bluuebunny/crossref_metadata_2025 huggingface dataset:
Ilaprazole and Clopidogrel Resistance in Acute Stroke Patients
Authors: Lim In Hwan , Lee Seung Jae , Shin Byoung-Soo , Kang Hyun Goo
Published: June 2022

Clopidogrel, an antiplatelet agent used for secondary prevention of cerebrovascular diseases, is often taken with proton pump inhibitors (PPIs). Generally, the combined use of clopidogrel and PPIs causes adverse drug–drug interactions. VerifyNow is a quick and convenient method to confirm clopidogrel resistance (CR), which compromises adequate antithrombotic effects. We aimed to confirm CR, identify its factors, and determine the influence of the combination of ilaprazole and clopidogrel on clopidogrel using VerifyNow. In this retrospective study, we examined patients who were receiving clopidogrel after three months, starting within one week from the onset of cerebral infarction symptoms. Clinical records, imaging records, and diagnostic laboratory results, including P2Y12 reaction units (PRU), were compared and analyzed to check for CR. Additionally, the groups treated with either both ilaprazole and clopidogrel or with medications other than ilaprazole were comparatively analyzed. CR was defined as a PRU ≥240 after clopidogrel for three months. Among factors influencing CR by affecting clopidogrel metabolism, positive statistical correlations with age and alcohol consumption were confirmed. The diagnostic tests revealed a lower glomerular filtration rate and platelet count of the CR-positive group. This finding proved that the combination therapy of ilaprazole and clopidogrel is safe, as it does not interfere with the metabolism of clopidogrel.
Clinical Value of Inflammatory and Neurotrophic Biomarkers in Bipolar Disorder: A Systematic Review and Meta-Analysis
Authors: Vega-Núñez Amanda , Gómez-Sánchez-Lafuente Carlos , Mayoral-Cleries Fermín , Bordallo Antonio , Rodríguez de Fonseca Fernando , Suárez Juan , Guzmán-Parra José
Published: June 2022

Bipolar disorder (BD) is a multifactorial chronic psychiatric disease highly defined by genetic, clinical, environmental and social risk factors. The present systematic review and meta-analysis aimed to examine the relationship between inflammatory and neurotrophic factors and clinical, social and environmental factors involved in the development and the characterization of BD. Web of Science, PubMed, PsycINFO, Scopus and Science Direct were searched by two independent reviewers. The systematic review was registered in PROSPERO (CRD42020180626). A total of 51 studies with 4547 patients with a diagnosis of BD were selected for systematic review. Among them, 18 articles were included for meta-analysis. The study found some evidence of associations between BDNF and/or inflammatory factors and different stressors and functional and cognitive impairment, but limitations prevented firm conclusions. The main finding of the meta-analysis was a negative correlation between circulating levels of BDNF and depression severity score (standardized mean difference = −0.22, Confidence Interval 95% = −0.38, −0.05, p = 0.01). Evidence indicates that BDNF has a role in the depressive component of BD. However, the poor consistency found for other inflammatory mediators clearly indicates that highly controlled studies are needed to identity precise biomarkers of this disorder.
Acute Sleep Deprivation Impairs Motor Inhibition in Table Tennis Athletes: An ERP Study
Authors: Xu Lin , Song Tao , Peng Ziyi , Dai Cimin , Wang Letong , Shao Yongcong , Wang Lanxiang , Weng Xiechuan , Han Mengfei
Published: June 2022

Excellent response inhibition is the basis for outstanding competitive athletic performance, and sleep may be an important factor affecting athletes’ response inhibition. This study investigates the effect of sleep deprivation on athletes’ response inhibition, and its differentiating effect on non-athlete controls’ performance, with the aim of helping athletes effectively improve their response inhibition ability through sleep pattern manipulation. Behavioral and event-related potential (ERP) data were collected from 36 participants (16 table tennis athletes and 20 general college students) after 36 h of sleep deprivation using ERP techniques and a stop-signal task. Sleep deprivation’s different effects on response inhibition in the two groups were explored through repeated-measures ANOVA. Behavioral data showed that in a baseline state, stop-signal response time was significantly faster in table tennis athletes than in non-athlete controls, and appeared significantly longer after sleep deprivation in both groups. ERP results showed that at baseline state, N2, ERN, and P3 amplitudes were lower in table tennis athletes than in non-athlete controls, and corresponding significant decreases were observed in non-athlete controls after 36 h of sleep deprivation. Table tennis athletes showed a decrease in P3 amplitude and no significant difference in N2 and ERN amplitudes, after 36 h of sleep deprivation compared to the baseline state. Compared to non-athlete controls, table tennis athletes had better response inhibition, and the adverse effects of sleep deprivation on response inhibition occurred mainly in the later top-down motor inhibition process rather than in earlier automated conflict detection and monitoring.
Focus on Peripheral Biomarkers of Mental Disorders
Authors: Bartoli Francesco , Carrà Giuseppe
Published: June 2022

Personalized approaches in psychiatry, albeit being extensively explored in the literature since the early 2010s [...]
A Multivariate Analysis of the Interest in Starting Family Businesses within a Developing Economy
Authors: Puiu Silvia , Bădîrcea Roxana Maria , Manta Alina Georgiana , Doran Nicoleta Mihaela , Meghisan-Toma Georgeta-Madalina , Meghisan Flaviu
Published: June 2022

