bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Four−Gene-Based Risk Score With High Prognostic Value in Gastric Cancer
Authors: Zhang Bingdong , Li Yuerui , Yang Liu , Chen Yongbing 
Published: September 2021

BackgroundGastric adenocarcinoma is an important contributor to cancer mortality and morbidity. This study aimed to explore the prognostic value of mutation patterns in gastric adenocarcinoma.Materials and MethodsWe extracted somatic mutation data for 437 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) cohort. Kaplan–Meier survival in the R package maftools was used to analyze associations between mutations and survival. Multivariate Cox proportional model was used to establish risk formula. A four-gene-based risk score was developed to predict the overall survival of patients with gastric adenocarcinoma. We used the Tianjin cohort dataset with survival information to further evaluate the clinical value of this mutation signature.ResultsForty-five survival-related mutated genes were identified and verified, most of which were co-occurring in their mutation pattern and co-occurring with MLH3 and polymerase ϵ (POLE) mutations. Gastric adenocarcinoma samples with the 45 mutated genes had a significantly higher mutation count. Four-gene [UTRN, MUC16, coiled-coil domain-containing protein 178 (CCDC178), and HYDIN] mutation status was used to build a prognostic risk score that could be translated into the clinical setting. The association between the four-gene-based signature and overall survival remained statistically significant after controlling for age, sex, TNM stage, and POLE mutation status in the multivariate model [hazard ratio (HR), 1.88; 95% CI, 1.33–2.7; p &lt; 0.001]. The prognostic significance of the four-gene-based risk score identified in TCGA cohort was validated in the Tianjin cohort.ConclusionA four-mutated gene risk formula was developed that correlated with the overall survival of patients with gastric adenocarcinoma using a multivariable Cox regression model. In two independent genomic datasets from TCGA and Tianjin cohorts, low risk scores were associated with higher tumor mutation loads and improved outcome in patients with gastric adenocarcinoma. This finding may have implications for prognostic prediction and therapeutic guidance for gastric adenocarcinoma.
Computed Tomography-Based Radiomics Nomogram: Potential to Predict Local Recurrence of Gastric Cancer After Radical Resection
Authors: Huang Liebin , Feng Bao , Li Yueyue , Liu Yu , Chen Yehang , Chen Qinxian , Li Changlin , Huang Wensi , Xue Huimin , Li Xuehua , Zhou Tao , Li Ronggang , Long Wansheng , Feng Shi-Ting 
Published: September 2021

ObjectiveAccurate prediction of postoperative recurrence risk of gastric cancer (GC) is critical for individualized precision therapy. We aimed to investigate whether a computed tomography (CT)-based radiomics nomogram can be used as a tool for predicting the local recurrence (LR) of GC after radical resection.Materials and Methods342 patients (194 in the training cohort, 78 in the internal validation cohort, and 70 in the external validation cohort) with pathologically proven GC from two centers were included. Radiomics features were extracted from the preoperative CT imaging. The clinical model, radiomics signature, and radiomics nomogram, which incorporated the radiomics signature and independent clinical risk factors, were developed and verified. Furthermore, the performance of these three models was assessed by using the area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA).ResultsThe radiomics signature, which was comprised of two selected radiomics features, namely, contrast_GLCM and dissimilarity_GLCM, showed better performance than the clinical model in predicting the LR of GC, with AUC values of 0.83 in the training cohort, 0.84 in the internal validation cohort, and 0.73 in the external cohort, respectively. By integrating the independent clinical risk factors (N stage, bile acid duodenogastric reflux and nodular or irregular outer layer of the gastric wall) into the radiomics signature, the radiomics nomogram achieved the highest accuracy in predicting LR, with AUC values of 0.89, 0.89 and 0.80 in the three cohorts, respectively. DCA in the validation cohort showed that radiomics nomogram added more net benefit than the clinical model within the range of 0.01-0.98.ConclusionThe CT-based radiomics nomogram has the potential to predict the LR of GC after radical resection.
The 100 Most Cited Papers in Radiotherapy or Chemoradiotherapy for Cervical Cancer: 1990–2020
Authors: Wang Weiping , Liu Xiaoliang , Wang Dunhuang , Ren Kang , Zhou Yuncan , Zhou Ziqi , Qiu Jie , Zhang Fuquan , Hu Ke 
Published: September 2021

