bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid Artificial Intelligence Models with Multi Objective Optimization for Prediction of Tribological Behavior of Polytetrafluoroethylene Matrix Composites
Authors: Ibrahim Musa Alhaji , Çamur Hüseyin , Savaş Mahmut A. , Sabo Alhassan Kawu , Mustapha Mamunu , Abba Sani I.
Published: August 2022

This study presents multi-response optimization and prediction tribological behaviors polytetrafluoroethylene (PTFE) matrix composites. For multi-response optimization, the Taguchi model was hybridized with grey relational analysis to produce grey relational grades (GRG). A support vector regression (SVR) model was combined with novel Harris Hawks’ optimization (HHO) and swarm particle optimization (PSO) models to form hybrid SVR–HHO and SVR–PSO models to predict the GRG. The prediction ability of the models was appraised using the coefficient of determination (R2), correlation coefficient (R), mean square error (MSE), root mean square (RMSE), and mean absolute percentage error (MAPE). The results of the multi-response optimization revealed that the optimal combination of parametric values of GRG for minimum tribological rate was 9 N-1000 mesh-0.14 ms−1-55 m (L3G1SD3SS3). An analysis of variance of the GRG showed that a grit size of 94.56% was the most significant parameter influencing the tribological behavior of PTFE matrix composites. The validation results revealed that an improvement of 52% in GRG was achieved. The prediction results of all models showed that the SVR–PSO and SVR–HHO models were superior to the SVR model. Furthermore, the SVR–HHO model produced superior prediction error and the best goodness of fit over the SVR–PSO model. These findings concluded that hybrids models are promising tools in the multi-response optimization and prediction of tribological behaviors of PTFE matrix composites. They can serve as a guide in the design and development of tribological materials.
Long-Term Prosthetic Aftercare of Mandibular Implant-Supported Overdenture
Authors: Zenziper Eran , Rosner Ofir , Ghelfan Oded , Nissan Joseph , Blumer Sigalit , Ben-Izhack Gil , Slutzky Hagay , Meinster Isabelle , Chaushu Liat , Naishlos Sarit
Published: August 2022

Background: Two of the most popular resilient attachment systems for mandibular implant-supported overdenture (MISOD) are locator and ball attachments. The purpose of the present retrospective cohort study was to assess the long-term prosthetic aftercare and oral hygiene status in edentulous patients rehabilitated with MISOD. Materials and Methods: Forty-five consecutive patients were included (22, group A- ball vs. 23, group B- locator attachments). Attachment incorporation into the MISOD was conducted in a direct (chair-side) intraoral technique at the time of denture insertion. Routine follow-up included yearly visits. The number of visits requiring prosthetic aftercare, either during the follow-up or during the additional visit, was recorded. Outcome parameters included—prosthetic aftercare—the number of aftercare (primary outcome parameter) visits, and dental treatment received (pressure sores relief, liner changes due to loss of retention, loss of retention due to debris accumulation, denture repair—secondary outcome parameters); oral hygiene—gingival index (primary outcome parameter). Results: The mean follow-up of the entire study population was 84 ± 21 months, range 39–120 months. Statistical analysis revealed a lower need for prosthetic aftercare interventions in group A (p < 0.001). The mean number of visits dedicated to pressure sores relief (6.09 ± 1.04 vs. 3.03 ± 0.77, p < 0.001) and liner exchange due to loss of retention (5.6 ± 1.03 vs. 2.09 ± 1.04, p < 0.001), were significantly lower in group A. Debris (food/calculus) accumulation inside the attachment was noted only for the locator’s group (p < 0.001). No statistically significant differences between the groups were noted for denture repair (p = 0.318). Oral hygiene also exhibited statistically significant differences in favor of group A (2.3 ± 0.3 vs. 1.03 ± 0.2, p < 0.001). Conclusions: It can be concluded that using ball attachments for MISOD yields less need for aftercare treatments and improved oral hygiene status over the years.
Retrieved XCO2 Accuracy Improvement by Reducing Aerosol-Induced Bias for China’s Future High-Precision Greenhouse Gases Monitoring Satellite Mission
Authors: Ke Ju , Wang Shuaibo , Chen Sijie , Dong Changzhe , Sun Yingshan , Liu Dong
Published: August 2022

China is developing the High-precision Greenhouse gases Monitoring Satellite (HGMS), carrying a high-spectral-resolution lidar (HSRL) for aerosol vertical profiles and imaging grating spectrometers for CO2 measurements at the same time. By providing simultaneous evaluation of the aerosol scattering effect, HGMS would reduce the bias of the XCO2 retrievals from the passive sensor. In this work, we propose a method to reduce aerosol-induced bias in XCO2 retrievals for the future HGMS mission based on the correlation analysis among simulated radiance, XCO2 bias, and aerosol optical depth (AOD) ratio. We exercise the method with the Orbiting Carbon Observatory-2 (OCO-2) XCO2 retrievals and AOD ratio inferred from the OCO-2 O2 A-band aerosol parameters at 755 nm and the Cloud–Aerosol Lidar with Orthogonal Polarization (CALIOP) AOD at 532 nm at several Total Carbon Column Observing Network (TCCON) sites in Europe. The results showed that 80% of measurements from OCO-2 were improved, and data from six TCCON sites show an average of 2.6 ppm reduction in mean bias and a 68% improvement in accuracy. We demonstrate the advantage of fused active–passive observation of the HGMS for more accurate global XCO2 measurements in the future.
Attribution Analysis of Runoff Change in the Upper Reaches of the Kaidu River Basin Based on a Modified Budyko Framework
Authors: Shi Guosen , Gao Bing
Published: August 2022