The main objective of the research is to analyze the factors which influence the intention to start an intergenerational family business in a developing economy, highlighting the measures that can be implemented by decision-makers to stimulate these initiatives. PLS-SEM was used to analyze the data issued from 200 valid questionnaires. The survey was applied to 950 individuals from Romania. We focused on four variables: the closeness to family members, the financial support expected from family, the independence of individuals regarding the intention to start their own business and the intention to form partnerships with family members. All the hypotheses were validated, according to the final results. Thus, closeness to family members has a direct and positive impact on both the financial support expected from the family and the intention to form intergenerational family businesses. There is also a direct correlation between the financial support received from family and the intention to have partnerships with family members. Individuals who are closer to their families are not interested in developing independent businesses. There are several studies on family businesses in Romania, but there is no research analyzing the impact of closeness to family on the intention to develop an intergenerational family business. The study is useful for the decision-makers who can create national strategies in order to stimulate families to develop their own businesses.
Multiple Identifications of Employees in an Organization: Salience and Relationships of Foci and Dimensions
Authors: Sidorenkov Andrey V. , Borokhovski Eugene F. , Stroh Wladimir A. , Naumtseva Elena A.
Published: June 2022

This research addresses: (1) the salience of employees’ social (organizational, sub-organizational, group, micro-group), interpersonal, and personal identifications and their dimensions (cognitive and affective); (2) and the relationship and structure of the identifications of employees in different areas of professional activity. The study was conducted on independent samples of employees in the socio-economic sphere (241 participants), in the law enforcement agency (265), and in higher education (172). To assess the respective identification foci and dimensions, the study employed four questionnaires. The personal identification was the weakest and the micro-group identification was the strongest for both dimensions in all samples. The affective dimension prevails over the cognitive in all identifications, except for interpersonal. Social identifications were significantly positively correlated to each other in all samples whereas personal identification was significantly negatively correlated with all social identifications (on the affective dimension) in two samples. The results expand our understanding of the identifications of employees in organizations.
Optimal Design of Tuned Mass-Damper-Inerter for Structure with Uncertain-but-Bounded Parameter
Authors: Zhou Shaoyi , Huang Jungang , Yuan Quan , Ma Dong , Peng Shuangling , Chesne Simon
Published: June 2022

In this study we focus on the H∞ optimization of a tuned mass damper inerter (TMDI), which is implemented on an harmonically forced structure of a single degree of freedom in the presence of stiffness uncertainty. Posed as a min-max optimization problem, its closed-form solutions are analytically derived via an algebraic approach that was newly developed in this work, and ready-to-use formulae of tuning parameters are provided herein for the optimal TMDI (referred to as the TMD). The accuracy of the derived solutions are examined by comparing them with the existing literature and with numerically solved solutions in both deterministic and uncertain scenarios. Our numerical investigation suggested that compared to the classic design, the proposed tuning strategy could effectively reduce the peak vibration amplitude of the host structure in the worst-case scenario. Moreover, its peak vibration amplitude decreases monotonically as the total amount of the tuned mass and inertance increases. Therefore, the incorporation of a grounded inerter in a traditional TMD could render the deteriorated performance of vibration control less important, thereby protecting the primary system against the detuning effect more effectively. Finally, the effectiveness of the proposed design under random excitation is also underlined.
A Brief Method for Rapid Seismic Damage Prediction of Buildings Based on Structural Strength
Authors: Zhang Siwei , Liu Yide , Li Shuang
Published: June 2022

Rapid prediction of the post-earthquake structural damage to a region is of great importance to community relief and rescue. Detailed information on buildings in earthquake disaster areas is commonly inaccessible in the aftermath of an earthquake. Accurately assessing the seismic damage to urban buildings using limited information is significant. This study proposes a design-strength-based method for regional seismic structural damage prediction based on structural strength. Only a few basic attributes of buildings are required, including the basic building plan size, building height, construction time, and structural type. Theoretically, the method is very brief, and can be applied to all types of structures, including irregular ones, compared with other commonly used regional seismic damage prediction methods. The proposed method is validated with acceptable accuracy and efficiency compared with the refined finite element (FE) model analysis and simplified model analysis. The proposed seismic structural damage prediction method was applied to a university campus, which can serve as a simple reference for community earthquake resistance evaluation and improvement.
Comparison of the Influence of Double-Limb Double-Plate Joint on the Stability Bearing Capacity of Triangular and Quadrilateral Transmission Tower Structures
Authors: Zhao Tengfei , Li Aimin , Yan Hong , Zhang Lei , Lan Zhiwen , Huang Mojia , Wu Han
Published: June 2022

The axial stiffness of the connection joints in a transmission tower will affect the stability bearing capacity of the tower. The axial stiffness of different forms of connection joints has different effects on the stability bearing capacities of triangular and quadrilateral lattice towers. This paper takes triangular and quadrilateral lattice towers as the comparative research objects and considers the influence of the stiffness of the single-limb, single-plate joint (SLSPJ) and double-limb, double-plate joint (DLDPJ) of the tower. Under vertical load, the vertical stability bearing capacities of triangular and quadrilateral transmission towers are studied from hte three aspects of theoretical analysis, numerical simulation and test result analysis. The influence rules of the SLSPJ and DLDPJ on the vertical stability bearing capacities of triangular and quadrilateral transmission towers are clarified. Through the energy method, considering the influence of the axial stiffness of connection joints, the calculation expressions of the vertical stability bearing capacities of triangular and quadrilateral lattice towers are derived. Through quantitative analysis, it is found that the axial stiffness of the connection joints has a more significant influence on the vertical stability bearing capacities of triangular lattice towers. The finite element models of the triangular and quadrilateral lattice towers including the SLSPJ and DLDPJ are further established. Through nonlinear finite element analysis, it is found that the DLDPJ can improve the vertical stability bearing capacity of the triangular lattice tower by 22.7% and the quadrilateral lattice tower by 14.9%. Through theoretical calculation, the expressions of the vertical stability bearing capacities of the triangular and quadrilateral lattice towers including the SLSPJ and DLDPJ are obtained. Combined with the test results of the SLSPJ and DLDPJ, it is found that the DLDPJ can improve the vertical stability bearing capacity of the triangular lattice tower by 23.4% and the quadrilateral lattice tower by 15.6%. The research results show that the DLDPJ can improve the vertical stability bearing capacities of triangular and quadrilateral lattice towers. The improvement effect of the vertical stability bearing capacity of the triangular lattice tower is 1.50∼1.52 times that of the quadrilateral lattice tower. The research results can provide a reference for the engineering popularization, application, and design of the DLDPJ in transmission towers.
Structural Health Monitoring of a Brazilian Concrete Bridge for Estimating Specific Dynamic Responses
Authors: Zacchei Enrico , Lyra Pedro H. C. , Lage Gabriel E. , Antonine Epaminondas , Soares Airton B. , Caruso Natalia C. , de Assis Cassia S.
Published: June 2022

