bluuebunny/crossref_metadata_2025 huggingface dataset:
The Neuroprotective Effects of Cannabis-Derived Phytocannabinoids and Resveratrol in Parkinson’s Disease: A Systematic Literature Review of Pre-Clinical Studies
Authors: Prakash Samay , Carter Wayne G.
Published: November 2021

Currently, there are no pharmacological treatments able to reverse nigral degeneration in Parkinson’s disease (PD), hence the unmet need for the provision of neuroprotective agents. Cannabis-derived phytocannabinoids (CDCs) and resveratrol (RSV) may be useful neuroprotective agents for PD due to their anti-oxidative and anti-inflammatory properties. To evaluate this, we undertook a systematic review of the scientific literature to assess the neuroprotective effects of CDCs and RSV treatments in pre-clinical in vivo animal models of PD. The literature databases MEDLINE, EMBASE, PsychINFO, PubMed, and Web of Science core collection were systematically searched to cover relevant studies. A total of 1034 publications were analyzed, of which 18 met the eligibility criteria for this review. Collectively, the majority of PD rodent studies demonstrated that treatment with CDCs or RSV produced a significant improvement in motor function and mitigated the loss of dopaminergic neurons. Biochemical analysis of rodent brain tissue suggested that neuroprotection was mediated by anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms. This review highlights the neuroprotective potential of CDCs and RSV for in vivo models of PD and therefore suggests their potential translation to human clinical trials to either ameliorate PD progression and/or be implemented as a prophylactic means to reduce the risk of development of PD.
Bond of Ribbed Steel Bar in High-Performance Steel Fiber Reinforced Expanded-Shale Lightweight Concrete
Authors: Zhao Mingshuang , Liu Guirong , Liu Lingli , Zhang Yanyan , Shi Kang , Zhao Shunbo
Published: November 2021

For the structural application of high-performance Steel Fiber Reinforced Expanded-shale Lightweight Concrete (SFRELC), a reliable bond of ribbed steel bar should be ensured. In this paper, an experimental study was carried out on the bond properties of ribbed steel bar embedded in SFRELC by the direct pull-out test. The SFRELC was produced with a strength grade of 35 MPa and a volume fraction of steel fiber as 0%, 0.8%, 1.2%, 1.6% and 2.0%, respectively. Fifteen groups of specimens were made with a central placed steel bar with diameter of 14 mm, 20 mm and 28 mm, respectively. Complete bond stress-slip curves were determined for each group of specimens, and the characteristic values of bond-stress and slip at key points of the curves were ascertained. Results show that the bond strength, peak-slip and residual bond strength increased with the increase of the volume fraction of steel fiber. With the increase of steel bar diameter, bond strength decreased while the peak-slip increased, and the descending curves became sharp with a decreased residual bond strength. Formulas for calculating the bond strength and peak-slip were proposed. The relationships were determined for the splitting bond strength, residual bond strength with the bond strength, the splitting bond slip and residual bond slip with the peak-slip. Combined with rational fitting analyses of bond strength and slip, a constitutive model was selected for predicting the bond stress-slip of ribbed steel bar in SFRELC.
Experimental Investigation of Unconfined Compressive Properties of Artificial Ice as a Green Building Material for Rinks
Authors: Zhang Wenyuan , Li Junxing , Yuan Baojiang , Wang Lin , Yang Qiyong
Published: November 2021

The construction of a prefabricated ice rink has recently attracted considerable interest owing to its detachability, short building period, and high cooling efficiency, among other benefits. Characterizing the compressive properties of an artificial ice sheet is crucial in the design, operation, and maintenance stages of the rink. Several uniaxial compressive tests were conducted in the present work to better understand the mechanical behavior of artificial ice in winter sports rinks. The artificial ice was produced using homemade equipment to simulate the real ice-making conditions in the rink. Comprehensive conditions such as strain rate, ice temperature, ice-making method, water quality, air temperature and humidity were considered in the experiments. The obtained results show that the compressive behavior of artificial ice is considerably affected by the strain rate and ice temperature, and slightly affected by the ice-making method and water quality, whereas the effects of air temperature and humidity are inconclusive. The identified range of strain rate for ductile-brittle transition was within 8.3 × 10−5 s–1 and 8.3 × 10−4 s−1, in which the strength reaches a maximum value at 1.7 × 10–4 s−1. The influencing factors on the compressive strength and effective modulus were analyzed based on the experimental observations, and fitting functions were established to describe the relationships. The results of this study will hopefully provide a reference for the design and optimization of ice rinks, particularly for prefabricated rinks.
Plan for the Sustainability of Public Buildings through the Energy Efficiency Certification System: Case Study of Public Sports Facilities, Korea
Authors: Baek Seon Gyeong
Published: November 2021

This study examines strategies for energy efficiency in public buildings in Korea and the implementation of certification systems. It also identifies the actual plan status and discusses improvements at the institutional level. The target is the national sports centers, where the discussion on energy efficiency has been assiduous, as they have recently expanded regionally in Korea. Among the 541 national sports centers in Korea, 90 facilities for which a preliminary review was performed on the plan by the National Public Building Center were analyzed. The energy efficiency plan is realized through Building Energy Efficiency, Zero Energy Building, and Green Standard for Energy and Environmental Design certifications. As a result of analyzing the plan status, omissions or errors in certification were confirmed in about 10% of each, even though more than 80% of the facilities were subject to mandatory application. In Korea’s condition, to revitalize the practice of the system, it is necessary to expand the government’s publicity and support initiatives, use differential application of evaluation items, and strengthen incentives. This study provides meaningful results and suggestions for implementing an energy efficiency system at the national level under similar conditions in the future.
An Assessment Methodology for the Evaluation of the Impacts of the COVID-19 Pandemic on the Italian Housing Market Demand
Authors: Tajani Francesco , Liddo Felicia Di , Guarini Maria Rosaria , Ranieri Rossana , Anelli Debora
Published: November 2021

