bluuebunny/crossref_metadata_2025 huggingface dataset:
Splatters and Aerosols Contamination in Dental Aerosol Generating Procedures
Authors: Han Pingping , Li Honghui , Walsh Laurence J. , Ivanovski Sašo
Published: February 2021

Dental aerosol-generating procedures produce a large amount of splatters and aerosols that create a major concern for airborne disease transmission, such as COVID-19. This study established a method to visualise splatter and aerosol contamination by common dental instrumentation, namely ultrasonic scaling, air-water spray, high-speed and low-speed handpieces. Mock dental procedures were performed on a mannequin model, containing teeth in a typodont and a phantom head, using irrigation water containing fluorescein dye as a tracer. Filter papers were placed in 10 different locations to collect splatters and aerosols, at distances ranging from 20 to 120 cm from the source. All four types of dental equipment produced contamination from splatters and aerosols. At 120 cm away from the source, the high-speed handpiece generated the greatest amount and size (656 ± 551 μm) of splatter particles, while the triplex syringe generated the largest amount of aerosols (particle size: 1.73 ± 2.23 μm). Of note, the low-speed handpiece produced the least amount and size (260 ± 142 μm) of splatter particles and the least amount of aerosols (particle size: 4.47 ± 5.92 μm) at 120 cm. All four dental AGPs produce contamination from droplets and aerosols, with different patterns of distribution. This simple model provides a method to test various preventive strategies to reduce risks from splatter and aerosols.
Evaluation of Emotional Satisfaction Using Questionnaires in Voice-Based Human–AI Interaction
Authors: Shin Jong-Gyu , Choi Ga-Young , Hwang Han-Jeong , Kim Sang-Ho
Published: February 2021

With the development of artificial intelligence technology, voice-based intelligent systems (VISs), such as AI speakers and virtual assistants, are intervening in human life. VISs are emerging in a new way, called human–AI interaction, which is different from existing human–computer interaction. Using the Kansei engineering approach, we propose a method to evaluate user satisfaction during interaction between a VIS and a user-centered intelligent system. As a user satisfaction evaluation method, a VIS comprising four types of design parameters was developed. A total of 23 subjects were considered for interaction with the VIS, and user satisfaction was measured using Kansei words (KWs). The questionnaire scores collected through KWs were analyzed using exploratory factor analysis. ANOVA was used to analyze differences in emotion. On the “pleasurability” and “reliability” axes, it was confirmed that among the four design parameters, “sentence structure of the answer” and “number of trials to get the right answer for a question” affect the emotional satisfaction of users. Four satisfaction groups were derived according to the level of the design parameters. This study can be used as a reference for conducting an integrated emotional satisfaction assessment using emotional metrics such as biosignals and facial expressions.
Impossible Origins: Trauma Narrative and Cinematic Adaptation
Authors: Belau Linda
Published: February 2021

In this essay, I explore the cinematic adaptation and the representation of trauma, while I further consider the role and significance of the notion of the origin in both trauma and in cinematic adaptation. Through an initial consideration of the relationship between the theory of the impossible origin, particularly as it is articulated by Walter Benjamin, the essay goes on to analyze the significance and role of an impossible origin in the elemental form of adaptation. To this end, the essay considers the movement of adaptation from an autobiographical trauma memoir to a feature film, considering the success or failure of adaptation in situations where the original literary work concerns an experience of extremity. As I consider the vicissitudes of trauma and its grounding in a repetitious structure that leaves the survivor suspended in a kind of missed experience (or missed origin), I further explore how this missing origin (or original text in the case of adaptation) can be represented at all.
Association between Long-Term Exposure to PM2.5 and Lung Imaging Phenotype in CODA Cohort
Authors: Kim Youlim , Bak So Hyeon , Kwon Sung Ok , Kim Ho , Kim Woo Jin , Lee Chang Youl
Published: February 2021

Background and Aims: Ambient particulate matter (PM) is causing respiratory symptoms of individuals at all ages and reducing their lung functions. These individuals could develop chronic pulmonary disease. Recent studies have shown that short-term exposure to PM affects acute exacerbation of respiratory disease. However, evidence about the association between long-term exposure and progression of respiratory diseases remains insufficient. The purpose of this study was to examine the association between long-term exposure of air pollution (PM2.5) and the effect on lung imaging phenotype in dust-exposed Korean adults living near cement factories. Methods: We conducted a cross-sectional analysis on the Chronic Obstructive Pulmonary Disease (COPD) in Dusty Areas (CODA) cohort, which was recruited from 2012 to 2014. Emphysema index and mean wall area were measured using an in-house software program developed by the Korean obstructive lung disease study group based on chest CT scan. A satellite-based model was used to estimate the long-term PM2.5 concentration at each participant’s address. Results: Of 504 eligible participants, 400 participants were analyzed. Their mean age was 71.7 years. Most participants were men (N = 301, 75.3%). The emphysema index of the whole group was 6.63 ± 0.70, and the mean wall area was 68.8 ± 5.2. Image measurement and PM2.5 concentration showed no significant difference in the whole group; however, in the group of subjects with normal lung function, there were significant associations between long-term PM2.5 exposure and emphysema index measurement: 1-year (ß = 0.758, p = 0.021), 3-year (ß = 0.629, p = 0.038), and 5-year (ß = 0.544, p = 0.045). There was no significant association between long-term PM2.5 exposure and mean wall area measurement: 1-year (ß = −0.389, p = 0.832), 3-year (ß = −3.677, p = 0.170), and 5-year (ß = −3.769, p = 0.124). Conclusions: This study suggests that long-term exposure of PM2.5 may affect the emphysematous change in patients with normal lung functions.
On Λ-Fractional Viscoelastic Models
Authors: Lazopoulos Anastassios K. , Karaoulanis Dimitrios
Published: February 2021