A 3D coupled model to simulate vehicle–bridge interactions (VBI) to estimate its structural responses and impact factors (IMs) was developed in this study. By structural health monitoring (SHM) of a real concrete bridge, several data were collected to calibrate the bridge model by the finite element method (FEM). These models provide the bridge response in terms of vertical displacements and accelerations. VBI models provide reliable outputs without significantly altering the dynamic properties of the bridge. Modified recent analytical equations, which account for the effects of the asymmetric two-axle vehicles, were developed numerically. These equations, plus some proposed solutions, also quantified the vehicle response in terms of accelerations to estimate a more conservative driving comfort. The goal consisted in fitting the SHM with numerical and analytical models to find a more appropriate response for safety purposes and maintenance. From the codes and the literature, it was shown that a unique IM factor was not found. Moreover, most approaches underestimate the phenomena; in fact, results show that a monitored IM factor is 2.5 greater than IM from codes. Proposed equations for vehicle accelerations provided more conservative values up to about three times the standard comfort value.
Window-Windcatcher for Enhanced Thermal Comfort, Natural Ventilation and Reduced COVID-19 Transmission
Authors: Fawwaz Alrebei Odi , Obeidat Laith M. , Ma’bdeh Shouib Nouh , Kaouri Katerina , Al-Radaideh Tamer , Amhamed Abdulkarem I.
Published: June 2022

We investigate and test the effectiveness of a novel window windcatcher device (WWC), as a means of improving natural ventilation in buildings. Using ANSYS CFX, the performance of the window-windcatcher is compared to a control case (no window-windcatcher), in three different geographic locations (Cardiff, Doha and Amman) which are representative of three different types of atmospheric conditions. The proposed window-windcatcher has been shown to improve both thermal comfort and indoor air quality by increasing the actual-to-required ventilation ratio by up to 9% compared to the control case as per the American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE) standards. In addition, the locations with minimum velocities have been identified. Those locations correspond to the regions with a lower infection risk of spreading airborne viruses such as SARS-CoV-2, which is responsible for the COVID-19 pandemic.
Investigation of Pedestrian-Level Wind Environment with Skyline Quantitative Factors
Authors: Ying Xiaoyu , Gao Jing , Liu Ziqiao , Qin Xiaoying , Chen Jiahui , Shen Liying , Han Xinyu
Published: June 2022

This paper presented a Computational Fluid Dynamics (CFD) study on the relationship between skyline quantitative factors and the wind environment. At present, most researches on skyline revealed the changes of skyline quantitative factors on the aesthetic degrees but neglected the influence of the factors on the outdoor wind environment. This paper addresses the gap in using the changing factors for the prediction of outdoor wind speed. It provides a standardized range for aesthetic degrees in the comfortable range of the wind environment and an exact relationship between the factors and the wind environment. To validate the effectiveness of the proposed approach, a case study is undertaken on the existing skyline of Qianjiang New City in Hangzhou and extracts the following three skyline quantitative factors in skyline contour: contour tortuosity, building undulation, and skyline rhythm index. The result shows that the proposed range and relationship are ready to provide a quantitative understanding of the skyline under outdoor wind conditions.
RP-Rs-fMRIomics as a Novel Imaging Analysis Strategy to Empower Diagnosis of Brain Gliomas
Authors: Liu Xiaoxue , Li Jianrui , Xu Qiang , Zhang Qirui , Zhou Xian , Pan Hao , Wu Nan , Lu Guangming , Zhang Zhiqiang
Published: June 2022

Rs-fMRI can provide rich information about functional processes in the brain with a large array of imaging parameters and is also suitable for investigating the biological processes in cerebral gliomas. We aimed to propose an imaging analysis method of RP-Rs-fMRIomics by adopting omics analysis on rs-fMRI with exhaustive regional parameters and subsequently estimating its feasibility on the prediction diagnosis of gliomas. In this retrospective study, preoperative rs-fMRI data were acquired from patients confirmed with diffuse gliomas (n = 176). A total of 420 features were extracted through measuring 14 regional parameters of rs-fMRI as much as available currently in 10 specific narrow frequency bins and three parts of gliomas. With a randomly split training and testing dataset (ratio 7:3), four classifiers were implemented to construct and optimize RP-Rs-fMRIomics models for predicting glioma grade, IDH status and Karnofsky Performance Status scores. The RP-Rs-fMRIomics models (AUROC 0.988, 0.905, 0.801) were superior to the corresponding traditional single rs-fMRI index (AUROC 0.803, 0.731, 0.632) in predicting glioma grade, IDH and survival. The RP-Rs-fMRIomics analysis, featuring high interpretability, was competitive for prediction of glioma grading, IDH genotype and prognosis. The method expanded the clinical application of rs-fMRI and also contributed a new imaging analysis for brain tumor research.
MALINC1 an Immune-Related Long Non-Coding RNA Associated with Early-Stage Breast Cancer Progression
Authors: Fabre María Laura , Canzoneri Romina , Gurruchaga Agustina , Lee Jaeho , Tatineni Pradeep , Kil Hyunsuk , Lacunza Ezequiel , Aldaz C. Marcelo , Abba Martín Carlos
Published: June 2022

