bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thyroid-associated ophthalmopathy: Using diffusion tensor imaging to evaluate visual pathway microstructural changes
Authors: Li Rui , Li Jing , Wang Zhenchang 
Published: November 2022

ObjectiveThe aim of this study was to determine whether the visual pathway is affected by thyroid-associated ophthalmopathy (TAO) before the development of dysthyroid optic neuropathy (DON) with diffusion tensor imaging (DTI).Materials and methodsFifty-seven TAO patients (22 mild, 35 moderate-severe TAO) and 30 healthy controls (HCs) were included. The DTI parameters of the lateral geniculate (LG) and optic radiation (OR) were measured. A full ophthalmic examination such as intraocular pressure, exophthalmos, and visual acuity was performed. Clinical activity scores (CAS) were also calculated. One-way ANOVA and Pearson's correlation were carried out. A binary logistic regression was used to identify variables that can diagnose TAO.ResultsModerate-severe TAO patients showed significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) than HCs for both LG and OR (p &lt; 0.05). FA of OR was negatively correlated with CAS and intraocular pressure (p &lt; 0.05). Multivariate analysis showed that FA of LG and FA of OR were a significant predictor for the diagnosis TAO.ConclusionDiffusion tensor imaging parameters of the visual pathway were significantly altered in moderate-severe TAO patients. The FA of LG, in particular, can be used as a sensitive imaging biomarker for assessing subclinical visual pathway damage in TAO.
Evaluation of pre-workout and recovery formulations on body composition and performance after a 6-week high-intensity training program
Authors: Cabre Hannah E. , Gordon Amanda N. , Patterson Noah D. , Smith-Ryan Abbie E. 
Published: November 2022

IntroductionActivities such as high-intensity resistance training (HIRT) and high-intensity interval training (HIIT) may be more time-efficient modes to stimulate rapid changes in performance and body composition. There is little research evaluating the combined effects of HIRT and HIIT on body composition and strength, particularly when paired with nutritional supplementation.PurposeTo evaluate the chronic effects of pre- and post-workout supplementation on body composition and strength, and to understand sex-specific responses.Materials and methods64 untrained males (n= 23) and females (n= 41) (mean ± standard deviation; age: 33.2 ± 10.0 years; %fat: 31.6 ± 7.4%) were randomized to either (1) pre-post supplementation [SUP (n= 25); pre = multi-ingredient caffeine/HMB/vit D; post = whey protein/carbohydrates/glucosamine/vitamins], (2) placebo [PL (n= 24); non-caloric], or (3) control [CON (n= 15)]. All participants completed one repetition max (1RM) strength testing for leg press and bench press at baseline and week 6. Estimates of fat mass (FM) and lean mass (LM) were measuredviadual energy x-ray absorptiometry. Participants in the SUP or PL group completed a 6-week supervised exercise intervention consisting of a full-body HIRT workout (3 × 6–8 reps) followed by a HIIT treadmill run (6 × 1 min run: 1 min rest) twice per week. Outcomes were evaluated by separate repeated measure ANOVAs (2 × 3).ResultsThere were no differences in FM between groups or sex (p= 0.133–0.851). LM increased from baseline to post-testing for all groups [Mean difference [MD(Post-Pre) ± Standard Error (SE) = 0.78 ± 0.12 kg;p&lt; 0.001]. While not significant (p= 0.081), SUP gained more LM compared to PL [MD(SUP-PL) ± SE = 3.5 ± 3.3 kg] and CON [MD(SUP-CON) ± SE = 5.2 ± 3.8 kg]. LM increased over time for both males (0.84 ± 0.24 kg;p= 0.003) and females (0.73 ± 0.14 kg;p&lt; 0.001). The SUP group resulted in a significant increase in 1RM leg press compared to the CON group (89.9 ± 30.8 kg;p= 0.015), with no significant differences compared to PL (p= 0.409). The SUP group had greater increases in 1RM bench press compared to the CON group (9.8 ± 1.8 kg;p&lt; 0.001), with no significant differences compared to PL (p= 0.99). Both sexes increased upper- (5.5 ± 0.7 kg;p&lt; 0.001) and lower-body strength (69.8 ± 4.5 kgp&lt; 0.001) with training.ConclusionNutrient supplementation timing appears to augment body composition changes and strength compared to control. Pre-/post-nutrient timing may support greater increases in LM and lower- and upper-body strength in both men and women.Clinical trial registration[https://clinicaltrials.gov/ct2/show/NCT04230824?cond=NCT04230824&amp;draw=2&amp;rank=1], identifier [NCT04230824].
Multiparametric MRI enables for differentiation of different degrees of malignancy in two murine models of breast cancer
Authors: Gerwing Mirjam , Hoffmann Emily , Kronenberg Katharina , Hansen Uwe , Masthoff Max , Helfen Anne , Geyer Christiane , Wachsmuth Lydia , Höltke Carsten , Maus Bastian , Hoerr Verena , Krähling Tobias , Hiddeßen Lena , Heindel Walter , Karst Uwe , Kimm Melanie A. , Schinner Regina , Eisenblätter Michel , Faber Cornelius , Wildgruber Moritz 
Published: November 2022

