bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrence Patterns After IMRT/VMAT in Head and Neck Cancer
Authors: Bollen Heleen , van der Veen Julie , Laenen Annouschka , Nuyts Sandra 
Published: September 2021

PurposeIntensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT), two advanced modes of high-precision radiotherapy (RT), have become standard of care in the treatment of head and neck cancer. The development in RT techniques has markedly increased the complexity of target volume definition and accurate treatment delivery. The aim of this study was to indirectly investigate the quality of current TV delineation and RT delivery by analyzing the patterns of treatment failure for head and neck cancer patients in our high-volume RT center.MethodsBetween 2004 and 2014, 385 patients with pharyngeal, laryngeal, and oral cavity tumors were curatively treated with primary RT (IMRT/VMAT). We retrospectively investigated locoregional recurrences (LRR), distant metastases (DM), and overall survival (OS).ResultsMedian follow-up was 6.4 years (IQR 4.7–8.3 years) during which time 122 patients (31.7%) developed LRR (22.1%) and DM (17.7%). The estimated 2- and 5-year locoregional control was 78.2% (95% CI 73.3, 82.3) and 74.2% (95% CI 69.0, 78.8). One patient developed a local recurrence outside the high-dose volume and five patients developed a regional recurrence outside the high-dose volume. Four patients (1.0%) suffered a recurrence in the electively irradiated neck and two patients had a recurrence outside the electively irradiated neck. No marginal failures were observed. The estimated 2- and 5-year DM-free survival rates were 83.3% (95% CI 78.9, 86.9) and 80.0% (95% CI 75.2, 84.0). The estimated 2- and 5-year OS rates were 73.6% (95% CI 68.9, 77.8) and 52. 6% (95% CI 47.3, 57.6). Median OS was 5.5 years (95% CI 4.5, 6.7).ConclusionTarget volume definition and treatment delivery were performed accurately, as only few recurrences occurred outside the high-dose regions and no marginal failures were observed. Research on dose intensification and identification of high-risk subvolumes might decrease the risk of locoregional relapses. The results of this study may serve as reference data for comparison with future studies, such as dose escalation or proton therapy trials.
Upregulation of ADAM12 Is Associated With a Poor Survival and Immune Cell Infiltration in Colon Adenocarcinoma
Authors: Huang Zigao , Lai Hao , Liao Jiankun , Cai Jinghua , Li Baojia , Meng Linghou , Wang Wentao , Mo Xianwei , Qin Haiquan 
Published: September 2021

BackgroundA disintegrin and metalloprotease 12 (ADAM12) is a member of the multidomain protein family, but the mechanisms by which it affects prognosis and immune cell infiltration in patients with colon adenocarcinoma (COAD) remain unclear. Here, our study aimed to analyze the prognostic value of ADAM12 and investigate the correlation between ADAM12 expression and immune cell infiltration in patients with COAD.MethodsDifferential expression analyses were performed using the Oncomine and UALCAN databases, and prognostic analyses were conducted using PrognoScan, Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan–Meier Plotter. Then, the cBioPortal database was used to analyze alterations in the ADAM12 gene, and the STRING and Metascape websites were used to conduct Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Additionally, relationships between ADAM12 and the immune microenvironment were evaluated based on the TIMER, GEPIA, and TISIDB databases.ResultsADAM12 was overexpressed in COAD tissues, and higher ADAM12 expression correlated with a worse prognosis for patients with COAD. The gene regulatory network suggested that ADAM12 was mainly enriched in extracellular matrix (ECM) organization, ECM proteoglycans, skeletal system development, and ossification, among other pathways. Moreover, ADAM12 expression significantly correlated with the abundance of CD4+ T cells, B cells, CD8+ T cells, neutrophils, macrophages, dendritic cells, and their markers, as well as lymphocytes, immunomodulators, and chemokines.ConclusionsIn colorectal tumors, ADAM12 may play vital roles in regulating the ECM and the recruitment of immune cells, and we suggest that ADAM12 will become a reliable biomarker for determining response to immunotherapy and the prognosis of patients with COAD.
A Novel Seven Gene Signature-Based Prognostic Model to Predict Distant Metastasis of Lymph Node-Negative Triple-Negative Breast Cancer
Authors: Peng Wenting , Lin Caijin , Jing Shanshan , Su Guanhua , Jin Xi , Di Genhong , Shao Zhiming 
Published: September 2021