Long non-coding RNAs are increasingly being recognized as cancer biomarkers in various malignancies, acting as either tumor suppressors or oncogenes. The long non-coding MALINC1 intergenic RNA was identified as significantly upregulated in breast ductal carcinoma in situ. The aim of this study was to characterize MALINC1 expression, localization, and phenotypic and molecular effects in non-invasive and invasive breast cancer cells. We determined that MALINC1 is an estrogen–estrogen receptor-modulated lncRNA enriched in the cytoplasmic fraction of luminal A/B breast cancer cells that is associated with worse overall survival in patients with primary invasive breast carcinomas. Transcriptomic studies in normal and DCIS cells identified the main signaling pathways modulated by MALINC1, which mainly involve bioprocesses related to innate and adaptive immune responses, extracellular matrix remodeling, cell adhesion, and activation of AP-1 signaling pathway. We determined that MALINC1 induces premalignant phenotypic changes by increasing cell migration in normal breast cells. Moreover, high MALINC1 expression in invasive carcinomas was associated with a pro-tumorigenic immune environment and a favorable predicted response to immunotherapy both in luminal and basal-like subtypes compared with low-MALINC1-expression tumors. We conclude that MALINC1 behaves as an oncogenic and immune-related lncRNA involved with early-stage breast cancer progression.
Role of Intraparotid and Neck Lymph Node Metastasis in Primary Parotid Cancer Surgery: A Population-Based Analysis
Authors: Kouka Mussab , Koehler Benjamin , Buentzel Jens , Kaftan Holger , Boeger Daniel , Mueller Andreas H. , Wittig Andrea , Schultze-Mosgau Stefan , Ernst Thomas , Schlattmann Peter , Guntinas-Lichius Orlando
Published: June 2022

This population-based study investigated the prognostic role of intraparotid (PAR) and cervical lymph node (LN) metastasis on overall survival (OS) of primary parotid cancer. All 345 patients (median age: 66 years; 43% female, 49% N+, 31% stage IV) of the Thuringian cancer registries with parotid cancer from 1996 to 2016 were included. OS was assessed in relation to the total number of removed PAR and cervical LN, number of positive intraparotid (PAR+), positive cervical LN, LN ratio, log odds of positive LN (LODDS), as well as including the PAR as LODDS-PAR. PAR was assessed in 42% of the patients (22% of these PAR+). T and N classification were not independent predictors of OS. When combining T with LODDS instead of N, higher T (T3/T4) became a prognosticator (hazard ratio (HR) = 2.588; CI = 1.329–5.040; p = 0.005) but not LODDS (p > 0.05). When combining T classification with LODDS-PAR, both higher T classification (HR = 2.256; CI = 1.288–3.950; p = 0.004) and the alternative classification with LODDS-PAR (≥median −1.11; HR 2.078; CI = 1.155–3.739; p = 0.015) became independent predictors of worse OS. LODDS-PAR was the only independent prognosticator out of the LN assessment for primary parotid cancer.
Somatic Mutations in Exon 7 of the TP53 Gene in Index Colorectal Lesions Are Associated with the Early Occurrence of Metachronous Adenoma
Authors: Hálková Tereza , Ptáčková Renata , Semyakina Anastasiya , Suchánek Štěpán , Traboulsi Eva , Ngo Ondřej , Hejcmanová Kateřina , Májek Ondřej , Bureš Jan , Zavoral Miroslav , Minárik Marek , Benešová Lucie
Published: June 2022

(1) Background: this prospective study was focused on detailed analysis of the mutation heterogeneity in colorectal lesions removed during baseline (index) colonoscopy to identify patients at high risk of early occurrence of metachronous adenomas. (2) Methods: a total of 120 patients after endoscopic therapy of advanced colorectal neoplasia size ≥10 mm (index lesion) with subsequent surveillance colonoscopy after 10–18 months were included. In total, 143 index lesions and 84 synchronous lesions in paraffin blocks were divided into up to 30 samples. In each of them, the detection of somatic mutations in 11 hot spot gene loci was performed. Statistical analysis to correlate the mutation profiles and the degree of heterogeneity of the lesions with the risk of metachronous adenoma occurrence was undertaken. (3) Results: mutation in exon 7 of the TP53 gene found in the index lesion significantly correlated with the early occurrence of metachronous adenoma (log-rank test p = 0.003, hazard ratio 2.73, 95% confidence interval 1.14–6.56). We did not find an association between the risk of metachronous adenomas and other markers monitored. (4) Conclusions: the findings of this study could lead to an adjustment of existing recommendations for surveillance colonoscopies in a specific group of patients with mutations in exon 7 of the TP53 gene in an index lesion, where a shortening of surveillance interval may be warranted.
Enhancer of Zeste Homolog 2 (EZH2) Is a Marker of High-Grade Neuroendocrine Neoplasia in Gastroenteropancreatic and Pulmonary Tract and Predicts Poor Prognosis
Authors: Bremer Sebastian C. B. , Bittner Gabi , Elakad Omar , Dinter Helen , Gaedcke Jochen , König Alexander O. , Amanzada Ahmad , Ellenrieder Volker , Freiherr von Hammerstein-Equord Alexander , Ströbel Philipp , Bohnenberger Hanibal
Published: June 2022