Λ-Fractional Derivative (Λ-FD) is a new groundbreaking Fractional Derivative (FD) introduced recently in mechanics. This derivative, along with Λ-Transform (Λ-T), provides a reliable alternative to fractional differential equations’ current solving. To put it straightforwardly, Λ-Fractional Derivative might be the only authentic non-local derivative that exists. In the present article, Λ-Fractional Derivative is used to describe the phenomenon of viscoelasticity, while the whole methodology is demonstrated meticulously. The fractional viscoelastic Zener model is studied, for relaxation as well as for creep. Interesting results are extracted and compared to other methodologies showing the value of the pre-mentioned method.
A Flexible Model for Benchmarking the Energy Usage of Automotive Lithium-Ion Battery Cell Manufacturing
Authors: Jinasena Asanthi , Burheim Odne Stokke , Strømman Anders Hammer
Published: February 2021

The increasing use of electric vehicle batteries in the world has a significant impact on both society and the environment. Thus, there is a need for the availability of transparent information on resource allocation. Battery manufacturing process details in this regard are not available in academia or the public. The available energy data on manufacturing has a high variation. Furthermore, different process steps have different energy and material demands. A process model can benchmark the energy usage, provide detailed process data, and compare various cell productions which in turn can be used in life-cycle assessment studies to reduce the variation and provide directions for improvements. Therefore, a cell manufacturing model is developed for the calculation of energy and material demands for different battery types, plant capacities, and process steps. The model consists of the main process steps, machines, intermediate products and building service units. Furthermore, the results are validated using literature values. For a case study of a 2 GWh plant that produces prismatic NMC333 cells, the total energy requirement on a theoretical and optimal basis is suggested to be 44.6Whinproduction/Whcellcapacity. This energy consumption in producing batteries is dominated by electrode drying, and dry room. Energy usage for a variety of cell types for a similar plant capacity shows that the standard deviation in the results is low (47.23±13.03Wh/Wh).
Development of a New Detection Algorithm to Identify Acute Coronary Syndrome Using Electrochemical Biosensors for Real-World Long-Term Monitoring
Authors: Redon Pau , Shahzad Atif , Iqbal Talha , Wijns William
Published: February 2021

Electrochemically based technologies are rapidly moving from the laboratory to bedside applications and wearable devices, like in the field of cardiovascular disease. Major efforts have focused on the biosensor component in contrast with those employed in creating more suitable detection algorithms for long-term real-world monitoring solutions. The calibration curve procedure presents major limitations in this context. The objective is to propose a new algorithm, compliant with current clinical guidelines, which can overcome these limitations and contribute to the development of trustworthy wearable or telemonitoring solutions for home-based care. A total of 123 samples of phosphate buffer solution were spiked with different concentrations of troponin, the gold standard method for the diagnosis of the acute coronary syndrome. These were classified as normal or abnormal according to established clinical cut-off values. Off-the-shelf screen-printed electrochemical sensors and cyclic voltammetry measurements (sweep between −1 and 1 V in a 5 mV step) was performed to characterize the changes on the surface of the biosensor and to measure the concentration of troponin in each sample. A logistic regression model was developed to accurately classify these samples as normal or abnormal. The model presents high predictive performance according to specificity (94%), sensitivity (92%), precision (92%), recall (92%), negative predictive value (94%) and F-score (92%). The area under the curve of the precision-recall curve is 97% and the positive and negative likelihood ratios are 16.38 and 0.082, respectively. Moreover, high discriminative power is observed from the discriminate odd ratio (201) and the Youden index (0.866) values. The promising performance of the proposed algorithm suggests its capability to overcome the limitations of the calibration curve procedure and therefore its suitability for the development of trustworthy home-based care solutions.
Establishing a Percutaneous Infection Model Using Zebrafish and a Salmon Pathogen
Authors: Nakatani Hajime , Hori Katsutoshi
Published: February 2021

To uncover the relationship between skin bacterial flora and pathogen infection, we developed a percutaneous infection model using zebrafish and Yersinia ruckeri, a pathogen causing enteric redmouth disease in salmon and in trout. Pathogen challenge, either alone or together with pricking by a small needle, did not cause infection of the fish. However, cold stress given by water temperature shift from the optimum 28 °C for zebrafish to 20 °C caused fatal infection of injured fish following pathogen challenge. We investigated the effects of cold stress, injury, and pathogen challenge, alone and in combination, on fish skin bacterial flora using 16S rDNA metagenomics. We found that cold stress drastically altered the skin bacterial flora, which was dominated by Y. ruckeri on infected fish. In addition, fish whose intrinsic skin bacterial flora was disrupted by antibiotics had their skin occupied by Y. ruckeri following a challenge with this pathogen, although the fish survived without injury to create a route for invasion into the fish body. Our results suggest that the intrinsic skin bacterial flora of fish protects them from pathogen colonization, and that its disruption by stress allows pathogens to colonize and dominate their skin.
Obesity-Related Changes in Human Plasma Lipidome Determined by the Lipidyzer Platform
Authors: Pikó Péter , Pál László , Szűcs Sándor , Kósa Zsigmond , Sándor János , Ádány Róza
Published: February 2021