The Kaidu River plays an important role in the water development and utilization in the Tarim River basin in northwestern China. In this study, we used a modified Budyko framework, which considered the snowmelt to analyze and attribute the runoff change in the upper Kaidu River basin based on the observations during the period of 1960–2010. The time series was divided into two periods: 1960–1995 and 1996–2010. The contribution rate of runoff change between these two periods and the elasticity coefficient of runoff were estimated to quantify the effect of climatic variables and landscape changes on runoff alteration. The results show that the increase in precipitation was the major cause of increase in runoff, whose contribution accounted for 81.42%. The contribution rate of the landscape change was lower than that of the precipitation change, accounting for 9.07%. The elasticity coefficient of runoff to precipitation was 1.24, and the elasticity coefficient of runoff to the landscape was −0.74. Compared with the original Budyko framework, without considering the snowmelt, the contribution rates of precipitation and potential evaporation to runoff change would decrease after considering the snowmelt in the modified Budyko framework, while the contribution rate of landscape would increase. The increased snow ratio would cause more fluctuations in the runoff. This study provides a valuable reference for the water resources management in the upper Kaidu River basin and deepens our understanding of the response of runoff to climate change in snowmelt-affected regions.
Simulation of the Impact of Instantaneous Solar UV Radiation Enhancements on the Middle Atmosphere via UV Radiation Reconstruction
Authors: Liu Dan , Yang Junfeng , Hu Xiong , Cheng Xuan , Xiao Cunying
Published: August 2022

This study reconstructed the 0.01–399.5 nm ultraviolet (UV) radiation band with a time resolution of 5 min under solar minimum conditions (18 October 2006) to investigate the effects of the solar flare event on the middle atmosphere. Five-minute resolution 0.01–399.5 nm UV radiation was used instead of daytime scale data to observe the response of the middle atmosphere to the instantaneous solar UV radiation enhancement. The results indicate that small temperature increases of 0.05 K in low latitudes were observed in the lower thermosphere and the stratosphere. The UV radiation enhancement led to an ozone increase of 0.6% in the stratosphere, which caused small temperature increases; and there is an ozone increase of up to 4% at 80 km, while a change of −2% occurred at 60–70 km and a change of −6% occurred in the low thermosphere. There was a 0.05% increase in atmospheric density above 60 km, and there was an increase of up to 0.15% at 80–90 km. The responses of the atmospheric temperature and density in the middle atmosphere to instantaneous UV radiation enhancements can therefore be captured via the UV radiation reconstruction. The simulation results were weaker than the previous study.
Changes in Air Pollutants from Fireworks in Chinese Cities
Authors: Lai Yonghang , Brimblecombe Peter
Published: August 2022

Chinese New Year has traditionally been welcomed with fireworks, but this has meant this holiday can experience intense peaks of pollutants, particularly as particulate matter. Such environmental issues add to other risks (e.g., accident, fire, and ecological and health threats) posed by firework displays, but cultural reasons encourage such celebrations. This study examines air pollution from fireworks across a time of increasingly stringent bans as a time series from 2014–2021 using a random forest (decision-tree) model to explore the effect of year-to-year weather changes on pollutant concentrations at Chinese New Year. Peak concentrations of firework pollutants have decreased in cities and hint at the importance of well-enforced regulation of these traditional celebrations, e.g., Beijing, Tianjin, and Chongqing. The model suggested relative humidity was an important controlling variable, perhaps as the presence of water vapor might also accelerate particle growth but also as a surrogate parameter related to atmospheric mixing. Bans on fireworks, resisted at first, have shown evidence of growing public acceptance. The regulations are increasingly effective, even in the outer parts of cities. Celebrations might safely return as public firework displays, including light shows and the use of lanterns.
Endophytic Fungi as Potential Biocontrol Agents against Rhizoctonia solani J.G. Kühn, the Causal Agent of Rice Sheath Blight Disease
Authors: Safari Motlagh Mohammad Reza , Jahangiri Bahar , Kulus Dariusz , Tymoszuk Alicja , Kaviani Behzad
Published: August 2022

The rice sheath blight disease, caused by Rhizoctonia solani J.G. Kühn fungus, is a major disease of Oryza sativa L. occurring all over the world. Therefore, efforts need to be undertaken to limit the spread of this pathogen, preferably by using environmentally friendly methods. In the present study, 57 fungal isolates were recovered by surface sterilization technique from 120 rice samples collected from paddy fields in Guilan province, Iran. Biological characterizations of the isolated taxa were performed in vitro, in the dual culture, volatile metabolites, and slide culture methods. Among the studied isolates, Trichoderma virens (J. H. Miller, Giddens and A. A. Foster) Arx was most effective in inhibiting the mycelial growth of R. solani in the dual culture (44.16% inhibition level), while Aspergillus fumigatus Fresen and T. virens had a 62.50–68.75% inhibition efficiency by volatile metabolites. In the slide culture, all of the isolates, except for T. harzianum Rifai, were effective in inhibiting the hyphae growth of R. solani. Under greenhouse conditions, rice plants inoculated with these potential antagonistic fungi showed a reduction in disease severity by even 41.4% as in the case of T. virens. Moreover, phenotypic properties of rice, such as plant height, fresh weight, and dry weight were increased in the plants inoculated with all antagonistic fungi tested, compared to the infected plants, except for the fresh weight of plants inoculated with Curnularia lunata (Wakker) Boedijn. The present in vivo and in vitro studies revealed that T. virens and A. fumigatus are the most effective antagonists in rice sheath blight disease control and could be applied in agricultural practice.
Comparison of Individual Penalties According to Gender and Weight Categories of Elite Judo Athletes from Four World Championships
Authors: Kajmovic Husnija , Karpljuk Damir , Kapo Safet , Simenko Jozef
Published: August 2022

