bluuebunny/crossref_metadata_2025 huggingface dataset:
Chasing the Target: New Phenomena of Resistance to Novel Selective RET Inhibitors in Lung Cancer. Updated Evidence and Future Perspectives
Authors: Fancelli Sara , Caliman Enrico , Mazzoni Francesca , Brugia Marco , Castiglione Francesca , Voltolini Luca , Pillozzi Serena , Antonuzzo Lorenzo
Published: March 2021

The potent, RET-selective tyrosine kinase inhibitors (TKIs) pralsetinib and selpercatinib, are effective against the RET V804L/M gatekeeper mutants, however, adaptive mutations that cause resistance at the solvent front RET G810 residue have been found, pointing to the need for the development of the next-generation of RET-specific TKIs. Also, as seen in EGFR- and ALK-driven NSCLC, the rising of the co-occurring amplifications of KRAS and MET could represent other escaping mechanisms from direct inhibition. In this review, we summarize actual knowledge on RET fusions, focusing on those involved in NSCLC, the results of main clinical trials of approved RET-inhibition drugs, with particular attention on recent published results of selective TKIs, and finally, pre-clinical evidence regarding resistance mechanisms and suggestion on hypothetical and feasible drugs combinations and strategies viable in the near future.
The Roadmap of Colorectal Cancer Screening
Authors: Ferlizza Enea , Solmi Rossella , Sgarzi Michela , Ricciardiello Luigi , Lauriola Mattia
Published: March 2021

Colorectal cancer (CRC) is the third most common form of cancer in terms of incidence and the second in terms of mortality worldwide. CRC develops over several years, thus highlighting the importance of early diagnosis. National screening programs based on fecal occult blood tests and subsequent colonoscopy have reduced the incidence and mortality, however improvements are needed since the participation rate remains low and the tests present a high number of false positive results. This review provides an overview of the CRC screening globally and the state of the art in approaches aimed at improving accuracy and participation in CRC screening, also considering the need for gender and age differentiation. New fecal tests and biomarkers such as DNA methylation, mutation or integrity, proteins and microRNAs are explored, including recent investigations into fecal microbiota. Liquid biopsy approaches, involving novel biomarkers and panels, such as circulating mRNA, micro- and long-non-coding RNA, DNA, proteins and extracellular vesicles are discussed. The approaches reported are based on quantitative PCR methods that could be easily applied to routine screening, or arrays and sequencing assays that should be better exploited to describe and identify candidate biomarkers in blood samples.
The Secreted Protein C10orf118 Is a New Regulator of Hyaluronan Synthesis Involved in Tumour-Stroma Cross-Talk
Authors: Caon Ilaria , D’Angelo Maria Luisa , Bartolini Barbara , Caravà Elena , Parnigoni Arianna , Contino Flavia , Cancemi Patrizia , Moretto Paola , Karamanos Nikos K. , Passi Alberto , Vigetti Davide , Karousou Evgenia , Viola Manuela
Published: March 2021

Interaction between cancer cells and their microenvironment is central in defining the fate of cancer development. Tumour cells secrete signals (cytokines, chemokines, growth factors) that modify the surrounding area, while the niche supplies structures and activities necessary for tumour maintenance and growth. Hyaluronan (HA) is a glycosaminoglycan that constitute cancer cell niche and is known to influence tumour functions such as proliferation, migration and neoangiogenesis. The knowledge of the factors regulating HA synthesis and size is crucial in understanding the mechanisms sustaining tumour development. Here we show that a yet uncharacterized protein secreted by breast tumour cell lines, named c10orf118 (accession number NM_018017 in NCBI/BLAST, and Q7z3E2 according to the Uniprot identifier), with a predicted length of 898 amino acids, can induce the secretion of HA by stromal fibroblasts through the up-regulation of the hyaluronan synthase 2 gene (HAS2). Intracellularly, this protein is localized in the Golgi apparatus with a possible role in vesicle maturation and transport. The expression of c10orf118 was verified in breast cancer patient specimens and was found to be associated with the presence of estrogen receptor that characterizes a good patient survival. We suggest c10orf118 as a new player that influences the HA amount in breast cancer microenvironment and is associated with low aggressiveness of cancer.
Proteasomes in Patient Rectal Cancer and Different Intestine Locations: Where Does Proteasome Pool Change?
Authors: Erokhov Pavel A. , Kulikov Alexey M. , Karpova Yaroslava D. , Rodoman Grigory V. , Sumedi Ilia R. , Goncharov Artem L. , Razbirin Dmitry V. , Gorelova Vera S. , Sharova Natalia P. , Astakhova Tatiana M.
Published: March 2021

A special problem in the surgery of rectal cancer is connected with a need for appropriate removal of intestine parts, along with the tumor, including the fragment close to the sphincter. To determine the length of fragments to remove, it is necessary to reveal areas without changes in molecule functioning, specific for tumor. The purpose of the present study was to investigate functioning the proteasomes, the main actors in protein hydrolysis, in patient rectal adenocarcinoma and different intestine locations. Chymotrypsin-like and caspase-like activities, open to complex influence of different factors, were analyzed in 43–54 samples by Suc-LLVY-AMC- and Z-LLE-AMC-hydrolysis correspondingly. Both activities may be arranged by the decrease in the location row: cancer→adjacent tissue→proximal (8–20 cm from tumor) and distal (2 and 4 cm from tumor) sides. These activities did not differ noticeably in proximal and distal locations. Similar patterns were detected for the activities and expression of immune subunits LMP2 and LMP7 and expression of 19S and PA28αβ activators. The largest changes in tumor were related to proteasome subtype containing LMP2 and PA28αβ that was demonstrated by native electrophoresis. Thus, the results indicate a significance of subtype LMP2-PA28αβ for tumor and absence of changes in proteasome pool in distal fragments of 2–4 cm from tumor.
Bacterial, Archaea, and Viral Transcripts (BAVT) Expression in Gynecological Cancers and Correlation with Regulatory Regions of the Genome
Authors: Gonzalez-Bosquet Jesus , Pedra-Nobre Silvana , Devor Eric J. , Thiel Kristina W. , Goodheart Michael J. , Bender David P. , Leslie Kimberly K.
Published: March 2021