BackgroundThe prognosis of lymph node-negative triple-negative breast cancer (TNBC) is still worse than that of other subtypes despite adjuvant chemotherapy. Reliable prognostic biomarkers are required to identify lymph node-negative TNBC patients at a high risk of distant metastasis and optimize individual treatment.MethodsWe analyzed the RNA sequencing data of primary tumor tissue and the clinicopathological data of 202 lymph node-negative TNBC patients. The cohort was randomly divided into training and validation sets. Least absolute shrinkage and selection operator Cox regression and multivariate Cox regression were used to construct the prognostic model.ResultsA clinical prognostic model, seven-gene signature, and combined model were constructed using the training set and validated using the validation set. The seven-gene signature was established based on the genomic variables associated with distant metastasis after shrinkage correction. The difference in the risk of distant metastasis between the low- and high-risk groups was statistically significant using the seven-gene signature (training set: P &lt; 0.001; validation set: P = 0.039). The combined model showed significance in the training set (P &lt; 0.001) and trended toward significance in the validation set (P = 0.071). The seven-gene signature showed improved prognostic accuracy relative to the clinical signature in the training data (AUC value of 4-year ROC, 0.879 vs. 0.699, P = 0.046). Moreover, the composite clinical and gene signature also showed improved prognostic accuracy relative to the clinical signature (AUC value of 4-year ROC: 0.888 vs. 0.699, P = 0.029; AUC value of 5-year ROC: 0.882 vs. 0.693, P = 0.038). A nomogram model was constructed with the seven-gene signature, patient age, and tumor size.ConclusionsThe proposed signature may improve the risk stratification of lymph node-negative TNBC patients. High-risk lymph node-negative TNBC patients may benefit from treatment escalation.
Folate Reverses NF-κB p65/Rela/IL-6 Level Induced by Hyperhomocysteinemia in Spontaneously Hypertensive Rats
Authors: Zhang Lihua , Li Zhongliang , Xing Changcheng , Gao Ning , Xu Rui 
Published: September 2021

Hyperhomocysteinemia (HHcy) is derived from the abnormal metabolism of homocysteine (Hcy) and is related to metabolic-related diseases. In addition, HHcy combined with hypertension increases the risk of cardiovascular diseases (CVD). However, the mechanism of HHcy aggravating hypertensive arterial damage and the efficacy of folate (FA) as a beneficial supplement have not been fully elucidated. In this study, we established a rat HHcy model and a hypertension combined with HHcy model. Rat tail artery blood pressure (BP), plasma Hcy, serum superoxide dismutase (SOD), and malondialdehyde (MDA) were measured. Rat thoracic aorta was for pathological analysis after 12 weeks of the experiment. The relative expression levels of oxidative stress and immune/inflammation in rat arterial tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The results demonstrated that the relative expression levels of oxidative stress and immune/inflammation were the highest in the hypertension combined with HHcy group, followed by the hypertension group. Compared with the hypertension group, the hypertension combined with HHcy group up-regulated the expression levels of interleukin-6 (IL-6) and nuclear factor-κ-gene binding (NF-κB) p65/Rela, but not NADPH oxidase (Nox). Furthermore, folate inhibited the expression of IL-6 and NF-κB p65/Rela, reduced the levels of MDA and HHcy, but significantly increased the SOD level. In conclusion, HHcy synergistically aggravated the arterial damage factor of hypertension through immune/inflammatory response. However, folate demonstrated anti-inflammatory properties and reversed the NF-κB p65/Rela/IL-6 level induced by HHcy in hypertensive rats.
Lido-OH, a Hydroxyl Derivative of Lidocaine, Produced a Similar Local Anesthesia Profile as Lidocaine With Reduced Systemic Toxicities
Authors: Yin Qinqin , Zhang Weiyi , Ke Bowen , Liu Jin , Zhang Wensheng 
Published: September 2021