ObjectiveThe objective of this study was to non-invasively differentiate the degree of malignancy in two murine breast cancer models based on identification of distinct tissue characteristics in a metastatic and non-metastatic tumor model using a multiparametric Magnetic Resonance Imaging (MRI) approach.MethodsThe highly metastatic 4T1 breast cancer model was compared to the non-metastatic 67NR model. Imaging was conducted on a 9.4 T small animal MRI. The protocol was used to characterize tumors regarding their structural composition, including heterogeneity, intratumoral edema and hemorrhage, as well as endothelial permeability using apparent diffusion coefficient (ADC), T1/T2 mapping and dynamic contrast-enhanced (DCE) imaging. Mice were assessed on either day three, six or nine, with an i.v. injection of the albumin-binding contrast agent gadofosveset. Ex vivo validation of the results was performed with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), histology, immunhistochemistry and electron microscopy.ResultsSignificant differences in tumor composition were observed over time and between 4T1 and 67NR tumors. 4T1 tumors showed distorted blood vessels with a thin endothelial layer, resulting in a slower increase in signal intensity after injection of the contrast agent. Higher permeability was further reflected in higher Ktrans values, with consecutive retention of gadolinium in the tumor interstitium visible in MRI. 67NR tumors exhibited blood vessels with a thicker and more intact endothelial layer, resulting in higher peak enhancement, as well as higher maximum slope and area under the curve, but also a visible wash-out of the contrast agent and thus lower Ktrans values. A decreasing accumulation of gadolinium during tumor progression was also visible in both models in LA-ICP-MS. Tissue composition of 4T1 tumors was more heterogeneous, with intratumoral hemorrhage and necrosis and corresponding higher T1 and T2 relaxation times, while 67NR tumors mainly consisted of densely packed tumor cells. Histogram analysis of ADC showed higher values of mean ADC, histogram kurtosis, range and the 90th percentile (p90), as markers for the heterogenous structural composition of 4T1 tumors. Principal component analysis (PCA) discriminated well between the two tumor models.ConclusionsMultiparametric MRI as presented in this study enables for the estimation of malignant potential in the two studied tumor models via the assessment of certain tumor features over time.
Development and validation of a prognostic model to predict the prognosis of patients with colorectal gastrointestinal stromal tumor: A large international population-based cohort study
Authors: Li Yiding , Zhang Yujie , Fu Yang , Yang Wanli , Wang Xiaoqian , Duan Lili , Niu Liaoran , Chen Junfeng , Zhou Wei , Liu Jinqiang , Wang Jing , Fan Daiming , Hong Liu 
Published: November 2022

