bluuebunny/crossref_metadata_2025 huggingface dataset:
Unsteady Aerodynamic Design of a Flapping Wing Combined with a Bionic Wavy Leading Edge
Authors: Bai Xuan , Zhan Hao , Mi Baigang
Published: January 2023

Based on the bionic design of the humpback whale fin, a passive flow control method is proposed to obtain greater flapping lift by applying the wavy leading edge structure to the straight symmetrical flapping wing. The leading edge of the conventional flapping wing is replaced by the wavy shape represented by regular trigonometric function to form a special passive flow control configuration imitating the leading edge of the humpback whale fin. The dynamic aerodynamic performance and flow field characteristics of straight wing and wavy leading edge flapping wing with different parameters are compared and analyzed by CFD numerical simulation. The simulation results show that the wavy leading edge structure changes the flow field of the baseline flapping wing and reduces the pressure on the upper surface of the flapping wing during the process of downward flapping, thereby increasing the pressure difference between the upper and lower surfaces of the flapping wing and increasing the lift. The sensitivity analysis of the design parameters shows that in order to obtain the maximum lift coefficient while losing the least thrust, the smaller amplitude should be selected on the premise of selecting the smaller wavelength. Among the configurations of different design parameters calculated in this paper, the optimal wavy leading edge flapping wing configuration increases the time average lift coefficient by 32.86% and decreases the time average thrust coefficient by 14.28%. Compared with the straight wing, it has better low-speed flight and can withstand greater take-off weight.
Special Issue on Advancements in Laser-Based Additive Manufacturing Technologies
Authors: Bi Guijun
Published: January 2023

As a unique and powerful heat source, lasers are very important for the surface modification, re-manufacturing, and direct fabrication of 3D components [...]
Warranty Cost Analysis for Multi-State Products Protected by Lemon Laws
Authors: Wang Liying , Song Yushuang , Qiu Qingan , Yang Li
Published: January 2023

The implementation of lemon laws in America has played an important role in improving the quality of after-sales service. Nowadays, many countries, such as China, Canada, Europe, Australia, Singapore, and South Korea, have adopted lemon laws in various industries to protect the interest of consumers. From the perspective of manufacturers, accurate estimation of the cost of the warranty service is of great importance in guiding product pricing, quality control, and design of warranty policies. According to the terms of different lemon laws, two warranty models considering the repair time and numbers for failures are proposed in this paper. Products under these models are multi-state, and Markov processes are used to model the degradation processes of products. In the first model, a product will be replaced by a new one if the time for a repair or the number of failures exceeds their respective thresholds over the warranty period. Under the second model, both catastrophic and minor failures are considered. A product will be replaced if one of the following three conditions is met over the warranty period: the time of one repair action (regardless of failure type) is longer than a time threshold; the number of minor failures is larger than a preset threshold; a catastrophic failure occurs. The expected warranty cost rates under the two proposed warranty models are derived under the assumption of renewable warranty terms. Numerical examples are given to illustrate the results obtained.
The Effect of Web Augmented Reality on Primary Pupils’ Achievement in English
Authors: Hussein Harith A. , Ali Majid Hamid , Al-Hashimi Muhaned , Majeed Nahida Taha , Hameed Qabas A. , Ismael Reem D.
Published: January 2023

The massive development of mobile computing and mobile networks attracts developers and researchers to emerge a new direction for augmented reality on the Web. Web augmented reality is inherently considered platform independent, no pre-installation is required, easy to apply, easy to access, and easy to develop. The current study aims to introduce a vision of including Web AR in school instructional material to keep the teaching methods in line with the tremendous technological growth and invest students’ knowledge in this field. The main objective of this study is to develop a QR code-based tracking Web AR application to investigate the effect of Web AR on the achievement of 4th-year primary school pupils in English. The procedure of Web AR application includes two basic steps. Firstly, the convincing Web AR development platform is selected according to three evaluation criteria. Secondly, developing the Web AR with 73 English vocabularies included in the last four units of the Iraqi English pupil’s book. The procedures of the study include; First, a random selection of a sample of pupils and assigning them to experimental and control groups. Second, equalize the elected pupils in the factors that may affect their performance. Then, the control and experimental groups have been taught English for 12 weeks, and finally, three achievement posttests are constructed and applied to the involved groups in order to assess their performance. Having a long period of learning on using Web AR is significant, as the pupils’ tendencies and acceptance of the experiment tools require time and effort.
Anthropogenic Emission Scenarios over Europe with the WRF-CHIMERE-v2020 Models: Impact of Duration and Intensity of Reductions on Surface Concentrations during the Winter of 2015
Authors: Cholakian Arineh , Bessagnet Bertrand , Menut Laurent , Pennel Romain , Mailler Sylvain
Published: January 2023