Due to the forced changes that the COVID-19 pandemic has had in many aspects of ordinary life (working, social life, training and learning in schools etc.), the characteristics of domestic spaces have significantly modified buying, selling and renting decisions in the real estate market. The aim of this research was to structure a methodology, articulated into four steps, to assess the variation that has occurred in residential market demand as a result of COVID-19 anti-contagion measures, with regard to six metropolitan Italian cities. We considered two samples of properties for each city, the first referencing the pre-COVID-19 pandemic spread and the second collected in the current situation. Consequently, we were able to determine variations in residential market appreciations through the application of a regressive econometric technique. The obtained results highlighted the relevance assumed by indoor acoustic and thermal comfort property factors, compared with the pre-COVID-19 condition. The proposed methodology could be useful to support the public and private entities involved in urban investment decision-making processes, allowing us to identify the most appreciated factors of the residential real estate market demand, in order to improve the conditions of existing and future assets and reduce the related risk levels.
Applications of Radiomics and Radiogenomics in High-Grade Gliomas in the Era of Precision Medicine
Authors: Fathi Kazerooni Anahita , Bagley Stephen J. , Akbari Hamed , Saxena Sanjay , Bagheri Sina , Guo Jun , Chawla Sanjeev , Nabavizadeh Ali , Mohan Suyash , Bakas Spyridon , Davatzikos Christos , Nasrallah MacLean P.
Published: November 2021

Machine learning (ML) integrated with medical imaging has introduced new perspectives in precision diagnostics of high-grade gliomas, through radiomics and radiogenomics. This has raised hopes for characterizing noninvasive and in vivo biomarkers for prediction of patient survival, tumor recurrence, and genomics and therefore encouraging treatments tailored to individualized needs. Characterization of tumor infiltration based on pre-operative multi-parametric magnetic resonance imaging (MP-MRI) scans may allow prediction of the loci of future tumor recurrence and thereby aid in planning the course of treatment for the patients, such as optimizing the extent of resection and the dose and target area of radiation. Imaging signatures of tumor genomics can help in identifying the patients who benefit from certain targeted therapies. Specifying molecular properties of gliomas and prediction of their changes over time and with treatment would allow optimization of treatment. In this article, we provide neuro-oncology, neuropathology, and computational perspectives on the promise of radiomics and radiogenomics for allowing personalized treatments of patients with gliomas and discuss the challenges and limitations of these methods in multi-institutional clinical trials and suggestions to mitigate the issues and the future directions.
Relationship between Treatment Plan Dosimetry, Toxicity, and Survival following Intensity-Modulated Radiotherapy, with or without Chemotherapy, for Stage III Inoperable Non-Small Cell Lung Cancer
Authors: Remmerts de Vries Isabel F. , Ronden Merle I. , Bahce Idris , Spoelstra Femke O. B. , De Haan Patricia F. , Haasbeek Cornelis J. A. , Lissenberg-Witte Birgit I. , Slotman Ben J. , Dahele Max , Verbakel Wilko F. A. R.
Published: November 2021

Concurrent chemoradiotherapy (cCRT) is the preferred treatment for stage III NSCLC because surgery containing multimodality treatment is often not appropriate. Alternatives, often for less fit patients, include sequential CRT and RT alone. Many reports describing the relationship between overall survival (OS), toxicity, and dosimetry are based on clinical trials, with strict criteria for patient selection. We performed an institutional analysis to study the relationship between dosimetric parameters, toxicity, and OS in inoperable patients with stage III NSCLC treated with (hybrid) IMRT/VMAT-based techniques in routine clinical practice. Eligible patients had undergone treatment with radical intent using cCRT, sCRT, or RT alone, planned to a total dose ≥ 50 Gy delivered in ≥15 fractions. All analyses were performed for two patient groups, (1) cCRT (n = 64) and (2) sCRT/RT (n = 65). The toxicity rate differences between the two groups were not significant, and OS was 29 and 17 months, respectively. For sCRT/RT, no dosimetric factors were associated with OS, whereas for cCRT, PTV-volume, esophagus V50 Gy, and contralateral lung V5 Gy were associated. cCRT OS was significantly lower in patients with esophagitis ≥ G2. The overall rate of ≥G3 pneumonitis was low (3%), and the rate of high-grade esophagitis the OS in this real-world patient population was comparable to those reported in clinical trials. Based on this hypothesis-generating data, more aggressive esophageal sparing merits consideration. Institutional auditing and benchmarking of the planning strategy, dosimetry, and outcome have an important role to play in the continuous quality improvement process.
Acceptability and Preliminary Efficacy of a Web- and Telephone-Based Personalised Exercise Intervention for Individuals with Metastatic Prostate Cancer: The ExerciseGuide Pilot Randomised Controlled Trial
Authors: Evans Holly E. L. , Galvão Daniel A. , Forbes Cynthia C. , Girard Danielle , Vandelanotte Corneel , Newton Robert U. , Vincent Andrew D. , Wittert Gary , Kichenadasse Ganessan , Chambers Suzanne , Brook Nicholas , Short Camille E.
Published: November 2021

