bluuebunny/crossref_metadata_2025 huggingface dataset:
Colorimetric Sensing of Lactate in Human Sweat Using Polyaniline Nanoparticles-Based Sensor Platform and Colorimeter
Authors: Kim Hyun Jung , Park Insu , Pack Seung Pil , Lee Gyudo , Hong Yoochan
Published: April 2022

In emergency medicine, the lactate level is commonly used as an indicator of the severity and response to the treatment of hypoperfusion-related diseases. Clinical lactate measurements generally require 3 h for clinical determination. To improve the current gold standard methods, the development of sensor devices that can reduce detection time while maintaining sensitivity and providing portability is gaining great attention. This study aimed to develop a polyaniline (PAni)-based single-sensor platform for sensing lactate in human sweat using a CIELAB color system-based colorimetric device. To establish a lactate sensing platform, PAni nanoparticles were synthesized and adsorbed on the filter paper surface using solvent shift and dip-coating methods, respectively. PAni is characterized by a chemical change accompanied by a color change according to the surrounding environment. To quantify the color change of PAni, a CIELAB color system-based colorimetric device was fabricated. The color change of PAni was measured according to the chemical state using a combination of a PAni-based filter paper sensor platform and a colorimetric device, based on the lactate concentration in deionized water. Finally, human sweat was spiked with lactate to measure the color change of the PAni-based filter paper sensor platform. Under these conditions, the combination of polyaniline-based sensor platforms and colorimetric systems has a limit of detection (LOD) and limit of quantitation (LOQ) of 1 mM, linearity of 0.9684, and stability of 14%. Tbe confirmed that the color of the substrate changes after about 30 s, and through this, the physical fatigue of the individual can be determined. In conclusion, it was confirmed through this study that a combination of the PAni paper sensor platform and colorimeter can detect clinically meaningful lactate concentration.
A Simple and Universal Nucleic Acid Assay Platform Based on Personal Glucose Meter Using SARS-CoV-2 N Gene as the Model
Authors: Li Tian , Pan Rui , Wen Yuhan , Xu Jiaqi , Zhang Liping , He Suna , Liang Gaofeng
Published: April 2022

A simple, selective, and quantitative platform for point-of-care diagnostic of COVID-19 is urgently needed as a complement in areas where resources are currently relatively scarce. To meet the needs of early diagnosis and intervention, a proof-of-concept demonstration of a universal personal glucose meter-based nucleic acid assay platform (PGM-NAAP) is presented, which converts to SARS-CoV-2 detection from glucose detection. By using magnetic bead separation together with the hand-held PGM for quantitative readout, PGM-NAAP achieves the 98 pM limit of detection for a sequence related to SARS-CoV-2. The ability to discriminate target nucleic acid from genomic DNA, the satisfactory spike recoveries of saliva and serum samples, as well as the good stability all together suggest the potential of the PGM-NAAP for the screening and diagnosis of suspected patients during the outbreaks of COVID-19 in resource-limited settings without sophisticated instruments. On the basis of these findings, PGM-NAAP can be expected to provide an accurate and convenient path for diagnosis of disease-associated nucleic acid.
Label-Free Differentiation of Cancer and Non-Cancer Cells Based on Machine-Learning-Algorithm-Assisted Fast Raman Imaging
Authors: He Qing , Yang Wen , Luo Weiquan , Wilhelm Stefan , Weng Binbin
Published: April 2022

This paper proposes a rapid, label-free, and non-invasive approach for identifying murine cancer cells (B16F10 melanoma cancer cells) from non-cancer cells (C2C12 muscle cells) using machine-learning-assisted Raman spectroscopic imaging. Through quick Raman spectroscopic imaging, a hyperspectral data processing approach based on machine learning methods proved capable of presenting the cell structure and distinguishing cancer cells from non-cancer muscle cells without compromising full-spectrum information. This study discovered that biomolecular information–nucleic acids, proteins, and lipids—from cells could be retrieved efficiently from low-quality hyperspectral Raman datasets and then employed for cell line differentiation.
Nanozymes with Multiple Activities: Prospects in Analytical Sensing
Authors: Niu Xiangheng , Liu Bangxiang , Hu Panwang , Zhu Hengjia , Wang Mengzhu
Published: April 2022

Given the superiorities in catalytic stability, production cost and performance tunability over natural bio-enzymes, artificial nanomaterials featuring enzyme-like characteristics (nanozymes) have drawn extensive attention from the academic community in the past decade. With these merits, they are intensively tested for sensing, biomedicine and environmental engineering. Especially in the analytical sensing field, enzyme mimics have found wide use for biochemical detection, environmental monitoring and food analysis. More fascinatingly, rational design enables one fabrication of enzyme-like materials with versatile activities, which show great promise for further advancement of the nanozyme-involved biochemical sensing field. To understand the progress in such an exciting field, here we offer a review of nanozymes with multiple catalytic activities and their analytical application prospects. The main types of enzyme-mimetic activities are first introduced, followed by a summary of current strategies that can be employed to design multi-activity nanozymes. In particular, typical materials with at least two enzyme-like activities are reviewed. Finally, opportunities for multi-activity nanozymes applied in the sensing field are discussed, and potential challenges are also presented, to better guide the development of analytical methods and sensors using nanozymes with different catalytic features.
NKCC1 Deficiency in Forming Hippocampal Circuits Triggers Neurodevelopmental Disorder: Role of BDNF-TrkB Signalling
Authors: Szymanski Jacek , Minichiello Liliana
Published: April 2022