Obesity is an increasing public health concern both in the developed and developing countries. Previous studies have demonstrated that considerable alterations in lipid metabolism and consequently marked changes in lipid profile are associated with the onset and progression of obesity-related complications. To characterize the full spectrum of obesity-induced changes in lipid metabolism, direct infusion tandem mass spectrometry analysis is the most promising approach. To better understand which of the many lipid species are the most strongly associated with obesity, the aim of our work was to measure and profile plasma lipids in normal (n = 57), overweight (n = 31), and obese (n = 48) individuals randomly selected from samples of Hungarian general and Roma populations by using the targeted quantitative lipidomics platform, the Lipidyzer. Principal component and stepwise regression analyses were used to identify the most significant clusters and species of lipids by increasing body mass index (BMI). From the 18 clusters identified four key lipid species (PE P-16:0/20:3, TG 20:4_33:1, TG 22:6_36:4, TG 18:3_33:0) showed a strong significant positive and three others (Hex-Cer 18:1;O2/22:0, LPC 18:2, PC 18:1_18:1) significant negative association with BMI. Compared to individual lipid species alone, the lipid species ratio (LSR) we introduced showed an extremely strong, at least 9 orders of magnitude stronger, association with BMI. The LSR can be used as a sensitive and predictive indicator to monitor obesity-related alterations in human plasma and control the effectiveness of treatment of obesity associated non-communicable diseases.
Dehydration-Induced WRKY Transcriptional Factor MfWRKY70 of Myrothamnus flabellifolia Enhanced Drought and Salinity Tolerance in Arabidopsis
Authors: Xiang Xiang-Ying , Chen Jia , Xu Wen-Xin , Qiu Jia-Rui , Song Li , Wang Jia-Tong , Tang Rong , Chen Duoer , Jiang Cai-Zhong , Huang Zhuo
Published: February 2021

The resurrection plants Myrothamnus flabellifolia can survive long term severe drought and desiccation conditions and soon recover after rewatering. However, few genes related to such excellent drought tolerance and underlying molecular mechanism have been excavated. WRKY transcription factors play critical roles in biotic and abiotic stress signaling, in which WRKY70 functions as a positive regulator in biotic stress response but a negative regulator in abiotic stress signaling in Arabidopsis and some other plant species. In the present study, the functions of a dehydration-induced MfWRKY70 of M. flabellifolia participating was investigated in the model plant Arabidopsis. Our results indicated that MfWRKY70 was localized in the nucleus and could significantly increase tolerance to drought, osmotic, and salinity stresses by promoting root growth and water retention, as well as enhancing the antioxidant enzyme system and maintaining reactive oxygen species (ROS) homeostasis and membrane-lipid stability under stressful conditions. Moreover, the expression of stress-associated genes (P5CS, NCED3 and RD29A) was positively regulated in the overexpression of MfWRKY70 Arabidopsis. We proposed that MfWRKY70 may function as a positive regulator for abiotic stress responses and can be considered as a potential gene for improvement of drought and salinity tolerance in plants.
Properties of the Extracellular Polymeric Substance Layer from Minimally Grown Planktonic Cells of Listeria monocytogenes
Authors: Nwaiwu Ogueri , Wong Lawrence , Lad Mita , Foster Timothy , MacNaughtan William , Rees Catherine
Published: February 2021

The bacterium Listeria monocytogenes is a serious concern to food processing facilities because of its persistence. When liquid cultures of L. monocytogenes were prepared in defined media, it was noted that planktonic cells rapidly dropped out of suspension. Zeta potential and hydrophobicity assays found that the cells were more negatively charged (−22, −18, −10 mV in defined media D10, MCDB 202 and brain heart infusion [BHI] media, respectively) and were also more hydrophobic. A SEM analysis detected a capsular-like structure on the surface of cells grown in D10 media. A crude extract of the extracellular polymeric substance (EPS) was found to contain cell-associated proteins. The proteins were removed with pronase treatment. The remaining non-proteinaceous component was not stained by Coomassie blue dye and a further chemical analysis of the EPS did not detect significant amounts of sugars, DNA, polyglutamic acid or any other specific amino acid. When the purified EPS was subjected to attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, the spectra obtained did not match the profile of any of the 12 reference compounds used. An x-ray diffraction (XRD) analysis showed that the EPS was amorphous and a nuclear magnetic resonance (NMR) analysis detected the presence of glycerol. An elemental energy dispersive x-ray (EDX) analysis showed traces of phosphorous as a major component. In conclusion, it is proposed that the non-proteinaceous component may be phospholipid in nature, possibly derived from the cell wall lipoteichoic acid.
Mitochondrial Oxidative Stress and “Mito-Inflammation”: Actors in the Diseases
Authors: Patergnani Simone , Bouhamida Esmaa , Leo Sara , Pinton Paolo , Rimessi Alessandro
Published: February 2021

A decline in mitochondrial redox homeostasis has been associated with the development of a wide range of inflammatory-related diseases. Continue discoveries demonstrate that mitochondria are pivotal elements to trigger inflammation and stimulate innate immune signaling cascades to intensify the inflammatory response at front of different stimuli. Here, we review the evidence that an exacerbation in the levels of mitochondrial-derived reactive oxygen species (ROS) contribute to mito-inflammation, a new concept that identifies the compartmentalization of the inflammatory process, in which the mitochondrion acts as central regulator, checkpoint, and arbitrator. In particular, we discuss how ROS contribute to specific aspects of mito-inflammation in different inflammatory-related diseases, such as neurodegenerative disorders, cancer, pulmonary diseases, diabetes, and cardiovascular diseases. Taken together, these observations indicate that mitochondrial ROS influence and regulate a number of key aspects of mito-inflammation and that strategies directed to reduce or neutralize mitochondrial ROS levels might have broad beneficial effects on inflammatory-related diseases.
Anomalous Angiogenesis in Retina
Authors: Vega Rocío , Carretero Manuel , Bonilla Luis L
Published: February 2021

