudden sensorineural hearing loss
Authors: Liu Lei , Fan Jun , Zhan Hui , Huang Junli , Cao Rui , Xiang Xiaoran , Tian Shuai , Ren Hongwei , Tong Miao , Li Qian 
Published: July 2022

ObjectiveWhile prior reports have characterized visible changes in neuroimaging findings in individuals suffering from sudden sensorineural hearing loss (SSNHL), the utility of regional homogeneity (ReHo) as a means of diagnosing SSNHL has yet to be established. The present study was thus conducted to assess ReHo abnormalities in SSNHL patients and to establish whether these abnormalities offer value as a diagnostic neuroimaging biomarker of SSNHL through a support vector machine (SVM) analysis approach.MethodsResting-state functional magnetic resonance imaging (rs-fMRI) analyses of 27 SSNHL patients and 27 normal controls were conducted, with the resultant imaging data then being analyzed based on a combination of ReHo and SVM approaches.ResultsRelative to normal control individuals, patients diagnosed with SSNHL exhibited significant reductions in ReHo values in the left cerebellum, bilateral inferior temporal gyrus (ITG), left superior temporal pole (STP), right parahippocampal gyrus (PHG), left posterior cingulum cortex (PCC), and right superior frontal gyrus (SFG). SVM analyses suggested that reduced ReHo values in the left cerebellum were associated with high levels of diagnostic accuracy (96.30%, 52/54), sensitivity (92.59%, 25/27), and specificity (100.00%, 27/27) when distinguishing between SSNHL patients and control individuals.ConclusionThese data suggest that SSNHL patients exhibit abnormal resting-state neurological activity, with changes in the ReHo of the left cerebellum offering value as a diagnostic neuroimaging biomarker associated with this condition.