Preliminary research has shown the effectiveness of supervised exercise-based interventions in alleviating sequela resulting from metastatic prostate cancer. However, many individuals encounter barriers that limit the uptake of face-to-face exercise. Technology-enabled interventions offer a distance-based alternative. This pilot study aimed to explore the acceptability, safety and preliminary efficacy of a web-based exercise intervention (ExerciseGuide) in individuals with metastatic prostate cancer. Forty participants (70.2 ± 8.5 years) with metastatic prostate cancer were randomised into the 8-week intervention (N = 20) or a wait-list control (N = 20). The intervention arm had access to a computer-tailored website, personalised exercise prescription and remote supervision. ExerciseGuide was deemed acceptable with a score ≥20 on the client satisfaction questionnaire; however, the usability score was just below the pre-specified score of ≥68 on the software usability scale. There were no serious adverse events reported. Moderate-to-vigorous physical activity levels between baseline and follow-ups were significantly higher (10.0 min per day; 95% CI = (1.3–18.6); p = 0.01) in the intervention group compared to wait-list control. There were also greater improvements in step count (1332; 95% CI = (159–2505); p = 0.02) and identified motivation (0.4, 95% CI = (0.0, 0.7); p = 0.04). Our findings provide preliminary evidence that ExerciseGuide is acceptable, safe and efficacious among individuals with metastatic prostate cancer.
The Clinical Feature and Treatment Outcome of Ocular Melanoma: A 34-Year Experience in a Tertiary Referral Center
Authors: Huang Yu-Yun , Hou Tzu-Yu , Yu Wei-Kuang , Tsai Chieh-Chih , Kao Shu-Ching , Hsu Wen-Ming , Liu Jui-Ling (Catherine)
Published: November 2021

Malignant melanoma can arise from melanocytes in various structures of the eye, orbit, and ocular adnexa. We reviewed the clinical features and long-term results of all subjects with histologically proved melanoma originating from any of the ocular and periocular structures in a tertiary referral center. Overall, 88 patients including 47 men were recruited. The tumor was primarily located in the uvea, followed by the conjunctiva, orbit, eyelid, and lacrimal sac. Patients with uveal melanoma were diagnosed at a relatively younger age (47.0 years), while those with orbital and eyelid melanomas were older at presentation (79.5 years and 78.5 years, respectively). The overall local recurrence rate was 9% at a median follow-up of 41.0 months, among which orbital and eyelid melanomas recurred most commonly. The overall mortality rate was 41% in a median duration of 27.2 months (IQR, 13–58 months) from diagnosis, with the highest for lacrimal sac melanoma, followed by melanoma of the orbit, uveal, conjunctiva, and eyelid. Despite prompt local control, the risk for metastasis and mortality was high. Therefore, efficient modalities for early diagnosis and treatment of ocular melanoma are necessary.
Identification of Key Genes Associated with Progression and Prognosis of Bladder Cancer through Integrated Bioinformatics Analysis
Authors: Verma Shiv , Shankar Eswar , Lin Spencer , Singh Vaibhav , Chan E. Ricky , Cao Shufen , Fu Pingfu , MacLennan Gregory T. , Ponsky Lee E. , Gupta Sanjay
Published: November 2021

Bladder cancer prognosis remains dismal due to lack of appropriate biomarkers that can predict its progression. The study aims to identify novel prognostic biomarkers associated with the progression of bladder cancer by utilizing three Gene Expression Omnibus (GEO) datasets to screen differentially expressed genes (DEGs). A total of 1516 DEGs were identified between non-muscle invasive and muscle invasive bladder cancer specimens. To identify genes of prognostic value, we performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A total of seven genes, including CDKN2A, CDC20, CTSV, FOXM1, MAGEA6, KRT23, and S100A9 were confirmed with strong prognostic values in bladder cancer and validated by qRT-PCR conducted in various human bladder cancer cells representing stage-specific disease progression. ULCAN, human protein atlas and The Cancer Genome Atlas datasets were used to confirm the predictive value of these genes in bladder cancer progression. Moreover, Kaplan–Meier analysis and Cox hazard ratio analysis were performed to determine the prognostic role of these genes. Univariate analysis performed on a validation set identified a 3-panel gene set viz. CDKN2A, CTSV and FOXM1 with 95.5% sensitivity and 100% specificity in predicting bladder cancer progression. In summary, our study screened and confirmed a 3-panel biomarker that could accurately predict the progression and prognosis of bladder cancer.
Prognostic Factors for Contralateral Recurrence of Upper Tract Urothelial Carcinoma after Nephroureterectomy: A Large Multiregional Study
Authors: Chien Tsu-Ming , Lee Hsiang-Ying , Singla Nirmish , Margulis Vitaly , Lotan Yair , Woldu Solomon Lukasz , Huang Chun-Nung , Li Ching-Chia , Ke Hung-Lung , Li Wei-Ming , Li Chia-Yang , Huang A-Mei , Yang Sheau-Fang , Tu Hung-Pin , Wu Wen-Jeng , Yeh Hsin-Chih
Published: November 2021

This study aimed to examine the prognostic significance of preoperative inflammation-associated blood cell markers in the metachronous contralateral recurrence of upper tract urothelial carcinoma (UTUC). Patients with nonmetastatic UTUC treated in Taiwan and the U.S. between 1990 and 2017 were included. The Kaplan–Meier method was used to calculate the contralateral recurrence rate, and multivariate logistic regression was performed to study the association of blood cell markers and clinicopathological characteristics with contralateral recurrence. Overall, a total of 1039 patients were included in this study, 52 of whom (5.0%) developed metachronous recurrence of the contralateral side. Kaplan–Meier analysis indicated that a history of bladder cancer (p = 0.006), multiple tumors (p = 0.016), advanced chronic kidney disease (CKD; p < 0.001), elevated serum white blood cell (WBC) count (p < 0.001), and decreased hemoglobin levels (p = 0.001) significantly reduced the contralateral recurrence-free survival. Multivariate analysis showed that multiple tumors (hazard ratio (HR), 1.87; p = 0.030), advanced CKD (HR, 2.63; p = 0.002) and increased WBC count (HR, 2.60; p = 0.001) were independent risk factors for higher contralateral recurrence rate. Notably, advanced CKD was a significant factor regardless of the patient’s region. In summary, multiple tumors, advanced CKD and elevated serum WBC count are independent predictors of contralateral recurrence in patients with UTUC. It is recommended that patients with these adverse characteristics be closely followed up to monitor the opposite upper urinary tract.
Orai3 Regulates Pancreatic Cancer Metastasis by Encoding a Functional Store Operated Calcium Entry Channel
Authors: Arora Samriddhi , Tanwar Jyoti , Sharma Nutan , Saurav Suman , Motiani Rajender K.
Published: November 2021