In the framework of the FAIRMODE initiative, a set of simulations was performed using the WRF and CHIMERE models. The simulation period is chosen to cover a Particulate Matter (PM) pollution episode that happened in February 2015 over the Parisian area. A thorough validation of the reference simulation is presented, showing a good agreement between the measurements and the model both for PM components and major gaseous species. The PM composition analysis shows that the major contributors to the PM total concentration are nitrates and organic aerosols, followed by ammonium. An analysis of emission reduction scenarios compared to the reference simulation is also presented and different configurations of these scenarios are analyzed. Exceedances regarding to the last World Health Organization (WHO) guidelines are assessed, concluding that even if the most severe mitigation analyzed here (−50% emissions reduction) was applied over Paris, exceedances would still happen for PM. Emission reduction scenarios show that ozone concentrations are sensitive to NOx reductions inside the city with an increase in concentrations, while for PM a systematic decrease is observed whichever precursor emission is reduced. Coupling effects are explored and the impact of PM concentrations on the radiative and thermodynamic budgets is quantified. Scenarios are repeated both with different durations and different intensities and the most efficient configuration leading to exceedances reduction is discussed.
Decadal Application of WRF/Chem under Future Climate and Emission Scenarios: Impacts of Technology-Driven Climate and Emission Changes on Regional Meteorology and Air Quality
Authors: Jena Chinmay , Zhang Yang , Wang Kai , Campbell Patrick C.
Published: January 2023

This work presents new climate and emissions scenarios to investigate changes on future meteorology and air quality in the U.S. Here, we employ a dynamically downscaled Weather Research and Forecasting model coupled with chemistry (WRF/Chem) simulations that use two Intergovernmental Panel on Climate Change scenarios (i.e., A1B and B2) integrated with explicitly projected emissions from a novel Technology Driver Model (TDM). The projected 2046–2055 emissions show widespread reductions in most gas and aerosol species under both TDM/A1B and TDM/B2 scenarios over the U.S. The WRF/Chem simulations show that under the combined effects of the TDM/A1B climate and emission changes, the maximum daily average 8-h ozone (MDA8 h O3) increases by ~3 ppb across the U.S. mainly due to widespread increases in near-surface temperature and background methane concentrations, with some contributions from localized TDM emission changes near urban centers. For the TDM/B2 climate and emission changes, however, the MDA8 h O3 is widely decreased, except near urban centers where the relative TDM emission changes and O3 formation regimes leads to increased O3. The number of O3 exceedance days (i.e., MDA8 h O3 > 70 ppb) for the entire domain is significantly reduced by a grid cell maximum of up to 43 days (domain average ~0.5 days) and 62 days (domain average ~2 days) for the TDM/A1B and TDM/B2 scenarios, respectively, while in the western U.S., larger O3 increases lead to increases in nonattainment areas, especially for the TDM/A1B scenario. The combined effects of climate and emissions (for both A1B and B2 scenarios) will lead to widespread decreases in the daily 24-h average (DA24 h) PM2.5 concentrations, especially in the eastern U.S. (max decrease up to 93 µg m−3). The PM2.5 changes are dominated by decreases in anthropogenic emissions for both the TDM/A1B and TDM/B2 scenarios, with secondary effects on decreasing PM2.5 from climate change. The number of PM2.5 exceedance days (i.e., DA24 h PM2.5 > 35 µg m−3) is significantly reduced over the eastern U.S. under both TDM/A1B and B2 scenarios, which suggests that both climate and emission changes may synergistically lead to decreases in PM2.5 nonattainment areas in the future.
New Studies to Measure the Effects of Climate Change on the Increase in Environmental Risks
Authors: Fernández-Raga María , Yu Yang , Campo Julian
Published: January 2023

The impacts of climate change already pose major challenges for the environment, and the trend is rising [...]
Macromolecular Crowding Is Surprisingly Unable to Deform the Structure of a Model Biomolecular Condensate
Authors: Shillcock Julian C. , Thomas David B. , Ipsen John H. , Brown Andrew D.
Published: January 2023

The crowded interior of a living cell makes performing experiments on simpler in vitro systems attractive. Although these reveal interesting phenomena, their biological relevance can be questionable. A topical example is the phase separation of intrinsically disordered proteins into biomolecular condensates, which is proposed to underlie the membrane-less compartmentalization of many cellular functions. How a cell reliably controls biochemical reactions in compartments open to the compositionally-varying cytoplasm is an important question for understanding cellular homeostasis. Computer simulations are often used to study the phase behavior of model biomolecular condensates, but the number of relevant parameters increases as the number of protein components increases. It is unfeasible to exhaustively simulate such models for all parameter combinations, although interesting phenomena are almost certainly hidden in their high-dimensional parameter space. Here, we have studied the phase behavior of a model biomolecular condensate in the presence of a polymeric crowding agent. We used a novel compute framework to execute dozens of simultaneous simulations spanning the protein/crowder concentration space. We then combined the results into a graphical representation for human interpretation, which provided an efficient way to search the model’s high-dimensional parameter space. We found that steric repulsion from the crowder drives a near-critical system across the phase boundary, but the molecular arrangement within the resulting biomolecular condensate is rather insensitive to the crowder concentration and molecular weight. We propose that a cell may use the local cytoplasmic concentration to assist the formation of biomolecular condensates, while relying on the dense phase to reliably provide a stable, structured, fluid milieu for cellular biochemistry despite being open to its changing environment.
Statistical Power Analysis for Designing Bulk, Single-Cell, and Spatial Transcriptomics Experiments: Review, Tutorial, and Perspectives
Authors: Jeon Hyeongseon , Xie Juan , Jeon Yeseul , Jung Kyeong Joo , Gupta Arkobrato , Chang Won , Chung Dongjun
Published: January 2023