BackgroundColorectal gastrointestinal stromal tumors (GISTs), mesenchymal malignancy, only accounts for about 6% of GISTs, but prognosis is generally poor. Given the rarity of colorectal GISTs, the prognostic values of clinicopathological features in the patients remain unclear. Nomograms can provide a visual interface to help calculate the predicted probability of a patient meeting a specific clinical endpoint and communicate it to the patient.MethodsWe included a total of 448 patients with colorectal GISTs diagnosed between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. For nomogram construction and validation, patients in the SEER database were divided randomly into the training cohort and internal validation cohort at a ratio of 7:3, while 44 patients with colorectal GISTs from our hospital patient data set between 2010 to 2016 served as the external validation cohort. The OS curves were drawn using the Kaplan–Meier method and assessed using the log-rank test. And, Fine and Gray’s competing-risks regression models were conducted to assess CSS. We performed univariate and multivariate analyses to select prognostic factors for survival time and constructed a predictive nomogram based on the results of the multivariate analysis.ResultsThrough univariate and multivariate analyses, it is found that age, primary site, SEER stage, surgery, and tumor size constitute significant risk factors for OS, and age, primary site, histological grade, SEER stage, American Joint Committee for Cancer (AJCC) stage, surgery, and tumor size constitute risk factors for CSS. We found that the nomogram provided a good assessment of OS and CSS at 1-, 3- and 5- year in patients with colorectal GISTs. The calibration plots for the training, internal validation and external validation cohorts at 1-, 3- and 5- year OS and CSS indicated that the predicted survival rates closely correspond to the actual survival rates.ConclusionWe constructed and validated an unprecedented nomogram to predict OS and CSS in patients with colorectal GISTs. The nomogram had the potential as a clinically predictive tool for colorectal GISTs prognosis, and can be used as a potential, objective and additional tool for clinicians in predicting the prognosis of colorectal GISTs patients worldwide. Clinicians could wield the nomogram to accurately evaluate patients’ OS and CSS, identify high-risk patients, and provide a baseline to optimize treatment plans.
Leveraging deep learning-based segmentation and contours-driven deformable registration for dose accumulation in abdominal structures
Authors: McCulloch Molly M. , Cazoulat Guillaume , Svensson Stina , Gryshkevych Sergii , Rigaud Bastien , Anderson Brian M. , Kirimli Ezgi , De Brian , Mathew Ryan T. , Zaid Mohamed , Elganainy Dalia , Peterson Christine B. , Balter Peter , Koay Eugene J. , Brock Kristy K. 
Published: November 2022

PurposeDiscrepancies between planned and delivered dose to GI structures during radiation therapy (RT) of liver cancer may hamper the prediction of treatment outcomes. The purpose of this study is to develop a streamlined workflow for dose accumulation in a treatment planning system (TPS) during liver image-guided RT and to assess its accuracy when using different deformable image registration (DIR) algorithms.Materials and MethodsFifty-six patients with primary and metastatic liver cancer treated with external beam radiotherapy guided by daily CT-on-rails (CTOR) were retrospectively analyzed. The liver, stomach and duodenum contours were auto-segmented on all planning CTs and daily CTORs using deep-learning methods. Dose accumulation was performed for each patient using scripting functionalities of the TPS and considering three available DIR algorithms based on: (i) image intensities only; (ii) intensities + contours; (iii) a biomechanical model (contours only). Planned and accumulated doses were converted to equivalent dose in 2Gy (EQD2) and normal tissue complication probabilities (NTCP) were calculated for the stomach and duodenum. Dosimetric indexes for the normal liver, GTV, stomach and duodenum and the NTCP values were exported from the TPS for analysis of the discrepancies between planned and the different accumulated doses.ResultsDeep learning segmentation of the stomach and duodenum enabled considerable acceleration of the dose accumulation process for the 56 patients. Differences between accumulated and planned doses were analyzed considering the 3 DIR methods. For the normal liver, stomach and duodenum, the distribution of the 56 differences in maximum doses (D2%) presented a significantly higher variance when a contour-driven DIR method was used instead of the intensity only-based method. Comparing the two contour-driven DIR methods, differences in accumulated minimum doses (D98%) in the GTV were &gt;2Gy for 15 (27%) of the patients. Considering accumulated dose instead of planned dose in standard NTCP models of the duodenum demonstrated a high sensitivity of the duodenum toxicity risk to these dose discrepancies, whereas smaller variations were observed for the stomach.ConclusionThis study demonstrated a successful implementation of an automatic workflow for dose accumulation during liver cancer RT in a commercial TPS. The use of contour-driven DIR methods led to larger discrepancies between planned and accumulated doses in comparison to using an intensity only based DIR method, suggesting a better capability of these approaches in estimating complex deformations of the GI organs.
The role of involved field irradiation versus elective nodal irradiation in definitive radiotherapy or chemoradiotherapy for esophageal cancer- a systematic review and meta-analysis
Authors: Wang Hesong , Song Chunyang , Zhao Xiaohan , Deng Wenzhao , Shen Wenbin 
Published: November 2022