Store operated Ca2+ entry (SOCE) mediated by Orai1/2/3 channels is a highly regulated and ubiquitous Ca2+ influx pathway. Although the role of Orai1 channels is well studied, the significance of Orai2/3 channels is still emerging in nature. In this study, we performed extensive bioinformatic analysis of publicly available datasets and observed that Orai3 expression is inversely associated with the mean survival time of PC patients. Orai3 expression analysis in a battery of PC cell lines corroborated its differential expression profile. We then carried out thorough Ca2+ imaging experiments in six PC cell lines and found that Orai3 forms a functional SOCE channel in PC cells. Our in vitro functional assays show that Orai3 regulates PC cell cycle progression, apoptosis and migration. Most importantly, our in vivo xenograft studies demonstrate a critical role of Orai3 in PC tumor growth and secondary metastasis. Mechanistically, Orai3 controls G1 phase progression, matrix metalloproteinase expression and epithelial-mesenchymal transition in PC cells. Taken together, this study for the first-time reports that Orai3 drives aggressive phenotypes of PC cells, i.e., migration in vitro and metastasis in vivo. Considering that Orai3 overexpression leads to poor prognosis in PC patients, it appears to be a highly attractive therapeutic target.
Indoor Tanning and the Risk of Overall and Early-Onset Melanoma and Non-Melanoma Skin Cancer: Systematic Review and Meta-Analysis
Authors: An Seokyung , Kim Kyungsik , Moon Sungji , Ko Kwang-Pil , Kim Inah , Lee Jung Eun , Park Sue K.
Published: November 2021

The aim of this study was to examine the association between indoor tanning use and the risk of overall and early-onset (age < 50) melanoma and non-melanoma skin cancer (NMSC). To evaluate the association between indoor tanning and skin cancer, a systematic review of the literature published until July 2021 was performed using PubMed, EMBASE, and MEDLINE. Summary relative risk (RR) from 18 studies with 10,406 NMSC cases and 36 studies with 14,583 melanoma cases showed significant association between skin cancer and indoor tanning (melanoma, RR= 1.27, 95% CI 1.16–1.39; NMSC, RR = 1.40, 95% CI 1.18–1.65; squamous cell carcinoma (SCC), RR = 1.58, 95% CI 1.38–1.81; basal cell carcinoma (BCC), RR = 1.24, 95% CI 1.00–1.55). The risk was more pronounced in early-onset skin cancer (melanoma, RR = 1.75, 95% CI 1.14–2.69; NMSC, RR = 1.99, 95% CI 1.48–2.68; SCC, RR = 1.81, 95% CI 1.38–2.37; BCC, RR = 1.75, 95% CI 1.15–2.77). Moreover, first exposure at an early age (age ≤ 20 years) and higher exposure (annual frequency ≥ 10 times) to indoor tanning showed increasing risk for melanoma (RR = 1.47, 95% CI 1.16–1.85; RR = 1.52, 1.22–1.89) and NMSC (RR = 2.02, 95% CI 1.44–2.83; RR = 1.56, 95% CI 1.31–1.86). These findings provide evidence supporting primary prevention policies regulating modifiable behaviors to reduce the additional risk of skin cancer among younger adults.
MEOX2 Transcription Factor Is Involved in Survival and Adhesion of Glioma Stem-like Cells
Authors: Tachon Gaëlle , Masliantsev Konstantin , Rivet Pierre , Desette Amandine , Milin Serge , Gueret Elise , Wager Michel , Karayan-Tapon Lucie , Guichet Pierre-Olivier
Published: November 2021

The high expression of MEOX2 transcription factor is closely associated with poor overall survival in glioma. MEOX2 has recently been described as an interesting prognostic biomarker, especially for lower grade glioma. MEOX2 has never been studied in glioma stem-like cells (GSC), responsible for glioma recurrence. The aim of our study was to investigate the role of MEOX2 in GSC. Loss of function approach using siRNA was used to assess the impact of MEOX2 on GSC viability and stemness phenotype. MEOX2 was localized in the nucleus and its expression was heterogeneous between GSCs. MEOX2 expression depends on the methylation state of its promoter and is strongly associated with IDH mutations. MEOX2 is involved in cell proliferation and viability regulation through ERK/MAPK and PI3K/AKT pathways. MEOX2 loss of function correlated with GSC differentiation and acquisition of neuronal lineage characteristics. Besides, inhibition of MEOX2 is correlated with increased expression of CDH10 and decreased pFAK. In this study, we unraveled, for the first time, MEOX2 contribution to cell viability and proliferation through AKT/ERK pathway and its potential involvement in phenotype and adhesion properties of GSC.
Radiotherapy in Medulloblastoma—Evolution of Treatment, Current Concepts and Future Perspectives
Authors: Seidel Clemens , Heider Sina , Hau Peter , Glasow Annegret , Dietzsch Stefan , Kortmann Rolf-Dieter
Published: November 2021