Background: This research aimed to compare individual penalties by gender and weight categories in judo from the Judo World Championships (WC): Budapest—2017, Baku—2018, Tokyo—2019 and Budapest—2021 in all individual weight categories for females and males. Methods: Data were collected by notational analysis of 2041 penalty videos for females and 3473 penalty videos for males (total n = 5514). All individual penalties—Shido 1, 2, 3 and Hansoku Make (direct disqualification) were analysed by the Pearson chi-square test at the level of statistical significance of 5%. Results: Significant differences were noted in the assigned individual penalties between individual categories (p < 0.001) in both genders. The significant difference was contributed mainly by the weight category +78 kg with penalties Non-combativity (5.3) and Avoid Grip (−3.4) in females, while in males it impacted by the +100 kg weight category and the Non-combativity (4.2) and Avoid Grip (−4.0) penalties. For females, the most dominant individual penalties were Non-combativity (41.6%), Avoid Grip (16.2%) and False Attack (15.0%), and were Non-combativity (40.3%), Avoid Grip (19.5%) and False Attack (16.4%) for males. The largest number of penalties in females were in −52 kg (16.7%), −57 kg (15.9%) and +78 kg (15.2%) categories, while in males, they were −66 kg (17.2%), −73 kg (16.1%) and −90 kg (15.6%). Conclusions: The findings of this study highlight the leading penalties in all weight categories for both genders on WC to be Non-combativity, Avoid Grip and False Attack. Additionally, a new trend in heavyweight athletes with a lower number of penalties is noted. The obtained results indicate the need to pay more attention to working with competitors of all ages and genders on education to implement tactical variants, forms and means to use penalties to athletes’ advantage, especially after a possible rule change and to lower the occurrence of injuries.
N-Acetylcysteine, an ROS Inhibitor, Alleviates the Pathophysiology of Hyperthyroidism-Induced Cardiomyopathy via the ROS/Ca2+ Pathway
Authors: Bao Mengni , Hua Xiumeng , Mo Han , Sun Zhe , Xu Bo , Chen Xiao , Xu Mengda , Xu Xinjie , Song Jiangping
Published: August 2022

Hyperthyroidism is common and can induce cardiomyopathy, but there is no effective therapeutic strategy. The purpose of this study was to investigate the molecular mechanism of hyperthyroidism-induced cardiomyopathy (HTC) and the effect of N-acetylcysteine (NAC), an ROS inhibitor, on the pathophysiology of HTC in vivo and in vitro. Compared with those in the control groups in vivo and in vitro, TT3 and TT4 were significantly increased, the structure of myocardial cells was enlarged and disordered, and interstitial fibrosis and the apoptosis of myocardial cells were markedly increased in the L-Thy group. The ROS and inflammatory response were increased in the hyperthyroidism group. In the NAC group, the contents of TT3 and TT4 were decreased, the myocardial cell structure was slightly disturbed, fibrosis and apoptosis were significantly reduced, and the ROS level and inflammatory response were significantly reduced. Interestingly, L-Thy decreased the viability of fibroblasts and H9c2 cells, suggesting that L-Thy-induced fibrosis was not caused by the proliferation of fibroblasts. The molecular mechanism of HTC could be explained by the fact that L-Thy could cause cardiac hypertrophy, inflammation, and fibrosis by regulating the Ca2+/calpain/Rcan1-dependent signalling pathway, the Ca2+/Rcan1/NF-κB/p65-dependent signalling pathway, and the Ca2+/ROS/Bcl-2/caspase-3-dependent signalling pathway. In conclusion, NAC can alleviate the pathophysiology of hyperthyroidism-induced cardiomyopathy, probably by regulating the ROS/Ca2+-dependent pathway.
Biosensor-Integrated Drug Delivery Systems as New Materials for Biomedical Applications
Authors: Cicha Iwona , Priefer Ronny , Severino Patrícia , Souto Eliana B. , Jain Sona
Published: August 2022

Biosensor-integrated drug delivery systems are innovative devices in the health area, enabling continuous monitoring and drug administration. The use of smart polymer, bioMEMS, and electrochemical sensors have been extensively studied for these systems, especially for chronic diseases such as diabetes mellitus, cancer and cardiovascular diseases as well as advances in regenerative medicine. Basically, the technology involves sensors designed for the continuous analysis of biological molecules followed by drug release in response to specific signals. The advantages include high sensitivity and fast drug release. In this work, the main advances of biosensor-integrated drug delivery systems as new biomedical materials to improve the patients’ quality of life with chronic diseases are discussed.
Infiltration Profile of Regulatory T Cells in Osteoarthritis-Related Pain and Disability
Authors: Nees Timo Albert , Zhang Jiji Alexander , Platzer Hadrian , Walker Tilman , Reiner Tobias , Tripel Elena , Moradi Babak , Rosshirt Nils
Published: August 2022

