bluuebunny/crossref_metadata_2025 huggingface dataset:
Microfluidic Lab-on-a-Chip Based on UHF-Dielectrophoresis for Stemness Phenotype Characterization and Discrimination among Glioblastoma Cells
Authors: Lambert Elisa , Manczak Rémi , Barthout Elodie , Saada Sofiane , Porcù Elena , Maule Francesca , Bessette Barbara , Viola Giampietro , Persano Luca , Dalmay Claire , Lalloué Fabrice , Pothier Arnaud
Published: October 2021

Glioblastoma (GBM) is one of the most aggressive solid tumors, particularly due to the presence of cancer stem cells (CSCs). Nowadays, the characterization of this cell type with an efficient, fast and low-cost method remains an issue. Hence, we have developed a microfluidic lab-on-a-chip based on dielectrophoresis (DEP) single cell electro-manipulation to measure the two crossover frequencies: fx01 in the low-frequency range (below 500 kHz) and fx02 in the ultra-high-frequency range (UHF, above 50 MHz). First, in vitro conditions were investigated. An U87-MG cell line was cultured in different conditions in order to induce an undifferentiated phenotype. Then, ex vivo GBM cells from patients’ primary cell culture were passed through the developed microfluidic system and characterized in order to reflect clinical conditions. This article demonstrates that the usual exploitation of low-frequency range DEP does not allow the discrimination of the undifferentiated GBM cells from the differentiated one. However, the presented study highlights the use of UHF-DEP as a relevant discriminant parameter. The proposed microfluidic lab-on-a-chip is able to follow the kinetics of U87-MG phenotype transformation in a CSC enrichment medium and the cancer stem cells phenotype acquirement.
Depressive Symptoms and Burnout in Football Players: A Systematic Review
Authors: Sarmento Hugo , Frontini Roberta , Marques Adilson , Peralta Miguel , Ordoñez-Saavedra Nestor , Duarte João Pedro , Figueiredo António , Campos Maria João , Clemente Filipe Manuel
Published: October 2021

The purpose of this article was to systematically review and organise the available literature devoted to the topic of depressive symptoms and burnout in football players. A systematic search was conducted in Web of Science, Scopus, SPORTdiscus, PubMed, and Psychinfo for articles published up to June 2020. The searches yielded 1589 articles, and after the screening process, a total of 18 studies met the eligibility criteria and were included for review. Playing position and conflicts with coach/management seems to have a direct influence on the prevalence of depressive symptoms in current players as do the injuries and life events of former players. During the pre-competition phase, most of the athletes displayed reduced rates, indicating burnout. An exploration of the mental health of football players will help to create models of care and guide professionals so that they may help players achieve better performance while also having better wellbeing. Understanding how to prevent and cope with the emotional wellbeing of football players will be possible to guide players and coaches.
PRMT5: An Emerging Target for Pancreatic Adenocarcinoma
Authors: Lee Michael K. C. , Grimmond Sean M. , McArthur Grant A. , Sheppard Karen E.
Published: October 2021

The overall survival of pancreatic ductal adenocarcinoma (PDAC) remains poor and its incidence is rising. Targetable mutations in PDAC are rare, thus novel therapeutic approaches are needed. Protein arginine methyltransferase 5 (PRMT5) overexpression is associated with worse survival and inhibition of PRMT5 results in decreased cancer growth across multiple cancers, including PDAC. Emerging evidence also suggests that altered RNA processing is a driver in PDAC tumorigenesis and creates a partial dependency on this process. PRMT5 inhibition induces altered splicing and this vulnerability can be exploited as a novel therapeutic approach. Three possible biological pathways underpinning the action of PRMT5 inhibitors are discussed; c-Myc regulation appears central to its action in the PDAC setting. Whilst homozygous MTAP deletion and symmetrical dimethylation levels are associated with increased sensitivity to PRMT5 inhibition, neither measure robustly predicts its growth inhibitory response. The immunomodulatory effect of PRMT5 inhibitors on the tumour microenvironment will also be discussed, based on emerging evidence that PDAC stroma has a significant bearing on disease behaviour and response to therapy. Lastly, with the above caveats in mind, current knowledge gaps and the implications and rationales for PRMT5 inhibitor development in PDAC will be explored.
Circular RNAs in Hedgehog Signaling Activation and Hedgehog-Mediated Medulloblastoma Tumors
Authors: Azatyan Ani , Zhang Shasha , Darabi Anna , Siesjö Peter , Wang Ting , Zaphiropoulos Peter G.
Published: October 2021