Medulloblastoma is the most frequent malignant brain tumor in children. During the last decades, the therapeutic landscape has changed significantly with craniospinal irradiation as the backbone of treatment. Survival times have increased and treatments were stratified according to clinical and later molecular risk factors. In this review, current evidence regarding the efficacy and toxicity of radiotherapy in medulloblastoma is summarized and discussed mainly based on data of controlled trials. Current concepts and future perspectives based on current risk classification are outlined. With the introduction of CSI, medulloblastoma has become a curable disease. Due to combination with chemotherapy, survival rates have increased significantly, allowing for a reduction in radiation dose and a decrease of toxicity in low- and standard-risk patients. Furthermore, modern radiotherapy techniques are able to avoid side effects in a fragile patient population. However, high-risk patients remain with relevant mortality and many patients still suffer from treatment related toxicity. Treatment needs to be continually refined with regard to more efficacious combinatorial treatment in the future.
Effect of Adjuvant and Palliative Chemotherapy in Large Cell Neuroendocrine Carcinoma of the Lung: A Systematic Review and Meta-Analysis
Authors: Chen Hao , Ishihara Masashi , Horita Nobuyuki , Kazahari Hiroki , Ochiai Ryusuke , Tanzawa Shigeru , Honda Takeshi , Ichikawa Yasuko , Watanabe Kiyotaka , Seki Nobuhiko
Published: November 2021

Background: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare subset of lung carcinoma with poor overall survival. Methods: A systematic review following a meta-analysis of studies was performed to identify the effect of different selections of chemotherapy in LCNEC. Articles providing overall survival data for adjuvant chemotherapy or palliative chemotherapy for LCNEC were eligible. The odds ratio (OR) of mortality at one or two years after chemotherapy was evaluated. Results: A total of 16 reports were finally included in the quantitative synthesis, involving a total of 5916 LCNEC patients. Adjuvant chemotherapy was administered to 1303 patients, and palliative chemotherapy was administered to 313 patients using either a small cell lung cancer (SCLC) or a non-small cell lung cancer (NSCLC) regimen. The OR for adjuvant chemotherapy was 0.73 (95% confidence interval (CI): 0.59 to 0.89, p = 0.002). The SCLC regimen showed an OR of 0.52 (95% CI: 0.11 to 2.38, p = 0.40) after one year, and 0.32 (95% CI: 0.11 to 0.89, p = 0.03) after two years, compared with the NSCLC regimen. Conclusions: Adjuvant chemotherapy for pulmonary large cell neuroendocrine carcinoma improved the outcome after surgery. The SCLC regimen showed better survival than the NSCLC regimen as palliative chemotherapy.
Progesterone Receptor Membrane Component (PGRMC)1 and PGRMC2 and Their Roles in Ovarian and Endometrial Cancer
Authors: Peluso John J. , Pru James K.
Published: November 2021

Cancers of the female reproductive tract are both lethal and highly prevalent. For example, the five-year survival rate of women diagnosed with ovarian cancer is still less than 50%, and endometrial cancer is the fourth most common cancer in women with > 65,000 new cases in the United States in 2020. Among the many genes already established as key participants in ovarian and endometrial oncogenesis, progesterone receptor membrane component (PGRMC)1 and PGRMC2 have gained recent attention given that there is now solid correlative information supporting a role for at least PGRMC1 in enhancing tumor growth and chemoresistance. The expression of PGRMC1 is significantly increased in both ovarian and endometrial cancers, similar to that reported in other cancer types. Xenograft studies using human ovarian and endometrial cancer cell lines in immunocompromised mice demonstrate that reduced expression of PGRMC1 results in tumors that grow substantially slower. While the molecular underpinnings of PGRMCs’ mechanisms of action are not clearly established, it is known that PGRMCs regulate survival pathways that attenuate stress-induced cell death. The objective of this review is to provide an overview of what is known about the roles that PGRMC1 and PGRMC2 play in ovarian and endometrial cancers, particularly as related to the mechanisms through which they regulate mitosis, apoptosis, chemoresistance, and cell migration.
Primary Skull Base Chondrosarcomas: A Systematic Review
Authors: Palmisciano Paolo , Haider Ali S. , Sabahi Mohammadmahdi , Nwagwu Chibueze D. , Bin Alamer Othman , Scalia Gianluca , Umana Giuseppe E. , Cohen-Gadol Aaron A. , El Ahmadieh Tarek Y. , Yu Kenny , Pathmanaban Omar N.
Published: November 2021

Background: Primary skull base chondrosarcomas (SBCs) can severely affect patients’ quality of life. Surgical-resection and radiotherapy are feasible but may cause debilitating complications. We systematically reviewed the literature on primary SBCs. Methods: PubMed, EMBASE, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA guidelines to include studies of patients with primary SBCs. Clinical characteristics, management strategies, and treatment outcomes were analyzed. Results: We included 33 studies comprising 1307 patients. Primary SBCs mostly involved the middle-fossa (72.7%), infiltrating the cavernous-sinus in 42.4% of patients. Cranial-neuropathies were reported in 810 patients (62%). Surgical-resection (93.3%) was preferred over biopsy (6.6%). The most frequent open surgical approaches were frontotemporal-orbitozygomatic (17.6%) and pterional (11.9%), and 111 patients (21.3%) underwent endoscopic-endonasal resection. Post-surgical cerebrospinal-fluid leaks occurred in 36 patients (6.5%). Radiotherapy was delivered in 1018 patients (77.9%): photon-based (41.4%), proton-based (64.2%), and carbon-based (13.1%). Severe post-radiotherapy complications, mostly hypopituitarism (15.4%) and hearing loss (7.1%) were experienced by 251 patients (30.7%). Post-treatment symptom-improvement (46.7%) and reduced/stable tumor volumes (85.4%) showed no differences based on radiotherapy-protocols (p = 0.165; p = 0.062). Median follow-up was 67-months (range, 0.1–376). SBCs recurrences were reported in 211 cases (16.1%). The 5-year and 10-year progression-free survival rates were 84.3% and 67.4%, and overall survival rates were 94% and 84%. Conclusion: Surgical-resection and radiotherapy are effective treatments in primary SBCs, with acceptable complication rates and favorable local tumor control.
Novel Perspectives in Pseudomyxoma Peritonei Treatment
Authors: Sommariva Antonio , Tonello Marco , Rigotto Giulia , Lazzari Nayana , Pilati Pierluigi , Calabrò Maria Luisa
Published: November 2021