Emerging evidence indicates that regulatory T cells (Treg) intervene in the inflammatory processes that drive osteoarthritis (OA). However, whether polarized Tregs affect clinical features of the disease in the short- or long-term, and if so, what their role in OA-related pain and functional disability really is, remains elusive. Thus, the aim of the current study was to characterize the infiltration profile of Tregs in systemic (peripheral blood) and joint-derived (synovial fluid and synovial membrane) samples from patients with knee OA in relation to OA-induced symptoms. To this end, Treg infiltration (CD4+CD25+/high CD127low/−) was analyzed in matched samples of peripheral blood (PB), synovial fluid (SF) and synovial membrane (SM) from a total of 47 patients undergoing elective knee arthroplasty using flow cytometry. At the same time, knee pain and function were assessed and correlated with Treg proportions in different compartments (PB, SF, SM). Interestingly, matched-pair analysis revealed significantly higher Treg proportions in joint-derived samples than in PB, which was mainly attributed to the high Treg frequency in SF. Moreover, we found significant associations between infiltrating Tregs and OA-related symptoms which indicate that lower Treg proportions—especially in the SM—are related to increased pain and functional disability in knee OA. In conclusion, this study highlights the importance of local cellular inflammatory processes in OA pathology. Intra-articular Treg infiltration might play an important role not only in OA pathogenesis but also in the development of OA-related symptoms.
Targeting Tyrosine Kinases in Ovarian Cancer: Small Molecule Inhibitor and Monoclonal Antibody, Where Are We Now?
Authors: Rendell Aimee , Thomas-Bland Isobel , McCuish Lee , Taylor Christopher , Binju Mudra , Yu Yu
Published: August 2022

Ovarian cancer is one of the most lethal gynaecological malignancies worldwide. Despite high success rates following first time treatment, this heterogenous disease is prone to recurrence. Oncogenic activity of receptor tyrosine kinases is believed to drive the progression of ovarian cancer. Here we provide an update on the progress of the therapeutic targeting of receptor tyrosine kinases in ovarian cancer. Broadly, drug classes that inhibit tyrosine kinase/pathways can be classified as small molecule inhibitors, monoclonal antibodies, or immunotherapeutic vaccines. Small molecule inhibitors tested in clinical trials thus far include sorafenib, sunitinib, pazopanib, tivantinib, and erlotinib. Monoclonal antibodies include bevacizumab, cetuximab, pertuzumab, trastuzumab, and seribantumab. While numerous trials have been carried out, the results of monotherapeutic agents have not been satisfactory. For combination with chemotherapy, the monoclonal antibodies appear more effective, though the efficacy is limited by low frequency of target alteration and a lack of useful predictive markers for treatment stratification. There remain critical gaps for the treatment of platinum-resistant ovarian cancers; however, platinum-sensitive tumours may benefit from the combination of tyrosine kinase targeting drugs and PARP inhibitors. Immunotherapeutics such as a peptide B-cell epitope vaccine and plasmid-based DNA vaccine have shown some efficacy both as monotherapeutic agents and in combination therapy, but require further development to validate current findings. In conclusion, the tyrosine kinases remain attractive targets for treating ovarian cancers. Future development will need to consider effective drug combination, frequency of target, and developing predictive biomarker.
Revertant Mosaicism in Genodermatoses: Natural Gene Therapy Right before Your Eyes
Authors: van den Akker Peter C. , Bolling Maria C. , Pasmooij Anna M. G.
Published: August 2022

Revertant mosaicism (RM) is the intriguing phenomenon in which nature itself has successfully done what medical science is so eagerly trying to achieve: correcting the effect of disease-causing germline variants and thereby reversing the disease phenotype back to normal. RM was molecularly confirmed for the first time in a genodermatosis in 1997, the genetic skin condition junctional epidermolysis bullosa (EB). At that time, RM was considered an extraordinary phenomenon. However, several important discoveries have changed this conception in the past few decades. First, RM has now been identified in all major subtypes of EB. Second, RM has also been identified in many other genodermatoses. Third, a theoretical mathematical exercise concluded that reverse mutations should be expected in all patients with a recessive subtype of EB or any other genodermatosis. This has shifted the paradigm from RM being an extraordinary phenomenon to it being something that every physician working in the field of genodermatoses should be looking for in every patient. It has also raised hope for new treatment options in patients with genodermatoses. In this review, we summarize the current knowledge on RM and discuss the perspectives of RM for the future treatment of patients with genodermatoses.
Intrathecal Injection of the Secretome from ALS Motor Neurons Regulated for miR-124 Expression Prevents Disease Outcomes in SOD1-G93A Mice
Authors: Barbosa Marta , Santos Marta , de Sousa Nídia , Duarte-Silva Sara , Vaz Ana Rita , Salgado António J. , Brites Dora
Published: August 2022