Within the past decade, circular RNAs have largely emerged as novel regulators of human biology, including brain function and cancer development. On the other hand, the Hedgehog pathway has established roles in regulating biological processes, including tumorigenesis. Here, the circular RNA transcriptome, in the context of Hedgehog signaling activation of medulloblastoma Daoy and human embryonic palatal mesenchyme HEPM cells, was determined. In total, 29 out of the 30 selected circular RNAs were validated by Sanger sequencing, with some regulated to a limited extent by Hedgehog signaling. Interestingly, back-spliced junctions, the marker of exonic RNA circles, were also identified at a low frequency within poly (A) mRNAs, reflecting exon repetition events. Thirteen circular RNAs had reduced expression in human medulloblastoma tumors in comparison to normal cerebellum. For seven out of these thirteen RNA circles, the linear mRNAs originating from the same genes did not exhibit a reduced expression. Depletion and/or overexpression of these seven circular RNAs minimally affected medulloblastoma cell proliferation. These findings highlight that differential expression of a gene product may not necessarily elicit an obvious phenotypic impact. Consequently, further analysis is required to determine the possible subtle contributions to the development of this cerebellar tumor.
Brain and Breast Cancer Cells with PTEN Loss of Function Reveal Enhanced Durotaxis and RHOB Dependent Amoeboid Migration Utilizing 3D Scaffolds and Aligned Microfiber Tracts
Authors: Wieland Annalena , Strissel Pamela L. , Schorle Hannah , Bakirci Ezgi , Janzen Dieter , Beckmann Matthias W. , Eckstein Markus , Dalton Paul D. , Strick Reiner
Published: October 2021

Background: Glioblastoma multiforme (GBM) and metastatic triple-negative breast cancer (TNBC) with PTEN mutations often lead to brain dissemination with poor patient outcome, thus new therapeutic targets are needed. To understand signaling, controlling the dynamics and mechanics of brain tumor cell migration, we implemented GBM and TNBC cell lines and designed 3D aligned microfibers and scaffolds mimicking brain structures. Methods: 3D microfibers and scaffolds were printed using melt electrowriting. GBM and TNBC cell lines with opposing PTEN genotypes were analyzed with RHO-ROCK-PTEN inhibitors and PTEN rescue using live-cell imaging. RNA-sequencing and qPCR of tumor cells in 3D with microfibers were performed, while scanning electron microscopy and confocal microscopy addressed cell morphology. Results: In contrast to the PTEN wildtype, GBM and TNBC cells with PTEN loss of function yielded enhanced durotaxis, topotaxis, adhesion, amoeboid migration on 3D microfibers and significant high RHOB expression. Functional studies concerning RHOB-ROCK-PTEN signaling confirmed the essential role for the above cellular processes. Conclusions: This study demonstrates a significant role of the PTEN genotype and RHOB expression for durotaxis, adhesion and migration dependent on 3D. GBM and TNBC cells with PTEN loss of function have an affinity for stiff brain structures promoting metastasis. 3D microfibers represent an important tool to model brain metastasizing tumor cells, where RHO-inhibitors could play an essential role for improved therapy.
Preclinical Studies in Small Animals for Advanced Drug Delivery Using Hyperthermia and Intravital Microscopy
Authors: Priester Marjolein I. , Curto Sergio , Seynhaeve Ann L. B. , Perdomo Anderson Cruz , Amin Mohamadreza , Agnass Pierre , Salimibani Milad , Faridi Pegah , Prakash Punit , van Rhoon Gerard C. , ten Hagen Timo L. M.
Published: October 2021