ObjectiveThis work aims to analyze the 100 most cited papers in radiotherapy or chemoradiotherapy for cervical cancer.MethodsThe 100 most cited papers in radiotherapy or chemoradiotherapy between 1990 and 2020 were identified with Thompson Reuters Web of Science citation indexing on August 24, 2020. The publication years, source titles, countries/regions, total citations, and average citations per year were extracted from the Web of Science. The research type and research domain were classified by the authors.ResultsThese 100 papers were cited a total of 28,714 times, and the median number of citations was 169.5 (ranging from 116 to 1,700 times). The most cited paper was “Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer” by Rose et al., with a total citation of 1,700 times. The International Journal of Radiation Oncology Biology Physics (40 papers), Radiotherapy and Oncology (14 papers), and the Journal of Clinical Oncology (12 papers) published the largest number of papers. USA (47 papers), Austria (18 papers), Canada (13 papers), and England (13 papers) contributed the largest number of papers. Image-guided adaptive brachytherapy (IGABT) had the largest number of papers (25 papers). Concurrent chemotherapy was the most cited research domain, with 10,663 total citations and 592.4 citations per paper.ConclusionIn the present study, we conducted a bibliometric analysis of the 100 most cited papers in radiotherapy or concurrent chemoradiotherapy for cervical cancer in the past 30 years. IGABT and concurrent chemotherapy were the most cited research domains.
EGFR Exon 18 Mutations in Advanced Non-Small Cell Lung Cancer: A Real-World Study on Diverse Treatment Patterns and Clinical Outcomes
Authors: Xu Haiyan , Yang Guangjian , Li Weihua , Li Junling , Hao Xuezhi , Xing Puyuan , Yang Yaning , Wang Yan 
Published: September 2021

BackgroundApproximately 3–5% of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) harbor exon 18 mutations. The appropriate treatment for such patients has not been clarified. The aim of this study was to investigate the response of patients with NSCLC harboring EGFR exon 18 mutations to different therapeutic options.MethodsBetween May 2014 and September 2020, the clinical outcomes of 82 patients harboring EGFR exon 18 mutations who received first-generation (1G) EGFR-tyrosine kinase inhibitor (TKI), second-generation (2G) EGFR-TKI afatinib, chemotherapy, and 1G TKI in combination with chemotherapy as the initial therapy were retrospectively analyzed.ResultsA total of 82 NSCLC patients harboring EGFR 18 mutations with whose treatment and survival outcomes were available were analyzed. The median age was 59 years, and 47 (57.3%) were female. The most common kind of EGFR exon 18 mutation was G719X (75.6%), followed by E709X (15.9%), E709_T710delinsD (3.6%), and other subtypes (4.9%). There was a significant difference in median progression-free survival (mPFS) by therapeutic strategy (P = 0.017). The mPFS of 1G TKI, 2G TKI afatinib, chemotherapy, and 1G TKI in combination with chemotherapy were 7.7 (95% CI, 4.2–11.2), 11.3 (95% CI, 5.6–17.0), 5.0 (95% CI, 2.3–17.7), and 11.1 (95% CI, 5.9–16.4) months, respectively. No significant difference in PFS was observed between afatinib and 1G TKI in combination with chemotherapy (P = 0.709).ConclusionsLike afatinib, 1G TKI in combination with chemotherapy might be an effective treatment option for patients harboring EGFR exon 18 mutations.
Long Noncoding RNA AC007639.1 Promotes the Pathogenesis and Progression of Hepatocellular Carcinoma Through Inhibiting Apoptosis and Stimulating Chemotherapeutic Resistance
Authors: Bai Yun , Ding Meijuan , Lu Dan , Li Yiwen , Yao Shuai , Wang Lei , Li Hui , Cui Guanghua , Li Xue , Sun Xiaoke , Yang Yu 
Published: September 2021