The time-sensitive GABA shift from excitatory to inhibitory is critical in early neural circuits development and depends upon developmentally regulated expression of cation-chloride cotransporters NKCC1 and KCC2. NKCC1, encoded by the SLC12A2 gene, regulates neuronal Cl− homeostasis by chloride import working opposite KCC2. The high NKCC1/KCC2 expression ratio decreases in early neural development contributing to GABA shift. Human SLC12A2 loss-of-function mutations were recently associated with a multisystem disorder affecting neural development. However, the multisystem phenotype of rodent Nkcc1 knockout models makes neurodevelopment challenging to study. Brain-Derived Neurotrophic Factor (BDNF)-NTRK2/TrkB signalling controls KCC2 expression during neural development, but its impact on NKCC1 is still controversial. Here, we discuss recent evidence supporting BDNF-TrkB signalling controlling Nkcc1 expression and the GABA shift during hippocampal circuit formation. Namely, specific deletion of Ntrk2/Trkb from immature mouse hippocampal dentate granule cells (DGCs) affects their integration and maturation in the hippocampal circuitry and reduces Nkcc1 expression in their target region, the CA3 principal cells, leading to premature GABA shift, ultimately influencing the establishment of functional hippocampal circuitry and animal behaviour in adulthood. Thus, immature DGCs emerge as a potential therapeutic target as GABAergic transmission is vital for specific neural progenitors generating dentate neurogenesis in early development and the mature brain.
Music and Psychology & Social Connections Program: Protocol for a Novel Intervention for Dyads Affected by Younger-Onset Dementia
Authors: Loi Samantha M. , Flynn Libby , Cadwallader Claire , Stretton-Smith Phoebe , Bryant Christina , Baker Felicity A.
Published: April 2022

Psychosocial interventions targeting the specific needs of people affected by younger-onset dementia are lacking. Younger-onset dementia refers to dementia where symptom onset occurs at less than 65 years old. Because of its occurrence in middle age, the impact on spouses is particularly marked and dyadic-based interventions are recommended. Music And Psychology & Social Connections (MAPS) is a novel online intervention, informed by the theory of adaptive coping by Bannon et al. (2021) for dyads affected by younger-onset dementia. MAPS combines therapeutic songwriting, cognitive behaviour therapy, and a private social networking group that focuses on the dyads. This will be a randomised controlled trial with a waitlist control. The primary aims are to assess whether MAPS improves depressive, anxiety, and stress symptoms in caregivers, with secondary aims to assess whether MAPS improves depressive symptoms in people with younger-onset dementia. The trial also aims to assess dyadic social connectedness; caregiver coping skills; and neuropsychiatric symptoms in people with younger-onset dementia. We will recruit 60 dyads to participate in a group-based weekly online program for 8 weeks facilitated by a credentialed music therapist and psychologist. Sessions 1 and 8 will include both caregivers and people with younger-onset dementia and Sessions 2–7 will involve separate group sessions for caregivers and those with dementia. There will be focus groups for qualitative feedback. Due to its online administration, MAPS has the potential to reach many dyads affected by younger-onset dementia.
Tumor Microenvironment in Glioma Invasion
Authors: Tamai Sho , Ichinose Toshiya , Tsutsui Taishi , Tanaka Shingo , Garaeva Farida , Sabit Hemragul , Nakada Mitsutoshi
Published: April 2022

A major malignant trait of gliomas is their remarkable infiltration capacity. When glioma develops, the tumor cells have already reached the distant part. Therefore, complete removal of the glioma is impossible. Recently, research on the involvement of the tumor microenvironment in glioma invasion has advanced. Local hypoxia triggers cell migration as an environmental factor. The transcription factor hypoxia-inducible factor (HIF) -1α, produced in tumor cells under hypoxia, promotes the transcription of various invasion related molecules. The extracellular matrix surrounding tumors is degraded by proteases secreted by tumor cells and simultaneously replaced by an extracellular matrix that promotes infiltration. Astrocytes and microglia become tumor-associated astrocytes and glioma-associated macrophages/microglia, respectively, in relation to tumor cells. These cells also promote glioma invasion. Interactions between glioma cells actively promote infiltration of each other. Surgery, chemotherapy, and radiation therapy transform the microenvironment, allowing glioma cells to invade. These findings indicate that the tumor microenvironment may be a target for glioma invasion. On the other hand, because the living body actively promotes tumor infiltration in response to the tumor, it is necessary to reconsider whether the invasion itself is friend or foe to the brain.
High Estrogen Levels Cause Greater Leg Muscle Fatigability in Eumenorrheic Young Women after 4 mA Transcranial Direct Current Stimulation
Authors: Deters Justin R. , Fietsam Alexandra C. , Workman Craig D. , Rudroff Thorsten
Published: April 2022