Age-related macular degeneration (AMD) may cause severe loss of vision or blindness, particularly in elderly people. Exudative AMD is characterized by the angiogenesis of blood vessels growing from underneath the macula, crossing the blood–retina barrier (which comprises Bruch’s membrane (BM) and the retinal pigmentation epithelium (RPE)), leaking blood and fluid into the retina and knocking off photoreceptors. Here, we simulate a computational model of angiogenesis from the choroid blood vessels via a cellular Potts model, as well as BM, RPE cells, drusen deposits and photoreceptors. Our results indicate that improving AMD may require fixing the impaired lateral adhesion between RPE cells and with BM, as well as diminishing Vessel Endothelial Growth Factor (VEGF) and Jagged proteins that affect the Notch signaling pathway. Our numerical simulations suggest that anti-VEGF and anti-Jagged therapies could temporarily halt exudative AMD while addressing impaired cellular adhesion, which could be more effective over a longer time-span.
Executive Functioning and Clinical Variables in Patients with Obsessive-Compulsive Disorder
Authors: Martínez-Esparza Inmaculada Concepción , Olivares-Olivares Pablo J. , Rosa-Alcázar Ángel , Rosa-Alcázar Ana I. , Storch Eric A.
Published: February 2021

Background: Cognitive flexibility, response inhibition, and working memory are considered the main mechanisms responsible for executive control. This study examined differences in cognitive flexibility, inhibition, and working memory in patients with obsessive–compulsive disorder (OCD) relative to a control group. Method: A total of 62 obsessive-compulsive participants (OCD = 32; healthy control = 32) aged between 17 and 56 years old (M = 33.16, SD = 9.23) were administered the computerized Wisconsin Card Sorting Test, Stroop Color–Word Test, Go/No-Go Task, Digit Test, and Corsi Block Test. Clinician-rated and self-reported obsessive–compulsive symptom severity, and anxiety, depression, and obsessive beliefs were evaluated. Results: The control group performed better than the OCD group in tasks involving cognitive flexibility, inhibition, and visuospatial working memory. Anxiety and obsessive beliefs influenced the participants’ performance on inhibition and working memory tasks. Similarly, comorbidity also influenced inhibition and working memory. In addition, the use of pharmacotherapy and the degree of OCD symptom severity influenced verbal working memory. Conclusions: Cognitive flexibility, inhibition, and visuospatial working memory deficits may be endophenotypes of OCD but require further examination for specificity. OCD severity, comorbidity patterns, anxiety, and obsessive beliefs may influence performance.
Prepulse Inhibition in Cocaine Addiction and Dual Pathologies
Authors: Gil-Miravet Isis , Fuertes-Saiz Alejandro , Benito Ana , Almodóvar Isabel , Ochoa Enrique , Haro Gonzalo
Published: February 2021

Cocaine addiction is frequently associated with different psychiatric disorders, especially schizophrenia and antisocial personality disorder. A small number of studies have used prepulse inhibition (PPI) as a discriminating factor between these disorders. This work evaluated PPI and the phenotype of patients with cocaine-related disorder (CRD) who presented a dual diagnosis of schizophrenia or antisocial personality disorder. A total of 74 men aged 18–60 years were recruited for this research. The sample was divided into four groups: CRD (n = 14), CRD and schizophrenia (n = 21), CRD and antisocial personality disorder (n = 16), and a control group (n = 23). We evaluated the PPI and other possible vulnerability factors in these patients by using different assessment scales. PPI was higher in the CRD group at 30 ms (F(3, 64) = 2.972, p = 0.038). Three discriminant functions were obtained which allowed us to use the overall Hare Psychopathy Checklist Revised score, reward sensitivity, and PPI at 30 ms to predict inclusion of these patients in the different groups with a success rate of 79.7% (42.9% for CRD, 76.2% for CRD and schizophrenia, 100% for CRD and antisocial personality disorder, and 91.3% in the control group). Despite the differences we observed in PPI, this factor is of little use for discriminating between the different diagnostic groups and it acts more as a non-specific endophenotype in certain mental disorders, such as in patients with a dual diagnosis.
Application of Multilayer Evidence for Annotation of C-Terminal BRCA2 Variants
Authors: Butz Henriett , Papp János , Bozsik Anikó , Krokker Lilla , Pócza Tímea , Oláh Edit , Patócs Attila
Published: February 2021