Background: lidocaine is one of the most commonly used local anesthetics for the treatment of pain and arrhythmia. However, it could cause systemic toxicities when plasma concentration is raised. To reduce lidocaine’s toxicity, we designed a hydroxyl derivative of lidocaine (lido-OH), and its local anesthesia effects and systemic toxicity in vivo were quantitively investigated.Method: the effectiveness for lido-OH was studied using mouse tail nerve block, rat dorsal subcutaneous infiltration, and rat sciatic nerve block models. The systemic toxicities for lido-OH were evaluated with altered state of consciousness (ASC), arrhythmia, and death in mice. Lidocaine and saline were used as positive and negative control, respectively. The dose-effect relationships were analyzed.Results: the half effective-concentration for lido-OH were 2.1 mg/ml with 95% confident interval (CI95) 1.6–3.1 (lidocaine: 3.1 mg/ml with CI95 2.6–4.3) in tail nerve block, 8.2 mg/ml with CI95 8.0–9.4 (lidocaine: 6.9 mg/ml, CI95 6.8–7.1) in sciatic nerve block, and 5.9 mg/ml with CI95 5.8–6.0 (lidocaine: 3.1 mg/ml, CI95 2.4–4.0) in dorsal subcutaneous anesthesia, respectively. The magnitude and duration of lido-OH were similar with lidocaine. The half effective doses (ED50) of lido-OH for ACS was 45.4 mg/kg with CI95 41.6–48.3 (lidocaine: 3.1 mg/kg, CI95 1.9–2.9), for arrhythmia was 16.0 mg/kg with CI95 15.4–16.8 (lidocaine: 3.0 mg/kg, CI95 2.7–3.3), and for death was 99.4 mg/kg with CI95 75.7–124.1 (lidocaine: 23.1 mg/kg, CI95 22.8–23.4). The therapeutic index for lido-OH and lidocaine were 35.5 and 5.6, respectively.Conclusion: compared with lidocaine, lido-OH produced local anesthesia at similar potency and efficacy, but with significantly reduced systemic toxicities.
Trends of High-Impact Studies in Pharmacology and Pharmacy: A Cross-Sectional Study
Authors: Chen Lingmin , Yang Yi , Fan Jin , Zhang Yonggang , Li Nian 
Published: September 2021

Objective: To investigate the trends of high-impact studies in pharmacology and pharmacy research and to provide evidence for future research in the field of pharmacology and pharmacy.Methods: A cross-sectional study was performed to understand the current status of high-impact studies (top 1%) in pharmacology and pharmacy research via InCites tool based on Web of Science Core Collection. VOSViewer software was used to visualize the results. The outcomes included development trends, countries, subject areas, research institutes, collaborative networks, and subject terms.Results: We found 4,273 high-impact (top 1%) studies between 2011 and 2020 in the field of pharmacology and pharmacy. The number of studies increased from 366 in 2011 to 510 in 2020. These studies were mainly distributed in the following Web of Science subject categories: pharmacology and pharmacy (n = 4,188); neurosciences (n = 397); chemistry, multidisciplinary (n = 359); chemistry, medicinal (n = 314); microbiology (n = 301); biotechnology and applied microbiology (n = 280). These studies were cited in 646,855 studies from more than 100 Web of Science subject categories, and studies in pharmacology pharmacy accounted for the largest share of these citations. The top three countries that contributed the highest number of studies were the United States, United Kingdom, and China. The top three institutions that contributed the highest number of studies in the United States were the University of California System, the National Institutes of Health (NIH), and Harvard University. The top research collaborative circle was from universities in the United States. The top international collaborative circle was from universities from the United States, United Kingdom, Australia, and China. The subject-term analysis indicated that cancer was still the top disease, NF-κB was the top signaling pathway, and drug-delivery and nanoparticles were the top methods.Conclusion: The high-impact studies in pharmacology and pharmacy research have grown over time. The United States, the United Kingdom, and China are the top countries that contributed the high-impact studies. Cancer is still the greatest challenge in the field of disease treatment. It calls for more international collaboration in pharmacology and pharmacy research, which will help discover novel drugs.
A Cost-Effective Photonic Radar Under Adverse Weather Conditions for Autonomous Vehicles by Incorporating a Frequency-Modulated Direct Detection Scheme
Authors: Sharma Abhishek , Chaudhary Sushank , Malhotra Jyoteesh , Saadi Muhammad , Al Otaibi Sattam , Nebhen Jamel , Wuttisittikulkij Lunchakorn 
Published: September 2021