BackgroundHepatocellular carcinoma (HCC) is known for its poor prognosis. Long noncoding RNAs (lncRNAs) are critical in the pathogenesis of various types of cancers. We tried to explore the role of lncRNA in the development of HCC.MethodsWe identified the role of lncRNA AC007639.1 in the pathogenesis of HCC through bioinformatics and biological experiments in HepG2, Hep3B, and SMMC-7721 cells as well as the nude mice xenograft model.ResultsWe found that lncRNA AC007639.1 was overexpressed in hepatocellular carcinoma. Knocking down of lncRNA AC007639.1 by specific siRNAs or shRNAs promoted cancer cell death. The growth of mouse xenograft tumor created using lncRNA AC007639.1 deficient HepG2 cells was significantly slowed down. Furthermore, the knockdown of lncRNA AC007639.1 in HCC cells led to the increased expression of p53 and decreased expression of angiopoietin-like 4.ConclusionLncRNA AC007639.1 was involved in the pathogenesis and progression of hepatocellular carcinoma by inhibition of apoptosis and increasing HCC resistance to chemotherapy.
A Pilot Study of Low-Dose Craniospinal Irradiation in Patients With Newly Diagnosed Average-Risk Medulloblastoma
Authors: Minturn Jane E. , Mochizuki Aaron Y. , Partap Sonia , Belasco Jean B. , Lange Beverly J. , Li Yimei , Phillips Peter C. , Gibbs Iris C. , Fisher Paul G. , Fisher Michael J. , Janss Anna J. 
Published: September 2021

PurposeMedulloblastoma is one of the most common malignant brain tumors in children. To date, the treatment of average-risk (non-metastatic, completely resected) medulloblastoma includes craniospinal radiation therapy and adjuvant chemotherapy. Modern treatment modalities and now risk stratification of subgroups have extended the survival of these patients, exposing the long-term morbidities associated with radiation therapy. Prior to advances in molecular subgrouping, we sought to reduce the late effects of radiation in patients with average-risk medulloblastoma.MethodsWe performed a single-arm, multi-institution study, reducing the dose of craniospinal irradiation by 25% to 18 Gray (Gy) with the goal of maintaining the therapeutic efficacy as described in CCG 9892 with maintenance chemotherapy.ResultsTwenty-eight (28) patients aged 3-30 years were enrolled across three institutions between April 2001 and December 2010. Median age at enrollment was 9 years with a median follow-up time of 11.7 years. The 3-year relapse-free (RFS) and overall survival (OS) were 79% (95% confidence interval [CI] 58% to 90%) and 93% (95% CI 74% to 98%), respectively. The 5-year RFS and OS were 71% (95% CI 50% to 85%) and 86% (95% CI 66% to 94%), respectively. Toxicities were similar to those seen in other studies; there were no grade 5 toxicities.ConclusionsGiven the known neurocognitive adverse effects associated with cranial radiation therapy, studies to evaluate the feasibility of dose reduction are needed. In this study, we demonstrate that select patients with average-risk medulloblastoma may benefit from a reduced craniospinal radiation dose of 18 Gy without impacting relapse-free or overall survival.Clinical Trial RegistrationClinicalTrials.gov identifier: NCT00031590
Kinesiophobia Severity Categories and Clinically Meaningful Symptom Change in Persons With Achilles Tendinopathy in a Cross-Sectional Study: Implications for Assessment and Willingness to Exercise
Authors: Chimenti Ruth L. , Post Andrew A. , Silbernagel Karin Grävare , Hadlandsmyth Katherine , Sluka Kathleen A. , Moseley G. Lorimer , Rio Ebonie 
Published: September 2021

Objectives: (1) Validate thresholds for minimal, low, moderate, and high fear of movement on the 11-item Tampa Scale of Kinesiophobia (TSK-11), and (2) Establish a patient-driven minimal clinically important difference (MCID) for Achilles tendinopathy (AT) symptoms of pain with heel raises and tendon stiffness.Methods: Four hundred and forty-two adults with chronic AT responded to an online survey, including psychosocial questionnaires and symptom-related questions (severity and willingness to complete heel raises and hops). Kinesiophobia subgroups (Minimal ≤ 22, Low 23–28, Moderate 29–35, High ≥ 36 scores on the TSK-11), pain MCID subgroups (10-, 20-, 30-, &gt;30-points on a 0- to 100-point scale), and stiffness MCID subgroups (5, 10, 20, &gt;20 min) were described as median [interquartile range] and compared using non-parametric statistics.Results: Subgroups with higher kinesiophobia reported were less likely to complete three heel raises (Minimal = 93%, Low = 74%, Moderate = 58%, High = 24%). Higher kinesiophobia was associated with higher expected pain (Minimal = 20.0 [9.3–40.0], Low = 43.0 [20.0–60.0], Moderate = 50.0 [24.0–64.0], High = 60.5 [41.3–71.0]) yet not with movement-evoked pain (Minimal = 25.0 [5.0–43.0], Low = 31.0 [18.0–59.0], Moderate = 35.0 [20.0–60.0], High = 43.0 [24.0–65.3]). The most common pain MCID was 10 points (39% of respondents). Half of respondents considered a 5-min (35% of sample) or 10-min (16%) decrease in morning stiffness as clinically meaningful.Conclusions: Convergent validity of TSK-11 thresholds was supported by association with pain catastrophizing, severity of expected pain with movement, and willingness to complete tendon loading exercises. Most participants indicated that reducing their pain severity to the mild range would be clinically meaningful.
Initial Esophageal Anastomosis Diameter Predicts Treatment Outcomes in Esophageal Atresia Patients With a High Risk for Stricture Development
Authors: Baghdadi Osama , Clark Susannah , Ngo Peter , Yasuda Jessica , Staffa Steven , Zendejas Benjamin , Hamilton Thomas , Jennings Russell , Manfredi Michael 
Published: September 2021