Transcranial direct current stimulation (tDCS) research has shown great outcome variability in motor performance tasks, with one possible source being sex differences. The goal of this study was to evaluate the effects of estrogen levels on leg muscle fatigability during a fatigue task (FT) after 4 mA tDCS over the left motor cortex (M1). Ten young, healthy eumenorrheic women received 4 mA anodal active or sham stimulation over the left M1 during periods of high and low estrogen levels. A fatigue index (FI) was calculated to quantify fatigability, and the electromyography (EMG) of the knee extensors and flexors was recorded during the FT. The findings showed that tDCS applied during high estrogen levels resulted in greater leg muscle fatigability. Furthermore, a significant increase in EMG activity of the right knee extensors was observed during periods of active stimulation, independent of estrogen level. These results suggest that estrogen levels should be considered in tDCS studies with young healthy women.
ER Stress in COVID-19 and Parkinson’s Disease: In Vitro and In Silico Evidences
Authors: Chaudhry Zahara L. , Gamal Mahmoud , Ferhati Ingrid , Warda Mohamad , Ahmed Bushra Y.
Published: April 2022

The outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signifies a serious worldwide concern to public health. Both transcriptome and proteome of SARS-CoV-2-infected cells synergize the progression of infection in host, which may exacerbate symptoms and/or progression of other chronic diseases such as Parkinson’s disease (PD). Oxidative stress is a well-known cause of endoplasmic reticulum (ER) stress observed in both SARS-CoV-2 and PD. In the current study, we aimed to explore the influence of PKR-like ER kinase (PERK) stress pathway under SARS-CoV-2-mediated infection and in human cell model of PD. Furthermore, we investigated whether they are interconnected and if the ER stress inhibitors could inhibit cell death and provide cellular protection. To achieve this aim, we have incorporated in silico analysis obtained from gene set enrichment analysis (GSEA), a literature review and laboratory data. The neurotoxin, 6-hydroxy dopamine (6OHDA), was used to mimic the biochemical and neuropathological characteristics of PD by inducing oxidative stress in dopamine-containing neurons differentiated from ReNVM cell line (dDCNs). Furthermore, we explored if ER stress influences activation of caspases-2, -4 and -8 in SARS-CoV-2 and in stressed dDCNs. Our laboratory data using Western blot, immunocytochemistry and 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) analyses indicated that 6OHDA-induced toxicity triggered activation of caspases-2, -4 and -8 in dDCNs. Under SARS-CoV-2 infection of different cell types, GSEA revealed cell-specific sensitivities to oxidative and ER stresses. Cardiomyocytes and type II alveolar epithelial-like cells were more vulnerable to oxidative stress than neural cells. On the other side, only cardiomyocytes activated the unfolded protein response, however, the PERK pathway was operative in both cardiomyocytes and neural cells. In addition, caspase-4 activation by a SARS-CoV-2 was observed via in silico analyses. These results demonstrate that the ER stress pathway under oxidative stress in SARS-CoV-2 and PD are interconnected using diverse pathways. Furthermore, our results using the ER stress inhibitor and caspase specific inhibitors provided cellular protection suggesting that the use of specific inhibitors can provide effective therapeutic approaches for the treatment of COVID-19 and PD.
Role of COVID-19 Anxiety and Community Risk Factors on Physical Distancing Practice
Authors: Wang Hsin-Yi , Cheng Cecilia
Published: April 2022

Existing studies have focused primarily on self-oriented anxiety (i.e., anxiety over one’s infection) in the pandemic context, and the role of community risk is largely ignored. This study addressed these gaps by examining (a) self-oriented anxiety and two forms of others-oriented anxiety (i.e., anxiety concerning others’ health and societal problems), (b) the associations between all these forms of anxiety and physical distancing practice during the COVID-19 pandemic, and (c) the hypothesized moderating role of community risk factors. The participants were 703 U.S. community-dwelling adults who completed an online survey. Geo-identifier data were extracted to identify the number of confirmed COVID-19 cases and four social vulnerability indexes for the county in which each participant resided. Both forms of others-oriented anxiety were positively associated with physical distancing adoption, and the association was stronger among the participants residing in lower-risk communities (i.e., fewer confirmed COVID-19 cases, higher socioeconomic status, and better housing conditions). The study’s novel findings reveal the protective role of anxiety, particularly anxiety concerning others’ well-being, in encouraging people to adopt physical distancing during a pandemic. However, the protective role of anxiety is contingent upon certain community risk factors. Anxiety is more beneficial to residents of low- rather than high-risk communities.
Simulation of Smartphone-Based Public Participation in Earthquake Structural Response Emergency Monitoring Using a Virtual Experiment and AI
Authors: Li Huan , Chen Xixian , Chen Hongliang , Wang Bowen , Li Weijie , Liu Shenglan , Li Peng , Qi Zuoqiu , He Zheng , Zhao Xuefeng
Published: April 2022

Structural health monitoring (SHM) is of great significance for post-earthquake damage assessment. Smartphone-based monitoring techniques provide the possibility to perform crowdsensing for all buildings in urban regions after an earthquake. However, this idea still faces many difficulties and is hard to realize. Fortunately, the development of game engines provides the opportunity for simulating this kind of experiment. The main objective of this study was to use Unity to simulate the whole process when a city is struck by an earthquake that consists of one main shock and one aftershock. During the emergency response, the citizens and the “city brain” in Unity, named Ground Eye, cooperate to finish the task of taking refuge and collecting data for regional damage assessment. Some basic assumptions were made first. Then the city model was established in Unity, and the behaviors of the citizens were directed by the behavior tree artificial intelligence (AI). OpenSees was utilized to determine the monitoring demand and simulate the monitoring results. A GUI was built to exhibit the data during the whole process. The results show that the evacuation and monitoring plan is feasible. The simulation framework presented in this paper can be used in other SHM application scenarios.
Influence of Treatment Methods of Recycled Concrete Aggregate on Behavior of High Strength Concrete
Authors: Alqarni Ali S. , Abbas Husain , Al-Shwikh Khattab M. , Al-Salloum Yousef A.
Published: April 2022