The clinical relevance of the BRCA2 C-terminal stop codon variants is controversial. The pathogenic role of the germline BRCA2 c.9976A>T and c.10095delinsGAATTATATCT variants in hereditary breast and ovarian cancer (HBOC) patients was evaluated. An association with clinicopathological parameters was performed in 2491 independent probands diagnosed with HBOC and in 122,209 cancer patients reported earlier. Loss-of-heterozygosity (LOH) in tumor samples and allelic imbalance in RNA extracted from peripheral blood cells were investigated. Neither c.10095delinsGAATTATATCT or c.9976A>T variants showed significant association with clinicopathological parameters or elevated risk for HBOC-associated tumors. Lung cancer was more prevalent in families carrying the c.9976A>T variant compared to pathogenic BRCA1 or BRCA2 carrier families. An increased prevalence of pancreatic cancer was found in families where c.9976A>T occurred together with other pathogenic BRCA1 variants. An increased risk for familial pancreatic, lung and upper aero-digestive tract cancers was confirmed in the validation set. Regarding BRCA2 C-terminal variants, no linkage with other pathogenic BRCA2 variants, no LOH in tumor tissue and no allelic imbalance in RNA level were confirmed. The c.9976A>T variant may be considered as a potential risk for lung cancer, and a potential modifying factor in pancreatic cancer when it occurs along with the pathogenic BRCA1 variant, although this observation should be validated in a larger sample cohort.
Biology and Clinical Applicability of Plasma Thymus and Activation-Regulated Chemokine (TARC) in Classical Hodgkin Lymphoma
Authors: Zijtregtop Eline A. M. , van der Strate Iris , Beishuizen Auke , Zwaan Christian M. , Scheijde-Vermeulen Marijn A. , Brandsma Arianne M. , Meyer-Wentrup Friederike
Published: February 2021

Thymus and activation-regulated chemokine (TARC) is produced by different cell types and is highly expressed in the thymus. It plays an important role in T cell development, trafficking and activation of mature T cells after binding to its receptor C-C chemokine receptor type 4 (CCR4) and consecutive signal transducer and activator of transcription 6 (STAT6) activation. Importantly, TARC is also produced by malignant Hodgkin and Reed–Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). In cHL, HRS cells survive and proliferate due to the micro-environment consisting primarily of type 2 T helper (Th2) cells. TARC-mediated signaling initiates a positive feedback loop that is crucial for the interaction between HRS and T cells. The clinical applicability of TARC is diverse. It is useful as diagnostic biomarker in both children and adults with cHL and in other Th2-driven diseases. In adult cHL patients, TARC is also a biomarker for treatment response and prognosis. Finally, blocking TARC signaling and thus inhibiting pathological Th2 cell recruitment could be a therapeutic strategy in cHL. In this review, we summarize the biological functions of TARC and focus on its role in cHL pathogenesis and as a biomarker for cHL and other diseases. We conclude by giving an outlook on putative therapeutic applications of antagonists and inhibitors of TARC-mediated signaling.
Unmet Medical Needs and Future Perspectives for Leiomyosarcoma Patients—A Position Paper from the National LeioMyoSarcoma Foundation (NLMSF) and Sarcoma Patients EuroNet (SPAEN)
Authors: Kasper Bernd , Achee Annie , Schuster Kathrin , Wilson Roger , van Oortmerssen Gerard , Gladdy Rebecca A. , Hemming Matthew L. , Huang Paul , Ingham Matthew , Jones Robin L. , Pollack Seth M. , Reinke Denise , Sanfilippo Roberta , Schuetze Scott M. , Somaiah Neeta , Van Tine Brian A. , Wilky Breelyn , Okuno Scott , Trent Jonathan
Published: February 2021

As leiomyosarcoma patients are challenged by the development of metastatic disease, effective systemic therapies are the cornerstone of outcome. However, the overall activity of the currently available conventional systemic treatments and the prognosis of patients with advanced or metastatic disease are still poor, making the treatment of this patient group challenging. Therefore, in a joint effort together with patient networks and organizations, namely Sarcoma Patients EuroNet (SPAEN), the international network of sarcoma patients organizations, and the National LeioMyoSarcoma Foundation (NLMSF) in the United States, we aim to summarize state-of-the-art treatments for leiomyosarcoma patients in order to identify knowledge gaps and current unmet needs, thereby guiding the community to design innovative clinical trials and basic research and close these research gaps. This position paper arose from a leiomyosarcoma research meeting in October 2020 hosted by the NLMSF and SPAEN.
Morphological Heterogeneity in Pancreatic Cancer Reflects Structural and Functional Divergence
Authors: Sántha Petra , Lenggenhager Daniela , Finstadsveen Anette , Dorg Linda , Tøndel Kristin , Amrutkar Manoj , Gladhaug Ivar P. , Verbeke Caroline
Published: February 2021

Inter- and intratumor heterogeneity is an important cause of treatment failure. In human pancreatic cancer (PC), heterogeneity has been investigated almost exclusively at the genomic and transcriptional level. Morphological heterogeneity, though prominent and potentially easily assessable in clinical practice, remains unexplored. This proof-of-concept study aims at demonstrating that morphological heterogeneity reflects structural and functional divergence. From the wide morphological spectrum of conventional PC, four common and distinctive patterns were investigated in 233 foci from 39 surgical specimens. Twenty-six features involved in key biological processes in PC were analyzed (immuno-)histochemically and morphometrically: cancer cell proliferation (Ki67) and migration (collagen fiber alignment, MMP14), cancer stem cells (CD44, CD133, ALDH1), amount, composition and spatial arrangement of extracellular matrix (epithelial proximity, total collagen, collagen I and III, fibronectin, hyaluronan), cancer-associated fibroblasts (density, αSMA), and cancer-stroma interactions (integrins α2, α5, α1; caveolin-1). All features differed significantly between at least two of the patterns. Stromal and cancer-cell-related features co-varied with morphology and allowed prediction of the morphological pattern. In conclusion, morphological heterogeneity in the cancer-cell and stromal compartments of PC correlates with structural and functional diversity. As such, histopathology has the potential to inform on the operationality of key biological processes in individual tumors.
Surveillance as Determinant of Long-Term Survival in Non-Transplanted Hepatocellular Carcinoma Patients
Authors: Pelizzaro Filippo , Vitale Alessandro , Sartori Anna , Vieno Andrea , Penzo Barbara , Russo Francesco , Frigo Anna , Giannini Edoardo , Piccinnu Manuela , Rapaccini Gian , Di Marco Maria , Caturelli Eugenio , Zoli Marco , Sacco Rodolfo , Celsa Ciro , Marra Fabio , Mega Andrea , Guarino Maria , Gasbarrini Antonio , Svegliati-Baroni Gianluca , Foschi Francesco , Olivani Andrea , Masotto Alberto , Coccoli Pietro , Raimondo Giovanni , Azzaroli Francesco , Vidili Gianpaolo , Brunetto Maurizia , Trevisani Franco , Farinati Fabio ,   on behalf of ITA.LI.CA Study Group
Published: February 2021