In recent years, there have been plenty of demands and growth in the autonomous vehicle industry, and thus, challenges of designing highly efficient photonic radars that can detect and range any target with the resolution of a few centimeters have been encountered. The existing radar technology is unable to meet such requirements due to limitations on available bandwidth. Another issue is to consider strong attenuation while working under diverse atmospheric conditions at higher frequencies. The proposed model of photonic radar is developed considering these requirements and challenges using the frequency-modulated direct detection technique and considering a free-space range of 750 m. The result depicts improved range detection in terms of received power and an acceptable signal-to-noise ratio and range under adverse climatic situations.
Interindividual Variability in Fat Mass Response to a 1-Year Randomized Controlled Trial With Different Exercise Intensities in Type 2 Diabetes: Implications on Glycemic Control and Vascular Function
Authors: Magalhães João P. , Hetherington-Rauth Megan , Júdice Pedro B. , Correia Inês R. , Rosa Gil B. , Henriques-Neto Duarte , Melo Xavier , Silva Analiza M. , Sardinha Luís B. 
Published: September 2021

Purpose: Little is known about the interindividual variability in fat mass (FM) loss in response to high-intensity interval training (HIIT) and moderate continuous training (MCT) in individuals with type 2 diabetes mellitus (T2DM). Moreover, the impact on health-related outcomes in those who fail to reduce FM is still unclear. The aims of this investigation were (1) to assess if the individuals with T2DM who FM differed across MCT, HIIT, and control groups over a 1-year intervention and (2) to assess the changes on glycemic control and vascular function in the exercising patients who failed to lose FM.Methods: Adults with T2DM were randomized into a 1-year intervention involving a control group (n=22), MCT with resistance training (RT; n=21), and HIIT with RT (n=19). FM was assessed using dual-energy X-ray absorptiometry and a change in total body FM above the typical error was used to categorize FM responders. Glycemic control and vascular stiffness and structure were assessed. A chi-square test and generalized estimating equations were used to model the outcomes.Results: Both MCT (n=10) and HIIT (n=10) had a similar proportion of individuals who were categorized as high responders for FM, with the percent change in FM on average −5.0±9.6% for the MCT and −6.0±12.1% for the HIIT, which differed from the control group (0.2±7.6%) after a 1-year intervention (p&lt;0.05). A time-by-group interaction for carotid artery intima-media thickness (cIMT) (p for interaction=0.042) and lower-limb pulse wave velocity (LL PWV; p for interaction=0.010) between those categorized as low FM responders and the control group. However, an interaction was observed between the high responders for FM loss and controls for both brachial and carotid hemodynamic indices, as well as in cIMT, carotid distensibility coefficient, carotid beta index, and LL PWV (p for interactions &lt;0.05). No interactions were found for glycaemic indices (p for interaction &gt;0.05).Conclusion: Our results suggest that the number of FM responders did not differ between the MCT or HIIT, compared to the control, following a 1-year exercise intervention in individuals with T2DM. However, low responders to FM may still derive reductions in arterial stiffness and structure.Clinical Trial Registration: Comparing Moderate and High-intensity Interval Training Protocols on Biomarkers in Type 2 Diabetes Patients (D2FIT study) – number: NCT03144505 (https://clinicaltrials.gov/ct2/show/NCT03144505).
Improving Reading Through Videogames and Digital Apps: A Systematic Review
Authors: Ostiz-Blanco Mikel , Bernacer Javier , Garcia-Arbizu Irati , Diaz-Sanchez Patricia , Rello Luz , Lallier Marie , Arrondo Gonzalo 
Published: September 2021

Background: The use of electronic interventions to improve reading is becoming a common resource. This systematic review aims to describe the main characteristics of randomized controlled trials or quasi-experimental studies that have used these tools to improve first-language reading, in order to highlight the features of the most reliable studies and guide future research.Methods: The whole procedure followed the PRISMA guidelines, and the protocol was registered before starting the process (doi: 10.17605/OSF.IO/CKM4N). Searches in Scopus, PubMed, Web of Science and an institutional reference aggregator (Unika) yielded 6,230 candidate articles. After duplicate removal, screening, and compliance of eligibility criteria, 55 studies were finally included.Results: They were research studies on improving first-language reading, both in children and adults, and including a control group. Thirty-three different electronic tools were employed, most of them in English, and studies were very diverse in sample size, length of intervention, and control tasks. Risk of bias was analyzed with the PEDro scale, and all studies had a medium or low risk. However, risk of bias due to conflicts of interest could not be evaluated in most studies, since they did not include a statement on this issue.Conclusion: Future research on this topic should include randomized intervention and control groups, with sample sizes over 65 per group, interventions longer than 15 h, and a proper disclosure of possible conflicts of interest.Systematic Review Registration: The whole procedure followed the PRISMA guidelines, and the protocol was registered before starting the process in the Open Science Framework (doi: 10.17605/OSF.IO/CKM4N).
Prevalence of Suicidality in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Comparative Studies
Authors: Cai Hong , Xie Xiao-Meng , Zhang Qinge , Cui Xiling , Lin Jing-Xia , Sim Kang , Ungvari Gabor S. , Zhang Ling , Xiang Yu-Tao 
Published: September 2021