Worldwide the concrete industry has started embracing the utilization of recycled concrete aggregates (RCAs) resulting from demolition and construction waste as full or partial substituents in the production of high-strength concrete (HSC) due to their economic and environmental benefits. Several parameters were experimentally investigated in this study. The first parameter analyzed the effect of replacing varying percentages of coarse aggregate with recycled aggregate. The second parameter examined the influence of two aggregate sizes (10 and 20 mm). The third parameter was intended for investigating the influence of three different RCA treatment methods utilizing sodium silicate immersion, cement slurry, and the Los Angeles (LA) abrasion simulation. The test results generally indicated degradation in the engineering properties of concrete produced using untreated RCA compared to the control. The degree of reduction increased as the replacement percentage was increased regardless of the aggregate size. The reduction in compressive strength appeared to have a more pronounced effect in comparison to the splitting tensile strength. The use of treated RCA improved concrete slump by 15–35%. This also caused enhancement in the engineering properties, especially for the LA abrasion mechanical treatment, which was very promising for both aggregate sizes. In comparison with the untreated RCA, the relative enhancement in water absorption was up to 76%, whereas splitting tensile and compressive strengths increased by 3–50% and 5–60%, respectively.
Energy Production of Solar DSF for Ceiling-Mounted Localized Air Distribution Systems in a Virtual Classroom
Authors: Conceição Eusébio , Gomes João , Lúcio Maria Manuela , Awbi Hazim
Published: April 2022

This paper presents an application of energy production in a solar Double Skin Facade (DSF) used in a Heating, Ventilation and Air-Conditioning (HVAC) system for a ceiling-mounted localized air distribution systems in a virtual classroom. In this numerical work, a virtual classroom, an inlet ceiling-mounted localized air distribution system, an exhaust ventilation system, and a DSF system are considered. The numerical simulations consider an integral building thermal response (BTR) and a coupling of an integral human thermal-physiology response (HTR) and differential computational fluid dynamics (CFD). The BTR numerical model calculates, among other parameters, the DSF indoor air temperature and energy production. The HTR numerical model calculates, among other parameters, the human thermal comfort. The CFD numerical model, among other parameters, calculates the indoor air quality. In this study which is performed for winter conditions, the energy produced in the DSF is used for driving the HVAC system. Six different airflow rates are used. The air temperature and energy production in the DSF are also evaluated. The influence of the airflow rate on the HVAC system performance is evaluated by the Air Distribution Index for mid-morning and mid-afternoon conditions. The results show that energy production reduces when the airflow increases and the operating point can be selected using the acceptable levels of thermal comfort and air quality levels or using the maximum Air Distribution Index value. In this study, the application of the thermal comfort and air quality levels criteria demonstrates that the HVAC system uses an optimum airflow rate.
Influence of Organisational Culture on Total Quality Management Implementation in the Australian Construction Industry
Authors: Coelho Carla , Mojtahedi Mohammad , Kabirifar Kamyar , Yazdani Maziar
Published: April 2022

This study explores the relationship between organisational culture and total quality management (TQM) implementation in Australia, with the purpose of identifying the particular culture that dominants the Australian construction industry, and distinguishing which cultures determine the successful implementation of TQM. Although the application of the competing values framework (CVF) for evaluating organisational culture (OC) in the construction industry has been studied by some scholars, research into OC and its impact on TQM procedures in connection to the CVF in project-based industries such as construction has received less attention. Thus, this research intends to determine the relationship between OC and TQM regarding the CVF in the Australian construction industry. The research methodology used the validated organisational culture assessment instrument (OCAI) CVF to frame OC, and TQM practices identified from the literature review. An online questionnaire was distributed through Qualtrics, whereby 42 valid responses representing various construction organisations in Australia were analysed through IBM SPSS Statistics 26 through endorsing k-means cluster analysis, and analysis of variance. The findings support that Australian construction organisations are dominated by the market and external focused cultures according to the CVF of organisational classification. Furthermore, the findings acknowledge that organisations that are dominated by hierarchical cultural characterises could provide an unfavourable environment for the successful implementation of TQM. Whilst an organisation that obtains a mix of cultures, specifically with the adhocracy and market cultures dominating could provide a favourable environment for the successful implementation of TQM.
Bioelectrical Phase Angle in Patients with Breast Cancer: A Systematic Review
Authors: Morlino Delia , Cioffi Iolanda , Marra Maurizio , Di Vincenzo Olivia , Scalfi Luca , Pasanisi Fabrizio
Published: April 2022