Purpose: We aimed at assessing the impact of surveillance on long-term survival in HCC patients. Methods: From the ITA.LI.CA database, we selected 1028 cases with long (≥5 years, LS group) and 2721 controls with short-term survival (<5 years, SS group). The association between surveillance and LS was adjusted for confounders by multivariable logistic regression analysis. Survival of surveilled patients was presented both as observed and corrected for the lead-time bias, and the comparison of survival between surveillance and no surveillance groups was also performed after balancing the baseline characteristics with inverse probability weights (IPW). Results: LS patients were more frequently diagnosed under surveillance (p < 0.0001), and had more favorable baseline characteristics. Surveillance was an independent predictor of LS (OR = 1.413, 95% CI 1.195–1.671; p < 0.0001). The observed and the lead-time corrected survival of surveilled patients were significantly longer compared to the survival of not surveilled patients (p < 0.0001 and p = 0.0008, respectively). In IPW adjusted populations, no survival differences were demonstrated between the two groups (p = 0.30). Conclusions: Surveillance, increasing early-stage diagnosis and applicability of curative treatments, is a fundamental determinant of long-term survival in HCC patients. A wide implementation of surveillance programs should be pursued in order to improve HCC patients’ prognosis.
CD44 Targeted Nanomaterials for Treatment of Triple-Negative Breast Cancer
Authors: Nabil Ghazal , Alzhrani Rami , Alsaab Hashem , Atef Mohammed , Sau Samaresh , Iyer Arun , Banna Hossny
Published: February 2021

Identified as the second leading cause of cancer-related deaths among American women after lung cancer, breast cancer of all types has been the focus of numerous research studies. Even though triple-negative breast cancer (TNBC) represents 15–20% of the number of breast cancer cases worldwide, its existing therapeutic options are fairly limited. Due to the pivotal role of the presence/absence of specific receptors to luminal A, luminal B, HER-2+, and TNBC in the molecular classification of breast cancer, the lack of these receptors has accounted for the aforementioned limitation. Thereupon, in an attempt to participate in the ongoing research endeavors to overcome such a limitation, the conducted study adopts a combination strategy as a therapeutic paradigm for TNBC, which has proven notable results with respect to both: improving patient outcomes and survivability rates. The study hinges upon an investigation of a promising NPs platform for CD44 mediated theranostic that can be combined with JAK/STAT inhibitors for the treatment of TNBC. The ability of momelotinib (MMB), which is a JAK/STAT inhibitor, to sensitize the TNBC to apoptosis inducer (CFM-4.16) has been evaluated in MDA-MB-231 and MDA-MB-468. MMB + CFM-4.16 combination with a combination index (CI) ≤0.5, has been selected for in vitro and in vivo studies. MMB has been combined with CD44 directed polymeric nanoparticles (PNPs) loaded with CFM-4.16, namely CD44-T-PNPs, which selectively delivered the payload to CD44 overexpressing TNBC with a significant decrease in cell viability associated with a high dose reduction index (DRI). The mechanism underlying their synergism is based on the simultaneous downregulation of P-STAT3 and the up-regulation of CARP-1, which has induced ROS-dependent apoptosis leading to caspase 3/7 elevation, cell shrinkage, DNA damage, and suppressed migration. CD44-T-PNPs showed a remarkable cellular internalization, demonstrated by uptake of a Rhodamine B dye in vitro and S0456 (NIR dye) in vivo. S0456 was conjugated to PNPs to form CD44-T-PNPs/S0456 that simultaneously delivered CFM-4.16 and S0456 parenterally with selective tumor targeting, prolonged circulation, minimized off-target distribution.
Analysis of Post-Transplant Lymphoproliferative Disorder (PTLD) Outcomes with Epstein–Barr Virus (EBV) Assessments—A Single Tertiary Referral Center Experience and Review of Literature
Authors: Lau Eric , Moyers Justin Tyler , Wang Billy Chen , Jeong Il Seok Daniel , Lee Joanne , Liu Lawrence , Kim Matthew , Villicana Rafael , Kim Bobae , Mitchell Jasmine , Kamal Muhammed Omair , Chen Chien-Shing , Liu Yan , Wang Jun , Chinnock Richard , Cao Huynh
Published: February 2021

