bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in Medium-Induced Conformational Plasticity Presumably Underlie Different Cytotoxic Activity of Ricin and Viscumin
Authors: Volynsky Pavel , Maltseva Diana , Tabakmakher Valentin , Bocharov Eduard V. , Raygorodskaya Maria , Zakharova Galina , Britikova Elena , Tonevitsky Alexander , Efremov Roman
Published: February 2022

Structurally similar catalytic subunits A of ricin (RTA) and viscumin (MLA) exhibit cytotoxic activity through ribosome inactivation. Ricin is more cytotoxic than viscumin, although the molecular mechanisms behind this difference are still poorly understood. To shed more light on this problem, we used a combined biochemical/molecular modeling approach to assess possible relationships between the activity of toxins and their structural/dynamic properties. Based on bioassay measurements, it was suggested that the differences in activity are associated with the ability of RTA and MLA to undergo structural/hydrophobic rearrangements during trafficking through the endoplasmic reticulum (ER) membrane. Molecular dynamics simulations and surface hydrophobicity mapping of both proteins in different media showed that RTA rearranges its structure in a membrane-like environment much more efficiently than MLA. Their refolded states also drastically differ in terms of hydrophobic organization. We assume that the higher conformational plasticity of RTA is favorable for the ER-mediated translocation pathway, which leads to a higher rate of toxin penetration into the cytoplasm.
Inuloxin A Inhibits Seedling Growth and Affects Redox System of Lycopersicon esculentum Mill. and Lepidium sativum L.
Authors: Villani Alessandra , Zonno Maria Chiara , de Leonardis Silvana , Vurro Maurizio , Paciolla Costantino
Published: February 2022

Allelochemicals are considered an environment-friendly and promising alternative for weed management, although much effort is still needed for understanding their mode of action and then promoting their use in plant allelopathy management practices. Here, we report that Inuloxin A (InA), an allelochemical isolated from Dittrichia viscosa, inhibited root elongation and growth of seedlings of Lycopersicon esculentum and Lepidium sativum at the highest concentrations tested. InA-induced antioxidant responses in the seedlings were investigated by analysing the contents of glutathione (GSH) and ascorbate (ASC), and their oxidized forms, dehydroascorbate (DHA), and glutathione disulphide (GSSG), as well as the redox state of thiol-containing proteins. An increase in ASC, DHA, and GSH levels at high concentrations of InA, after 3 and 6 days, were observed. Moreover, the ASC/DHA + ASC and GSH/GSSG + GSH ratios showed a shift towards the oxidized form. Our study provides the first insight into how the cell redox system responds and adapts to InA phytotoxicity, providing a framework for further molecular studies.
Tumor Suppressor Role of Wild-Type P53-Dependent Secretome and Its Proteomic Identification in PDAC
Authors: Butera Giovanna , Manfredi Marcello , Fiore Alessandra , Brandi Jessica , Pacchiana Raffaella , De Giorgis Veronica , Barberis Elettra , Vanella Virginia , Galasso Marilisa , Scupoli Maria Teresa , Marengo Emilio , Cecconi Daniela , Donadelli Massimo
Published: February 2022

The study of the cancer secretome is gaining even more importance in cancers such as pancreatic ductal adenocarcinoma (PDAC), whose lack of recognizable symptoms and early detection assays make this type of cancer highly lethal. The wild-type p53 protein, frequently mutated in PDAC, prevents tumorigenesis by regulating a plethora of signaling pathways. The importance of the p53 tumor suppressive activity is not only primarily involved within cells to limit tumor cell proliferation but also in the extracellular space. Thus, loss of p53 has a profound impact on the secretome composition of cancer cells and marks the transition to invasiveness. Here, we demonstrate the tumor suppressive role of wild-type p53 on cancer cell secretome, showing the anti-proliferative, apoptotic and chemosensitivity effects of wild-type p53 driven conditioned medium. By using high-resolution SWATH-MS technology, we characterized the secretomes of p53-deficient and p53-expressing PDAC cells. We found a great number of secreted proteins that have known roles in cancer-related processes, 30 of which showed enhanced and 17 reduced secretion in response to p53 silencing. These results are important to advance our understanding on the link between wt-p53 and cancer microenvironment. In conclusion, this approach may detect a secreted signature specifically driven by wild-type p53 in PDAC.
Roux-en-Y Gastric Bypass Modulates AMPK, Autophagy and Inflammatory Response in Leukocytes of Obese Patients
Authors: Abad-Jiménez Zaida , López-Domènech Sandra , García-Gargallo Celia , Vezza Teresa , Gómez-Abril Segundo Ángel , Morillas Carlos , Díaz-Pozo Pedro , Falcón Rosa , Bañuls Celia , Víctor Víctor M. , Rocha Milagros
Published: February 2022