Bacteria, archaea, and viruses are associated with numerous human cancers. To date, microbiome variations in transcription have not been evaluated relative to upper female genital tract cancer risk. Our aim was to assess differences in bacterial, archaea, and viral transcript (BAVT) expression between different gynecological cancers and normal fallopian tubes. In this case-control study we performed RNA sequencing on 12 normal tubes, 112 serous ovarian cancers (HGSC) and 62 endometrioid endometrial cancers (EEC). We used the centrifuge algorithm to classify resultant transcripts into four indexes: bacterial, archaea, viral, and human genomes. We then compared BAVT expression from normal samples, HGSC and EEC. T-test was used for univariate comparisons (correcting for multiple comparison) and lasso for multivariate modelling. For validation we performed DNA sequencing of normal tubes in comparison to HGSC and EEC BAVTs in the TCGA database. Pathway analyses were carried out to evaluate the function of significant BAVTs. Our results show that BAVT expression levels vary between different gynecological cancers. Finally, we mapped some of these BAVTs to the human genome. Numerous map locations were close to regulatory genes and long non-coding RNAs based on the pathway enrichment analysis. BAVTs may affect gynecological cancer risk and may be part of potential targets for cancer therapy.
The Frontal Aslant Tract and Supplementary Motor Area Syndrome: Moving towards a Connectomic Initiation Axis
Authors: Briggs Robert G. , Allan Parker G. , Poologaindran Anujan , Dadario Nicholas B. , Young Isabella M. , Ahsan Syed A. , Teo Charles , Sughrue Michael E.
Published: March 2021

Connectomics is the use of big data to map the brain’s neural infrastructure; employing such technology to improve surgical planning may improve neuro-oncological outcomes. Supplementary motor area (SMA) syndrome is a well-known complication of medial frontal lobe surgery. The ‘localizationist’ view posits that damage to the posteromedial bank of the superior frontal gyrus (SFG) is the basis of SMA syndrome. However, surgical experience within the frontal lobe suggests that this is not entirely true. In a study on n = 45 patients undergoing frontal lobe glioma surgery, we sought to determine if a ‘connectomic’ or network-based approach can decrease the likelihood of SMA syndrome. The control group (n = 23) underwent surgery avoiding the posterior bank of the SFG while the treatment group (n = 22) underwent mapping of the SMA network and Frontal Aslant Tract (FAT) using network analysis and DTI tractography. Patient outcomes were assessed post operatively and in subsequent follow-ups. Fewer patients (8.3%) in the treatment group experienced transient SMA syndrome compared to the control group (47%) (p = 0.003). There was no statistically significant difference found between the occurrence of permanent SMA syndrome between control and treatment groups. We demonstrate how utilizing tractography and a network-based approach decreases the likelihood of transient SMA syndrome during medial frontal glioma surgery. We found that not transecting the FAT and the SMA system improved outcomes which may be important for functional outcomes and patient quality of life.
Preparation of Ti-Nb-Fe-O Nanotubes on Ti10NbxFe Alloy and the Application for Photocatalytic Degradation under Solar Irradiation
Authors: Zhao Yujie , Li Qiquan , Li Yan
Published: March 2021

Highly oriented and self-ordered titanium-niobium-iron mixed oxide nanotubes were synthesized by anodizing Ti10NbxFe alloys in ethylene glycol electrolytes containing NH4F and water at 20 °C. The nanostructure morphologies were found to depend closely on the nature of the alloy substrates. The results demonstrate the possibility of growing mixed oxide nanotubes possessing several-micrometer-thick layers by a simple and straightforward electrochemical route. The methylene blue degradation rate of fabricated Ti-Nb-Fe-O nanotubes increased by 33% compared to TiO2 nanotubes and TiO2 nanoparticle films under solar irradiation. The combination of the gully-like morphology and the rich defects introduced by Nb and Fe co-doping in Ti-Nb-Fe-O mixed nanotube oxides was demonstrated to be beneficial for enhanced photocatalytic degradation performance. Ti-Nb-Fe-O nanotubes can achieve effective photodegradation without secondary pollution with more reusability than powder photocatalysts.
rGO Functionalized ZnO–TiO2 Core-Shell Flower-Like Architectures for Visible Light Photocatalysis
Authors: Vasilaki Evangelia , Katsarakis Nikos , Dokianakis Spyros , Vamvakaki Maria
Published: March 2021