Tumor grading is a robust prognostic predictor in patients with neuroendocrine neoplasms (NEN) and guides therapy, especially in tumors with high proliferation. NEN can be separated into well-differentiated and poorly differentiated types. The more aggressive NEN have been further separated into neuroendocrine tumors (NET G3) with a better prognosis and neuroendocrine carcinomas (NEC) with a worse prognosis. Despite this distinction’s tremendous clinical and therapeutic relevance, optimal diagnostic biomarkers are still lacking. In this study, we analyzed the protein expression and prognostic impact of Enhancer of Zeste Homolog 2 (EZH2) by immunohistochemistry in 219 tissue samples of gastroenteropancreatic (GEP-NEN) and pulmonary NEN (P-NEN). EZH2 was almost exclusively expressed in NEN with a proliferation rate above 20% (G3), while all low-grade tumors were nearly negative. Among high-grade NEN, 65% showed high and 35% low expression of EZH2. In this group, the high expression of EZH2 was significantly associated with poor overall survival and NEC histology. Interestingly, EZH2 seems to act independently of Polycomb Repressive Complex 2 (PRC2) in NEN. In conclusion, we propose EZH2 as a robust biomarker for distinguishing between NET G3 and NEC among gastroenteropancreatic and pulmonary NEN.
The Prognostic Reliability of Lymphovascular Invasion for Patients with T3N0 Colorectal Cancer in Adjuvant Chemotherapy Decision Making
Authors: Lee Hayoung , Yoo Seung-Yeon , Park In Ja , Hong Seung-Mo , Lim Seok-Byung , Yu Chang Sik , Kim Jin Cheon
Published: June 2022

Lymphovascular invasion (LVI) is a high-risk feature guiding decision making for adjuvant chemotherapy. We evaluated the prognostic importance and reliability of LVI as an adjuvant chemotherapy indicator in 1634 patients with pT3N0 colorectal cancer treated with curative radical resection between 2012 and 2016. LVI and perineural invasion (PNI) were identified in 382 (23.5%) and 269 (16.5%) patients, respectively. In total, 772 patients received adjuvant chemotherapy. The five-year recurrence-free survival (RFS) and OS rates were 92% and 94.8%, respectively. Preoperative obstruction, PNI, and positive margins were significantly associated with RFS and OS; however, adjuvant chemotherapy and LVI were not. Pathologic slide central reviews of 242 patients using dual D2-40 and CD31 immunohistochemical staining was performed. In the review cohort, the diagnosis of LVI and PNI was changed in 82 (33.9%) and 61 (25.2%) patients, respectively. Reviewed LVI, encompassing small vessel invasion, lymphatic invasion, and large vessel invasion, was not an independent risk factor associated with OS but was related to RFS. The prognostic importance of LVI and adjuvant chemotherapy was not defined because LVI may be underrecognized in pathologic diagnoses using hematoxylin and eosin staining slides only, leading to low recurrence rate predictions. Using LVI as a guiding factor for adjuvant chemotherapy requires further consideration.
Taxifolin and Lucidin as Potential E6 Protein Inhibitors: p53 Function Re-Establishment and Apoptosis Induction in Cervical Cancer Cells
Authors: Gomes Diana , Yaduvanshi Shivani , Silvestre Samuel , Duarte Ana Paula , Santos Adriana O. , Soares Christiane P. , Kumar Veerendra , Passarinha Luís , Sousa Ângela
Published: June 2022

Cervical cancer is the fourth leading cause of death in women worldwide, with 99% of cases associated with a human papillomavirus (HPV) infection. Given that HPV prophylactic vaccines do not exert a therapeutic effect in individuals previously infected, have low coverage of all HPV types, and have poor accessibility in developing countries, it is unlikely that HPV-associated cancers will be eradicated in the coming years. Therefore, there is an emerging need for the development of anti-HPV drugs. Considering HPV E6’s oncogenic role, this protein has been proposed as a relevant target for cancer treatment. In the present work, we employed in silico tools to discover potential E6 inhibitors, as well as biochemical and cellular assays to understand the action of selected compounds in HPV-positive cells (Caski and HeLa) vs. HPV-negative (C33A) and non-carcinogenic (NHEK) cell lines. In fact, by molecular docking and molecular dynamics simulations, we found three phenolic compounds able to dock in the E6AP binding pocket of the E6 protein. In particular, lucidin and taxifolin were able to inhibit E6-mediated p53 degradation, selectively reduce the viability, and induce apoptosis in HPV-positive cells. Altogether, our data can be relevant for discovering promising leads for the development of specific anti-HPV drugs.
PET-CT in Clinical Adult Oncology—VI. Primary Cutaneous Cancer, Sarcomas and Neuroendocrine Tumors
Authors: Fine Gabriel C. , Covington Matthew F. , Koppula Bhasker R. , Salem Ahmed Ebada , Wiggins Richard H. , Hoffman John M. , Morton Kathryn A.
Published: June 2022