Obesity is characterized by low-grade chronic inflammation, metabolic overload, and impaired endothelial and cardiovascular function. Roux-en-Y gastric bypass (RYGB) results in amelioration of the pro-oxidant status of leukocytes and the metabolic profile. Nevertheless, little is known about the precise mechanism that drives systemic and metabolic improvements following bariatric surgery. In this cohort study, we investigated the effect of RYGB on molecular pathways involving energy homeostasis in leukocytes in 43 obese subjects one year after surgery. In addition to clinical and biochemical parameters, we determined protein expression of systemic proinflammatory cytokines by Luminex®, different markers of inflammation, endoplasmic reticulum (ER) stress, autophagy/mitophagy by western blot, and mitochondrial membrane potential by fluorescence imaging. Bariatric surgery induced an improvement in metabolic outcomes that was accompanied by a systemic drop in hsCRP, IL6, and IL1β levels, and a slowing down of intracellular inflammatory pathways in leukocytes (NF-κB and MCP-1), an increase in AMPK content, a reduction of ER stress (ATF6 and CHOP), augmented autophagy/mitophagy markers (Beclin 1, ATG5, LC3-I, LC3-II, NBR1, and PINK1), and a decrease of mitochondrial membrane potential. These findings shed light on the specific molecular mechanisms by which RYGB facilitates metabolic improvements, highlighting the relevance of pathways involving energy homeostasis as key mediators of these outcomes. In addition, since leukocytes are particularly exposed to physiological changes, they could be used in routine clinical practice as a good sensor of the whole body’s responses.
Decoding Vagus-Nerve Activity with Carbon Nanotube Sensors in Freely Moving Rodents
Authors: Marmerstein Joseph T. , McCallum Grant A. , Durand Dominique M.
Published: February 2022

The vagus nerve is the largest autonomic nerve and a major target of stimulation therapies for a wide variety of chronic diseases. However, chronic recording from the vagus nerve has been limited, leading to significant gaps in our understanding of vagus nerve function and therapeutic mechanisms. In this study, we use a carbon nanotube yarn (CNTY) biosensor to chronically record from the vagus nerves of freely moving rats for over 40 continuous hours. Vagal activity was analyzed using a variety of techniques, such as spike sorting, spike-firing rates, and interspike intervals. Many spike-cluster-firing rates were found to correlate with food intake, and the neural-firing rates were used to classify eating and other behaviors. To our knowledge, this is the first chronic recording and decoding of activity in the vagus nerve of freely moving animals enabled by the axon-like properties of the CNTY biosensor in both size and flexibility and provides an important step forward in our ability to understand spontaneous vagus-nerve function.
Silicon Nanowires Length and Numbers Dependence on Sensitivity of the Field-Effect Transistor Sensor for Hepatitis B Virus Surface Antigen Detection
Authors: Wu Chi-Chang
Published: February 2022

Silicon nanowire field effect transistor (NWFET) sensors have been demonstrated to have high sensitivity, are label free, and offer specific detection. This study explored the effect of nanowire dimensions on sensors’ sensitivity. We used sidewall spacer etching to fabricate polycrystalline silicon NWFET sensors. This method does not require expensive nanoscale exposure systems and reduces fabrication costs. We designed transistor sensors with nanowires of various lengths and numbers. Hepatitis B surface antigen (HBsAg) was used as the sensing target to explore the relationships of nanowire length and number with biomolecule detection. The experimental results revealed that the sensor with a 3 µm nanowire exhibited high sensitivity in detecting low concentrations of HBsAg. However, the sensor reached saturation when the biomolecule concentration exceeded 800 fg/mL. Sensors with 1.6 and 5 µm nanowires exhibited favorable linear sensing ranges at concentrations from 800 ag/mL to 800 pg/mL. The results regarding the number of nanowires revealed that the use of few nanowires in transistor sensors increases sensitivity. The results demonstrate the effects of nanowire dimensions on the silicon NWFET biosensors.
Electrical Impedance-Based Characterization of Hepatic Tissue with Early-Stage Fibrosis
Authors: Fuentes-Vélez Susana , Fagoonee Sharmila , Sanginario Alessandro , Pizzi Marco , Altruda Fiorella , Demarchi Danilo
Published: February 2022

Liver fibrosis is a key pathological precondition for hepatocellular carcinoma in which the severity is confidently correlated with liver cancer. Liver fibrosis, characterized by gradual cell loss and excessive extracellular matrix deposition, can be reverted if detected at the early stage. The gold standard for staging and diagnosis of liver fibrosis is undoubtedly biopsy. However, this technique needs careful sample preparation and expert analysis. In the present work, an ex vivo, minimally destructive, label-free characterization of liver biopsies is presented. Through a custom-made experimental setup, liver biopsies of bile-duct-ligated and sham-operated mice were measured at 8, 15, and 21 days after the procedure. Changes in impedance were observed with the progression of fibrosis, and through data fitting, tissue biopsies were approximated to an equivalent RC circuit model. The model was validated by means of 3D hepatic cell culture measurement, in which the capacitive part of impedance was proportionally associated with cell number and the resistive one was proportionally associated with the extracellular matrix. While the sham-operated samples presented a decrease in resistance with time, the bile-duct-ligated ones exhibited an increase in this parameter with the evolution of fibrosis. Moreover, since the largest difference in resistance between healthy and fibrotic tissue, of around 2 kΩ, was found at 8 days, this method presents great potential for the study of fibrotic tissue at early stages. Our data point out the great potential of exploiting the proposed needle setup in clinical applications.
Hammerstein–Wiener Multimodel Approach for Fast and Efficient Muscle Force Estimation from EMG Signals
Authors: Chihi Ines , Sidhom Lilia , Kamavuako Ernest Nlandu
Published: February 2022