Breast cancer (BC) is the most common cancer diagnosed among women worldwide. Phase angle (PhA), a proxy measure of membrane integrity and function, has gained relevance in clinical practice and it has been suggested to be a prognostic and nutritional indicator. This systematic review aimed to explore PhA and its relationship with nutritional status and survival in BC patients. Four databases (PubMed, EMBASE, Web of Science, and CINAHL) were systematically searched until September 2021 for studies evaluating PhA in BC patients. A total of 16 studies met the inclusion criteria, where 11 were observational studies and 5 were interventional studies. Baseline PhA-value varied from 4.9 to 6.30 degrees, showing a great variability and heterogeneity across the selected studies. Available data suggested that PhA decreased by 5–15% after completing chemotherapy, and those effects might persist in the long term. However, the use of tailored nutritional and/or exercise programs during and after therapy could prevent PhA reduction and body derangement. High PhA values were found in women displaying a better nutritional status, while inconsistent data were found on survival. Therefore, further studies are needed to focus on the clinical relevance of PhA in BC patients, evaluating its association with disease outcomes and survival.
An Osteosarcoma Model by 3D Printed Polyurethane Scaffold and In Vitro Generated Bone Extracellular Matrix
Authors: Contessi Negrini Nicola , Ricci Claudio , Bongiorni Federica , Trombi Luisa , D’Alessandro Delfo , Danti Serena , Farè Silvia
Published: April 2022

Osteosarcoma is a primary bone tumor characterized by a dismal prognosis, especially in the case of recurrent disease or metastases. Therefore, tools to understand in-depth osteosarcoma progression and ultimately develop new therapeutics are urgently required. 3D in vitro models can provide an optimal option, as they are highly reproducible, yet sufficiently complex, thus reliable alternatives to 2D in vitro and in vivo models. Here, we describe 3D in vitro osteosarcoma models prepared by printing polyurethane (PU) by fused deposition modeling, further enriched with human mesenchymal stromal cell (hMSC)-secreted biomolecules. We printed scaffolds with different morphologies by changing their design (i.e., the distance between printed filaments and printed patterns) to obtain different pore geometry, size, and distribution. The printed PU scaffolds were stable during in vitro cultures, showed adequate porosity (55–67%) and tunable mechanical properties (Young’s modulus ranging in 0.5–4.0 MPa), and resulted in cytocompatible. We developed the in vitro model by seeding SAOS-2 cells on the optimal PU scaffold (i.e., 0.7 mm inter-filament distance, 60° pattern), by testing different pre-conditioning factors: none, undifferentiated hMSC-secreted, and osteo-differentiated hMSC-secreted extracellular matrix (ECM), which were obtained by cell lysis before SAOS-2 seeding. Scaffolds pre-cultured with osteo-differentiated hMSCs, subsequently lysed, and seeded with SAOS-2 cells showed optimal colonization, thus disclosing a suitable biomimetic microenvironment for osteosarcoma cells, which can be useful both in tumor biology study and, possibly, treatment.
Deep-Tissue Activation of Photonanomedicines: An Update and Clinical Perspectives
Authors: Shah Nimit , Squire John , Guirguis Mina , Saha Debabrata , Hoyt Kenneth , Wang Ken Kang-Hsin , Agarwal Vijay , Obaid Girgis
Published: April 2022

With the continued development of nanomaterials over the past two decades, specialized photonanomedicines (light-activable nanomedicines, PNMs) have evolved to become excitable by alternative energy sources that typically penetrate tissue deeper than visible light. These sources include electromagnetic radiation lying outside the visible near-infrared spectrum, high energy particles, and acoustic waves, amongst others. Various direct activation mechanisms have leveraged unique facets of specialized nanomaterials, such as upconversion, scintillation, and radiosensitization, as well as several others, in order to activate PNMs. Other indirect activation mechanisms have leveraged the effect of the interaction of deeply penetrating energy sources with tissue in order to activate proximal PNMs. These indirect mechanisms include sonoluminescence and Cerenkov radiation. Such direct and indirect deep-tissue activation has been explored extensively in the preclinical setting to facilitate deep-tissue anticancer photodynamic therapy (PDT); however, clinical translation of these approaches is yet to be explored. This review provides a summary of the state of the art in deep-tissue excitation of PNMs and explores the translatability of such excitation mechanisms towards their clinical adoption. A special emphasis is placed on how current clinical instrumentation can be repurposed to achieve deep-tissue PDT with the mechanisms discussed in this review, thereby further expediting the translation of these highly promising strategies.
ERα36-High Cancer-Associated Fibroblasts as an Unfavorable Factor in Triple-Negative Breast Cancer
Authors: Nagel Anna , Popeda Marta , Muchlinska Anna , Sadej Rafal , Szade Jolanta , Zielinski Jacek , Skokowski Jaroslaw , Niemira Magdalena , Kretowski Adam , Markiewicz Aleksandra , Zaczek Anna J.
Published: April 2022