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with short life expectancy and no effective therapy. We previously identified upregulated miR-124 in NSC-34-motor neurons (MNs) expressing human SOD1-G93A (mSOD1) and established its implication in mSOD1 MN degeneration and glial cell activation. When anti-miR-124-treated mSOD1 MN (preconditioned) secretome was incubated in spinal cord organotypic cultures from symptomatic mSOD1 mice, the dysregulated homeostatic balance was circumvented. To decipher the therapeutic potential of such preconditioned secretome, we intrathecally injected it in mSOD1 mice at the early stage of the disease (12-week-old). Preconditioned secretome prevented motor impairment and was effective in counteracting muscle atrophy, glial reactivity/dysfunction, and the neurodegeneration of the symptomatic mSOD1 mice. Deficits in corticospinal function and gait abnormalities were precluded, and the loss of gastrocnemius muscle fiber area was avoided. At the molecular level, the preconditioned secretome enhanced NeuN mRNA/protein expression levels and the PSD-95/TREM2/IL-10/arginase 1/MBP/PLP genes, thus avoiding the neuronal/glial cell dysregulation that characterizes ALS mice. It also prevented upregulated GFAP/Cx43/S100B/vimentin and inflammatory-associated miRNAs, specifically miR-146a/miR-155/miR-21, which are displayed by symptomatic animals. Collectively, our study highlights the intrathecal administration of the secretome from anti-miR-124-treated mSOD1 MNs as a therapeutic strategy for halting/delaying disease progression in an ALS mouse model.
Dwarf Kingfisher-Inspired Bionic Flapping Wing and Its Aerodynamic Performance at Lowest Flight Speed
Authors: Abas Mohd Firdaus Bin , Singh Balbir , Ahmad Kamarul Arifin , Ng Eddie Yin Kwee , Khan Tabrej , Sebaey Tamer A.
Published: August 2022

This paper aims to understand the aerodynamic performance of a bio-inspired flapping-wing model using the dwarf Kingfisher wing as the bionic reference. The paper demonstrates the numerical investigation of the Kingfisher-inspired flapping-wing followed by experimental validation to comprehend the results fully and examine the aerodynamic characteristics at a flight velocity of 4.4 m/s, with wingbeat frequencies of 11 Hz, 16 Hz, and 21 Hz, at various angles of rotation ranging from 0° to 20° for each stroke cycle. The motivation to study the performance at low speed is based on lift generation as a challenge at low speed as per quasi-steady theory. The temporal evolution of the mean force coefficients has been plotted for various angles of rotation. The results show amplification of the maximum value for the cycle average lift and drag coefficient as the rotation angle increases. The history of vertical force and the flow patterns around the wing is captured in a full cycle with asymmetric lift development in a single stroke cycle. It is observed from the results that the downstroke generates more lift force in magnitude compared to the upstroke. In addition to the rotation angle, lift asymmetry is also affected by wing–wake interaction. Experimental results reveal that there is a stable leading-edge vortex developed in the downstroke, which sheds during the upstroke. An optimum lift and thrust flapping flight can be achieved, with a lift coefficient of 3.45 at 12°. The experimental and parametric study results also reveal the importance of passive rotation in wings for aerodynamic performance and wing flexibility as an important factor for lift generation.
Recent Progress of Triboelectric Nanogenerators for Biomedical Sensors: From Design to Application
Authors: Rahimi Sardo Fatemeh , Rayegani Arash , Matin Nazar Ali , Balaghiinaloo Mohammadali , Saberian Mohammadhossein , Mohsan Syed Agha Hassnain , Alsharif Mohammed H. , Cho Ho-Shin
Published: August 2022

Triboelectric nanogenerators (TENG) have gained prominence in recent years, and their structural design is crucial for improvement of energy harvesting performance and sensing. Wearable biosensors can receive information about human health without the need for external charging, with energy instead provided by collection and storage modules that can be integrated into the biosensors. However, the failure to design suitable components for sensing remains a significant challenge associated with biomedical sensors. Therefore, design of TENG structures based on the human body is a considerable challenge, as biomedical sensors, such as implantable and wearable self-powered sensors, have recently advanced. Following a brief introduction of the fundamentals of triboelectric nanogenerators, we describe implantable and wearable self-powered sensors powered by triboelectric nanogenerators. Moreover, we examine the constraints limiting the practical uses of self-powered devices.
Clinical Safety and Effectiveness of Robotic-Assisted Surgery in Patients with Rectal Cancer: Real-World Experience over 8 Years of Multiple Institutions with High-Volume Robotic-Assisted Surgery
Authors: Huang Ching-Wen , Wei Po-Li , Chen Chien-Chih , Kuo Li-Jen , Wang Jaw-Yuan
Published: August 2022

The perioperative and short-term oncological outcomes of robotic-assisted rectal surgery (RRS) are unclear. This retrospective observational study enrolled patients with rectal adenocarcinoma undergoing RRS from three high-volume institutions in Taiwan. Of the 605 enrolled patients, 301 (49.75%), 176 (29.09%), and 116 (19.17%) had lower, middle, and upper rectal cancers, respectively. Low anterior resection (377, 62.31%) was the most frequent surgical procedure. Intraoperative blood transfusion was performed in 10 patients (2%). The surgery was converted to an open one for one patient (0.2%), and ten (1.7%) patients underwent reoperation. The overall complication rate was 14.5%, including 3% from anastomosis leakage. No deaths occurred during surgery and within 30 days postoperatively. The positive rates of distal resection margin and circumferential resection margin were observed in 21 (3.5%) and 30 (5.0%) patients, respectively. The 5-year overall and disease-free survival rates for patients with stage I–III rectal cancer were 91.1% and 86.3%, respectively. This is the first multi-institutional study in Taiwan with 605 patients from three high-volume hospitals. The overall surgical and oncological outcomes were equivalent or superior to those estimated in other studies. Hence, RRS is an effective and safe technique for rectal resection in high-volume hospitals.
Recurrent Endometrial Cancer: Which Is the Best Treatment? Systematic Review of the Literature
Authors: Restaino Stefano , Dinoi Giorgia , La Fera Eleonora , Gui Benedetta , Cappuccio Serena , Campitelli Maura , Vizzielli Giuseppe , Scambia Giovanni , Fanfani Francesco
Published: August 2022