This paper develops a novel approach to characterise muscle force from electromyography (EMG) signals, which are the electric activities generated by muscles. Based on the nonlinear Hammerstein–Wiener model, the first part of this study outlines the estimation of different sub-models to mimic diverse force profiles. The second part fixes the appropriate sub-models of a multimodel library and computes the contribution of sub-models to estimate the desired force. Based on a pre-existing dataset, the obtained results show the effectiveness of the proposed approach to estimate muscle force from EMG signals with reasonable accuracy. The coefficient of determination ranges from 0.6568 to 0.9754 using the proposed method compared with a range of 0.5060 to 0.9329 using an artificial neural network (ANN), generating significantly different accuracy (p < 0.03). Results imply that the use of multimodel approach can improve the accuracy in proportional control of prostheses.
Verbal Fluency in Metabolic Syndrome
Authors: Gierach Marcin , Rasmus Anna , Orłowska Edyta
Published: February 2022

Metabolic syndrome (MetS) or otherwise insulin resistance (IR) is described as a cluster of several commonly occurring disorders, including abdominal obesity; lipids disorders, such as hypertriglyceridemia; and low levels of high-density-lipoprotein cholesterol (HDL-C), hypertension (≥130/85 mmHg), and carbohydrates disorders, such as impaired fasting glucose or diabetes mellitus type 2. Type 2 diabetes (T2DM) constitutes insulin resistance, which is a strong risk factor for strokes. Patients with MetS are often prone to cognitive decline. Metabolic risk factors, hypertension, and diabetes, amongst them, have been hypothesized to play a great role in the pathogenesis of Alzheimer’s disease (AD) and the development of vascular dementia. For neuropsychological diagnostic and theoretical purposes verbal fluency is defined as a cognitive function that facilitates information retrieval from memory. It engages executive control and other cognitive processes, such as selective attention, selective inhibition, mental set shifting, internal response generation, and self-monitoring, as well as imagination and psychomotor skills. A total of 90 subjects, divided into 2 groups, patients with MetS (45) and healthy controls (45), were assessed. A significant difference in performance was found between the patients and controls, both in the phonetic (p < 0.01) and semantic fluency trials (p < 0.001). The MetS patients produced less words in the letter K and animal categories. The analysis of descriptive statistics shows that the group of patients with metabolic syndrome generated fewer words in both the phonetic and semantic categories. Our study shows that there is an association between metabolic factors and the verbal fluency performance of MetS patients. This is true, especially for phonetic verbal fluency, which is traditionally connected with the frontal cortex. Lower switching signifies possible executive dysfunctions amongst people with MetS. Subjects with this condition generated more diverse words and created less standard associations. This further implies the existence of dysexecutive syndrome and the need for diagnosing patients in this direction and involving this group of people in therapy. The proper correction of MetS components may improve cognitive function.
Profiling the Skeletal Muscle Proteome in Patients on Atypical Antipsychotics and Mood Stabilizers
Authors: Burghardt Kyle J. , Calme Griffin , Caruso Michael , Howlett Bradley H. , Sanders Elani , Msallaty Zaher , Mallisho Abdullah , Seyoum Berhane , Qi Yue A. , Zhang Xiangmin , Yi Zhengping
Published: February 2022

Atypical antipsychotics (AAP) are used in the treatment of severe mental illness. They are associated with several metabolic side effects including insulin resistance. The skeletal muscle is the primary tissue responsible for insulin-stimulated glucose uptake. Dysfunction of protein regulation within the skeletal muscle following treatment with AAPs may play a role in the associated metabolic side effects. The objective of this study was to measure protein abundance in the skeletal muscle of patients on long-term AAP or mood stabilizer treatment. Cross-sectional muscle biopsies were obtained from patients with bipolar disorder and global protein abundance was measured using stable isotope labeling by amino acid (SILAC) combined with high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Sixteen patients completed muscle biopsies and were included in the proteomic analyses. A total of 40 proteins were significantly different between the AAP group and the mood stabilizer group. In-silico pathway analysis identified significant enrichment in several pathways including glucose metabolism, cell cycle, apoptosis, and folate metabolism. Proteome abundance changes also differed based on protein biological processes and function. In summary, significant differences in proteomic profiles were identified in the skeletal muscle between patients on AAPs and mood stabilizers. Future work is needed to validate these findings in prospectively sampled populations.
A Macaque Brain Extraction Model Based on U-Net Combined with Residual Structure
Authors: Wang Qianshan , Fei Hong , Abdu Nasher Saddam Naji , Xia Xiaoluan , Li Haifang
Published: February 2022

Accurately extracting brain tissue is a critical and primary step in brain neuroimaging research. Due to the differences in brain size and structure between humans and nonhuman primates, the performance of the existing tools for brain tissue extraction, working on macaque brain MRI, is constrained. A new transfer learning training strategy was utilized to address the limitations, such as insufficient training data and unsatisfactory model generalization ability, when deep neural networks processing the limited samples of macaque magnetic resonance imaging(MRI). First, the project combines two human brain MRI data modes to pre-train the neural network, in order to achieve faster training and more accurate brain extraction. Then, a residual network structure in the U-Net model was added, in order to propose a ResTLU-Net model that aims to improve the generalization ability of multiple research sites data. The results demonstrated that the ResTLU-Net, combined with the proposed transfer learning strategy, achieved comparable accuracy for the macaque brain MRI extraction tasks on different macaque brain MRI volumes that were produced by various medical centers. The mean Dice of the ResTLU-Net was 95.81% (no need for denoise and recorrect), and the method required only approximately 30–60 s for one extraction task on an NVIDIA 1660S GPU.
Bicultural Minds: A Cultural Priming Approach to the Self-Bias Effect
Authors: Jiang Mengyin , Sui Jie
Published: February 2022