Background: Cancer-associated fibroblasts (CAFs) are the most abundant cell type in the tumor microenvironment (TME). Estrogen receptor alpha 36 (ERα36), the alternatively spliced variant of ERα, is described as an unfavorable factor when expressed in cancer cells. ERα can be expressed also in CAFs; however, the role of ERα36 in CAFs is unknown. Methods: Four CAF cultures were isolated from chemotherapy-naïve BC patients and characterized for ERα36 expression and the NanoString gene expression panel using isolated RNA. Conditioned media from CAF cultures were used to assess the influence of CAFs on triple-negative breast cancer (TNBC) cells using a matrigel 3D culture assay. Results: We found that ERα36high CAFs significantly induced the branching of TNBC cells in vitro (p < 0.001). They also produced a set of pro-tumorigenic cytokines compared to ERα36low CAFs, among which hepatocyte growth factor (HGF) was the main inducer of TNBC cell invasive phenotype in vitro (p < 0.001). Tumor stroma rich in ERα36high CAFs was correlated with high Ki67 expression (p = 0.041) and tumor-associated macrophages markers (CD68 and CD163, p = 0.041 for both). HGF was found to be an unfavorable prognostic factor in TCGA database analysis (p = 0.03 for DFS and p = 0.04 for OS). Conclusions: Breast cancer-associated fibroblasts represent distinct subtypes based on ERα36 expression. We propose that ERα36high CAFs could account for an unfavorable prognosis for TNBC patients.
Male Breast Cancer: From Molecular Genetics to Clinical Management
Authors: Pensabene Matilde , Von Arx Claudia , De Laurentiis Michelino
Published: April 2022

MBC is a rare disease accounting for almost 1% of all cancers in men and less than 1% of breast cancer. Emerging data on the genetic drivers of predisposition for MBC are available and different risk factors have been associated with its pathogenesis. Genetic alterations, such as pathogenetic variants in BRCA1/2 and other moderate-/low-penetrance genes, along with non-genetic risk factors, have been recognized as pathogenic factors for MBC. Preventive and therapeutic implications could be related to the detection of alterations in predisposing genes, especially BRCA1/2, and to the identification of oncogenic drivers different from FBC. However, approved treatments for MBC remain the same as FBC. Cancer genetic counseling has to be considered in the diagnostic work-up of MBC with or without positive oncological family history. Here, we review the literature, reporting recent data about this malignancy with a specific focus on epidemiology, and genetic and non-genetic risk factors. We introduce the perspective of cancer genetic counseling for MBC patients and their healthy at-risk family members, with a focus on different hereditary cancer syndromes.
Deep Neural Networks and Machine Learning Radiomics Modelling for Prediction of Relapse in Mantle Cell Lymphoma
Authors: Lisson Catharina Silvia , Lisson Christoph Gerhard , Mezger Marc Fabian , Wolf Daniel , Schmidt Stefan Andreas , Thaiss Wolfgang M. , Tausch Eugen , Beer Ambros J. , Stilgenbauer Stephan , Beer Meinrad , Goetz Michael
Published: April 2022

Mantle cell lymphoma (MCL) is a rare lymphoid malignancy with a poor prognosis characterised by frequent relapse and short durations of treatment response. Most patients present with aggressive disease, but there exist indolent subtypes without the need for immediate intervention. The very heterogeneous behaviour of MCL is genetically characterised by the translocation t(11;14)(q13;q32), leading to Cyclin D1 overexpression with distinct clinical and biological characteristics and outcomes. There is still an unfulfilled need for precise MCL prognostication in real-time. Machine learning and deep learning neural networks are rapidly advancing technologies with promising results in numerous fields of application. This study develops and compares the performance of deep learning (DL) algorithms and radiomics-based machine learning (ML) models to predict MCL relapse on baseline CT scans. Five classification algorithms were used, including three deep learning models (3D SEResNet50, 3D DenseNet, and an optimised 3D CNN) and two machine learning models based on K-nearest Neighbor (KNN) and Random Forest (RF). The best performing method, our optimised 3D CNN, predicted MCL relapse with a 70% accuracy, better than the 3D SEResNet50 (62%) and the 3D DenseNet (59%). The second-best performing method was the KNN-based machine learning model (64%) after principal component analysis for improved accuracy. Our optimised CNN developed by ourselves correctly predicted MCL relapse in 70% of the patients on baseline CT imaging. Once prospectively tested in clinical trials with a larger sample size, our proposed 3D deep learning model could facilitate clinical management by precision imaging in MCL.
Quality Assessment of a Large Multi-Center Flow Cytometric Dataset of Acute Myeloid Leukemia Patients—A EuroFlow Study
Authors: Bras Anne E. , Matarraz Sergio , Nierkens Stefan , Fernández Paula , Philippé Jan , Aanei Carmen-Mariana , de Mello Fabiana Vieira , Burgos Leire , van der Sluijs-Gelling Alita J. , Grigore Georgiana Emilia , van Dongen Jacques J. M. , Orfao Alberto , van der Velden Vincent H. J. ,   on behalf of the EuroFlow Consortium
Published: April 2022