ObjectiveThis study aimed to analyze whether involved field irradiation (IFI) is associated with improving survival outcomes and reducing adverse events compared with elective nodal irradiation (ENI) in patients of esophageal cancer who underwent definitive radiotherapy or chemoradiotherapy.Summary background dataRadiotherapy plays an important role for not surgery patients. However, the role of radiation target size is still uncertain.MethodsWe searched Web of Science, Embase, PubMed, and Cochrane Central for English and non-English publications comparing esophageal cancer patients who received radiotherapy with IFI with those with ENI. Primary outcomes included overall survival (OS) and adverse events related to radiotherapy. The risk of bias was assessed using the Cochrane Risk of Bias tool for randomized studies and the Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality Standard for non-randomized studies. We evaluated the certainty of evidence by Grading of Recommendations, Assessment, Development, and Evaluation.ResultsTotally, 23 studies with 4120 patients were included. IFI group demonstrated significant improvement in the OS rates at 5 years, but not at 1, 2, and 3 years, compared with the ENI group (pooled Risk Ratio [RR], 0.78; 95% confidence interval [CI], 0.68–0.90; P = 0.0004; high certainty). In addition, IFI demonstrated a significant decrease in the incidence of grade ≥2 acute esophagitis (AE) (pooled RR, 0.79; 95% CI, 0.69–0.90; P = 0.0005; high certainty) and grade ≥3 AE (pooled RR, 0.51; 95% CI, 0.38–0.69; P &lt; 0.00001; high certainty) compared with ENI, but not in the incidence of grades ≥3 acute pneumonia, late esophagitis, and late pneumonia.ConclusionsCompared to ENI, IFI demonstrated significant improvement in OS at 5 years. The addition of intensity-modulated radiotherapy (IMRT) to IFI increased the 5-year OS; however, similar results were not observed with the addition of three-dimensional conformal radiotherapy to IFI and ENI. Furthermore, IFI demonstrated a significant decrease in grade ≥2 and grade ≥3 AE, while IMRT demonstrated no difference in the incidence of grade ≥3 AE. IFI and ENI do not differ in the incidence of grades ≥3 acute pneumonia, late esophagitis, and late pneumonia.
Polyclonal antibody-induced downregulation of HER1/EGFR and HER2 surpasses the effect of combinations of specific registered antibodies
Authors: Bergado-Báez Gretchen , Gonzalez Suarez Narjara , García Lisset Chao , Pérez-Martínez Dayana , Hernández-Fernández Diana Rosa , Fundora-Barrios Talia , Rodríguez-Álvarez Antonio , Díaz-Ordaz Geidy Diana , Lindzen Moshit , Yarden Yosef , Sánchez-Ramírez Belinda 
Published: November 2022

BackgroundAntitumor therapies targeting HER1/EGFR and HER2, such as monoclonal antibodies (MAbs) and tyrosine-kinase inhibitors (TKIs), have demonstrated a significant clinical benefit, but the emergence of resistance limits long-term efficacy. While secondary HER1 mutations confer tolerance to TKI, compensatory upregulation of HER2 drives resistance to anti-HER1 MAbs, which identifies MAb combinations targeting both receptors as an attractive therapeutic strategy. Nevertheless, toxicity hampers the clinical validation of this approach. Alternatively, cancer vaccines may induce antibodies directed against several antigens with less concern about induced toxicity.MethodsPolyclonal antibodies (PAbs) targeting HER1 and HER2 were induced in mice or rabbits through immunization. Recognition of different epitopes on targets by PAbs was validated by phage-display technology. Receptor downregulation was evaluated by flow cytometry, immunofluorescence, and Western blot. MTT assays assessed cytotoxicity, while the antitumor effect of PAbs was assayed in nude mice.ResultsPAbs promoted degradation of HER1 and HER2 regarding clinical MAbs or their combinations. As a result, inhibition of cytotoxicity on tumor cell lines was improved, even in the presence of oncogenic mutations in HER1, as well as in cetuximab-insensitive cells. Accordingly, the antitumor effect of vaccination-induced PAbs was observed in lung tumor lines representative of sensitivity or resistance to HER1 targeting therapies.ConclusionsImmunization against HER1 and HER2 receptors offers an alternative to passive administration of combinations of MAbs, since vaccination-induced PAbs promote the downregulation of both receptors and they have a higher impact on the survival of tumor cells.
Retinal hemangioblastoma in a patient with Von Hippel-Lindau disease: A case report and literature review
Authors: Huang Yikeng , Hu Weiwen , Huang Xionggao 
Published: November 2022