Pseudomyxoma Peritonei (PMP) is an anatomo-clinical condition characterized by the implantation of neoplastic cells on peritoneal surfaces with the production of a large amount of mucin. The rarity of the disease precludes the evaluation of treatment strategies within randomized controlled trials. Cytoreductive Surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) has proven to be the only therapeutic option with potential chances of cure and long-term disease control. The present review discusses the epidemiology, pathogenesis, clinical presentation and treatment of PMP, focusing on the molecular factors involved in tumor progression and mucin production that could be used, in the upcoming future, to improve patient selection for surgery and to expand the therapeutic armamentarium.
RAP1/TERF2IP—A Multifunctional Player in Cancer Development
Authors: Deregowska Anna , Wnuk Maciej
Published: November 2021

Mammalian RAP1 (TERF2IP), the most conserved shelterin component, plays a pleiotropic role in the regulation of a variety of cellular processes, including cell metabolism, DNA damage response, and NF-κB signaling, beyond its canonical telomeric role. Moreover, it has been demonstrated to be involved in oncogenesis, progression, and chemoresistance in human cancers. Several mutations and different expression patterns of RAP1 in cancers have been reported. However, the functions and mechanisms of RAP1 in various cancers have not been extensively studied, suggesting the necessity of further investigations. In this review, we summarize the main roles of RAP1 in different mechanisms of cancer development and chemoresistance, with special emphasis on the contribution of RAP1 mutations, expression patterns, and regulation by non-coding RNA, and briefly discuss telomeric and non-telomeric functions.
Characterization of Total RNA, CD44, FASN, and PTEN mRNAs from Extracellular Vesicles as Biomarkers in Gastric Cancer Patients
Authors: Rhode Philipp , Mehdorn Matthias , Lyros Orestis , Kahlert Christoph , Kurth Thomas , Venus Tom , Schierle Katrin , Estrela-Lopis Irina , Jansen-Winkeln Boris , Lordick Florian , Gockel Ines , Thieme René
Published: November 2021

In-depth characterization has introduced new molecular subtypes of gastric cancer (GC). To identify these, new approaches and techniques are required. Liquid biopsies are trendsetting and provide an easy and feasible method to identify and to monitor GC patients. In a prospective cohort of 87 GC patients, extracellular vesicles (EVs) were isolated from 250 µL of plasma. The total RNA was isolated with TRIZOL. The total RNA amount and the relative mRNA levels of CD44, PTEN, and FASN were measured by qRT-PCR. The isolation of EVs and their contained mRNA was possible in all 87 samples investigated. The relative mRNA levels of PTEN were higher in patients already treated by chemotherapy than in chemo-naïve patients. In patients who had undergone neoadjuvant chemotherapy followed by gastrectomy, a decrease in the total RNA amount was observed after neoadjuvant chemotherapy and gastrectomy, while FASN and CD44 mRNA levels decreased only after gastrectomy. The amount of RNA and the relative mRNA levels of FASN and CD44 in EVs were affected more significantly by chemotherapy and gastrectomy than by chemotherapy alone. Therefore, they are a potential biomarker for monitoring treatment response. Future analyses are needed to identify GC-specific key RNAs in EVs, which could be used for the diagnosis of gastric cancer patients in order to determine their molecular subtype and to accompany the therapeutic response.
Pre-Transplant Alpha-Fetoprotein > 25.5 and Its Dynamic on Waitlist Are Predictors of HCC Recurrence after Liver Transplantation for Patients Meeting Milan Criteria
Authors: Magro Bianca , Pinelli Domenico , De Giorgio Massimo , Lucà Maria Grazia , Ghirardi Arianna , Carrobio Alessandra , Baronio Giuseppe , Del Prete Luca , Nounamo Franck , Gianatti Andrea , Colledan Michele , Fagiuoli Stefano
Published: November 2021

Background and Aim: Hepatocellular carcinoma (HCC) recurrence rates after liver transplantation (LT) range between 8 and 20%. Alpha-fetoprotein (AFP) levels at transplant can predict HCC recurrence, however a defined cut-off value is needed to better stratify patients. The aim of this study was to evaluate the rate of HCC recurrence at our centre and to identify predictors, focusing on AFP. Methods: We retrospectively analysed 236 consecutive patients that were waitlisted for HCC who all met the Milan criteria from January 2001 to December 2017 at our liver transplant centre. A total of twenty-nine patients dropped out while they were waitlisted, and 207 patients were included in the final analysis. All survival analyses included the competing-risk model. Results: The mean age was 56.8 ± 6.8 years. A total of 14% were female (n = 29/207). The median MELD (model for end-stage liver disease) at LT was 12 (9–16). The median time on the waitlist was 92 (41–170) days. The HCC recurrence rate was 16.4% (n = 34/208). The mean time to recurrence was 3.3 ± 2.8 years. The median AFP levels at transplant were higher in patients with HCC recurrence (p < 0.001). At multivariate analysis, the AFP value at transplant that was greater than 25.5 ng/mL (AUC 0.69) was a strong predictor of HCC recurrence after LT [sHR 3.3 (1.6–6.81); p = 0.001]. The HCC cumulative incidence function (CIF) of recurrence at 10 years from LT was significantly higher in patients with AFP > 25.5 ng/mL [34.3% vs. 11.5% (p = 0.001)]. Moreover, an increase in AFP > 20.8%, was significantly associated with HCC recurrence (p = 0.034). Conclusions: In conclusion, in our retrospective study, the AFP level at transplant > 25.5 ng/mL and its increase greater than 20.8% on the waitlist were strong predictors of HCC recurrence after LT in a cohort of patients that were waitlisted within the Milan criteria. However further studies are needed to validate these data.
Molecular Mechanisms of Resistance to Immunotherapy and Antiangiogenic Treatments in Clear Cell Renal Cell Carcinoma
Authors: Ballesteros Pablo Álvarez , Chamorro Jesús , Román-Gil María San , Pozas Javier , Gómez Dos Santos Victoria , Granados Álvaro Ruiz , Grande Enrique , Alonso-Gordoa Teresa , Molina-Cerrillo Javier
Published: November 2021