Background: Suicidality is common in major depressive disorder (MDD), but there has been no systematic review published about all aspects of suicidality. This meta-analysis and systematic review compared the prevalence of the whole range of suicidality comprising suicidal ideation (SI), suicide plan (SP), suicide attempt (SA), and completed suicide (CS), between patients with MDD and non-MDD controls.Methods: Major international (PubMed, PsycINFO, Web of Science, EMBASE) and Chinese (Chinese Nation Knowledge Infrastructure and WANFANG) databases were systematically and independently searched from their inception until January 12, 2021.Results: Fifteen studies covering 85,768 patients (12,668 in the MDD group and 73,100 in the non-MDD group) were included in the analyses. Compared to non-MDD controls, the odds ratios (ORs) for lifetime, past month, past year, and 2-week prevalence of SI in MDD were 2.88 [95% confidence interval (CI) = 0.30–27.22, p = 0.36], 49.88 (95% CI = 2–8.63, p &lt; 0.001), 13.97 (95% CI = 12.67–15.41, p &lt; 0.001), and 24.81 (95% CI = 15.70–39.22, p &lt; 0.001), respectively. Compared to non-MDD controls, the OR for lifetime SP in MDD was 9.51 (95% CI = 7.62–11.88, p &lt; 0.001). Compared to non-MDD controls, the ORs of lifetime and past-year prevalence of SA were 3.45 (95% CI = 1.58–7.52, p = 0.002), and 7.34 (95% CI = 2.14–25.16, p = 0.002), respectively, in MDD patients. No difference in the prevalence of CS between MDD and controls was found (OR = 0.69, 95% CI = 0.23–2.02, p = 0.50).Conclusions: MDD patients are at a higher risk of suicidality, compared to non-MDD controls. Routine screening for a range of suicidality should be included in the management of MDD, followed by timely treatment for suicidal patients.Systematic Review Registration: Identifier [INPLASY202120078].
Combined Associations of Smoking and Bullying Victimization With Binge Drinking Among Adolescents in Beijing, China
Authors: Chen Li , Lu Ruo-Ran , Duan Jia-Li , Ma Jun , Zhu Guangrong , Song Yi , Lau Patrick W. C. , Prochaska Judith J. 
Published: September 2021

Background: Binge drinking and smoking among adolescents are serious public concerns. However, very few studies have explored the reinforcement of bullying victimization by such behavior. Our study aimed at examining the individual and combined associations of smoking and bullying victimization with binge drinking among adolescents in Beijing, China.Methods: A total of 33,694 students aged 13–17 years old in Beijing, China were anonymously investigated via the cross-sectional Chinese Youth Risk Behavior Surveillance Survey from April to May 2014. A three-stage stratified sampling was used to select participants. Factors such as sociodemographic variables and indicators of smoking, bullying victimization, and binge drinking were analyzed with multiple logistic regressions, and joint and additive interaction effects were tested.Results: Overall, ever-drinking prevalence was 59.1% (boys: 64.4%; girls: 53.7%). Past 30-day binge drinking was 11.5% (boys: 15.6%; girls: 7.4%) and frequent binge drinking was 2.3% (boys: 3.3%; girls: 1.0%). Past 30-day smoking was 10.7% (boys: 16.4%; girls: 5.0%) and past 30-day bullying victimization was 48.7% (boys: 57.3%; girls: 40.1%). The combined effects of smoking and bullying victimization on occasional binge drinking (OR = 6.49, 95% CI = 5.60–7.52) and frequent binge drinking (OR = 10.32, 95% CI = 7.52–14.14) were significant, and the additive interaction effect was significant for current smoking and bullying victimization on frequent binge drinking (OR = 10.22, 95% CI = 9.43–11.07). The additive interaction effect for current smoking and bullying victimization on frequent binge drinking was significant among boys.Conclusion: Bullying victimization reinforced the association of smoking with frequent binge drinking, especially with findings specific to boys. Programs to prevent smoking or bullying or both may reduce binge drinking among adolescents in China.