Core-shell heterostructures with a complex, flower-like morphology, comprising a ZnO core and a TiO2 shell decorated with reduced graphene oxide (rGO) sheets by hydrothermal wrapping, are reported to extend the absorption properties of the semiconductors toward the visible light range. The ternary photocatalysts were characterized by X-ray diffraction, field emission scanning electron microscopy, Raman spectroscopy, diffuse reflectance UV–Vis, and attenuated total reflectance-Fourier transform infrared spectroscopy. Its photocatalytic performance was evaluated under visible light irradiation using methylene blue dye as a model pollutant. The rGO-modified ZnO–TiO2 photocatalyst exhibited superior photoactivity compared to that of the parent ZnO–TiO2 core-shell structures, which was dependent on its graphene content. The enhanced photocatalytic response was attributed to the higher absorption in the visible light range, as well as the pronounced electron and hole separation in the ternary system.
Decursin Alleviates Mechanical Allodynia in a Paclitaxel-Induced Neuropathic Pain Mouse Model
Authors: Son Dang Bao , Choi Woosik , Kim Mingu , Go Eun Jin , Jeong Dabeen , Park Chul-Kyu , Kim Yong Ho , Lee Hanki , Suh Joo-Won
Published: March 2021

Chemotherapy-induced neuropathic pain (CINP) is a severe adverse effect of platinum- and taxane-derived anticancer drugs. The pathophysiology of CINP includes damage to neuronal networks and dysregulation of signal transduction due to abnormal Ca2+ levels. Therefore, methods that aid the recovery of neuronal networks could represent a potential treatment for CINP. We developed a mouse model of paclitaxel-induced peripheral neuropathy, representing CINP, to examine whether intrathecal injection of decursin could be effective in treating CINP. We found that decursin reduced capsaicin-induced intracellular Ca2+ levels in F11 cells and stimulated neurite outgrowth in a concentration-dependent manner. Decursin directly reduced mechanical allodynia, and this improvement was even greater with a higher frequency of injections. Subsequently, we investigated whether decursin interacts with the transient receptor potential vanilloid 1 (TRPV1). The web server SwissTargetPrediction predicted that TRPV1 is one of the target proteins that may enable the effective treatment of CINP. Furthermore, we discovered that decursin acts as a TRPV1 antagonist. Therefore, we demonstrated that decursin may be an important compound for the treatment of paclitaxel-induced neuropathic pain that functions via TRPV1 inhibition and recovery of damaged neuronal networks.
Emerging Role of Pericytes and Their Secretome in the Heart
Authors: Su Han , Cantrell Aubrey C. , Zeng Heng , Zhu Shai-Hong , Chen Jian-Xiong
Published: March 2021

Pericytes, as mural cells covering microvascular capillaries, play an essential role in vascular remodeling and maintaining vascular functions and blood flow. Pericytes are crucial participants in the physiological and pathological processes of cardiovascular disease. They actively interact with endothelial cells, vascular smooth muscle cells (VSMCs), fibroblasts, and other cells via the mechanisms involved in the secretome. The secretome of pericytes, along with diverse molecules including proinflammatory cytokines, angiogenic growth factors, and the extracellular matrix (ECM), has great impacts on the formation, stabilization, and remodeling of vasculature, as well as on regenerative processes. Emerging evidence also indicates that pericytes work as mesenchymal cells or progenitor cells in cardiovascular regeneration. Their capacity for differentiation also contributes to vascular remodeling in different ways. Previous studies primarily focused on the roles of pericytes in organs such as the brain, retina, lung, and kidney; very few studies have focused on pericytes in the heart. In this review, following a brief introduction of the origin and fundamental characteristics of pericytes, we focus on pericyte functions and mechanisms with respect to heart disease, ending with the promising use of cardiac pericytes in the treatment of ischemic heart failure.
Selective Proliferation of Highly Functional Adipose-Derived Stem Cells in Microgravity Culture with Stirred Microspheres
Authors: Mashiko Takanobu , Kanayama Koji , Saito Natsumi , Shirado Takako , Asahi Rintaro , Mori Masanori , Yoshimura Kotaro
Published: March 2021

Therapeutic effects of adult stem-cell transplantations are limited by poor cell-retention in target organs, and a reduced potential for optimal cell differentiation compared to embryonic stem cells. However, contemporary studies have indicated heterogeneity within adult stem-cell pools, and a novel culturing technique may address these limitations by selecting those for cell proliferation which are highly functional. Here, we report the preservation of stemness in human adipose-derived stem cells (hASCs) by using microgravity conditions combined with microspheres in a stirred suspension. The cells were bound to microspheres (100−300 μm) and cultured using a wave-stirring shaker. One-week cultures using polystyrene and collagen microspheres increased the proportions of SSEA-3(+) hASCs 4.4- and 4.3-fold (2.7- and 2.9-fold increases in their numbers), respectively, compared to normal culture conditions. These cultured hASCs expressed higher levels of pluripotent markers (OCT4, SOX2, NANOG, MYC, and KLF), and had improved abilities for proliferation, colony formation, network formation, and multiple-mesenchymal differentiation. We believe that this novel culturing method may further enhance regenerative therapies using hASCs.
Towards a Framework for Better Understanding of Quiescent Cancer Cells
Authors: Nik Nabil Wan Najbah , Xi Zhichao , Song Zejia , Jin Lei , Zhang Xu Dong , Zhou Hua , De Souza Paul , Dong Qihan , Xu Hongxi
Published: March 2021