PET-CT is an advanced imaging modality with many oncologic applications, including staging, therapeutic assessment, restaging and surveillance for recurrence. The goal of this series of six review articles is to provide practical information to providers and imaging professionals regarding the best use of PET-CT for specific oncologic indications, the potential pitfalls and nuances that characterize these applications, and guidelines for image interpretation. Tumor-specific clinical information and representative PET-CT images are provided. The current, sixth article in this series addresses PET-CT in an evaluation of aggressive cutaneous malignancies, sarcomas and neuroendocrine tumors. A discussion of the role of FDG PET for all types of tumors in these categories is beyond the scope of this review. Rather, this article focuses on the most common malignancies in adult patients encountered in clinical practice. It also focuses on Food and Drug Agency (FDA)-approved and clinically available radiopharmaceuticals rather than research tracers or those requiring a local cyclotron. This information will serve as a guide to primary providers for the appropriate role of PET-CT in managing patients with cutaneous malignancies, sarcomas and neuroendocrine tumors. The nuances of PET-CT interpretation as a practical guide for imaging providers, including radiologists, nuclear medicine physicians and their trainees, are also addressed.
Non-Melanoma Skin Cancer Clearance after Medical Treatment Detected with Noninvasive Skin Imaging: A Systematic Review and Meta-Analysis
Authors: Guida Stefania , Alma Antonio , Shaniko Kaleci , Chester Johanna , Ciardo Silvana , Proietti Ilaria , Giuffrida Roberta , Zalaudek Iris , Manfredini Marco , Longo Caterina , Farnetani Francesca , Pellacani Giovanni
Published: June 2022

Background/Objectives: Non-melanoma skin cancer (NMSC) treated with nonsurgical therapies can be monitored with noninvasive skin imaging. The precision of dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in detecting clearance is unclear. We aim to report the proportion of persisting tumors identified with noninvasive technologies available in the literature. Methods: A systematic literature search was conducted on the PubMed and Cochrane Public Library Databases for articles published prior to November 2021. Statistical analyses were conducted with MedCalc 14.8.1 software. Results: A total of eight studies (352 lesions) reporting noninvasive imaging for NMSC clearance following nonsurgical treatment were included. Most (n = 7) reported basal cell carcinoma (BCC), and one study reported squamous cell carcinoma (SCC) clearance. A meta-analysis of the BCC clearance revealed that the summary effect for RCM was higher, as compared to the other techniques. Interestingly, the sensitivity and specificity for OCT were 86.4% (95% CI: 65.1–97.1) and 100% (95% CI: 94.8–100.0), respectively, whilst, for RCM, they reached 100% (95%CI: 86.8–100) and 72.5% (95% CI: 64.4–79.7), respectively. Conclusions: Routine clinical examination and dermoscopy underperform when employed for NMSC clearance monitoring, although they represent the first approach to the patient. OCT and RCM seem to improve the detection of persistent BCC after medical treatment.
Genome-Wide Meta-Analysis Identifies Variants in DSCAM and PDLIM3 That Correlate with Efficacy Outcomes in Metastatic Renal Cell Carcinoma Patients Treated with Sunitinib
Authors: Diekstra Meta H. M. , Swen Jesse J. , van der Zanden Loes F. M. , Vermeulen Sita H. , Boven Epie , Mathijssen Ron H. J. , Fukunaga Koya , Mushiroda Taisei , Hongo Fumiya , Oosterwijk Egbert , Cambon-Thomsen Anne , Castellano Daniel , Fritsch Achim , Donas Jesus Garcia , Rodriguez-Antona Cristina , Ruijtenbeek Rob , Radu Marius T. , Eisen Tim , Junker Kerstin , Roessler Max , Jaehde Ulrich , Miki Tsuneharu , Böhringer Stefan , Kubo Michiaki , Kiemeney Lambertus A. L. M. , Guchelaar Henk-Jan
Published: June 2022

Individual response to sunitinib in metastatic renal cell carcinoma (mRCC) patients is highly variable. Earlier, sunitinib outcome was related to single nucleotide polymorphisms (SNPs) in CYP3A5 and ABCB1. Our aim is to provide novel insights into biological mechanisms underlying sunitinib action. We included mRCC patients from the European EuroTARGET consortium (n = 550) and the RIKEN cohort in Japan (n = 204) which were analysed separately and in a meta-analysis of genome-wide association studies (GWAS). SNPs were tested for association with progression-free survival (PFS) and overall survival (OS) using Cox regression. Summary statistics were combined using a fixed effect meta-analysis. SNP rs28520013 in PDLIM3 and the correlated SNPs rs2205096 and rs111356738 both in DSCAM, showed genome-wide significance (p < 5 × 10−8) with PFS and OS in the meta-analysis. The variant T-allele of rs28520013 associated with an inferior PFS of 5.1 months compared to 12.5 months in non-carriers (p = 4.02 × 10−10, HR = 7.26). T-allele carriers of rs28520013 showed an inferior OS of 6.9 months versus 30.2 months in non-carriers (p = 1.62 × 10−8, HR = 5.96). In this GWAS we identified novel genetic variants in PDLIM3 and DSCAM that impact PFS and OS in mRCC patients receiving sunitinib. The underlying link between the identified genes and the molecular mechanisms of sunitinib action needs to be elucidated.
Diabetes Mellitus and Pancreatic Ductal Adenocarcinoma—Prevalence, Clinicopathological Variables, and Clinical Outcomes
Authors: Badowska-Kozakiewicz Anna , Fudalej Marta , Kwaśniewska Daria , Durlik Marek , Nasierowska-Guttmejer Anna , Mormul Agata , Włoszek Emilia , Czerw Aleksandra , Banaś Tomasz , Deptała Andrzej
Published: June 2022