Recent research has discovered a robust bias towards the processing of self-relevant information in perceptual matching. Self-associated stimuli are processed faster and more accurately than other-associated stimuli. Priming of independent or interdependent self-construal can dynamically modulate self-biases in high-level cognitive tasks. This study explored whether priming of independent/interdependent mindsets can modulate the self-bias effect in perceptual matching. In two experiments, British participants performed a priming task (Experiment 1 using a word-search task—an implicit priming approach, Experiment 2 with a reflective thinking task—an explicit priming method) immediately followed by a perceptual matching task, where they first learned to associate geometric shapes with labels (e.g., circle is you, square is friend, triangle is stranger) and then made judgments on whether shape-label pairs displayed on-screen were the correct associations or not. The analysis in Experiment 1 revealed that priming the interdependent self-construal led to a reduced self-bias effect in perceptual matching in participants who had low bias compared to those with high bias in the neutral/non-priming condition. In contrast, priming the independent self-construal did not modulate the self-bias in perceptual matching. The effects were replicated in Experiment 2. The results indicate that the self is a dynamic concept that can modulate perceptual processing by accessing different cultural contexts.
Formwork System Selection Criteria for Building Construction Projects: A Structural Equation Modelling Approach
Authors: Terzioglu Taylan , Polat Gul , Turkoglu Harun
Published: February 2022

Selecting the appropriate formwork system (FWS) is a critical aspect in the successful completion of reinforced concrete (RC) building construction projects. The selected FWS has a significant impact on the cost, time, and quality performances of the project. As there are many FWSs and formwork fabricators (FWFs) available, the selection of the FWS depends on several compromising and conflicting criteria. This study aims to identify the FWS selection criteria groupings (e.g., latent factors) and investigate the quantitative interrelationships among them. For this purpose, 35 FWS selection criteria were identified through literature review, and a questionnaire was developed. The data from the questionnaire were statistically analyzed, and five latent factors were identified: FWS-FWF characteristics, structural design, local conditions, cost, and performance indicators. A conceptual framework was developed based on the latent factors, and a structural equation modelling (SEM) approach was utilized to identify the effects among the latent factors. The results of the SEM approach confirmed that FWS-FWF characteristics are affected by the structural design and local conditions and FWS-FWF characteristics have a substantial effect on cost and the performance indicators of the project. The findings of this study may assist construction professionals in selecting the FWS in building construction projects.
Proportion and Performance Optimization of Lightweight Foamed Phosphogypsum Material Based on an Orthogonal Experiment
Authors: Zheng Tao , Miao Xun , Kong Dewen , Wang Lin , Cheng Lili , Yu Ke
Published: February 2022

A lightweight foam phosphogypsum material (LFPM) was prepared by multi-factor orthogonal and optimization experiments. The effects of foam, quicklime, silica fume and cement on the mechanical and physical properties of this LFPM were studied. The orthogonal experimental results showed that the silica fume content exhibited the most significant effect on the strength of this material, and the cement content exhibited the most obvious influence on the softening coefficient. The comprehensive index analysis indicated that the LFPM with 8% foam, 3.5% quicklime, 3% silica fume and 15% cement was selected as the optimal proportion. The 28 d compressive strength and flexural strength were 3.15 and 0.97 MPa, respectively. The dry density was 809.1 kg/m3, and the 28 d softening coefficient was 0.628. The optimization experimental results showed that the strength and dry density of the sample increased first and then decreased with an increase in the foam stabilizer content. The strength and dry density increased, and water absorption decreased with increasing waterproof agent content.
Applicability-Compatibility Analysis of PMBOK Seventh Edition from the Perspective of the Construction Industry Distinctive Peculiarities
Authors: Faraji Amir , Rashidi Maria , Perera Srinath , Samali Bijan
Published: February 2022

Project management standards, like PMBOK, have had a considerable role in developing this field of knowledge and promoting it as a professional expertise in project-oriented industries, such as the construction industry. The latest version of PMBOK, seventh edition—2021, has been released with substantial changes, and the conventional process-based system has been converted to a performance-based approach. This study aimed to investigate the recent edition of PMBOK, to explore its application and adaptation regarding the specific characteristics of the construction industry. For this purpose, utilizing a hybrid methodology of text mining and survey method, at first, the content of the text was analyzed by software in combination with experts’ opinions. In a parallel survey, the distinctive attributes of the construction industry were investigated, and in the next step, the way that this sector can benefit from the emerging framework was examined. The results show the construction industry has special peculiarities in the form of four different project types with specific phases in typical lifecycle and reveal the potential applicability of performance domains in the construction projects and the compatibility of project management principles. This study is one of the first attempts to review the novel presented standard of PMBOK seventh edition and contributes to the present knowledge by analyzing the construction industry in relation to this issue.
Heterogeneous Heat Absorption Is Complementary to Radiotherapy
Authors: Szasz Andras
Published: February 2022