Background: Endometrial cancer is the most common gynaecological tumour in developed countries. The overall rate of relapse has remained unchanged in recent decades. Recurrences occur in approximately 20% of endometrioid and 50% of non-endometrioid cases. The aim of this systematic review is to compare different therapeutic strategies in the treatment of endometrial cancer recurrence to evaluate their prognostic and curative effects based on site and type of recurrence. Methods: This systematic review of literature was conducted in accordance with the PRISMA guidelines. The study protocol was registered on PROSPERO (CRD42020154042). PubMed, Embase, Chocrane and Cinahl databases were searched from January 1995 to September 2021. Five retrospective studies were selected. Results: A total of 3571 studies were included in the initial search. Applying the screening criteria, 299 articles were considered eligible for full-text reading, of which, after applying the exclusion criteria, 4 studies were selected for the final analysis and included in the systematic review. No studies were included for a quantitative analysis. We divided the results according to the location of the recurrence: locoregional recurrence, abdominal recurrence and extra abdominal recurrence. Conclusion: the treatment of choice should be assessed according to the relapse location and to the presence of single or multiple lesions. A crucial role in the decision-making algorithm is also the type of adjuvant treatment received at the time of the first diagnosis.
Convection-Enhanced Delivery of Antiangiogenic Drugs and Liposomal Cytotoxic Drugs to Heterogeneous Brain Tumor for Combination Therapy
Authors: Bhandari Ajay , Jaiswal Kartikey , Singh Anup , Zhan Wenbo
Published: August 2022

Although convection-enhanced delivery can successfully bypass the blood-brain barrier, its clinical performance remains disappointing. This is primarily attributed to the heterogeneous intratumoral environment, particularly the tumor microvasculature. This study investigates the combined convection-enhanced delivery of antiangiogenic drugs and liposomal cytotoxic drugs in a heterogeneous brain tumor environment using a transport-based mathematical model. The patient-specific 3D brain tumor geometry and the tumor’s heterogeneous tissue properties, including microvascular density, porosity and cell density, are extracted from dynamic contrast-enhanced magnetic resonance imaging data. Results show that antiangiogenic drugs can effectively reduce the tumor microvascular density. This change in tissue structure would inhibit the fluid loss from the blood to prevent drug concentration from dilution, and also reduce the drug loss by blood drainage. The comparisons between different dosing regimens demonstrate that the co-infusion of liposomal cytotoxic drugs and antiangiogenic drugs has the advantages of homogenizing drug distribution, increasing drug accumulation, and enlarging the volume where tumor cells can be effectively killed. The delivery outcomes are susceptible to the location of the infusion site. This combination treatment can be improved by infusing drugs at higher microvascular density sites. In contrast, infusion at a site with high cell density would lower the treatment effectiveness of the whole brain tumor. Results obtained from this study can deepen the understanding of this combination therapy and provide a reference for treatment design and optimization that can further improve survival and patient quality of life.
Factors Predicting 30-Day Grade IIIa–V Clavien–Dindo Classification Complications and Delayed Chemotherapy Initiation after Cytoreductive Surgery for Advanced-Stage Ovarian Cancer: A Prospective Cohort Study
Authors: Kengsakul Malika , Nieuwenhuyzen-de Boer Gatske M. , Udomkarnjananun Suwasin , Kerr Stephen J. , van Doorn Helena C. , van Beekhuizen Heleen J.
Published: August 2022

Objective: The aim of this study was to evaluate factors associated with 30-day postoperative Clavien–Dindo classification (CDC) grade IIIa or greater complications and delayed initiation of chemotherapy after cytoreductive surgery (CRS) for primary advanced-stage epithelial ovarian cancer (AEOC). Methods: This was a prospective study involving 300 patients who underwent primary or interval CRS for AEOC between February 2018 and September 2020. Postoperative complications were graded according to the CDC. Logistic regression analysis was used to evaluate factors predicting CDC grade ≥IIIa and time to chemotherapy (TTC) >42 days. Results: Interval CRS was performed in 255 (85%) patients. CDC grade ≥IIIa occurred in 51 (17%) patients. In multivariable analysis, age (p = 0.036), cardiovascular comorbidity (p < 0.001), diaphragmatic surgery (p < 0.001), intraoperative urinary tract injury (p = 0.017), and upper-abdominal visceral injury (e.g., pancreas, stomach, liver, or spleen) (p = 0.012) were associated with CDC grade ≥IIIa. In 26% of cases, TTC was >42 days (median (IQR) 39 (29–50) days) in patients with CDC grade ≥IIIa versus 33 (25–41) days in patients without CDC grade ≥ IIIa (p = 0.008). The adjusted odds ratio of developing TTC >42 days was significantly higher in patients associated with WHO performance grade ≥2 (p = 0.045), intraoperative bowel injury (p = 0.043), upper-abdominal visceral injury (p = 0.008), and postoperative CDC grade ≥IIIa (p = 0.032). Conclusions: Patients with advanced age, with cardiovascular comorbidity, and who required diaphragmatic surgery had an increased adjusted odds ratio of developing CDC grade ≥IIIa complications. CDC grade ≥IIIa complications were independently associated with TTC >42 days. Proper patient selection and prevention of intraoperative injury are essential in order to prevent postoperative complications and delayed initiation of chemotherapy.
Critical Role of Aquaporins in Cancer: Focus on Hematological Malignancies
Authors: Allegra Alessandro , Cicero Nicola , Mirabile Giuseppe , Cancemi Gabriella , Tonacci Alessandro , Musolino Caterina , Gangemi Sebastiano
Published: August 2022