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype arising from renal cell carcinomas. This tumor is characterized by a predominant angiogenic and immunogenic microenvironment that interplay with stromal, immune cells, and tumoral cells. Despite the obscure prognosis traditionally related to this entity, strategies including angiogenesis inhibition with tyrosine kinase inhibitors (TKIs), as well as the enhancement of the immune system with the inhibition of immune checkpoint proteins, such as PD-1/PDL-1 and CTLA-4, have revolutionized the treatment landscape. This approach has achieved a substantial improvement in life expectancy and quality of life from patients with advanced ccRCC. Unfortunately, not all patients benefit from this success as most patients will finally progress to these therapies and, even worse, approximately 5 to 30% of patients will primarily progress. In the last few years, preclinical and clinical research have been conducted to decode the biological basis underlying the resistance mechanisms regarding angiogenic and immune-based therapy. In this review, we summarize the insights of these molecular alterations to understand the resistance pathways related to the treatment with TKI and immune checkpoint inhibitors (ICIs). Moreover, we include additional information on novel approaches that are currently under research to overcome these resistance alterations in preclinical studies and early phase clinical trials.
Clinical Response to Anti-CD47 Immunotherapy Is Associated with Rapid Reduction of Exhausted Bystander CD4+ BTLA+ T Cells in Tumor Microenvironment of Mycosis Fungoides
Authors: Jiang Tony T. , Kruglov Oleg , Lin Gloria H. Y. , Minic Angela , Jordan Kimberly , Uger Robert A. , Wong Mark , Shou Yaping , Akilov Oleg E.
Published: November 2021

Cancer progression in mycosis fungoides, the most common form of cutaneous T-cell lymphoma, occurs in a predictable, sequential pattern that starts from patches and that evolves to plaques and later to tumors. Therefore, unlocking the relationship between the microarchitecture of mycosis fungoides and the clinical counterparts of that microstructure represents important steps for the design of targeted therapies. Using multispectral fluorescent imaging, we show that the progression of mycosis fungoides from plaque to tumor parallels the cutaneous expansion of the malignant CD4+ T cells that express TOX. The density of exhausted BTLA+ CD4+ T cells around malignant CD4+TOX+ cells was higher in tumors than it was in plaques, suggesting that undesired safeguards are in place within the tumor microenvironment that prevent immune activation and subsequent cancer eradication. Overriding the CD47 checkpoint with an intralesional SIRPαFc fusion decoy receptor induced the resolution of mycosis fungoides in patients that paralleled an amplified expansion of NK and CD8+ T cells in addition to a reduction of the exhausted BTLA+ CD4+ T cells that were engaged in promiscuous intercellular interactions. These therapeutic benefits of the CD47 blockade were further unleashed by adjuvant interferon-α, which stimulates cytotoxic cells, underscoring the importance of an inflamed microenvironment in facilitating the response to immunotherapy. Collectively, these findings support CD47 as a therapeutic target in treating mycosis fungoides and demonstrate a synergistic role of interferon-α in exploiting these clinical benefits.
Impact of Interobserver Variability in Manual Segmentation of Non-Small Cell Lung Cancer (NSCLC) Applying Low-Rank Radiomic Representation on Computed Tomography
Authors: Hershman Michelle , Yousefi Bardia , Serletti Lacey , Galperin-Aizenberg Maya , Roshkovan Leonid , Luna José Marcio , Thompson Jeffrey C. , Aggarwal Charu , Carpenter Erica L. , Kontos Despina , Katz Sharyn I.
Published: November 2021

This study tackles interobserver variability with respect to specialty training in manual segmentation of non-small cell lung cancer (NSCLC). Four readers included for segmentation are: a data scientist (BY), a medical student (LS), a radiology trainee (MH), and a specialty-trained radiologist (SK) for a total of 293 patients from two publicly available databases. Sørensen–Dice (SD) coefficients and low rank Pearson correlation coefficients (CC) of 429 radiomics were calculated to assess interobserver variability. Cox proportional hazard (CPH) models and Kaplan-Meier (KM) curves of overall survival (OS) prediction for each dataset were also generated. SD and CC for segmentations demonstrated high similarities, yielding, SD: 0.79 and CC: 0.92 (BY-SK), SD: 0.81 and CC: 0.83 (LS-SK), and SD: 0.84 and CC: 0.91 (MH-SK) in average for both databases, respectively. OS through the maximal CPH model for the two datasets yielded c-statistics of 0.7 (95% CI) and 0.69 (95% CI), while adding radiomic and clinical variables (sex, stage/morphological status, and histology) together. KM curves also showed significant discrimination between high- and low-risk patients (p-value < 0.005). This supports that readers’ level of training and clinical experience may not significantly influence the ability to extract accurate radiomic features for NSCLC on CT. This potentially allows flexibility in the training required to produce robust prognostic imaging biomarkers for potential clinical translation.
The Emerging Role of Non-Coding RNAs in Pituitary Gland Tumors and Meningioma
Authors: Ghafouri-Fard Soudeh , Abak Atefe , Hussen Bashdar Mahmud , Taheri Mohammad , Sharifi Guive
Published: November 2021