(1) Background: Hyperthermia in oncology conventionally seeks the homogeneous heating of the tumor mass. The expected isothermal condition is the basis of the dose calculation in clinical practice. My objective is to study and apply a heterogenic temperature pattern during the heating process and show how it supports radiotherapy. (2) Methods: The targeted tissue’s natural electric and thermal heterogeneity is used for the selective heating of the cancer cells. The amplitude-modulated radiofrequency current focuses the energy absorption on the membrane rafts of the malignant cells. The energy partly “nonthermally” excites and partly heats the absorbing protein complexes. (3) Results: The excitation of the transmembrane proteins induces an extrinsic caspase-dependent apoptotic pathway, while the heat stress promotes the intrinsic caspase-dependent and independent apoptotic signals generated by mitochondria. The molecular changes synergize the method with radiotherapy and promote the abscopal effect. The mild average temperature (39–41 °C) intensifies the blood flow for promoting oxygenation in combination with radiotherapy. The preclinical experiences verify, and the clinical studies validate the method. (4) Conclusions: The heterogenic, molecular targeting has similarities with DNA strand-breaking in radiotherapy. The controlled energy absorption allows using a similar energy dose to radiotherapy (J/kg). The two therapies are synergistically combined.
PARP Inhibitors and Radiometabolic Approaches in Metastatic Castration-Resistant Prostate Cancer: What’s Now, What’s New, and What’s Coming?
Authors: Marchetti Andrea , Rosellini Matteo , Nuvola Giacomo , Tassinari Elisa , Mollica Veronica , Rizzo Alessandro , Santoni Matteo , Cimadamore Alessia , Farolfi Andrea , Montironi Rodolfo , Fanti Stefano , Massari Francesco
Published: February 2022

In recent years, the advances in the knowledge on the molecular characteristics of prostate cancer is allowing to explore novel treatment scenarios. Furthermore, technological discoveries are widening diagnostic and treatment weapons at the clinician disposal. Among these, great relevance is being gained by PARP inhibitors and radiometabolic approaches. The result is that DNA repair genes need to be altered in a high percentage of patients with metastatic prostate cancer, making these patients optimal candidates for PARP inhibitors. These compounds have already been proved to be active in pretreated patients and are currently being investigated in other settings. Radiometabolic approaches combine specific prostate cancer cell ligands to radioactive particles, thus allowing to deliver cytotoxic radiations in cancer cells. Among these, radium-223 and lutetium-177 have shown promising activity in metastatic pretreated prostate cancer patients and further studies are ongoing to expand the applications of this therapeutic approach. In addition, nuclear medicine techniques also have an important diagnostic role in prostate cancer. Herein, we report the state of the art on the knowledge on PARP inhibitors and radiometabolic approaches in advanced prostate cancer and present ongoing clinical trials that will hopefully expand these two treatment fields.
Rescuing SLAMF3 Expression Restores Sorafenib Response in Hepatocellular Carcinoma Cells through the Induction of Mesenchymal-to-Epithelial Transition
Authors: Fouquet Grégory , Marié Constance , Collet Louison , Vilpoux Catherine , Ouled-Haddou Hakim , Nguyen-Khac Eric , Bayry Jagadeesh , Naassila Mickaël , Marcq Ingrid , Bouhlal Hicham
Published: February 2022

Background: Acquired resistance to sorafenib in hepatocellular carcinoma (HCC) patients results in poor prognosis. Epithelial-to-mesenchymal transition (EMT) is the major mechanism implicated in the resistance to sorafenib. We have reported the tumor suppressor role of SLAMF3 (signaling lymphocytic activation molecules family 3) in HCC progression and highlighted its implication in controlling the MRP-1 transporter activity. These data suggest the implication of SLAMF3 in sorafenib resistance mechanisms. Methods: We evaluated the resistance to sorafenib in Huh-7 cells treated with progressive doses (Res cells). We investigated the link between acquired resistance to sorafenib and SLAMF3 expression by flow cytometry and Western blot methods. Furthermore, we analyzed the EMT and the stem cell potential of cells resistant to sorafenib. Results: Sorafenib resistance was confirmed in Res cells by analyzing the cell viability in the presence of sorafenib. The mesenchymal transition, in Res cells, was confirmed by high migratory index and the expression of EMT antigens. Interestingly, we found that loss of SLAMF3 expression corresponded to sorafenib-resistant phenotypes. The overexpression of SLAMF3 reversed EMT, decreased metastatic potential and inhibited mTOR/ERK1/2 in Res cells. Conclusions: We propose that rescuing SLAMF3 expression in resistant cells could represent a potential therapeutic strategy to enhance sorafenib efficacy in HCC patients.
Heterogeneity of Small Intestinal Neuroendocrine Tumors Metastasis: Biologic Patterns of a Series with Virchow’s Node Involvement
Authors: Wedin Maria , Tsoli Marina , Wallin Göran , Janson Eva Tiensuu , Koumarianou Anna , Kaltsas Gregory , Daskalakis Kosmas
Published: February 2022