Gene expression profiling technologies have been used in various applications such as cancer biology. The development of gene expression profiling has expanded the scope of target discovery in transcriptomic studies, and each technology produces data with distinct characteristics. In order to guarantee biologically meaningful findings using transcriptomic experiments, it is important to consider various experimental factors in a systematic way through statistical power analysis. In this paper, we review and discuss the power analysis for three types of gene expression profiling technologies from a practical standpoint, including bulk RNA-seq, single-cell RNA-seq, and high-throughput spatial transcriptomics. Specifically, we describe the existing power analysis tools for each research objective for each of the bulk RNA-seq and scRNA-seq experiments, along with recommendations. On the other hand, since there are no power analysis tools for high-throughput spatial transcriptomics at this point, we instead investigate the factors that can influence power analysis.
Effect of Ethanol on Exosome Biogenesis: Possible Mechanisms and Therapeutic Implications
Authors: Sundar Vaishnavi , Saraswathi Viswanathan
Published: January 2023

Most eukaryotic cells, including hepatocytes, secrete exosomes into the extracellular space, which are vesicles facilitating horizontal cell-to-cell communication of molecular signals and physiological cues. The molecular cues for cellular functions are carried by exosomes via specific mRNAs, microRNAs, and proteins. Exosomes released by liver cells are a vital part of biomolecular communication in liver diseases. Importantly, exosomes play a critical role in mediating alcohol-associated liver disease (ALD) and are potential biomarkers for ALD. Moreover, alcohol exposure itself promotes exosome biogenesis and release from the livers of humans and rodent models. However, the mechanisms by which alcohol promotes exosome biogenesis in hepatocytes are still unclear. Of note, alcohol exposure leads to liver injury by modulating various cellular processes, including autophagy, ER stress, oxidative stress, and epigenetics. Evidence suggests that there is a link between each of these processes with exosome biogenesis. The aim of this review article is to discuss the interplay between ethanol exposure and these altered cellular processes in promoting hepatocyte exosome biogenesis and release. Based on the available literature, we summarize and discuss the potential mechanisms by which ethanol induces exosome release from hepatocytes, which in turn leads to the progression of ALD.
Cholesterol Redistribution in Pancreatic β-Cells: A Flexible Path to Regulate Insulin Secretion
Authors: Galli Alessandra , Arunagiri Anoop , Dule Nevia , Castagna Michela , Marciani Paola , Perego Carla
Published: January 2023

Pancreatic β-cells, by secreting insulin, play a key role in the control of glucose homeostasis, and their dysfunction is the basis of diabetes development. The metabolic milieu created by high blood glucose and lipids is known to play a role in this process. In the last decades, cholesterol has attracted significant attention, not only because it critically controls β-cell function but also because it is the target of lipid-lowering therapies proposed for preventing the cardiovascular complications in diabetes. Despite the remarkable progress, understanding the molecular mechanisms responsible for cholesterol-mediated β-cell function remains an open and attractive area of investigation. Studies indicate that β-cells not only regulate the total cholesterol level but also its redistribution within organelles, a process mediated by vesicular and non-vesicular transport. The aim of this review is to summarize the most current view of how cholesterol homeostasis is maintained in pancreatic β-cells and to provide new insights on the mechanisms by which cholesterol is dynamically distributed among organelles to preserve their functionality. While cholesterol may affect virtually any activity of the β-cell, the intent of this review is to focus on early steps of insulin synthesis and secretion, an area still largely unexplored.
Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Phosphate Accelerates Cellular Cholesterol Efflux in THP-1 Cells
Authors: Komatsu Tomohiro , Abe Satomi , Nakashima Shihoko , Sasaki Kei , Higaki Yasuki , Saku Keijiro , Miura Shin-ichiro , Uehara Yoshinari
Published: January 2023

Cholesterol efflux is a major atheroprotective function of high-density lipoproteins (HDLs) which removes cholesterol from the foam cells of lipid-rich plaques in Type 2 diabetes. The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin phosphate increases plasma glucagon-like peptide-1 (GLP-1) concentrations and is used to treat Type 2 diabetes. GLP-1 plays an important role in regulating insulin secretion and expression via the GLP-1 receptor (GLP-1R), which is expressed in pancreatic islets as well as freshly isolated human monocytes and THP-1 cells. Here, we identified a direct role of GLP-1 and DPP-4 inhibition in HDL function. Cholesterol efflux was measured in cultivated phorbol 12-myristate 13-acetate-treated THP-1 cells radiolabeled with 3H-cholesterol and stimulated with liver X receptor/retinoid X receptor agonists. Contrary to vildagliptin, sitagliptin phosphate together with GLP-1 significantly (p < 0.01) elevated apolipoprotein (apo)A1-mediated cholesterol efflux in a dose-dependent manner. The sitagliptin-induced increase in cholesterol efflux did not occur in the absence of GLP-1. In contrast, adenosine triphosphate-binding cassette transporter A1 (ABCA1) mRNA and protein expressions in the whole cell fraction were not changed by sitagliptin in the presence of GLP-1, although sitagliptin treatment significantly increased ABCA1 protein expression in the membrane fraction. Furthermore, the sitagliptin-induced, elevated efflux in the presence of GLP-1 was significantly decreased by a GLP-1R antagonist, an effect that was not observed with a protein kinase A inhibitor. To our knowledge, the present study reports for the first time that sitagliptin elevates cholesterol efflux in cultivated macrophages and may exert anti-atherosclerotic actions that are independent of improvements in glucose metabolism. Our results suggest that sitagliptin enhances HDL function by inducing a de novo HDL synthesis via cholesterol efflux.
Glucose-Responsive Silk Fibroin Microneedles for Transdermal Delivery of Insulin
Authors: Tan Guohongfang , Jiang Fujian , Jia Tianshuo , Qi Zhenzhen , Xing Tieling , Kundu Subhas C. , Lu Shenzhou
Published: January 2023