Background and Aims: Children with esophageal atresia (EA) who undergo surgical repair are at risk for anastomotic stricture, which may need multiple dilations or surgical resection if the stricture proves refractory to endoscopic therapy. To date, no studies have assessed the predictive value of anastomotic diameter on long-term treatment outcomes. Our aim was to evaluate the relationship between anastomotic diameter in the early postoperative period and need for frequent dilations and stricture resection within 1 year of surgical repair.Methods: A retrospective chart review was performed of patients who had EA repair or stricture resection (SR). Medical records were reviewed to evaluate the diameter of the anastomosis at the first endoscopy after surgery, number and timing of dilations needed to treat the anastomotic stricture, and need for stricture resection. A generalized estimating equations (GEE) modeling with a logit link and binomial family was done to analyze the relationship between initial endoscopic anastomosis diameter and the outcome of needing a stricture resection. Median regression was implemented to estimate the association between number of dilations needed based on initial diameter.Results: A total of 121 patients (56 females) with a history of EA (64% long-gap EA) were identified who either underwent Foker repair at 46% or stricture resection with end-to-end esophageal anastomosis at 54%. The first endoscopy occurred a median of 22 days after surgery. Among all cases, a narrower anastomoses were more likely to need stricture resection with an OR of 12.9 (95% CI, 3.52, 47; p &lt; 0.001) in patients with an initial diameter of &lt;3 mm. The number of dilations that patients underwent also decreased as anastomotic diameter increased. This observation showed a significant difference when comparing all diameter categories when looking at all surgeries taken as a whole (p &lt; 0.008).Conclusion: Initial anastomotic diameter as assessed via endoscopy performed after high-risk EA repair predicts which patients will require more esophageal dilations as well as the likelihood for stricture resection. This data may serve to stratify patients into different endoscopic treatment plans.
Ten-Year Trend of Retinopathy of Prematurity Among Extremely Preterm Infants in One Neonatal Intensive Care Unit in China
Authors: Dai Yi , Zhu Li , Zhou Yequn , Chen Chao , Zhang Shulian 
Published: September 2021

Background: Extremely preterm (EP) infants are at the highest risk of retinopathy of prematurity (ROP). With more EP infants survived in China, recent data of ROP is lacking. The aim of the study is to report the trend of incidence of ROP among EP infants in a large neonatal intensive care unit in China over the past 10-year period, in relation with the overall survival rate and the change of oxygen saturation targets.Methods: This retrospective cohort study enrolled all EP infants born before 28 weeks' gestation and admitted to one of the largest tertiary neonatal intensive care units in China from 2010 to 2019. Data were compared between two time periods according to different oxygen saturation targets: 2010–2014 (P1) with low saturation target and 2015–2019 (P2) with higher target.Results: Of 630 EP infants admitted during the 10 years, 447 (71.0%) infants survived to discharge. The survival rate increased significantly from 61.6% in P1 to 75.8% in P2 (P &lt; 0.05). Of the 472 infants who had ROP data, 318 (67.4%) developed ROP of any stage, 67 (14.2%) developed severe ROP, and 44 (9.3%) received treatment. The incidence of any ROP increased significantly from 51.7% in P1 to 74.3% in P2 (P &lt; 0.05). The incidence of severe ROP increased from 11.0% in P1 to 15.6% in P2, and ROP treatment increased from 6.9% in P1 to 10.4% in P2, but neither reached statistical significance (both P &gt; 0.05).Conclusions: We observed an increasing trend in the incidence of ROP across the 10-year period in one of the largest neonatal care units in China. The increased survival rate and the use of high-target oxygen saturation in the later period may partly explain this trend. Further investigations are needed to improve the care practices and to reduce the incidence of severe ROP.
Genetic Testing in Various Neurodevelopmental Disorders Which Manifest as Cerebral Palsy: A Case Study From Iran
Authors: Nejabat Marzieh , Inaloo Soroor , Sheshdeh Afsaneh Taghipour , Bahramjahan Shima , Sarvestani Fatima Masoomi , Katibeh Pegah , Nemati Hamid , Tabei Seyed Mohammad Bagher , Faghihi Mohammad Ali 
Published: September 2021