Quiescent cancer cells (QCCs) are cancer cells that are reversibly suspended in G0 phase with the ability to re-enter the cell cycle and initiate tumor growth, and, ultimately, cancer recurrence and metastasis. QCCs are also therapeutically challenging due to their resistance to most conventional cancer treatments that selectively act on proliferating cells. Considering the significant impact of QCCs on cancer progression and treatment, better understanding of appropriate experimental models, and the evaluation of QCCs are key questions in the field that have direct influence on potential pharmacological interventions. Here, this review focuses on existing and emerging preclinical models and detection methods for QCCs and discusses their respective features and scope for application. By providing a framework for selecting appropriate experimental models and investigative methods, the identification of the key players that regulate the survival and activation of QCCs and the development of more effective QCC-targeting therapeutic agents may mitigate the consequences of QCCs.
The Interface Characterization of 2-Mercapto-1-methylimidazole Corrosion Inhibitor on Brass
Authors: Finšgar Matjaž
Published: March 2021

This work presents a detailed surface analytical study and surface characterization, with an emphasis on the X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) analyses of 2‑mercapto‑1‑methylimidazole (MMI) as a corrosion inhibitor for brass. First, the electrochemical measurements demonstrated a corrosion inhibition effect of MMI in a 3 wt.% NaCl solution. Next, the formation of the MMI surface layer and its properties after 1 month of immersion was analyzed with attenuated total reflectance–Fourier-transform infrared spectroscopy, atomic force microscopy, field-emission scanning electron microscopy, and contact angle analysis. Moreover, to gradually remove the organic surface layer, a gas cluster ion beam (GCIB) sputtering source at different accelerated voltages and cluster sizes was employed. After each sputtering cycle, a high-resolution XPS analysis was performed. Moreover, an angle‑resolved XPS analysis was carried out for the MMI-treated brass sample to analyze the heterogeneous layered structure (the interface of the MMI organic/inorganic brass substrate). The interface properties were also investigated in detail using ToF-SIMS for spectra measurements and 2D imaging. Special attention was devoted to the possible spectral interferences for MMI‑related species. The thermal stability of different MMI-related species using molecular-specific signals without possible spectral interferences was determined by performing a cooling/heating experiment associated with ToF-SIMS measurements. It was shown that these species desorbed from the brass surface in the temperature range of 310–370 °C.
Finite Element Analysis of Composite Repair for Damaged Steel Pipeline
Authors: Chen Jiaqi , Wang Hao , Salemi Milad , Balaguru Perumalsamy N.
Published: March 2021

Carbon fiber reinforced polymer (CFRP) matrix composite overwrap repair systems have been introduced and accepted as an alternative repair system for steel pipeline. This paper aimed to evaluate the mechanical behavior of damaged steel pipeline with CFRP repair using finite element (FE) analysis. Two different repair strategies, namely wrap repair and patch repair, were considered. The mechanical responses of pipeline with the composite repair system under the maximum allowable operating pressure (MAOP) was analyzed using the validated FE models. The design parameters of the CFRP repair system were analyzed, including patch/wrap size and thickness, defect size, interface bonding, and the material properties of the infill material. The results show that both the stress in the pipe wall and CFRP could be reduced by using a thicker CFRP. With the increase in patch size in the hoop direction, the maximum von Mises stress in the pipe wall generally decreased as the maximum hoop stress in the CFRP increased. The reinforcement of the CFRP repair system could be enhanced by using infill material with a higher elastic modulus. The CFRP patch tended to cause higher interface shear stress than CFRP wrap, but the shear stress could be reduced by using a thicker CFRP. Compared with the fully bonded condition, the frictional interface causes a decrease in hoop stress in the CFRP but an increase in von Mises stress in the steel. The study results indicate the feasibility of composite repair for damaged steel pipeline.
Efficient Separation of Silicon and Vanadium by Sodium Roasting-Water Leaching from Vanadium Slag and CaV2O6 Preparation
Authors: Li Changqing , Zhang Haichao , Tao Ma , Wang Xufeng , Li Hang , Li Yungang , Tian Ying
Published: March 2021

Calcium vanadate (CaV2O6), a new product of vanadium precipitation, was obtained from vanadium slag by sodium roasting-water leaching and calcium precipitation. The separation behavior of vanadium and silicon in vanadium slag during sodium roasting and water leaching was systematically studied, and micro-morphology and valence migration behavior of vanadium and Fe in vanadium slag, roasting slag, and residue were revealed. The Na2CO3 was added to the vanadium slag at 20% mass fraction, roasted at 790 °C, and kept for 120 min, the roasted sample was added to the deionized aqueous solution with a liquid-solid ratio of (L/S) 5mL/g, and then heated at 90 °C for 60 min, 89.54% vanadium and 1.96% chromium were extracted. Sodium carbonate tends to combine with vanadium to form sodium vanadate, while silicon is easy to combine with Fe and Na to form acmite (NaFeSi2O6). When the molar ratio of N (Ca/V) is 0.6 and CaO, is added to adjust the pH of vanadium leaching solution to 6.7 ± 0.1 and precipitate 90 min at 90 °C, vanadium is precipitated in the form of CaV2O6 with a purity of 95.69%, under these conditions, the precipitation ratio is 95.03%.
Synovial Complement Factors in Patients with Periprosthetic Joint Infection after Undergoing Revision Arthroplasty of the Hip or Knee Joint
Authors: Fröschen Frank Sebastian , Schell Sophia , Wimmer Matthias Dominik , Hischebeth Gunnar Thorben Rembert , Kohlhof Hendrik , Gravius Sascha , Randau Thomas Martin
Published: March 2021