Microneedles (MNs) have attracted great interest as a drug delivery alternative to subcutaneous injections for treating diabetes mellitus. We report MNs prepared from polylysine-modified cationized silk fibroin (SF) for responsive transdermal insulin delivery. Scanning electron microscopy analysis of MNs’ appearance and morphology revealed that the MNs were well arranged and formed an array with 0.5 mm pitch, and the length of single MNs is approximately 430 μm. The average breaking force of an MN is above 1.25 N, which guarantees that it can pierce the skin quickly and reach the dermis. Cationized SF MNs are pH-responsive. MNs dissolution rate increases as pH decreases and the rate of insulin release are accelerated. The swelling rate reached 223% at pH = 4, while only 172% at pH = 9. After adding glucose oxidase, cationized SF MNs are glucose-responsive. As the glucose concentration increases, the pH inside the MNs decreases, the MNs’ pore size increases, and the insulin release rate accelerates. In vivo experiments demonstrated that in normal Sprague Dawley (SD) rats, the amount of insulin released within the SF MNs was significantly smaller than that in diabetic rats. Before feeding, the blood glucose (BG) of diabetic rats in the injection group decreased rapidly to 6.9 mmol/L, and the diabetic rats in the patch group gradually reduced to 11.7 mmol/L. After feeding, the BG of diabetic rats in the injection group increased rapidly to 33.1 mmol/L and decreased slowly, while the diabetic rats in the patch group increased first to 21.7 mmol/L and then decreased to 15.3 mmol/L at 6 h. This demonstrated that the insulin inside the microneedle was released as the blood glucose concentration increased. Cationized SF MNs are expected to replace subcutaneous injections of insulin as a new modality for diabetes treatment.
A Sensitive Hydroquinone Amperometric Sensor Based on a Novel Palladium Nanoparticle/Porous Silicon/Polypyrrole-Carbon Black Nanocomposite
Authors: Alrashidi Abdullah , El-Sherif Anas M. , Ahmed Jahir , Faisal M. , Alsaiari Mabkhoot , Algethami Jari S. , Moustafa Mohamed I. , Abahussain Abdulaziz A. M. , Harraz Farid A.
Published: January 2023

Exposure to hydroquinone (HQ) can cause various health hazards and negative impacts on the environment. Therefore, we developed an efficient electrochemical sensor to detect and quantify HQ based on palladium nanoparticles deposited in a porous silicon-polypyrrole-carbon black nanocomposite (Pd@PSi−PPy−C)-fabricated glassy carbon electrode. The structural and morphological characteristics of the newly fabricated Pd@PSi−PPy−C nanocomposite were investigated utilizing FESEM, TEM, EDS, XPS, XRD, and FTIR spectroscopy. The exceptionally higher sensitivity of 3.0156 μAμM−1 cm−2 and a low limit of detection (LOD) of 0.074 μM were achieved for this innovative electrochemical HQ sensor. Applying this novel modified electrode, we could detect wide-ranging HQ (1–450 μM) in neutral pH media. This newly fabricated HQ sensor showed satisfactory outcomes during the real sample investigations. During the analytical investigation, the Pd@PSi−PPy−C/GCE sensor demonstrated excellent reproducibility, repeatability, and stability. Hence, this work can be an effective method in developing a sensitive electrochemical sensor to detect harmful phenol derivatives for the green environment.
SERS-Tags: Selective Immobilization and Detection of Bacteria by Strain-Specific Antibodies and Surface-Enhanced Raman Scattering
Authors: Benešová Markéta , Bernatová Silvie , Mika Filip , Pokorná Zuzana , Ježek Jan , Šiler Martin , Samek Ota , Růžička Filip , Rebrošová Katarina , Zemánek Pavel , Pilát Zdeněk
Published: January 2023

Efficient separation and sensitive identification of pathogenic bacterial strains is essential for a prosperous modern society, with direct applications in medical diagnostics, drug discovery, biodefense, and food safety. We developed a fast and reliable method for antibody-based selective immobilization of bacteria from suspension onto a gold-plated glass surface, followed by detection using strain-specific antibodies linked to gold nanoparticles decorated with a reporter molecule. The reporter molecules are subsequently detected by surface-enhanced Raman spectroscopy (SERS). Such a multi-functionalized nanoparticle is called a SERS-tag. The presented procedure uses widely accessible and cheap materials for manufacturing and functionalization of the nanoparticles and the immobilization surfaces. Here, we exemplify the use of the produced SERS-tags for sensitive single-cell detection of opportunistic pathogen Escherichia coli, and we demonstrate the selectivity of our method using two other bacterial strains, Staphylococcus aureus and Serratia marcescens, as negative controls. We believe that the described approach has a potential to inspire the development of novel medical diagnostic tools for rapid identification of bacterial pathogens.
Carbon Nanotube-Based Biosensors Using Fusion Technologies with Biologicals & Chemicals for Food Assessment
Authors: Lee Jinyoung
Published: January 2023