Small intestinal neuroendocrine tumors (SI-NETs) may rarely metastasize to the left supraclavicular lymph nodes, also known as Virchow’s node metastasis (VM). Data on prevalence, prognostic significance, and clinical course of disease for SI-NET patients with VM is limited. In this retrospective analysis of 230 SI-NET patients treated at two tertiary referral centers, we found nine patients with VM (prevalence 3.9%). Among those, there were 5 females and median age at SI-NET and VM diagnosis was 61 and 65 years, respectively. Two patients had G1 tumors and five G2, while two tumors were of unspecified grade (median Ki67: 7%, range 2–15%). Four patients presented with synchronous VM, whereas five developed metachronous VM after a median of twenty-four months (range: 4.8–117.6 months). Hepatic metastases were present in seven patients, extrahepatic metastases (EM) in eight (six para-aortic distant lymph node metastases, one lung and one pancreatic metastasis), whereas peritoneal carcinomatosis (PC) in two patients. We used a control group of 18 age- and sex-matched SI-NET patients from the same cohort with stage IV disease but no extra-abdominal metastases. There was no difference in best-recorded response to first line treatment according to RECIST 1.1 as well as progression-free survival (PFS) between patients with VM and those in the control group (Chi-square test p = 0.516; PFS 71.7 vs. 106.9 months [95% CI 38.1–175.8]; log-rank p = 0.855). In addition, median overall survival (OS) of SI-NET patients with VM did not differ from those in the control group (138.6 [95% CI 17.2–260] vs. 109.9 [95% CI 91.7–128] months; log-rank p = 0.533). In conclusion, VM, although relatively rare in patients with SI-NETs, is more often encountered in patients with G2 tumors and established distant para-aortic lymph node metastases. The presence of VM in SI-NET patients does not seem to impact patients’ survival outcomes and treatment responses, when compared to age- and sex-matched SI-NET patients with stage IV disease confined in the abdomen.
Evaluating the Feasibility and Acceptability of an Artificial-Intelligence-Enabled and Speech-Based Distress Screening Mobile App for Adolescents and Young Adults Diagnosed with Cancer: A Study Protocol
Authors: Zhang Anao , Kamat Aarti , Acquati Chiara , Aratow Michael , Kim Johnny S. , DuVall Adam S. , Walling Emily
Published: February 2022

Adolescents and young adults (AYAs) diagnosed with cancer are an age-defined population, with studies reporting up to 45% of the population experiencing psychological distress. Although it is essential to screen and monitor for psychological distress throughout AYAs’ cancer journeys, many cancer centers fail to effectively implement distress screening protocols largely due to busy clinical workflow and survey fatigue. Recent advances in mobile technology and speech science have enabled flexible and engaging methods to monitor psychological distress. However, patient-centered research focusing on these methods’ feasibility and acceptability remains lacking. Therefore, in this project, we aim to evaluate the feasibility and acceptability of an artificial intelligence (AI)-enabled and speech-based mobile application to monitor psychological distress among AYAs diagnosed with cancer. We use a single-arm prospective cohort design with a stratified sampling strategy. We aim to recruit 60 AYAs diagnosed with cancer and to monitor their psychological distress using an AI-enabled speech-based distress monitoring tool over a 6 month period. The primary feasibility endpoint of this study is defined by the number of participants completing four out of six monthly distress assessments, and the acceptability endpoint is defined both quantitatively using the acceptability of intervention measure and qualitatively using semi-structured interviews.
SOX9 Triggers Different Epithelial to Mesenchymal Transition States to Promote Pancreatic Cancer Progression
Authors: Carrasco-Garcia Estefania , Lopez Lidia , Moncho-Amor Veronica , Carazo Fernando , Aldaz Paula , Collado Manuel , Bell Donald , Gaafar Ayman , Karamitopoulou Eva , Tzankov Alexandar , Hidalgo Manuel , Rubio Ángel , Serrano Manuel , Lawrie Charles H. , Lovell-Badge Robin , Matheu Ander
Published: February 2022

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers mainly due to spatial obstacles to complete resection, early metastasis and therapy resistance. The molecular events accompanying PDAC progression remain poorly understood. SOX9 is required for maintaining the pancreatic ductal identity and it is involved in the initiation of pancreatic cancer. In addition, SOX9 is a transcription factor linked to stem cell activity and is commonly overexpressed in solid cancers. It cooperates with Snail/Slug to induce epithelial-mesenchymal transition (EMT) during neural development and in diseases such as organ fibrosis or different types of cancer. Methods: We investigated the roles of SOX9 in pancreatic tumor cell plasticity, metastatic dissemination and chemoresistance using pancreatic cancer cell lines as well as mouse embryo fibroblasts. In addition, we characterized the clinical relevance of SOX9 in pancreatic cancer using human biopsies. Results: Gain- and loss-of-function of SOX9 in PDAC cells revealed that high levels of SOX9 increased migration and invasion, and promoted EMT and metastatic dissemination, whilst SOX9 silencing resulted in metastasis inhibition, along with a phenotypic reversion to epithelial features and loss of stemness potential. In both contexts, EMT factors were not altered. Moreover, high levels of SOX9 promoted resistance to gemcitabine. In contrast, overexpression of SOX9 was sufficient to promote metastatic potential in K-Ras transformed MEFs, triggering EMT associated with Snail/Slug activity. In clinical samples, SOX9 expression was analyzed in 198 PDAC cases by immunohistochemistry and in 53 patient derived xenografts (PDXs). SOX9 was overexpressed in primary adenocarcinomas and particularly in metastases. Notably, SOX9 expression correlated with high vimentin and low E-cadherin expression. Conclusions: Our results indicate that SOX9 facilitates PDAC progression and metastasis by triggering stemness and EMT.
Pheochromocytomas and Abdominal Paragangliomas: A Practical Guidance
Authors: Calissendorff Jan , Juhlin Carl Christofer , Bancos Irina , Falhammar Henrik
Published: February 2022