Long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) are non-coding transcripts which are involved in the pathogenesis of pituitary gland tumors. LncRNAs that participate in the pathogenesis of pituitary gland tumors mainly serve as sponges for miRNAs. CLRN1-AS1/miR-217, XIST/miR-424-5p, H19/miR-93a, LINC00473/miR-502-3p, SNHG7/miR-449a, MEG8/miR-454-3p, MEG3/miR-23b-3p, MEG3/miR-376B-3P, SNHG6/miR-944, PCAT6/miR-139-3p, lncRNA-m433s1/miR-433, TUG1/miR-187-3p, SNHG1/miR-187-3p, SNHG1/miR-302, SNHG1/miR-372, SNHG1/miR-373, and SNHG1/miR-520 are identified lncRNA/miRNA pairs that are involved in this process. Hsa_circ_0001368 and circOMA1 are two examples of circRNAs that contribute to the pathogenesis of pituitary gland tumors. Meanwhile, SNHG1, LINC00702, LINC00460, and MEG3 have been found to partake in the pathogenesis of meningioma. In the current review, we describe the role of non-coding RNAs in two types of brain tumors, i.e., pituitary tumors and meningioma.
Research on Coal Tar Pitch Catalytic Oxidation and Its Effect on the Emission of PAHs during Co-Carbonation with Coal
Authors: Chen Liqing , Guo Fanhui , Wu Jianjun , Li Ping , Zhang Yixin
Published: November 2021

Coal tar pitch (CTP) is abundant and widely used, but its properties will be affected due to oxidation aging during storage. In this study, CTP was oxidized by simulating the air oxidation process, and the change of chemical structure has been analyzed by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and both gas chromatography and mass spectrometry (GCMS). The effects of the oxidized and unoxidized CTP co-carbonization with coal on the polycyclic aromatic hydrocarbons (PAHs) emission were detected by GCMS. The small and medium-molecule aromatic substances were reduced during CTP oxidation, while the intermolecular condensation reaction increased the macromolecules content. The catalytic can effectively facilitate the dehydrogenation and condensation reaction of CTP and the entry of oxygen molecules, which leads to the increase of oxygen-containing groups and the decrease of PAHs. Compared to the raw CTP, the catalytic oxidized CTP significantly reduced the emissions of toxic PAHs during the co-carbonization with coal. A possible catalytic mechanism of CTP catalytic oxidation is proposed.
One-Pot Microwave-Assisted Synthesis of Graphene-Supported PtCoM (M = Mn, Ru, Mo) Catalysts for Low-Temperature Fuel Cells
Authors: Nacys Antanas , Kilmonis Teofilius , Kepenienė Virginija , Balčiūnaitė Aldona , Stagniūnaitė Raminta , Upskuvienė Daina , Jablonskienė Jolita , Vaičiūnienė Jūratė , Skapas Martynas , Tamašauskaitė-Tamašiūnaitė Loreta , Norkus Eugenijus
Published: November 2021

In this study, one-pot microwave-assisted synthesis was used to fabricate the graphene (GR)-supported PtCoM catalysts where M = Mn, Ru, and Mo. The catalysts with the molar ratios of metals Pt:Co:Mn, Pt:Co:Ru, and Pt:Co:Mo equal to 1:3:1, 1:2:2, and 7:2:1, respectively, were prepared. Catalysts were characterized using Transmission Electron Microscopy (TEM). The electrocatalytic activity of the GR-supported PtCoMn, PtCoRu, and PtCoMo catalysts was evaluated toward methanol oxidation in an alkaline medium employing cyclic voltammetry and chrono-techniques. The most efficient electrochemical characteristics demonstrated the PtCoMn/GR catalyst with a current density value of 144.5 mA cm−2, which was up to 4.8 times higher than that at the PtCoRu(1:2:2)/GR, PtCoMo(7:2:1)/GR, and bare Pt/GR catalysts.
Influence of the Metabolic Activity of Microorganisms on Disinfection Efficiency of the Visible Light and P25 TiO2 Photocatalyst
Authors: Sakalauskaite Sandra , Vasiliauske Deimante , Demikyte Emilija , Daugelavicius Rimantas , Lelis Martynas
Published: November 2021

The beneficial photocatalytic properties of UV light activated TiO2 powder are well-known and have been demonstrated with various pollutants and pathogens. However, traditionally observed photocatalytic activity of visible light activated pristine TiO2 is insignificant but there are a few studies which have reported that under some specific conditions commercially available TiO2 powder could at least partially disinfect microorganisms even under visible light. To better understand this phenomenon, in the current study we focused on bacteria response to the treatment by visible light and P25 TiO2 powder. More specifically, we analyzed the relationship between the bacteria viability, outer membrane permeability, metabolism, and its capacity to generate intracellular reactive oxygen species. During the study we assayed the viability of treated bacteria by the spread plate technique and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction method. Changes in bacterial outer membrane permeability were determined by measuring the fluorescence of N-phenyl-1-naphthylamine (NPN). To detect intracellular reactive oxygen species formation, the fluorescence of dichlorodihydrofluorescein diacetate (DCFH-DA) was assayed. Results of our study indicated that TiO2 and wide spectrum visible light irradiation damaged the integrity of the outer membrane and caused oxidative stress in the metabolizing bacteria. When favorable conditions were created, these effects added up and unexpectedly high bacterial inactivation was achieved.