High-sensitivity sensors applied in various diagnostic systems are considered to be a promising technology in the era of the fourth industrial revolution. Biosensors that can quickly detect the presence and concentration of specific biomaterials are receiving research attention owing to the breakthroughs in detection technology. In particular, the latest technologies involving the miniaturization of biosensors using nanomaterials, such as nanowires, carbon nanotubes, and nanometals, have been widely studied. Nano-sized biosensors applied in food assessment and in in vivo measurements have the advantages of rapid diagnosis, high sensitivity and selectivity. Nanomaterial-based biosensors are inexpensive and can be applied to various fields. In the present society, where people are paying attention to health and wellness, high-technology food assessment is becoming essential as the consumer demand for healthy food increases. Thus, biosensor technology is required in the food and medical fields. Carbon nanotubes (CNTs) are widely studied for use in electrochemical biosensors. The sensitive electrical characteristics of CNTs allow them to act as electron transfer mediators in electrochemical biosensors. CNT-based biosensors require novel technologies for immobilizing CNTs on electrodes, such as silicon wafers, to use as biosensor templates. CNT-based electrochemical biosensors that serve as field-effect transistors (FET) increase sensitivity. In this review, we critically discuss the recent advances in CNT-based electrochemical biosensors applied with various receptors (antibodies, DNA fragments, and other nanomaterials) for food evaluation, including pathogens, food allergens, and other food-based substances.
Neural Correlates of Impaired Cognitive Control in Individuals with Methamphetamine Dependence: An fMRI Study
Authors: Zerekidze Ani , Li Meng , Javaheripour Nooshin , Huff Laura , Weiss Thomas , Walter Martin , Wagner Gerd
Published: January 2023

Impaired cognitive and behavioral control has often been observed in people who use methamphetamine (MA). However, a comprehensive understanding of the neural substrates underlying these impairments is still lacking. The goal of the present study was to study the neural correlates of impaired cognitive control in individuals with MA dependence according to DSM-IV criteria. Eighteen individuals with MA dependence and 21 healthy controls were investigated using Stroop task, fMRI, and an impulsivity questionnaire. Overall, patients were found to have significantly poorer accuracy on the Stroop task and higher self-rated impulsivity. Comparing brain activations during the task, decreased activation in the dorsolateral prefrontal cortex (DLPFC), anterior midcingulate cortex (aMCC), and dorsal striatum was observed in individuals with MA dependence, compared to healthy controls. Altered fMRI signal in DLPFC and aMCC significantly correlated with impaired behavioral task performance in individuals with MA dependence. Furthermore, significantly lower and pronounced brain activations in the MA group were additionally detected in several sensory cortical regions, i.e., in the visual, auditory, and somatosensory cortices. The results of the current study provide evidence for the negative impact of chronic crystal meth consumption on the proper functioning of the fronto-cingulate and striatal brain regions, presumably underlying the often-observed deficits in executive functions in individuals with MA use disorder. As a new finding, we also revealed abnormal activation in several sensory brain regions, suggesting the negative effect of MA use on the proper neural activity of these regions. This blunted activation could be the cause of the observed deficits in executive functions and the associated altered brain activation in higher-level brain networks.
Existing Mono-Cell and Multi-Cell Low-Rise Dry, Hollowed Constructions
Authors: Corbi Ileana , Baratta Alessandro , Corbi Ottavia , Li Haitao
Published: January 2023

The paper focuses on trulli, which are ancient typical drystone constructions with inner hollow largely spread in the Puglia region in the southern part of Italy. The trullo is the cheapest structure that can be built in a calcareous territory using plain stones without using any mortar, and has assumed a number of different forms, initially used as protection for the farm equipment, and later evolving into a house. This paper presents the evolution over time of these structures, as well as their description and treatment from a structural point of view. The simplicity of both the materials and techniques for realizing these structures is currently the basis of many projects for the development and progress in emerging countries, and makes the study of their mechanics very topical.
Intracranial Solitary Fibrous Tumour Management: A French Multicentre Retrospective Study
Authors: Lottin Marine , Escande Alexandre , Bauchet Luc , Albert-Thananayagam Marie , Barthoulot Maël , Peyre Matthieu , Boone Mathieu , Zouaoui Sonia , Guyotat Jacques , Penchet Guillaume , Pallud Johan , Dufour Henry , Emery Evelyne , Lefranc Michel , Freppel Sébastien , Namaki Houman , Gueye Edouard , Lemaire Jean-Jacques , Muckensturm Bertrand , Srour Robin , Derrey Stéphane , Monfilliette Apolline , Constans Jean-Marc , Maurage Claude-Alain , Chauffert Bruno , Penel Nicolas
Published: January 2023