Pheochromocytomas and abdominal paragangliomas (PPGLs) are rare tumors arising from the adrenal medulla or the sympathetic nervous system. This review presents a practical guidance for clinicians dealing with PPGLs. The incidence of PPGLs has risen. Most cases are detected via imaging and less present with symptoms of catecholamine excess. Most PPGLs secrete catecholamines, with diffuse symptoms. Diagnosis is made by imaging and tests of catecholamines. Localized disease can be cured by surgery. PPGLs are the most heritable of all human tumors, and germline variants are found in approximately 30–50% of cases. Such variants can give information regarding the risk of developing recurrence or metastases as well as the risk of developing other tumors and may identify relatives at risk for disease. All PPGLs harbor malignant potential, and current histological and immunohistochemical algorithms can aid in the identification of indolent vs. aggressive tumors. While most patients with metastatic PPGL have slowly progressive disease, a proportion of patients present with an aggressive course, highlighting the need for more effective therapies in these cases. We conclude that PPGLs are rare but increasing in incidence and management should be guided by a multidisciplinary team.
Effects of Endocrine Therapy on Cognitive Function in Patients with Breast Cancer: A Comprehensive Review
Authors: Haggstrom Lucy R. , Vardy Janette L. , Carson Emma-Kate , Segara Davendra , Lim Elgene , Kiely Belinda E.
Published: February 2022

Endocrine therapy forms the backbone of systemic therapy for the majority of persons with early and late-stage breast cancer. However, the side effects can negatively affect quality of life, and impact treatment adherence and overall oncological outcomes. Adverse effects on cognition are common, underreported and challenging to manage. We aim to describe the nature, incidence, risk factors and underlying mechanisms of endocrine therapy-induced cognitive dysfunction. We conducted a comprehensive literature review of the studies reporting on cognitive dysfunction associated with endocrine therapies for breast cancer. We also summarise prevention and treatment strategies, and ongoing research. Given that patients are taking endocrine therapies for longer durations than ever before, it is essential that these side effects are managed pro-actively within a multi-disciplinary team in order to promote adherence to endocrine therapy and improve patients’ quality of life.
DKK3, Downregulated in Invasive Epithelial Ovarian Cancer, Is Associated with Chemoresistance and Enhanced Paclitaxel Susceptibility via Inhibition of the β-Catenin-P-Glycoprotein Signaling Pathway
Authors: Nguyen Que Thanh Thanh , Park Hwang Shin , Lee Tae Jin , Choi Kyung-Mi , Park Joong Yull , Kim Daehan , Kim Jae Hyung , Park Junsoo , Lee Eun-Ju
Published: February 2022

Dickkopf-3 (DKK3), a tumor suppressor, is frequently downregulated in various cancers. However, the role of DKK3 in ovarian cancer has not been evaluated. This study aimed to assess aberrant DKK3 expression and its role in epithelial ovarian carcinoma. DKK3 expression was assessed using immunohistochemistry with tissue blocks from 82 patients with invasive carcinoma, and 15 normal, 19 benign, and 10 borderline tumors as controls. Survival data were analyzed using Kaplan–Meier and Cox regression analysis. Paclitaxel-resistant cells were established using TOV-21G and OV-90 cell lines. Protein expression was assessed using Western blotting and immunofluorescence analysis. Cell viability was assessed using the MT assay and 3D-spheroid assay. Cell migration was determined using a migration assay. DKK3 was significantly downregulated in invasive carcinoma compared to that in normal, benign, and borderline tumors. DKK3 loss occurred in 56.1% invasive carcinomas and was significantly associated with disease-free survival and chemoresistance in serous adenocarcinoma. DKK3 was lost in paclitaxel-resistant cells, while β-catenin and P-glycoprotein were upregulated. Exogenous secreted DKK3, incorporated by cells, enhanced anti-tumoral effect and paclitaxel susceptibility in paclitaxel-resistant cells, and reduced the levels of active β-catenin and its downstream P-glycoprotein, suggesting that DKK3 can be used as a therapeutic for targeting paclitaxel-resistant cancer.
Overweight and Obesity Determine the Risk for Gastrointestinal Cancer in a Sex-Dependent Manner: A Retrospective Cohort Study of 287,357 Outpatients in Germany
Authors: Loosen Sven H. , Roderburg Christoph , Jördens Markus S. , Fluegen Georg , Luedde Tom , Kostev Karel
Published: February 2022

Cancer represents the second leading cause of death worldwide, implementing a major health care and socioeconomic burden. Overweight and obesity, both of which are dramatically on the rise in both highly and less developed regions worldwide, have been established as modifiable risk factors for the development of various tumor entities including gastrointestinal (GI) cancers such as colorectal or gastric cancer. However, systematic data on an association between excessive body fat and GI cancer development from Germany are missing. Methods: A total of 287,357 adult outpatients with an available BMI value between 2010 and 2019 were identified from the Disease Analyzer database (IQVIA). The main outcome was the association between pre-obesity (BMI 25–30 kg/m2) and obesity (BMI ≥ 30 kg/m2) compared to normal weight (BMI 18.5–25 kg/m2) and the incident of a GI cancer diagnoses (including colon, rectum, stomach, pancreas, and liver cancer). Results: Within the observation period, the proportion of colon cancer patients increased stepwise from 0.5% and 0.64% in normal weight to 0.71% and 0.91% in obese female and male patients, respectively, which was confirmed in multivariable regression models (ORfemale obesity: 1.23; 95% CI: 1.03–1.48; ORmale obesity: 1.43, 95% CI: 1.17–1.74). In contrast, multivariable regression models revealed that obesity was significantly associated with rectal cancer (OR: 1.36, 95% CI: 1.01–1.84) as well as liver cancer (OR: 1.79, 95% CI: 1.17–2.73) in men only. Conclusions: Our data suggest that obesity represents a decisive risk factor for the development of colon, rectal, and liver cancer, partly in a sex-dependent manner. Since overweight and obesity are modifiable risk factors, the current results may help to establish appropriate prevention and lifestyle programs to reduce both the incidence as well as the high morbidity and mortality of GI tumors in the future.
Identification of Atypical Circulating Tumor Cells with Prognostic Value in Metastatic Breast Cancer Patients
Authors: Lopresti Alexia , Acquaviva Claire , Boudin Laurys , Finetti Pascal , Garnier Séverine , Aulas Anaïs , Liberatoscioli Maria Lucia , Cabaud Olivier , Guille Arnaud , de Nonneville Alexandre , Da Costa Quentin , Denicolai Emilie , Pakradouni Jihane , Goncalves Anthony , Birnbaum Daniel , Bertucci François , Mamessier Emilie
Published: February 2022