Aquaporins are transmembrane molecules regulating the transfer of water and other compounds such as ions, glycerol, urea, and hydrogen peroxide. Their alteration has been reported in several conditions such as cancer. Tumor progression might be enhanced by aquaporins in modifying tumor angiogenesis, cell volume adaptation, proteases activity, cell–matrix adhesions, actin cytoskeleton, epithelial–mesenchymal transitions, and acting on several signaling pathways facilitating cancer progression. Close connections have also been identified between the aquaporins and hematological malignancies. However, it is difficult to identify a unique action exerted by aquaporins in different hemopathies, and each aquaporin has specific effects that vary according to the class of aquaporin examined and to the different neoplastic cells. However, the expression of aquaporins is altered in cell cultures and in patients with acute and chronic myeloid leukemia, in lymphoproliferative diseases and in multiple myeloma, and the different expression of aquaporins seems to be able to influence the efficacy of treatment and could have a prognostic significance, as greater expression of aquaporins is correlated to improved overall survival in leukemia patients. Finally, we assessed the possibility that modifying the aquaporin expression using aquaporin-targeting regulators, specific monoclonal antibodies, and even aquaporin gene transfer could represent an effective therapy of hematological malignancies.
Hsa_circ_0044301 Regulates Gastric Cancer Cell’s Proliferation, Migration, and Invasion by Modulating the Hsa-miR-188-5p/DAXX Axis and MAPK Pathway
Authors: Jiang Fei , Liu Guangxi , Chen Xiaowei , Li Qiong , Fang Fujin , Shen Xiaobing
Published: August 2022

Background: Despite advances in diagnostic and therapeutic technologies, the prognosis of patients with gastric cancer (GC) remains poor, necessitating further search for more effective therapeutic targets and markers for prognosis prediction. Circular RNA (circRNA) plays a role in various diseases, including GC. Methods: CircRNA expression in GC tissues was detected by circRNA microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The correlation between circRNA-0044301 and patient survival was analyzed by log-rank test and Cox regression analysis. Next, in vitro characterization and functional analysis of circRNA-0044301 was done by various assays using RNase R, actinomycin D, and RNA fluorescence in situ hybridization, as well as investigations into its use as a drug to treat tumors in a subcutaneous tumorigenesis model. RNA immunoprecipitation and dual-luciferase reporter assays were used to identify circRNA-0044301-related miRNA (miRNA-188-5p), key proteins of the related pathway (ERK1/2), and the downstream target DAXX. Finally, we investigated the relationship between circRNA-0044301 and ravoxertinib (GDC-0994) and 5-fluorouracil (5-FU) using qRT-PCR, Western blotting, and CCK8 assays. Results: CircRNA-0044301 was upregulated in tissues and cancer cells compared to its levels in controls, related to patient prognosis, and its specific siRNA-vivo could slow tumor growth. On the mechanism, it acted as a sponge of miRNA-188-5p, could regulate the downstream target DAXX, and modulated the effect of GDC-0994 on ERK1/2 and 5-FU in cells. Conclusions: CircRNA-0044301/miRNA-188-5p/DAXX (ERK1/2) may be a key axis in GC progression, and circRNA-0044301 has immense potential to be a therapeutic target for GC.
Management of Early-Stage Vulvar Cancer
Authors: Pedrão Priscila Grecca , Guimarães Yasmin Medeiros , Godoy Luani Rezende , Possati-Resende Júlio César , Bovo Adriane Cristina , Andrade Carlos Eduardo Mattos Cunha , Longatto-Filho Adhemar , dos Reis Ricardo
Published: August 2022

Vulvar cancer is a rare gynecological malignancy since it represents 4% of all cancers of the female genital tract. The most common histological type is squamous cell carcinoma (90%). This type can be classified into two clinicopathological subtypes according to the etiology. The first subtype is associated with persistent human papillomavirus infection and is usually diagnosed in younger women. The second subtype is associated with lichen sclerosus condition, and in most cases is diagnosed in postmenopausal women. Currently, an increase in first subtype cases has been observed, which raised the concern about associated mortality and treatment morbidity among young women. Vulvar cancer treatment depends on histopathology grade and staging, but surgery with or without radiotherapy as adjuvant treatment is considered the gold standard. In recent decades, sentinel lymph node biopsy has been incorporated as part of the treatment. Therefore, we sought to review and discuss the advances documented in the literature about vulvar cancer focusing on the treatment of early-stage disease. Relevant articles, such as the GROINS-V studies and the GOG protocols, are presented in this review. Additionally, we discuss key points such as the evolution of treatment from invasive surgery with high morbidity, to more conservative approaches without compromising oncologic safety; the role of sentinel lymph node mapping in the initial staging, since it reduces the complications caused by inguinofemoral lymphadenectomy; the recurrences rates, since local recurrence is common and curable, however, groin-associated, or distant recurrences have a poor prognosis; and, finally, the long-term follow-up that is essential for all patients.
Targeted Approaches in Metastatic Castration-Resistant Prostate Cancer: Which Data?
Authors: Mosillo Claudia , Calandrella Maria Letizia , Caserta Claudia , Macrini Serena , Guida Annalisa , Sirgiovanni Grazia , Bracarda Sergio
Published: August 2022