Post-transplant lymphoproliferative disorders (PTLDs) are lymphoid or plasmacytic proliferations ranging from polyclonal reactive proliferations to overt lymphomas that develop as consequence of immunosuppression in recipients of solid organ transplantation (SOT) or allogeneic bone marrow/hematopoietic stem cell transplantation. Immunosuppression and Epstein–Barr virus (EBV) infection are known risk factors for PTLD. Patients with documented histopathologic diagnosis of primary PTLD at our institution between January 2000 and October 2019 were studied. Sixty-six patients with PTLD following SOT were followed for a median of 9.0 years. The overall median time from transplant to PTLD diagnosis was 5.5 years, with infant transplants showing the longest time to diagnosis at 12.0 years, compared to pediatric and adolescent transplants at 4.0 years and adult transplants at 4.5 years. The median overall survival (OS) was 19.0 years. In the monomorphic diffuse large B-cell (M-DLBCL-PTLD) subtype, median OS was 10.7 years, while median OS for polymorphic subtype was not yet reached. There was no significant difference in OS in patients with M-DLBCL-PTLD stratified by quantitative EBV viral load over and under 100,000 copies/mL at time of diagnosis, although there was a trend towards worse prognosis in those with higher copies.
Brain Metastases from Colorectal Cancer: A Systematic Review of the Literature and Meta-Analysis to Establish a Guideline for Daily Treatment
Authors: Müller Sophie , Köhler Franziska , Hendricks Anne , Kastner Carolin , Börner Kevin , Diers Johannes , Lock Johan F. , Petritsch Bernhard , Germer Christoph-Thomas , Wiegering Armin
Published: February 2021

Colorectal cancer (CRC) is the third most common malignancy worldwide. Most patients with metastatic CRC develop liver or lung metastases, while a minority suffer from brain metastases. There is little information available regarding the presentation, treatment, and overall survival of brain metastases (BM) from CRC. This systematic review and meta-analysis includes data collected from three major databases (PubMed, Cochrane, and Embase) based on the key words “brain”, “metastas*”, “tumor”, “colorectal”, “cancer”, and “malignancy”. In total, 1318 articles were identified in the search and 86 studies matched the inclusion criteria. The incidence of BM varied between 0.1% and 11.5%. Most patients developed metastases at other sites prior to developing BM. Lung metastases and KRAS mutations were described as risk factors for additional BM. Patients with BM suffered from various symptoms, but up to 96.8% of BM patients were asymptomatic at the time of BM diagnosis. Median survival time ranged from 2 to 9.6 months, and overall survival (OS) increased up to 41.1 months in patients on a multimodal therapy regimen. Several factors including age, blood levels of carcinoembryonic antigen (CEA), multiple metastases sites, number of brain lesions, and presence of the KRAS mutation were predictors of OS. For BM diagnosis, MRI was considered to be state of the art. Treatment consisted of a combination of surgery, radiation, or systemic treatment.
Molecular Profiling of 22 Primary Atypical Meningiomas Shows the Prognostic Significance of 18q Heterozygous Loss and CDKN2A/B Homozygous Deletion on Recurrence-Free Survival
Authors: Barresi Valeria , Simbolo Michele , Fioravanzo Adele , Piredda Maria , Caffo Maria , Ghimenton Claudio , Pinna Giampietro , Longhi Michele , Nicolato Antonio , Scarpa Aldo
Published: February 2021

The use of adjuvant therapy is controversial in atypical meningiomas with gross total resection. Predictors of recurrence risk could be useful in selecting patients for additional treatments. The aim of this study was to investigate whether molecular features are associated with recurrence risk of atypical meningiomas. According to WHO classification, the diagnosis of atypical meningioma was based on the presence of one major criteria (mitotic activity, brain invasion) or three or more minor criteria. The molecular profile of 22 cases (eight mitotically active, eight brain-invasive, and six with minor criteria) was assessed exploring the mutational status and copy number variation of 409 genes using next generation sequencing. Of the 22 patients with a median follow up of 53.5 months, 13 had recurrence of disease within 68 months. NF2 mutation was the only recurrent alteration (11/22) and was unrelated to clinical-pathological features. Recurring meningiomas featured a significantly higher proportion of copy number losses than non-recurring ones (p = 0.027). Chromosome 18q heterozygous loss or CDKN2A/B homozygous deletion was significantly associated with shorter recurrence-free survival (p = 0.008; hazard ratio: 5.3). Atypical meningiomas could be tested routinely for these genetic alterations to identify cases for adjuvant treatment.
Amongst Women Stratified to Receive Endocrine Therapy on the Basis of Their Tumor Estrogen and Progesterone Receptor Levels, Those with Higher Tumor Progesterone Receptor Levels Had a Better Outcome Than Those with Lower Levels of Tumor Progesterone Receptor
Authors: Lin Tai-Han , Gao Hong-Wei , Liao Guo-Shiou , Yu Jyh-Cherng , Dai Ming-Shen , Ho Jar-Yi , Yu Cheng-Ping
Published: February 2021

Background: To realize the association between stratified expression levels of ER and PgR and long-term prognosis of breast cancer patients who received adjuvant hormone therapy, this study aimed to propose better prognostic cut-off levels for estrogen receptor (ER) and progesterone receptor (PgR). Methods: Patients who received adjuvant hormone therapy after surgical intervention were selected. The ER and PgR status and their effects on breast cancer-specific survival (BCSS) and disease-free survival (DFS) over 5 and 10 years were evaluated. Next, subgroups were generated based on ER and PgR expression percentage and Allred scores. Survival curves were constructed using the Kaplan–Meier method. Results: ER and PgR expression were significantly associated with better prognosis in 5 years, whereas only PgR expression was significantly associated during the 10-year follow-up. The optimal cut-off values for better 5-year BCSS were ER > 50%; ER Allred score > 7; PgR ≥ 1%; or PgR Allred score ≥ 3; the corresponding values for DFS were ER > 40%; ER Allred score > 6; PgR > 10%; or PgR Allred score ≥ 3. In the long-term follow-up, PgR of > 50% or Allred score of > 5 carriers revealed a better prognosis of both BCSS and DFS. Conclusion: Patients with a PgR expression > 50% or an Allred score > 5 exhibited better 10-year BCSS and DFS.
Role of Thermal Ablation in Colorectal Cancer Lung Metastases
Authors: Delpla Alexandre , de Baere Thierry , Varin Eloi , Deschamps Frederic , Roux Charles , Tselikas Lambros
Published: February 2021