Background: Intracranial solitary fibrous tumour (iSFT) is an exceptional mesenchymal tumour with high recurrence rates. We aimed to analyse the clinical outcomes of newly diagnosed and recurrent iSFTs. Methods: We carried out a French retrospective multicentre (n = 16) study of histologically proven iSFT cases. Univariate and multivariate Cox models were used to estimate the prognosis value of the age, location, size, WHO grade, and surgical extent on overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS). Results: Eighty-eight patients were included with a median age of 54.5 years. New iSFT cases were treated with gross tumour resection (GTR) (n = 75) or subtotal resection (STR) (n = 9) and postoperative radiotherapy (PORT) (n = 32, 57%). The median follow-up time was 7 years. The median OS, PFS, and LRFS were 13 years, 7 years, and 7 years, respectively. Forty-two patients experienced recurrence. Extracranial metastasis occurred in 16 patients. Median OS and PFS after the first recurrence were 6 years and 15.4 months, respectively. A higher histological grade was a prognosis factor for PFS (p = 0.04) and LRFS (p = 0.03). GTR influenced LRFS (p = 0.03). Conclusion: GTR provided benefits as a first treatment for iSFTs. However, approximately 40% of patients experienced relapse, which remains a challenging state.
A Suggested Modification to FIGO Stage IV Epithelial Ovarian Cancer
Authors: Métairie Marie , Benoit Louise , Koual Meriem , Bentivegna Enrica , Wohrer Henri , Bolze Pierre-Adrien , Kerbage Yohan , Raimond Emilie , Akladios Cherif , Carcopino Xavier , Canlorbe Geoffroy , Uzan Jennifer , Lavoué Vincent , Mimoun Camille , Huchon Cyrille , Koskas Martin , Costaz Hélène , Margueritte François , Dabi Yohann , Touboul Cyril , Bendifallah Sofiane , Ouldamer Lobna , Delanoy Nicolas , Nguyen-Xuan Huyen-Thu , Bats Anne-Sophie , Azaïs Henri
Published: January 2023

International Federation of Gynecology and Obstetrics (FIGO) staging classification for stage IV epithelial ovarian cancer (EOC) separates stages IVA (pleural effusion) and IVB (parenchymal and/or extra-abdominal lymph node metastases). We aimed to evaluate its prognostic impact and to compare survival according to the initial metastatic location. We conducted a multicenter study between 2000 and 2020, including patients with a FIGO stage IV EOC. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and recurrence rates. We included 307 patients: 98 (32%) had FIGO stage IVA and 209 (68%) had FIGO stage IVB. The median OS and PFS of stage IVA patients were significantly lower than those of stage IVB patients (31 versus 45 months (p = 0.02) and 18 versus 25 months (p = 0.01), respectively). Recurrence rate was higher in stage IVA than IVB patients (65% versus 47% (p = 0.004)). Initial pleural involvement was a poor prognostic factor with a median OS of 35 months versus 49 months for patients without initial pleural involvement (p = 0.024). Patients with FIGO stage IVA had a worse prognosis than patients with FIGO stage IVB EOC. Pleural involvement appears to be relevant for predicting survival. We suggest a modification of the current FIGO staging classification.
Diagnostic Performance of Biomarkers for Bladder Cancer Detection Suitable for Community and Primary Care Settings: A Systematic Review and Meta-Analysis
Authors: Papavasiliou Evie , Sills Valerie A. , Calanzani Natalia , Harrison Hannah , Snudden Claudia , di Martino Erica , Cowan Andy , Behiyat Dawnya , Boscott Rachel , Tan Sapphire , Bovaird Jennifer , Stewart Grant D. , Walter Fiona M. , Zhou Yin
Published: January 2023

Evidence on the use of biomarkers to detect bladder cancer in the general population is scarce. This study aimed to systematically review evidence on the diagnostic performance of biomarkers which might be suitable for use in community and primary care settings [PROSPERO Registration: CRD42021258754]. Database searches on MEDLINE and EMBASE from January 2000 to May 2022 resulted in 4914 unique citations, 44 of which met inclusion criteria. Included studies reported on 112 biomarkers and combinations. Heterogeneity of designs, populations and outcomes allowed for the meta-analysis of three biomarkers identified in at least five studies (NMP-22, UroVysion, uCyt+). These three biomarkers showed similar discriminative ability (adjusted AUC estimates ranging from 0.650 to 0.707), although for NMP-22 and UroVysion there was significant unexplained heterogeneity between included studies. Narrative synthesis revealed the potential of these biomarkers for use in the general population based on their reported clinical utility, including effects on clinicians, patients, and the healthcare system. Finally, we identified some promising novel biomarkers and biomarker combinations (N < 3 studies for each biomarker/combination) with negative predictive values of ≥90%. These biomarkers have potential for use as a triage tool in community and primary care settings for reducing unnecessary specialist referrals. Despite promising emerging evidence, further validation studies in the general population are required at different stages within the diagnostic pathway.
MAPK Pathway Inhibitors in Thyroid Cancer: Preclinical and Clinical Data
Authors: Schubert Louis , Mariko Mohamed Lamine , Clerc Jérôme , Huillard Olivier , Groussin Lionel
Published: January 2023