Purpose: Cerebral palsy (CP) is a heterogeneous permanent disorder impacting movement and posture. Investigations aimed at diagnosing this disorder are expensive and time-consuming and can eventually inconclusive. This study aimed to determine the diagnostic yield of next generation sequencing in patients with atypical CP (ACP).Methods: Patient eligibility criteria included impaired motor function with onset at birth or within the first year of life, and one or more of the following conditions: severe intellectual disability, positive family history, brain imaging findings not typical for cerebral palsy, abnormal neurometabolic profile, intractable seizure, normal neuroimaging despite severe psychomotor disability, after pediatric neurologist assessment including neuroimaging and biochemical-metabolic study offered for genetic study.Results: Exome sequencing was done for 66 patients which revealed pathogenic, likely pathogenic, and variants of unknown significance in 36.2, 9, and 43.9%, respectively. We also found 10 new mutations and were able to suggest specific and personalized treatments for nine patients. We also found three different mutations with different phenotypical spectrum in one gene that have not been reported for cerebral palsy.Conclusion: An accurate history and physical examination and determination of patients with atypical cerebral palsy for doing exome sequencing result in improved genetic counseling and personalized management.
Comparative Effects of Metamizole (Dipyrone) and Naproxen on Renal Function and Prostacyclin Synthesis in Salt-Depleted Healthy Subjects - A Randomized Controlled Parallel Group Study
Authors: Blaser Lea S , Duthaler Urs , Bouitbir Jamal , Leuppi-Taegtmeyer Anne B , Liakoni Evangelia , Dolf Reto , Mayr Michael , Drewe Jürgen , Krähenbühl Stephan , Haschke Manuel 
Published: September 2021

Aim: The objective was to investigate the effect of metamizole on renal function in healthy, salt-depleted volunteers. In addition, the pharmacokinetics of the four major metamizole metabolites were assessed and correlated with the pharmacodynamic effect using urinary excretion of the prostacyclin metabolite 6-keto-prostaglandin F1α.Methods: Fifteen healthy male volunteers were studied in an open-label randomized controlled parallel group study. Eight subjects received oral metamizole 1,000 mg three times daily and seven subjects naproxen 500 mg twice daily for 7 days. All subjects were on a low sodium diet (50 mmol sodium/day) starting 1 week prior to dosing until the end of the study. Glomerular filtration rate was measured using inulin clearance. Urinary excretion of sodium, potassium, creatinine, 6-keto-prostaglandin F1α, and pharmacokinetic parameters of naproxen and metamizole metabolites were assessed after the first and after repeated dosing.Results: In moderately sodium-depleted healthy subjects, single or multiple dose metamizole or naproxen did not significantly affect inulin and creatinine clearance or sodium excretion. Both drugs reduced renal 6-keto-prostaglandin F1α excretion after single and repeated dosing. The effect started 2 h after intake, persisted for the entire dosing period and correlated with the concentration-profile of naproxen and the active metamizole metabolite 4-methylaminoantipyrine (4-MAA). PKPD modelling indicated less potent COX-inhibition by 4-MAA (EC50 0.69 ± 0.27 µM) compared with naproxen (EC50 0.034 ± 0.033 µM).Conclusions: Short term treatment with metamizole or naproxen has no significant effect on renal function in moderately sodium depleted healthy subjects. At clinically relevant doses, 4-MAA and naproxen both inhibit COX-mediated renal prostacyclin synthesis.