Flowcytometric analysis allows for detailed identification and characterization of large numbers of cells in blood, bone marrow, and other body fluids and tissue samples and therefore contributes to the diagnostics of hematological malignancies. Novel data analysis tools allow for multidimensional analysis and comparison of patient samples with reference databases of normal, reactive, and/or leukemia/lymphoma patient samples. Building such reference databases requires strict quality assessment (QA) procedures. Here, we compiled a dataset and developed a QA methodology of the EuroFlow Acute Myeloid Leukemia (AML) database, based on the eight-color EuroFlow AML panel consisting of six different antibody combinations, including four backbone markers. In total, 1142 AML cases and 42 normal bone marrow samples were included in this analysis. QA was performed on 803 AML cases using multidimensional analysis of backbone markers, as well as tube-specific markers, and data were compared using classical analysis employing median and peak expression values. Validation of the QA procedure was performed by re-analysis of >300 cases and by running an independent cohort of 339 AML cases. Initial evaluation of the final cohort confirmed specific immunophenotypic patterns in AML subgroups; the dataset therefore can reliably be used for more detailed exploration of the immunophenotypic variability of AML. Our data show the potential pitfalls and provide possible solutions for constructing large flowcytometric databases. In addition, the provided approach may facilitate the building of other databases and thereby support the development of novel tools for (semi)automated QA and subsequent data analysis.
Leaping the Boundaries in Laparoscopic Liver Surgery for Hepatocellular Carcinoma
Authors: Cassese Gianluca , Han Ho-Seong , Lee Boram , Lee Hae Won , Cho Jai Young , Troisi Roberto
Published: April 2022

The minimally invasive approach for hepatocellular carcinoma (HCC) had a slower diffusion compared to other surgical fields, mainly due to inherent peculiarities regarding the risks of uncontrollable bleeding, oncological inadequacy, and the need for both laparoscopic and liver major skills. Recently, laparoscopic liver resection (LLR) has been associated with an improved postoperative course, including reduced postoperative decompensation, intraoperative blood losses, length of hospitalization, and unaltered oncological outcomes, leading to its adoption within international guidelines. However, LLR for HCC still faces several limitations, mainly linked to the impaired function of underlying parenchyma, tumor size and numbers, and difficult tumor position. The aim of this review is to highlight the state of the art and future perspectives of LLR for HCC, focusing on key points for overcoming currents limitations and pushing the boundaries in minimally invasive liver surgery (MILS).
Diagnostic Challenges in the Cytology of Thymic Epithelial Neoplasms
Authors: Willner Jonathan , Zhou Fang , Moreira Andre L.
Published: April 2022

Thymic epithelial neoplasms are rare tumors that constitute the majority of anterior mediastinal masses. They are classified as thymomas, thymic carcinomas, and thymic neuroendocrine neoplasms. Biopsy diagnosis is not common, and most tumors are surgically resected. Biopsy, including cytology, is indicated when a non-surgical entity is suspected or in cases of locally advanced disease. Smears of thymomas consist of round or spindle epithelial cells admixed with varying amounts of lymphocytes depending on the type of thymoma. Smears of thymic carcinoma and thymic neuroendocrine neoplasms are often indistinguishable from corresponding tumor types from other organs. Accurate cytological diagnosis can be difficult due to the histological diversity of thymomas, as well as the morphological features that certain thymic tumors share with similar tumors from other organs. However, fine needle aspiration (FNA) of anterior mediastinal masses can provide clinically actionable information and can be used to determine whether lesions require surgical, systemic, or local noninvasive treatments. Ancillary studies, namely, immunocytochemical stains, flow cytometry, and radiology, are important tools in the evaluation of thymic aspirates. This review discusses the utility and limitations of thymic FNAs and illustrates the diagnostic features and pitfalls of these specimens.
Where Do We Stand in the Management of Oligometastatic Prostate Cancer? A Comprehensive Review
Authors: Juan Gómez Rivas , Laura Fernández Hernández , Javier Puente Vázquez , Natalia Vidal Casinello , Mᵃ Isabel Galante Romo , Enrique Redondo González , José Luis Senovilla Pérez , Pablo Abad López , Noelia Sanmamed Salgado , Roser Vives Dilme , Jesús Moreno-Sierra
Published: April 2022

Oligometastatic prostate cancer (OMPC) is an intermediate state between localised disease and widespread metastases that includes a spectrum of disease biology and clinical behaviours. This narrative review will cover the current OMPC scenario. We conducted comprehensive English language literature research for original and review articles using the Medline database and grey literature through December 2021. OMPC is a unique clinical state with inherently more indolent tumour biology susceptible to multidisciplinary treatment (MDT). With the development of new imaging techniques, patients with OMPC are likely to be identified at an earlier stage, and the paradigm for treatment is shifting towards a more aggressive approach to treating potentially curable patients. Multimodal management is necessary to improve patient outcomes due to the combination of available therapies, such as local therapy of primary tumour, metastasis directed therapy or systemic therapy, to reduce tumour load and prevent further disease progression. Additional prospective data are needed to select patients most likely to benefit from a given therapeutic approach.
Current Landscape of Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma
Authors: Machairas Nikolaos , Tsilimigras Diamantis I. , Pawlik Timothy M.
Published: April 2022