The role and diagnostic value of the synovial complement system in patients with low-grade periprosthetic joint infection (PJI) are unclear. We sought to evaluate, for the first time, the usefulness of synovial complement factors in these patients by measuring the individual synovial fluid levels of complement factors (C1q, C3b/iC3b, C4b, C5, C5a, C9, factor B, factor D, factor H, factor I, properdin, and mannose-binding lectin [MBL]). The patients (n = 74) were classified into septic (n = 28) and aseptic (n = 46). Receiver-operator characteristic curves and a multiple regression model to determine the feasibility of a combination of the tested cytokines to determine the infection status were calculated. The synovial fluid levels of C1q, C3b/C3i, C4b, C5, C5a, MBL, and properdin were significantly elevated in the PJI group. The best sensitivity and specificity was found for C1q. The multiple regression models revealed that the combination of C1q, C3b/C3i, C4b, C5, C5a, and MBL was associated with the best sensitivity (83.3%) and specificity (79.2%) for a cutoff value of 0.62 (likelihood ratio: 4.0; area under the curve: 0.853). Nevertheless, only a combined model showed acceptable results. The expression patterns of the complement factors suggested that PJI activates all three pathways of the complement system.
Body Position Affects Capillary Blood Flow Regulation Measured with Wearable Blood Flow Sensors
Authors: Fedorovich Andrey A. , Loktionova Yulia I. , Zharkikh Elena V. , Mikhailova Maria A. , Popova Julia A. , Suvorov Alexander V. , Zherebtsov Evgeny A.
Published: March 2021

In this study we demonstrate what kind of relative alterations can be expected in average perfusion and blood flow oscillations during postural changes being measured in the skin of limbs and on the brow of the forehead by wearable laser Doppler flowmetry (LDF) sensors. The aims of the study were to evaluate the dynamics of cutaneous blood perfusion and the regulatory mechanisms of blood microcirculation in the areas of interest, and evaluate the possible significance of those effects for the diagnostics based on blood perfusion monitoring. The study involved 10 conditionally healthy volunteers (44 ± 12 years). Wearable laser Doppler flowmetry monitors were fixed at six points on the body: two devices were fixed on the forehead, on the brow; two were on the distal thirds of the right and left forearms; and two were on the distal thirds of the right and left lower legs. The protocol was used to record three body positions on the tilt table for orthostatic test for each volunteer in the following sequence: (a) supine body position; (b) upright body position (+75°); (c) tilted with the feet elevated above the head and the inclination of body axis of 15° (−15°, Trendelenburg position). Skin blood perfusion was recorded for 10 min in each body position, followed by the amplitude–frequency analysis of the registered signals using wavelet decomposition. The measurements were supplemented with the blood pressure and heart rate for every body position analysed. The results identified a statistically significant transformation in microcirculation parameters of the average level of skin blood perfusion and oscillations of amplitudes of neurogenic, myogenic and cardiac sensors caused by the postural changes. In paper, we present the analysis of microcirculation in the skin of the forehead, which for the first time was carried out in various positions of the body. The area is supplied by the internal carotid artery system and can be of particular interest for evaluation of the sufficiency of blood supply for the brain.
A Simple, Affordable, Rapid, Stabilized, Colorimetric, Versatile RT-LAMP Assay to Detect SARS-CoV-2
Authors: García-Bernalt Diego Juan , Fernández-Soto Pedro , Domínguez-Gil Marta , Belhassen-García Moncef , Bellido Juan Luis Muñoz , Muro Antonio
Published: March 2021

The SARS-CoV-2 pandemic has forced all countries worldwide to rapidly develop and implement widespread testing to control and manage the Coronavirus Disease 2019 (COVID-19). reverse-transcription (RT)-qPCR is the gold standard molecular diagnostic method for COVID-19, mostly in automated testing platforms. These systems are accurate and effective, but also costly, time-consuming, high-technological, infrastructure-dependent, and currently suffer from commercial reagent supply shortages. The reverse-transcription loop-mediated isothermal amplification (RT-LAMP) can be used as an alternative testing method. Here, we present a novel versatile (real-time and colorimetric) RT-LAMP for the simple (one-step), affordable (~1.7 €/sample), and rapid detection of SARS-CoV-2 targeting both ORF1ab and N genes of the novel virus genome. We demonstrate the assay on RT-qPCR-positive clinical samples, obtaining most positive results under 25 min. In addition, a novel 30-min one-step drying protocol has been developed to stabilize the RT-LAMP reaction mixtures, allowing them to be stored at room temperature functionally for up to two months, as predicted by the Q10. This Dry-RT-LAMP methodology is suitable for potentially ready-to-use COVID-19 diagnosis. After further testing and validation, it could be easily applied both in developed and in low-income countries yielding rapid and reliable results.
Validating METCAM/MUC18 as a Novel Biomarker to Predict the Malignant Potential of Prostate Cancer at an Early Stage by Using a Modified Gold Nanoparticles-Based Lateral Flow Immunoassay
Authors: Wu Jui-Chuang , Chuang Yin-Huan , Wei Yu-Chun , Hsieh Chia-Chi , Pong Yuan-Hung , Su Yenn-Rong , Tsai Vincent F.-S. , Wu Guang-Jer
Published: March 2021