Background: pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer-related deaths with increasing incidence and link to the onset of diabetes mellitus (DM). The aim of this study is to describe the prevalence of DM among patients with the diagnosis of PDAC, analyse the association between the occurrence of DM and clinicopathological factors, and detect variables influencing overall survival. Methods: a retrospective analysis of medical records was performed. The patients were divided into non-DM (n = 101) and DM (n = 74) groups. Statistical analysis with the usage of appropriate tests was conducted. Results: Patients in the groups of DM and NODM had significantly longer median OS than the non-DM group. Nodal involvement, tumour location, level of CEA, CRP and CRP/lymphocytes ratio were significantly associated with OS among patients with any type of DM. Neutropenia was less frequently observed in the DM group. Conclusions: DM is prevalent among patients with pancreatic cancer. In our study, patients with DM receiving palliative chemotherapy had significantly higher median OS than those without DM. The increased comprehension of the mechanisms of the relationship between DM and pancreatic cancer needs further research, which might provide avenues for the development of novel preventive and therapeutic strategies.
Metabolomic Analysis Points to Bioactive Lipid Species and Acireductone Dioxygenase 1 (ADI1) as Potential Therapeutic Targets in Poor Prognosis Endometrial Cancer
Authors: Gatius Sònia , Jove Mariona , Megino-Luque Cristina , Albertí-Valls Manel , Yeramian Andree , Bonifaci Nuria , Piñol Miquel , Santacana Maria , Pradas Irene , Llobet-Navas David , Pamplona Reinald , Matías-Guiu Xavier , Eritja Núria
Published: June 2022

Metabolomic profiling analysis has the potential to highlight new molecules and cellular pathways that may serve as potential therapeutic targets for disease treatment. In this study, we used an LC-MS/MS platform to define, for the first time, the specific metabolomic signature of uterine serous carcinoma (SC), a relatively rare and aggressive variant of endometrial cancer (EC) responsible for 40% of all endometrial cancer-related deaths. A metabolomic analysis of 31 ECs (20 endometrial endometrioid carcinomas (EECs) and 11 SCs) was performed. Following multivariate statistical analysis, we identified 232 statistically different metabolites among the SC and EEC patient samples. Notably, most of the metabolites identified (89.2%) were lipid species and showed lower levels in SCs when compared to EECs. In addition to lipids, we also documented metabolites belonging to amino acids and purine nucleotides (such as 2-Oxo-4-methylthiobutanoic acid, synthesised by acireductone dioxygenase 1 (ADI1) enzyme), which showed higher levels in SCs. To further investigate the role of ADI1 in SC, we analysed the expression protein levels of ADI1 in 96 ECs (67 EECs and 29 SCs), proving that the levels of ADI1 were higher in SCs compared to EECs. We also found that ADI1 mRNA levels were higher in p53 abnormal ECs compared to p53 wild type tumours. Furthermore, elevated ADI1 mRNA levels showed a statistically significant negative correlation with overall survival and progression-free survival among EEC patients. Finally, we tested the ability of ADI1 to induce migration and invasion capabilities in EC cell lines. Altogether, these results suggest that ADI1 could be a potential therapeutic target in poor-prognosis SCs and other Ecs with abnormal p53 expression.
The Impact of Cancer-Related Fatigue on HRQOL in Survivors of Childhood Cancer: A DCCSS LATER Study
Authors: Penson Adriaan , Walraven Iris , Bronkhorst Ewald , Maurice-Stam Heleen , Grootenhuis Martha A. , Van der Heiden-van der Loo Margriet , Tissing Wim J. E. , Van der Pal Helena J. H. , De Vries Andrica C. H. , Bresters Dorine , Ronckers Cécile , Van den Heuvel Marry M. , Neggers Sebastian J. C. M. M. , Versluys Birgitta A. B. , Louwerens Marloes , Pluijm Saskia M. F. , Kremer Leontien C. M. , Blijlevens Nicole , Van Dulmen-den Broeder Eline , Knoop Hans , Loonen Jacqueline
Published: June 2022

Background: Early detection and management of late effects of treatment and their impact on health-related quality of life (HRQOL) has become a key goal of childhood cancer survivorship care. One of the most prevalent late effects is chronic fatigue (CF). The current study aimed to investigate the association between CF and HRQOL in a nationwide cohort of CCS. Methods: Participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort, a nationwide cohort of CCS. Participants completed the Checklist Individual Strength (CIS) to indicate CF (CIS fatigue severity subscale ≥ 35 and duration of symptoms ≥6 months) and the Short Form-36 (SF-36) and TNO (Netherlands Organization for Applied Scientific Research) and AZL (Leiden University Medical Centre) Adult’s Health-Related Quality of Life questionnaire (TAAQOL) as measures for HRQOL. Differences in mean HRQOL domain scores between CF and non-CF participants were investigated using independent samples t-tests and ANCOVA to adjust for age and sex. The association between CF and impaired HRQOL (scoring ≥ 2 SD below the population norm) was investigated using logistic regression analyses, adjusting for confounders. Results: A total of 1695 participants were included in the study. Mean HRQOL domain scores were significantly lower in participants with CF. In addition, CF was associated with impaired HRQOL on all of the domains (except physical functioning) with adjusted odds ratios ranging from 2.1 (95% CI 1.3–3.4; sexuality domain) to 30.4 (95% CI 16.4–56.2; vitality domain). Conclusions: CF is associated with impaired HRQOL, urging for the screening and regular monitoring of fatigue, and developing possible preventative programs and interventions.
Role of Peritoneal Mesothelial Cells in the Progression of Peritoneal Metastases
Authors: Li Junliang , Guo Tiankang
Published: June 2022