BackgroundRetinal hemangioblastoma (RH) is a rare benign tumor and a considerable number of which are caused by Von Hippel-Lindau disease (VHL). Herein, we described a case of VHL-associated RH with retinal detachment who underwent both laser photocoagulation and vitreoretinal surgery and received satisfactory visual recovery. In addition, we reviewed the current diagnosis, genotype-phenotype association, and treatment of VHL-associated RH.Case descriptionA 34-year-old woman presented with vision loss in the right eye at our hospital. Fundus photography and angiography showed retinal detachment and multiple large hemangiomas in the right eye. The visual acuity improved significantly after laser photocoagulation and vitreoretinal surgery. Genetic analyses showed a p.Asn78Ser (c.233A&gt;G) heterozygous missense mutation in the VHL gene.ConclusionWe described a rare case of VHL-associated RH and may provide a new perspective towards diagnosis and treatment of this disease. RH is one of the most common manifestations of VHL and poses a serious threat to vision. Ophthalmic examination methods include fundus examination and fundus photography, etc. The management of the disease emphasizes timely follow-up, early detection of the lesion, and the decision of treatment options according to the size, location and complications of the lesion, including ablation therapy and vitreoretinal surgery. Clinicians should strengthen the understanding of this rare disease for early detection and treatment.
Identification and validation of a novel phagocytosis regulators-related signature with potential prognostic and immunotherapeutic value in patients with lung adenocarcinoma
Authors: Li Jingyang , Du Qinyun , Sun Jiayi , Xiang Li , Wang Shaohui 
Published: November 2022

BackgroundLung adenocarcinoma (LUAD) is a malignant tumor that seriously affects the prognosis of patients. Tumor-associated macrophages (TAMs) play a vital role in the tumor microenvironment and can be used as a potential target for tumor therapy, and phagocytosis regulators (PRs) are particularly important in this process. However, the PRs-related signature that can predict the potential prognostic and immunotherapeutic value in patients with LUAD has not been discovered.MethodsIn this study, we mainly analyzed the effect of phagocytosis regulators on the prognosis of LUAD, and based on multiple screening analyses including differential analysis, univariate Cox analysis, and Lasso analysis, we constructed a prognostic risk model consisting of five genes. To verify the stability of the model, survival analysis and ROC curve verification were carried out through multiple data sets. In addition, we also combined many factors, such as immune infiltrating cells, clinical grouping characteristics, immune examination sites, pro-inflammatory factors, and other factors as well as in vitro cell experiments and clinical tissue samples for further validation analysis.ResultsAfter identifying 29 differentially expressed PRs in LUAD samples, we further constructed a prognostic model consisting of five prognostic signatures (FURIN, KIF23, SASH3, GNPNAT1, and ITGAL). Further survival analysis tests, ROC verification, as well as univariate and multivariate Cox regression analysis showed that the risk score of the model could well predict the prognosis of LUAD patients and could be used as an independent prognostic factor. In addition, we further found that these phagocytic regulators-related signatures were closely related to the immune microenvironment and immunotherapy in LUAD patients, and could well predict the efficacy of immunotherapy in patients. In vitro cell experiments and Immunohistochemistry of clinical tissues showed that the expressions of FURIN, KIF23, SASH3, GNPNAT1 and ITGAL in normal lung cells/tissues and LUAD cells/tissues were consistent with bioinformatics results, and 3 of them had significant differences.ConclusionOur study identified a novel PRs-related signature that has potential application value in predicting the prognosis of LUAD patients and predicting the efficacy of immunotherapy. This provides a new basis for the prognosis assessment of LUAD patients and provides a novel target for immunotherapy of LUAD patients.