(1) Background: To further validate METCAM/MUC18 as a diagnostic biomarker for prostate cancer, a modified Lateral Flow Immune Assay (LFIA) with increased sensitivity and specificity was designed by taking advantage of the extremely high affinity between biotin and streptavidin and used. (2) Methods: The combination of a commercial biotinylated rabbit antibody (EPP11278), or the home-made biotinylated chicken antibody, and the nano-gold conjugated home-made chicken antibody or a commercial rabbit antibody (EPP11278), had the higher sensitivity and specificity in this modified LFIA to establish calibration curves from the two recombinant METCAM/MUC18 proteins and were used for determining METCAM/MUC18 concentrations in serum specimens from normal individuals, benign prostatic hyperplasia (BPH) patients, prostatic intraepithelial neoplasia (PIN) patients, prostate cancer patients with various Gleason scores, and treated patients. (3) Results: Data obtained by this modified LFIA were statistically better than traditional LFIA and prostate-specific antigen (PSA) test. Interestingly, serum METCAM/MUC18 concentrations were higher in pre-malignant PIN patients than prostate cancer patients and both were higher than normal individuals, BPH patients, and treated patients. Serum METCAM/MUC18 concentrations were directly proportional to most serum PSA. (4) Conclusions: Elevated serum METCAM/MUC18 concentrations may be used for predicting the malignant potential of prostate cancer at an early premalignant (PIN) stage, which is not achievable by the current PSA test.
Interpretation According to Clone-Specific PD-L1 Cutoffs Reveals Better Concordance in Muscle-Invasive Urothelial Carcinoma
Authors: Huang Tzu-Hao , Cheng Wei , Wang Yeh-Han
Published: March 2021

Because immune checkpoint inhibitors have been approved for treating advanced urothelial carcinoma (UC), programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assays have been widely used as companion or complementary diagnostic tests for predicting treatment outcomes. Because different clones, scoring algorithms, and cutoffs have been used for interpretation, this study investigated the variation, correlation, and concordance of four validated PD-L1 clones (SP142, SP263, 22C3, and 28-8) and proposed a practical solution for the harmonization of PD-L1 IHC. A tissue microarray, including 46 muscle-invasive UCs, was constructed for PD-L1 testing with the four clones. Tumor cell (TC) and immune cell (IC) expression was analyzed. SP142 had significantly low TC expression, whereas SP263, 22C3, and 28-8 exhibited a moderate correlation (rho ≥ 0.6), with almost perfect concordance (intraclass correlation coefficient > 0.8) in TC expression. Fair to moderate correlation and concordance were observed in IC expression in most pairwise comparisons of clones. Substantial concordance (kappa > 0.6) was noted when high PD-L1 expression was defined by applying clone-specific cutoffs to each clone. Our findings imply that a universal cutoff value is not feasible for UC; we propose that PD-L1 IHC assays for UC should be interpreted according to a clone-specific scoring algorithm and cutoff value.
Neurogenic Thoracic Outlet Syndrome with Supraclavicular Release: Long-Term Outcome without Rib Resection
Authors: Ruopsa Niina , Ristolainen Leena , Vastamäki Martti , Vastamäki Heidi
Published: March 2021

Our aim was to define clinical long-term outcome of surgery for neurogenic thoracic outlet syndrome without rib resection, and to find factors predicting long-term results. For the 94 patients, the main outcomes were pain, numbness, weakness, and upper-extremity function. The Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) survey, the Cervical-Brachial Symptom Questionnaire (CBSQ), and a numerical rating system served as functional outcome measures. Mean follow-up was 12.9 years. Preoperative pain diminished from 7.8 to 2.2, numbness from 7.4 to 4.0, and weakness from 7.3 to 3.8. Grip strength increased from 25.7 to 31.8 kg. QuickDASH averaged at follow-up 37.1 and CBSQ 51.5. No correlation appeared between smoking and long-term results regarding pain, numbness, weakness, or functioning. Positive TOS provocative tests or intraoperative anatomical findings like consistency of the scaleni muscles showed no correlation with outcome. 82% of female and 57% of male patients reported that aid from this surgery had been excellent or good; 69% reported that surgery helped considerably for at least a mean 9.9 years. The risk for worse self-reported long-term outcome was higher among men, but neither BMI nor age at surgery associated with self-reported outcome. Pain, numbness, and weakness significantly decreased and function improved after supraclavicular release without rib resection. We found no significant preoperative nor per-operative factors predicting long-term results.
Transient Dynamics in the Random Growth and Reset Model
Authors: Biró Tamás S. , Csillag Lehel , Néda Zoltán
Published: March 2021

A mean-field type model with random growth and reset terms is considered. The stationary distributions resulting from the corresponding master equation are relatively easy to obtain; however, for practical applications one also needs to know the convergence to stationarity. The present work contributes to this direction, studying the transient dynamics in the discrete version of the model by two different approaches. The first method is based on mathematical induction by the recursive integration of the coupled differential equations for the discrete states. The second method transforms the coupled ordinary differential equation system into a partial differential equation for the generating function. We derive analytical results for some important, practically interesting cases and discuss the obtained results for the transient dynamics.
Promoting Diversity and Belonging: Preschool Staff’s Perspective on Inclusive Factors in the Swedish Preschool
Authors: Karlsudd Peter
Published: March 2021

This article reports the Swedish results and experiences from the survey study “Educators’ perspectives of belonging in early years education,” which was part of the research project “Politics of belonging: Promoting children’s inclusion in educational settings across borders”. The purpose of the survey study was to gain knowledge about the preschool staff’s perspective on factors and pedagogical approaches that promote diversity and belonging. The research questions and study instruments were co-produced by researchers from Finland, Iceland, Norway, the Netherlands and Sweden. This Swedish part reports the answers from 180 respondents/staff from preschools. The experiences and the way the results are analysed and discussed are entirely from the investigation conducted in Sweden. The results show that the staff’s work environment, values and working methods are important for an inclusive programme. Preschool children are a source of strength for building a sense of belonging for all children, and increased confidence in their ability provides better conditions for creating an inclusive preschool; that is, giving children more influence and trust promotes the sense of belonging. In addition to these results, the survey has provided important methodological experience and initiated a discussion on how the contact between academia and preschool programmes can be improved.
Particle Swarm Optimization Combined with Inertia-Free Velocity and Direction Search
Authors: Miao Kun , Feng Qian , Kuang Wei
Published: March 2021