Thyroid cancer is the most common endocrine cancer, with a good prognosis in most cases. However, some cancers of follicular origin are metastatic or recurrent and eventually become radioiodine refractory thyroid cancers (RAIR-TC). These more aggressive cancers are a clinical concern for which the therapeutic arsenal remains limited. Molecular biology of these tumors has highlighted a hyper-activation of the Mitogen-Activated Protein Kinases (MAPK) pathway (RAS-RAF-MEK-ERK), mostly secondary to the BRAFV600E hotspot mutation occurring in about 60% of papillary cancers and 45% of anaplastic cancers. Therapies targeting the different protagonists of this signaling pathway have been tested in preclinical and clinical models: first and second generation RAF inhibitors and MEK inhibitors. In clinical practice, dual therapies with a BRAF inhibitor and a MEK inhibitor are being recommended in anaplastic cancers with the BRAFV600E mutation. Concerning RAIR-TC, these inhibitors can be used as anti-proliferative drugs, but their efficacy is inconsistent due to primary or secondary resistance. A specific therapeutic approach in thyroid cancers consists of performing a short-term treatment with these MAPK pathway inhibitors to evaluate their capacity to redifferentiate a refractory tumor, with the aim of retreating the patients by radioactive iodine therapy in case of re-expression of the sodium–iodide symporter (NIS). In this work, we report data from recent preclinical and clinical studies on the efficacy of MAPK pathway inhibitors and their resistance mechanisms. We will also report the different preclinical and clinical studies that have investigated the redifferentiation with these therapies.
Long-Term Non-Cancer Risks in People with BRCA Mutations following Risk-Reducing Bilateral Salpingo-Oophorectomy and the Role of Hormone Replacement Therapy: A Review
Authors: Nitschke Amanda S. , do Valle Helena Abreu , Dawson Lesa , Kwon Janice S. , Hanley Gillian E.
Published: January 2023

Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is the gold standard preventative option for BRCA mutation carriers at high risk for ovarian and breast cancer. However, when performed at the recommended ages of 35–45 years, RRBSO induces immediate premature surgical menopause, along with the accompanying adverse psychosocial, cardiovascular, bone, and cognitive health consequences. While these health consequences have been thoroughly studied in the general population, little is known about the long-term health outcomes in the BRCA population. Hormone replacement therapy (HRT) until the average age of natural menopause can help mitigate these health risks, yet the initiation of HRT is a complex decision among BRCA carriers due to concern of increasing the already high risk of breast cancer in these people. This review summarizes the current research on long-term non-cancer risks in BRCA carriers following RRBSO-induced premature surgical menopause, and highlights the existing evidence in support of HRT use in this population.
Seaweed-Derived Sulfated Polysaccharides; The New Age Chemopreventives: A Comprehensive Review
Authors: Bhuyan Prajna Paramita , Nayak Rabindra , Patra Srimanta , Abdulabbas Hadi Sajid , Jena Mrutyunjay , Pradhan Biswajita
Published: January 2023

Seaweed-derived bioactive compounds are regularly employed to treat human diseases. Sulfated polysaccharides are potent chemotherapeutic or chemopreventive medications since it has been discovered. They have exhibited anti-cancer properties by enhancing immunity and driving apoptosis. Through dynamic modulation of critical intracellular signalling pathways, such as control of ROS generation and preservation of essential cell survival and death processes, sulfated polysaccharides’ antioxidant and immunomodulatory potentials contribute to their disease-preventive effectiveness. Sulfated polysaccharides provide low cytotoxicity and good efficacy therapeutic outcomes via dynamic modulation of apoptosis in cancer. Understanding how sulfated polysaccharides affect human cancer cells and their molecular involvement in cell death pathways will showcase a new way of chemoprevention. In this review, the significance of apoptosis and autophagy-modulating sulfated polysaccharides has been emphasized, as well as the future direction of enhanced nano-formulation for greater clinical efficacy. Moreover, this review focuses on the recent findings about the possible mechanisms of chemotherapeutic use of sulfated polysaccharides, their potential as anti-cancer drugs, and proposed mechanisms of action to drive apoptosis in diverse malignancies. Because of their unique physicochemical and biological properties, sulfated polysaccharides are ideal for their bioactive ingredients, which can improve function and application in disease. However, there is a gap in the literature regarding the physicochemical properties and functionalities of sulfated polysaccharides and the use of sulfated polysaccharide-based delivery systems in functional cancer. Furthermore, the preclinical and clinical trials will reveal the drug’s efficacy in cancer.
Oral Somatosensory Alterations in Head and Neck Cancer Patients—An Overview of the Evidence and Causes
Authors: Riantiningtyas Reisya R. , Carrouel Florence , Bruyas Amandine , Bredie Wender L.P. , Kwiecien Camille , Giboreau Agnès , Dougkas Anestis
Published: January 2023

Food-related sensory alterations are prevalent among cancer patients and negatively impact their relationship with food, quality of life, and overall health outcome. In addition to taste and smell, food perception is also influenced by somatosensation comprising tactile, thermal, and chemesthetic sensations; yet studies on oral somatosensory perception of cancer patients are lacking to provide patients with tailored nutritional solutions. The present review aimed to summarise findings on the oral somatosensory perception of head and neck cancer (HNC) patients and the potential aetiologies of somatosensory alterations among this population. Subjective assessments demonstrated alterations in oral somatosensory perception such as sensitivity to certain textures, spices, and temperatures. Physiological changes in oral somatosensation have been observed through objective assessments of sensory function, showing reduced localised tactile function and thermal sensitivity. Changes in whole-mouth tactile sensation assessed using texture discrimination and stereognosis ability seem to be less evident. Available evidence indicated oral somatosensory alterations among HNC patients, which may affect their eating behaviour, but more studies with larger sample sizes and standardised assessment methods are needed. Unlike other types of cancers, sensory alterations in HNC patients are not only caused by the treatments, but also by the cancer itself, although the exact mechanism is not fully understood. Prevalent oral complications, such as xerostomia, dysphagia, mucositis, and chemosensory alterations, further modify their oral condition and food perception. Oral somatosensory perception of cancer patients is an under-investigated topic, which constitutes an important avenue for future research due to its potential significance on eating behaviour and quality of life.
Advances in the Molecular Landscape of Lung Cancer Brain Metastasis
Authors: Souza Vanessa G. P. , de Araújo Rachel Paes , Santesso Mariana R. , Seneda Ana Laura , Minutentag Iael W. , Felix Tainara Francini , Hamamoto Filho Pedro Tadao , Pewarchuk Michelle E. , Brockley Liam J. , Marchi Fábio A. , Lam Wan L. , Drigo Sandra A. , Reis Patricia P.
Published: January 2023