Peritoneal metastatic cancer comprises a heterogeneous group of primary tumors that originate in the peritoneal cavity or metastasize into the peritoneal cavity from a different origin. Metastasis is a characteristic of end-stage disease, often indicative of a poor prognosis with limited treatment options. Peritoneal mesothelial cells (PMCs) are a thin layer of cells present on the surface of the peritoneum. They display differentiated characteristics in embryonic development and adults, representing the first cell layer encountering peritoneal tumors to affect their progression. PMCs have been traditionally considered a barrier to the intraperitoneal implantation and metastasis of tumors; however, recent studies indicate that PMCs can either inhibit or actively promote tumor progression through distinct mechanisms. This article presents a review of the role of PMCs in the progression of peritoneum implanted tumors, offering new ideas for therapeutic targets and related research.
Liquid Biopsy in Head and Neck Cancer: Current Evidence and Future Perspective on Squamous Cell, Salivary Gland, Paranasal Sinus and Nasopharyngeal Cancers
Authors: Cabezas-Camarero Santiago , Pérez-Segura Pedro
Published: June 2022

Head and neck cancer (HNC) is currently the sixth most common solid malignancy, accounting for a 50% five-year mortality rate. In the past decade, substantial improvements in understanding its molecular biology have allowed for a growing development of new biomarkers. Among these, the field of liquid biopsy has seen a sustained growth in HNC, demonstrating the feasibility to detect different liquid biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTC), extracellular vesicles and microRNAs. Liquid biopsy has been studied in HPV-negative squamous cell carcinoma of the head and neck (SCCHN) but also in other subentities such as HPV-related SCCHN, EBV-positive nasopharyngeal cancer and oncogene-driven salivary gland cancers. However, future studies should be internally and externally validated, and ideally, clinical trials should incorporate the use of liquid biomarkers as endpoints in order to prospectively demonstrate their role in HNC. A thorough review of the current evidence on liquid biopsy in HNC as well as its prospects will be conducted.
Interface Synergistic Effect from Hierarchically Porous Cu(OH)2@FCN MOF/CF Nanosheet Arrays Boosting Electrocatalytic Oxygen Evolution
Authors: Li Xue , Zheng Yinan , Yao Hu , Bai Jiayu , Yue Siliang , Guo Xiaohui
Published: June 2022

The electrolysis of water is an efficient and environmentally friendly technology for large-scale hydrogen production. However, the oxygen evolution reaction (OER) involves a multi-electron–proton coupling transfer step that limits the efficiency of water splitting. Therefore, there is an urgent need to develop electrocatalysts with expected activity and stability to accelerate the kinetics of the oxygen evolution reaction. In this paper, hierarchically porous Cu(OH)2@(Fe, Co, Ni)MOF/CF nanosheet (denoted as Cu(OH)2@FCN MOF/CF) arrays were successfully prepared by the hydrothermally induced in situ growth of FCN MOF nanosheets using modified Cu(OH)2 nanowires as carriers; herein, the tuned active species of metal ligands in the FCN MOF composition structure are used as the main catalytic reaction size in the OER. The synergistic effect of a unique porous structure and the active metal-ligand species in the MOF render the catalyst a large electrochemically active surface area and more active species. Then, the active material is fully contacted with the electrolyte to expose more electrochemically active sites, thus greatly improving the electrocatalytic activity and durability of the OER. Specifically, the Cu(OH)2@FCN MOF/CF delivers a minimum overpotential of 290 mV and low Tafel slope of 96.15 mV·dec−1 at 10 mA·cm−2 as well as ultra-long cycling stability. The resulted OER performance is superior to most reported MOF-based electrocatalysts. This novel structural design not only provides a new strategy for the facile preparation of low-cost and high-efficiency OER electrocatalysts but also paves an avenue for the development of other MOF-based composite electrocatalysts with excellent electrocatalytic performances.
Magnetic Sulfonated Melamine-Formaldehyde Resin as an Efficient Catalyst for the Synthesis of Antioxidant and Antimicrobial Pyrazolone Derivatives
Authors: Nezhad Shefa Mirani , Pourmousavi Seied Ali , Zare Ehsan Nazarzadeh , Heidari Golnaz , Makvandi Pooyan
Published: June 2022

Sulfonated polymer-based materials, among heterogeneous catalysts, are frequently utilized in chemical transformations due to their outstanding chemical and physical durability. In this regard, a magnetic sulfonated melamine–formaldehyde resin (MSMF) catalyst was successfully prepared from a mixture of sulfonated melamine–formaldehyde and Fe3O4 nanoparticles in two steps. MSMF was used as a heterogeneous catalyst for the one-pot, three-component condensation of benzyl pyrazolyl naphthoquinones in water as a green solvent and 4-[(indol-3-yl)-arylmethyl]-1-phenyl-3-methyl-5-pyrazolones. The antimicrobial and antioxidant activities of catalyst, benzyl pyrazolyl naphthoquinones, and 4-[(indol-3-yl)-arylmethyl]-1-phenyl-3-methyl-5-pyrazolones were evaluated using agar disk-diffusion and DPPH assays, respectively. The antioxidant activity of the catalyst and 4-[(indol-3-yl)-arylmethyl]-1-phenyl-3-methyl-5-pyrazolones was found to be 75% and 90%, respectively. Furthermore, catalyst, benzyl pyrazolyl naphthoquinones, and 4-[(indol-3-yl)-arylmethyl]-1-phenyl-3-methyl-5-pyrazolones exhibited antimicrobial activity against Staphylococcus aureus and Escherichia coli. In conclusion, MSMF is a superior catalyst for green chemical processes, owing to its high catalytic activity, stability, and reusability.