The particle swarm optimization algorithm (PSO) is a widely used swarm-based natural inspired optimization algorithm. However, it suffers search stagnation from being trapped into a sub-optimal solution in an optimization problem. This paper proposes a novel hybrid algorithm (SDPSO) to improve its performance on local searches. The algorithm merges two strategies, the static exploitation (SE, a velocity updating strategy considering inertia-free velocity), and the direction search (DS) of Rosenbrock method, into the original PSO. With this hybrid, on the one hand, extensive exploration is still maintained by PSO; on the other hand, the SE is responsible for locating a small region, and then the DS further intensifies the search. The SDPSO algorithm was implemented and tested on unconstrained benchmark problems (CEC2014) and some constrained engineering design problems. The performance of SDPSO is compared with that of other optimization algorithms, and the results show that SDPSO has a competitive performance.
Forest Resources Assessments: Mensuration, Inventory and Planning
Authors: Alberdi Iciar
Published: March 2021

There is much demand for forest information at the regional, national, and international level, covering aspects as varied as growing stock, carbon pools, and non-wood forest products, as well as information on forest biodiversity, risks, and disturbances, or social indicators [...]
Assessment of Forest Certification as a Tool to Support Forest Ecosystem Services
Authors: Paluš Hubert , Krahulcová Martina , Parobek Ján
Published: March 2021

Certification provides a way to demonstrate the positive impacts of sustainable forest management (SFM) on ecosystem services. Ecosystem services provide society with a wide range of benefits, from clean water and carbon sequestration to the production of wood and non-wood products. This study evaluates forest owners’ and managers’ perceptions of forest certification as a tool to support SFM and forest ecosystem services in Slovakia. The questionnaire survey focused on the understanding of the concept of SFM, the objectives of forest certification schemes, and especially on the examination of the perceptions of 288 PEFC- and FSC-certified forest owners and managers on how forest certification helps to support individual ecosystem services. Among the important factors influencing the level of understanding of forest certification and its role in ensuring forest ecosystem services is the size of the managed forest area and the implemented certification scheme. The results of this study indicate that forest certification is positively perceived as a supporting tool for ecosystem services, and certified forest owners are sufficiently aware of the objectives of SFM. Regardless of the size of the managed forest area and the type of the implemented certification scheme, forest certification is mainly perceived as a tool which improves the company image and represents a commitment to environmental responsibility while promoting SFM. Certified companies managing large forest areas see the role of certification as being more significant in ensuring selected ecosystem services, in particular, the provision of woody biomass and water. However, in general, forest certification is mainly perceived as a supporting tool for the ecosystem services related to the control of erosion, soil formation, and natural composition, as well as the function of species and ecosystem diversity, followed by the provision of aesthetic, scientific, and educational values.
The Genetic and Clinical Features of FOXL2-Related Blepharophimosis, Ptosis and Epicanthus Inversus Syndrome
Authors: Méjécase Cécile , Nigam Chandni , Moosajee Mariya , Bladen John C.
Published: March 2021

Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a craniofacial disorder caused by heterozygous variants of the forkhead box L2 (FOXL2) gene. It shows autosomal dominant inheritance but can also occur sporadically. Depending on the mutation, two phenotypic subtypes have been described, both involving the same craniofacial features: type I, which is associated with premature ovarian failure (POF), and type II, which has no systemic features. The genotype–phenotype correlation is not fully understood, but it has been hypothesised that type I BPES involves more severe loss of function variants spanning the whole gene. Type II BPES has been linked to frameshift mutations that result in elongation of the protein rather than complete loss of function. A mutational hotspot has been identified within the poly-alanine domain, although the exact function of this region is still unknown. However, the BPES subtype cannot be determined genetically, necessitating informed genetic counselling and careful discussion of family planning advice in view of the associated POF particularly as the patient may still be a child. Following puberty, female patients should be referred for ovarian reserve and response assessment. Oculofacial features can be managed with surgical intervention and regular monitoring to prevent amblyopia.
Ophthalmologic Manifestations of Primary Sjögren’s Syndrome
Authors: Roszkowska Anna Maria , Oliverio Giovanni William , Aragona Emanuela , Inferrera Leandro , Severo Alice Antonella , Alessandrello Federica , Spinella Rosaria , Postorino Elisa Imelde , Aragona Pasquale
Published: March 2021