Prostate cancer is the second most common diagnosed cancer and the fifth leading cause of cancer-related deaths in men worldwide. Despite significant advances in the management of castration-sensitive prostate cancer, the majority of patients develop a castration-resistant disease after a median duration of treatment of 18–48 months. The transition to a castrate resistance state could rely on alternative survival pathways, some related to androgen-independent mechanisms. Although several agents have been approved in this setting, metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease. Recent studies revealed some of the complex pathways underlying inherited and acquired mechanisms of resistance to available treatments. A better understanding of these pathways may lead to significant improvements in survival by providing innovative therapeutic targets. The present comprehensive review attempts to provide an overview of recent progress in novel targeted therapies and near-future directions.
Survival Study: International Multicentric Minimally Invasive Liver Resection for Colorectal Liver Metastases (SIMMILR-2)
Authors: Gumbs Andrew A. , Croner Roland , Lorenz Eric , Cacciaguerra Andrea Benedetti , Tsai Tzu-Jung , Starker Lee , Flanagan Joe , Yu Ng Jing , Chouillard Elie , Abu Hilal Mohammad
Published: August 2022

Introduction: Study: International Multicentric Minimally Invasive Liver Resection for Colorectal Liver Metastases (SIMMILR-CRLM) was a propensity score matched (PSM) study that reported short-term outcomes of patients with CRLM who met the Milan criteria and underwent either open (OLR), laparoscopic (LLR) or robotic liver resection (RLR). This study, designated as SIMMILR-2, reports the long-term outcomes from that initial study, now referred to as SIMMILR-1. Methods: Data regarding neoadjuvant chemotherapeutic (NC) and neoadjuvant biological (NB) treatments received were collected, and Kaplan–Meier curves reporting the 5-year overall (OS) and recurrence-free survival (RFS) for OLR, LLR and RLR were created for patients who presented with synchronous lesions only, as there was insufficient follow-up for patients with metachronous lesions. Results: A total of 73% of patients received NC and 38% received NB in the OLR group compared to 70% and 28% in the LLR group, respectively (p = 0.5 and p = 0.08). A total of 82% of patients received NC and 40% received NB in the OLR group compared to 86% and 32% in the RLR group, respectively (p > 0.05). A total of 71% of patients received NC and 53% received NB in the LLR group compared to 71% and 47% in the RLR group, respectively (p > 0.05). OS at 5 years was 34.8% after OLR compared to 37.1% after LLR (p = 0.4), 34.3% after OLR compared to 46.9% after RLR (p = 0.4) and 30.3% after LLR compared to 46.9% after RLR (p = 0.9). RFS at 5 years was 12.1% after OLR compared to 20.7% after LLR (p = 0.6), 33.3% after OLR compared to 26.3% after RLR (p = 0.6) and 22.7% after LLR compared to 34.6% after RLR (p = 0.6). Conclusions: When comparing OLR, LLR and RLR, the OS and RFS were all similar after utilization of the Milan criteria and PSM. Biological agents tended to be utilized more in the OLR group when compared to the LLR group, suggesting that highly aggressive tumors are still managed through an open approach.
Paving the Way to Solid Tumors: Challenges and Strategies for Adoptively Transferred Transgenic T Cells in the Tumor Microenvironment
Authors: Füchsl Franziska , Krackhardt Angela M.
Published: August 2022

T cells are important players in the antitumor immune response. Over the past few years, the adoptive transfer of genetically modified, autologous T cells—specifically redirected toward the tumor by expressing either a T cell receptor (TCR) or a chimeric antigen receptor (CAR)—has been adopted for use in the clinic. At the moment, the therapeutic application of CD19- and, increasingly, BCMA-targeting-engineered CAR-T cells have been approved and have yielded partly impressive results in hematologic malignancies. However, employing transgenic T cells for the treatment of solid tumors remains more troublesome, and numerous hurdles within the highly immunosuppressive tumor microenvironment (TME) need to be overcome to achieve tumor control. In this review, we focused on the challenges that these therapies must face on three different levels: infiltrating the tumor, exerting efficient antitumor activity, and overcoming T cell exhaustion and dysfunction. We aimed to discuss different options to pave the way for potent transgenic T cell-mediated tumor rejection by engineering either the TME or the transgenic T cell itself, which responds to the environment.
Performance of the Use of Genetic Information to Assess the Risk of Colorectal Cancer in the Basque Population
Authors: Garcia-Etxebarria Koldo , Etxart Ane , Barrero Maialen , Nafria Beatriz , Segues Merino Nerea Miren , Romero-Garmendia Irati , Franke Andre , D’Amato Mauro , Bujanda Luis
Published: August 2022

Although the genetic contribution to colorectal cancer (CRC) has been studied in various populations, studies on the applicability of available genetic information in the Basque population are scarce. In total, 835 CRC cases and 940 controls from the Basque population were genotyped and genome-wide association studies were carried out. Mendelian Randomization analyses were used to discover the effect of modifiable risk factors and microbiota on CRC. In total, 25 polygenic risk score models were evaluated to assess their performance in CRC risk calculation. Moreover, 492 inflammatory bowel disease cases were used to assess whether that genetic information would not confuse both conditions. Five suggestive (p < 5 × 10−6) loci were associated with CRC risk, where genes previously associated with CRC were located (e.g., ABCA12, ATIC or ERBB4). Moreover, the analyses of CRC locations detected additional genes consistent with the biology of CRC. The possible contribution of cholesterol, BMI, Firmicutes and Cyanobacteria to CRC risk was detected by Mendelian Randomization. Finally, although polygenic risk score models showed variable performance, the best model performed correctly regardless of the location and did not misclassify inflammatory bowel disease cases. Our results are consistent with CRC biology and genetic risk models and could be applied to assess CRC risk in the Basque population.