Hepatocellular carcinoma (HCC) is the most frequent primary liver tumor. As a result of advanced disease being often present at diagnosis, only a small percentage of patients are amenable to curative-intent treatment options such as surgical resection and liver transplantation. Systemic therapy consisting of tyrosine kinase inhibitors such as sorafenib had been used for over a decade with limited efficacy. More recently, treatment with immune checkpoint inhibitors has revolutionized the treatment landscape of various malignant tumors. With this shifting paradigm, recent data have demonstrated encouraging outcomes among patients with HCC. In particular, several trials have investigated the safety and efficacy of various immune checkpoint inhibitors (ICI) either as monotherapy or in the form of combined treatments. We sought to provide an overview of recent clinical trials among patients with advanced HCC as well as to highlight predictors of response and immune-related adverse events and to review the evidence on perioperative administration of ICI in patients with resectable HCC.
Multicenter Observational Study on Metastatic Non-Small Cell Lung Cancer Harboring BRAF Mutations: Focus on Clinical Characteristics and Treatment Outcome of V600E and Non-V600E Subgroups
Authors: Perrone Fabiana , Mazzaschi Giulia , Minari Roberta , Verzè Michela , Azzoni Cinzia , Bottarelli Lorena , Nizzoli Rita , Pluchino Monica , Altimari Annalisa , Gruppioni Elisa , Sperandi Francesca , Andrini Elisa , Guaitoli Giorgia , Bertolini Federica , Barbieri Fausto , Bettelli Stefania , Longo Lucia , Pagano Maria , Bonelli Candida , Tagliavini Elena , Nicoli Davide , Ubiali Alessandro , Zangrandi Adriano , Trubini Serena , Proietto Manuela , Gnetti Letizia , Tiseo Marcello
Published: April 2022

Introduction: BRAF mutation involved 2–4% of lung adenocarcinoma. Differences in clinicopathologic features and patient outcome exist between V600E and non-V600E BRAF mutated NSCLC. Thus, we sought to assess the frequency and clinical relevance of BRAF mutations in a real-life population of advanced-NSCLC, investigating the potential prognostic significance of distinct genetic alterations. Materials and Methods: The present multicenter Italian retrospective study involved advanced BRAF mutant NSCLC. Complete clinicopathologic data were evaluated for BRAF V600E and non-V600E patients. Results: A total of 44 BRAFmut NSCLC patients were included (V600E, n = 23; non-V600E, n = 21). No significant differences in survival outcome and treatment response were documented, according to V600E vs. non-V600E mutations, although a trend towards prolonged PFS was observed in the V600E subgroup (median PFS = 11.3 vs. 6.0 months in non-V600E). In the overall population, ECOG PS and age significantly impacted on OS, while bone lesions were associated with shorter PFS. Compared to immunotherapy, first-line chemotherapy was associated with longer OS in the overall population, and especially in the BRAF V600E subtype. Conclusions: Here, we report on real-life data from a retrospective cohort of advanced-NSCLC harboring BRAF alterations. Our study offers relevant clues on survival outcome, therapeutic response, and clinicopathologic correlations of BRAF-mutant NSCLC.
Feasibility of Tumor Treating Fields with Pemetrexed and Platinum-Based Chemotherapy for Unresectable Malignant Pleural Mesothelioma: Single-Center, Real-World Data
Authors: Kutuk Tugce , Appel Haley , Avendano Maria Carolina , Albrecht Federico , Kaywin Paul , Ramos Suyen , Suarez-Murias Melanie E. , Mehta Minesh P. , Kotecha Rupesh
Published: April 2022

Purpose: The objectives of this study were to evaluate the implementation, device usage rates, clinical outcomes, and treatment-related toxicities associated with TTFields and pemetrexed plus platinum-based chemotherapy in patients with unresectable MPM, outside the initial trial results. Methods: Consecutive patients with unresectable MPM were enrolled onto an FDA-required HDE protocol from 2019 to 2021. All patients were treated with a protocol-defined regimen of continuous TTFields (150 kHz) and pemetrexed plus platinum-based chemotherapy. Results: Five patients with unresectable MPM were enrolled. The median number of 4-week TTFields cycles was 5 (range: 2–7 cycles). Median TTFields device usage in the first 3 months was 12.5 h per day (range: 5–16.8 h), representing 52% (21–70%) of the potential daily duration. The median follow-up was 5.4 months (range: 1.1–20.9 months). Treatment-related dermatitis was the only side effect associated with TTFields and was reported as grade 1–2 in all patients; no patient had grade 3+ device-related toxicities. Conclusions: This study represents the first results of real-world implementation of TTFields for MPM. In comparison to the initial clinical trial (STELLAR), compliance rates were lower, although skin-related toxicities appeared similar. Further initiatives and guidelines should be developed to manage treatment-related dermatitis and improve device usage.
Recent Advances in Treatment Options for Childhood Acute Lymphoblastic Leukemia
Authors: Malczewska Marta , Kośmider Kamil , Bednarz Kinga , Ostapińska Katarzyna , Lejman Monika , Zawitkowska Joanna
Published: April 2022

Acute lymphoblastic leukemia is the most common blood cancer in pediatric patients. There has been enormous progress in ALL treatment in recent years, which is reflected by the increase in the 5-year OS from 57% in the 1970s to up to 96% in the most recent studies. ALL treatment is based primarily on conventional methods, which include chemotherapy and radiotherapy. Their main weakness is severe toxicity, which prompts dose reduction, decreases the effectiveness of the treatment, and, in some cases, can lead to death. Currently, numerous modifications in treatment regimens are applied in order to limit toxicities emerging from conventional approaches and improve outcomes. Hematological treatment of pediatric patients is reaching for more novel treatment options, such as targeted treatment, CAR-T-cells therapy, and immunotherapy. These methods are currently used in conjunction with chemotherapy. Nevertheless, the swift progress in their development and increasing efficacity can lead to applying those novel therapies as standalone therapeutic options for pediatric ALL.