Circulating tumor cells have a strong potential as a quasi-non-invasive tool for setting up a precision medicine strategy for cancer patients. Using a second-generation “filtration-based” technology to isolate CTCs, the Screencell™ technology (Sarcelles, France), we performed a large and simultaneous analysis of all atypical circulating tumor cells (aCTCs) isolated from the blood of metastatic breast cancer (mBC) patients. We correlated their presence with clinicopathological and survival data. We included 91 mBC patients from the PERMED-01 study. The median number of aCTCs was 8.3 per mL of blood. Three subsets of aCTCs, absent from controls, were observed in patients: single (s-aCTCs), circulating tumor micro-emboli (CTM), and giant-aCTCs (g-aCTCs). The presence of g-aCTCs was associated with shorter progression free survival and overall survival. This study highlights the heterogeneity of aCTCs in mBC patients both at the cytomorphological and molecular levels. In addition, it suggests the usefulness of the g-aCTC subset as a prognostic factor and a potential stratification tool to treat late-stage mBC patients and improve their chances of benefiting from early clinical trials.
Application of Biochar as Functional Material for Remediation of Organic Pollutants in Water: An Overview
Authors: Gasim Mohamed Faisal , Choong Zheng-Yi , Koo Pooi-Ling , Low Siew-Chun , Abdurahman Mohamed-Hussein , Ho Yeek-Chia , Mohamad Mardawani , Suryawan I Wayan Koko , Lim Jun-Wei , Oh Wen-Da
Published: February 2022

In recent years, numerous studies have focused on the use of biochar as a biological material for environmental remediation due to its low-cost precursor (waste), low toxicity, and diversity of active sites, along with their facile tailoring techniques. Due to its versatility, biochar has been employed as an adsorbent, catalyst (for activating hydrogen peroxide, ozone, persulfate), and photocatalyst. This review aims to provide a comprehensive overview and compare the application of biochar in water remediation. First, the biochar active sites with their functions are presented. Secondly, an overview and summary of biochar performance in treating organic pollutants in different systems is depicted. Thereafter, an evaluation on performance, removal mechanism, active sites involvement, tolerance to different pH values, stability, and reusability, and an economic analysis of implementing biochar for organic pollutants decontamination in each application is presented. Finally, potential prospects to overcome the drawbacks of each application are provided.
CO and CO2 Methanation over CeO2-Supported Cobalt Catalysts
Authors: Nguyen Thuy Ha , Kim Han Bom , Park Eun Duck
Published: February 2022

CO2 methanation is a promising reaction for utilizing CO2 using hydrogen generated by renewable energy. In this study, CO and CO2 methanation were examined over ceria-supported cobalt catalysts with low cobalt contents. The catalysts were prepared using a wet impregnation and co-precipitation method and pretreated at different temperatures. These preparation variables affected the catalytic performance as well as the physicochemical properties. These properties were characterized using various techniques including N2 physisorption, X-ray diffraction, H2 chemisorption, temperature-programmed reduction with H2, and temperature-programmed desorption after CO2 chemisorption. Among the prepared catalysts, the ceria-supported cobalt catalyst that was prepared using a wet impregnation method calcined in air at 500 °C, and reduced in H2 at 500 °C, showed the best catalytic performance. It is closely related to the large catalytically active surface area, large surface area, and large number of basic sites. The in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) study revealed the presence of carbonate, bicarbonate, formate, and CO on metallic cobalt.
Experimental and Theoretical Investigations of Low-Dimensional BiFeO3 System for Photocatalytic Applications
Authors: Benyoussef Manal , Saitzek Sébastien , Rajput Nitul S. , Courty Matthieu , El Marssi Mimoun , Jouiad Mustapha
Published: February 2022

We report on the fabrication of sub-20 nm BiFeO3 (BFO) nanoparticles using a solid-state approach and preferential leching process. The nanoparticles were subsequently used to deposit, through spray pyrolysis, BFO thin films in a rhombohedral (R3c) crystallographic structure. Then, systematic investigations of the optical and the photocatalytic properties were conducted to determine the effects of the particles size, the microstructure and the increased surface area on their catalytic performances. Especially, improved optical properties were observed, with an optical bandgap energy of 2.20 eV compared to reported 2.7 eV for the bulk system. In addition, high optical absorption was obtained in the UV–visible light region reaching up to 90% at 400 nm. The photoelectrochemical measurements revealed a high photocurrent density under visible light irradiation. Besides, density functional theory calculations were performed on both bulk and thin film BFO structures, revealing an interesting comparison of the electronic, magnetic, ferroelectric and optical properties for bulk and thin film BFO systems. Both theoretical and experimental findings show that the alignment of the band edges of BFO thin film is coherent with good photocatalytic water splitting potential, making them desirable photoanode materials.