Lung cancer is one of the most frequent tumors that metastasize to the brain. Brain metastasis (BM) is common in advanced cases, being the major cause of patient morbidity and mortality. BMs are thought to arise via the seeding of circulating tumor cells into the brain microvasculature. In brain tissue, the interaction with immune cells promotes a microenvironment favorable to the growth of cancer cells. Despite multimodal treatments and advances in systemic therapies, lung cancer patients still have poor prognoses. Therefore, there is an urgent need to identify the molecular drivers of BM and clinically applicable biomarkers in order to improve disease outcomes and patient survival. The goal of this review is to summarize the current state of knowledge on the mechanisms of the metastatic spread of lung cancer to the brain and how the metastatic spread is influenced by the brain microenvironment, and to elucidate the molecular determinants of brain metastasis regarding the role of genomic and transcriptomic changes, including coding and non-coding RNAs. We also present an overview of the current therapeutics and novel treatment strategies for patients diagnosed with BM from NSCLC.
Feasibility of Continuous Monitoring of Endoscopy Performance and Adverse Events: A Single-Center Experience
Authors: Zandanell Stephan , Gensluckner Sophie , Wolkersdoerfer Gernot , Berr Frieder , Dienhart Christiane , Gantschnigg Antonia , Singhartinger Franz , Wagner Andrej
Published: January 2023

Background: We integrated a standardized questionnaire focusing on adverse events and performance measures in gastrointestinal endoscopy as a mandatory component of the electronical medical record. Methods: This retrospective study was conducted using prospectively collected data on quality parameters and adverse events (AEPM) for all diagnostic and therapeutic endoscopic procedures at our center between 2018 and 2020. Results: A total of 7532 consecutive endoscopic procedures were performed in 5035 patients. The proportion of high-risk examinations and high-risk patients was 20% and 23%, respectively. Severe adverse events (AEs, n = 21) occurred in 0.3% of procedures and significantly more often in patients with an ASA score > II (0.6%, p < 0.01). We observed no long-term morbidity after severe AEs. Mortality was 0.03% (n = 2). Following screening colonoscopy (n = 242), four endoscopists documented AEPM in more than 98% of the examinations. The cecal intubation rate was 97%, and the mean adenoma detection rate 60%. The quality of lavage was documented in 97% (rated as good in 70% and moderate in 24%). Conclusions: The risk of adverse events is significantly increased in patients with an ASA score > II, which should be considered when choosing treatment methods and precautionary measures. Continuous recording of AEPM can be effectively integrated into the clinical reporting process, enabling analysis of the data and feedback to be provided to endoscopists.
Diagnostic and Therapeutic Algorithm for Appendiceal Tumors and Pseudomyxoma Peritonei: A Consensus of the Peritoneal Malignancies Oncoteam of the Italian Society of Surgical Oncology (SICO)
Authors: Vaira Marco , Robella Manuela , Guaglio Marcello , Berchialla Paola , Sommariva Antonio , Valle Mario , Pasqual Enrico Maria , Roviello Franco , Framarini Massimo , Fiorentini Giammaria , Sammartino Paolo , Ilari Civit Alba , Di Giorgio Andrea , Ansaloni Luca , Deraco Marcello
Published: January 2023

Aim: Pseudomyxoma peritonei (PMP) is an uncommon pathology, and its rarity causes a lack of scientific evidence, precluding the design of a prospective trial. A diagnostic and therapeutic algorithm (DTA) is necessary in order to standardize the disease treatment while balancing optimal patient management and the correct use of resources. The Consensus of the Italian Society of Surgical Oncology (SICO) Oncoteam aims at defining a diagnostic and therapeutic pathway for PMP and appendiceal primary tumors applicable in Italian healthcare. Method: The consensus panel included 10 delegated representatives of oncological referral centers for Peritoneal Surface Malignancies (PSM) affiliated to the SICO PSM Oncoteam. A list of statements regarding the DTA of patients with PMP was prepared according to recommendations based on the review of the literature and expert opinion. Results: A consensus was obtained on 33 of the 34 statements linked to the DTA; two flowcharts regarding the management of primary appendiceal cancer and peritoneal disease were approved. Conclusion: Currently, consensus has been reached on pathological classification, preoperative evaluation, cytoreductive surgery technical detail, and systemic treatment; some controversies still exist regarding the exclusion criteria for HIPEC treatment. A shared Italian model of DTA is an essential tool to ensure the appropriateness and equity of treatment for these patients.