Sjögren’s syndrome (SS) is a chronic, progressive, inflammatory, autoimmune disease, characterized by the lymphocyte infiltration of exocrine glands, especially the lacrimal and salivary, with their consequent destruction. The onset of primary SS (pSS) may remain misunderstood for several years. It usually presents with different types of severity, e.g., dry eye and dry mouth symptoms, due to early involvement of the lacrimal and salivary glands, which may be associated with parotid enlargement and dry eye; keratoconjunctivitis sicca (KCS) is its most common ocular manifestation. It is still doubtful if the extent ocular surface manifestations are secondary to lacrimal or meibomian gland involvement or to the targeting of corneal and conjunctival autoantigens. SS is the most representative cause of aqueous deficient dry eye, and the primary role of the inflammatory process was evidenced. Recent scientific progress in understanding the numerous factors involved in the pathogenesis of pSS was registered, but the exact mechanisms involved still need to be clarified. The unquestionable role of both the innate and adaptive immune system, participating actively in the induction and evolution of the disease, was recognized. The ocular surface inflammation is a central mechanism in pSS leading to the decrease of lacrimal secretion and keratoconjunctival alterations. However, there are controversies about whether the ocular surface involvement is a direct autoimmune target or secondary to the inflammatory process in the lacrimal gland. In this review, we aimed to present actual knowledge relative to the pathogenesis of the pSS, considering the role of innate immunity, adaptive immunity, and genetics.
The Unique Biology behind the Early Onset of Breast Cancer
Authors: Siddig Alaa , Tengku Din Tengku Ahmad Damitri Al-Astani , Mohd Nafi Siti Norasikin , Yahya Maya Mazuwin , Sulong Sarina , Wan Abdul Rahman Wan Faiziah
Published: March 2021

Breast cancer commonly affects women of older age; however, in developing countries, up to 20% of breast cancer cases present in young women (younger than 40 years as defined by oncology literature). Breast cancer in young women is often defined to be aggressive in nature, usually of high histological grade at the time of diagnosis and negative for endocrine receptors with poor overall survival rate. Several researchers have attributed this aggressive nature to a hidden unique biology. However, findings in this aspect remain controversial. Thus, in this article, we aimed to review published work addressing somatic mutations, chromosome copy number variants, single nucleotide polymorphisms, differential gene expression, microRNAs and gene methylation profile of early-onset breast cancer, as well as its altered pathways resulting from those aberrations. Distinct biology behind early-onset of breast cancer was clear among estrogen receptor-positive and sporadic cases. However, further research is needed to determine and validate specific novel markers, which may help in customizing therapy for this group of patients.
Inverted Basins by Africa–Eurasia Convergence at the Southern Back-Arc Tyrrhenian Basin
Authors: Loreto Maria Filomena , Palmiotto Camilla , Muccini Filippo , Ferrante Valentina , Zitellini Nevio
Published: March 2021

The southern part of Tyrrhenian back-arc basin (NW Sicily), formed due to the rifting and spreading processes in back-arc setting, is currently undergoing contractional tectonics. The analysis of seismic reflection profiles integrated with bathymetry, magnetic data and seismicity allowed us to map a widespread contractional tectonics structures, such as positive flower structures, anticlines and inverted normal faults, which deform the sedimentary sequence of the intra-slope basins. Two main tectonic phases have been recognised: (i) a Pliocene extensional phase, active during the opening of the Vavilov Basin, which was responsible for the formation of elongated basins bounded by faulted continental blocks and controlled by the tear of subducting lithosphere; (ii) a contractional phase related to the Africa-Eurasia convergence coeval with the opening of the Marsili Basin during the Quaternary time. The lithospheric tear occurred along the Drepano paleo-STEP (Subduction-Transform-Edge-Propagator) fault, where the upwelling of mantle, intruding the continental crust, formed a ridge. Since Pliocene, most of the contractional deformation has been focused along this ridge, becoming a good candidate for a future subduction initiation zone.
The Relationship between Dark Triad Personality Traits and Sexting Behaviors among Adolescents and Young Adults across 11 Countries
Authors: Morelli Mara , Urbini Flavio , Bianchi Dora , Baiocco Roberto , Cattelino Elena , Laghi Fiorenzo , Sorokowski Piotr , Misiak Michal , Dziekan Martyna , Hudson Heather , Marshall Alexandra , Nguyen Thanh Truc T. , Mark Lauren , Kopecky Kamil , Szotkowski René , Toplu Demirtaş Ezgi , Van Ouytsel Joris , Ponnet Koen , Walrave Michel , Zhu Tingshao , Chen Ya , Zhao Nan , Liu Xiaoqian , Voiskounsky Alexander , Bogacheva Nataliya , Ioannou Maria , Synnott John , Tzani-Pepelasi Kalliopi , Balakrishnan Vimala , Okumu Moses , Small Eusebius , Pavlova Nikolova Silviya , Drouin Michelle , Chirumbolo Antonio
Published: March 2021

Background: Sexting is an increasingly common phenomenon among adolescents and young adults. Some studies have investigated the role of personality traits in different sexting behaviors within mainstream personality taxonomies like Big Five and HEXACO. However, very few studies have investigated the role of maladaptive personality factors in sexting. Therefore, the present study investigated the relationship between Dark Triad Personality Traits and experimental (i.e., sharing own sexts), risky (i.e., sexting under substance use and with strangers), and aggravated sexting (i.e., non-consensual sexting and sexting under pressure) across 11 countries. Methods: An online survey was completed by 6093 participants (Mage = 20.35; SDage = 3.63) from 11 different countries which covered four continents (Europe, Asia, Africa, and America). Participants completed the Sexting Behaviors Questionnaire and the 12-item Dark Triad Dirty Dozen scale. Results: Hierarchical regression analyses showed that sharing own sexts was positively predicted by Machiavellianism and Narcissism. Both risky and aggravated sexting were positively predicted by Machiavellianism and Psychopathy. Conclusions: The present study provided empirical evidence that different sexting behaviors were predicted by Dark Triad Personality Traits, showing a relevant role of Machiavellianism in all kinds of investigated sexting behaviors. Research, clinical, and education implications for prevention programs are discussed.