Background: Consensus guidelines of the European Society for Medical Oncology (ESMO) (2016) provided recommendations for the management of lung metastases. Thermal ablation appears as a tool in the management of these secondary pulmonary lesions, in the same manner as surgical resection or stereotactic ablative radiotherapy (SABR). Methods: Indications, technical considerations, oncological outcomes such as survival (OS) or local control (LC), prognostic factors and complications of thermal ablation in colorectal cancer lung metastases were reviewed and put into perspective with results of surgery and SABR. Results: LC rates varied from 62 to 91%, with size of the metastasis (<2 cm), proximity to the bronchi or vessels, and size of ablation margins (>5 mm) as predictive factors of LC. Median OS varied between 33 and 68 months. Pulmonary free disease interval <12 months, positive carcinoembryonic antigen, absence of neoadjuvant chemotherapy and uncontrolled extra-pulmonary metastases were poor prognostic factors for OS. While chest drainage for less than 48 h was required in 13 to 47% of treatments, major complications were rare. Conclusions: Thermal ablation of a selected subpopulation of patients with colorectal cancer lung metastases is safe and can provide excellent LC and delay systemic chemotherapy.
Preclinical Models in Prostate Cancer: Resistance to AR Targeting Therapies in Prostate Cancer
Authors: Devlies Wout , Handle Florian , Devos Gaëtan , Joniau Steven , Claessens Frank
Published: February 2021

Prostate cancer is an androgen-driven tumor. Different prostate cancer therapies consequently focus on blocking the androgen receptor pathway. Clinical studies reported tumor resistance mechanisms by reactivating and bypassing the androgen pathway. Preclinical models allowed the identification, confirmation, and thorough study of these pathways. This review looks into the current and future role of preclinical models to understand resistance to androgen receptor-targeted therapies. Increasing knowledge on this resistance will greatly improve insights into tumor pathophysiology and future treatment strategies in prostate cancer.
Isoforms of the p53 Family and Gastric Cancer: A Ménage à Trois for an Unfinished Affair
Authors: Blanchet Anais , Bourgmayer Agathe , Kurtz Jean-Emmanuel , Mellitzer Georg , Gaiddon Christian
Published: February 2021

Gastric cancer is one of the most aggressive cancers, with a median survival of 12 months. This illustrates its complexity and the lack of therapeutic options, such as personalized therapy, because predictive markers do not exist. Thus, gastric cancer remains mostly treated with cytotoxic chemotherapies. In addition, less than 20% of patients respond to immunotherapy. TP53 mutations are particularly frequent in gastric cancer (±50% and up to 70% in metastatic) and are considered an early event in the tumorigenic process. Alterations in the expression of other members of the p53 family, i.e., p63 and p73, have also been described. In this context, the role of the members of the p53 family and their isoforms have been investigated over the years, resulting in conflicting data. For instance, whether mutations of TP53 or the dysregulation of its homologs may represent biomarkers for aggressivity or response to therapy still remains a matter of debate. This uncertainty illustrates the lack of information on the molecular pathways involving the p53 family in gastric cancer. In this review, we summarize and discuss the most relevant molecular and clinical data on the role of the p53 family in gastric cancer and enumerate potential therapeutic innovative strategies.
Research Progress of Biliary Tract Cancers
Authors: Fonkoua Lionel Aurelien A. Kankeu , Mahipal Amit
Published: February 2021

This series of nine articles (three original articles, six reviews) is presented by international leaders in biliary tract cancers (BTC) [...]
Metal-Organic Frameworks in Oxidation Catalysis with Hydrogen Peroxide
Authors: Kholdeeva Oxana , Maksimchuk Nataliya
Published: February 2021

In recent years, metal–organic frameworks (MOFs) have received increasing attention as selective oxidation catalysts and supports for their construction. In this short review paper, we survey recent findings concerning use of MOFs in heterogeneous liquid-phase selective oxidation catalysis with the green oxidant–aqueous hydrogen peroxide. MOFs having outstanding thermal and chemical stability, such as Cr(III)-based MIL-101, Ti(IV)-based MIL-125, Zr(IV)-based UiO-66(67), Zn(II)-based ZIF-8, and some others, will be in the main focus of this work. The effects of the metal nature and MOF structure on catalytic activity and oxidation selectivity are analyzed and the mechanisms of hydrogen peroxide activation are discussed. In some cases, we also make an attempt to analyze relationships between liquid-phase adsorption properties of MOFs and peculiarities of their catalytic performance. Attempts of using MOFs as supports for construction of single-site catalysts through their modification with heterometals will be also addressed in relation to the use of such catalysts for activation of H2O2. Special attention is given to the critical issues of catalyst stability and reusability. The scope and limitations of MOF catalysts in H2O2-based selective oxidation are discussed.