This paper presents three devices suitable for the preclinical application of hyperthermia via the simultaneous high-resolution imaging of intratumoral events. (Pre)clinical studies have confirmed that the tumor micro-environment is sensitive to the application of local mild hyperthermia. Therefore, heating is a promising adjuvant to aid the efficacy of radiotherapy or chemotherapy. More so, the application of mild hyperthermia is a useful stimulus for triggered drug release from heat-sensitive nanocarriers. The response of thermosensitive nanoparticles to hyperthermia and ensuing intratumoral kinetics are considerably complex in both space and time. To obtain better insight into intratumoral processes, longitudinal imaging (preferable in high spatial and temporal resolution) is highly informative. Our devices are based on (i) an external electric heating adaptor for the dorsal skinfold model, (ii) targeted radiofrequency application, and (iii) a microwave antenna for heating of internal tumors. These models, while of some technical complexity, significantly add to the understanding of effects of mild hyperthermia warranting implementation in research on hyperthermia.
Janus Kinase Signaling: Oncogenic Criminal of Lymphoid Cancers
Authors: Li Boheng , Wan Qin , Li Zhubo , Chng Wee-Joo
Published: October 2021

The Janus kinase (JAK) family are known to respond to extracellular cytokine stimuli and to phosphorylate and activate signal transducers and activators of transcription (STAT), thereby modulating gene expression profiles. Recent studies have highlighted JAK abnormality in inducing over-activation of the JAK/STAT pathway, and that the cytoplasmic JAK tyrosine kinases may also have a nuclear role. A couple of anti-JAK therapeutics have been developed, which effectively harness lymphoid cancer cells. Here we discuss mutations and fusions leading to JAK deregulations, how upstream nodes drive JAK expression, how classical JAK/STAT pathways are represented in lymphoid malignancies and the noncanonical and nuclear role of JAKs. We also summarize JAK inhibition therapeutics applied alone or synergized with other drugs in treating lymphoid malignancies.
Estimated Risk of Radiation-Induced Cancer after Thymoma Treatments with Proton- or X-ray Beams
Authors: Lideståhl Anders , Johansson Gracinda , Siegbahn Albert , Lind Pehr A.
Published: October 2021

We compared the calculated risks of radiation-induced secondary malignant neoplasms (SMNs) for patients treated for thymic tumors with 3D-CRT, IMRT, or single-field uniform dose (SFUD) proton beam therapy (PBT) using the pencil beam scanning (PBS) technique. A cancer-induction model based on the organ equivalent dose (OED) concept was used. For twelve patients, treated with 3D-CRT for thymic tumors, alternative IMRT and SFUD plans were retrospectively prepared. The resulting DVHs for organs at risk (OARs) were extracted and used to estimate the risk of SMNs. The OED was calculated using a mechanistic model for carcinoma induction. Two limit cases were considered; the linear-exponential model, in which the repopulation/repair of the cells is neglected, and the plateau model, in which full repopulation/repair of the irradiated cells is assumed. The calculated risks for SMNs for the different radiation modalities and dose-relation models were used to calculate relative risks, which were compared pairwise. The risks for developing SMNs were reduced for all OARs, and for both dose-relation models, if SFUD was used, compared to 3D-CRT and IMRT. In conclusion, PBS shows a potential benefit to reduce the risk of SMNs compared to 3D-CRT and IMRT in the treatment of thymic tumors.
Relapsed/Refractory Multiple Myeloma in 2020/2021 and Beyond
Authors: Podar Klaus , Leleu Xavier
Published: October 2021

Despite the challenges imposed by the COVID-19 pandemic, exciting therapeutic progress continues to be made in MM. New drug approvals for relapsed/refractory (RR)MM in 2020/2021 include the second CD38 monoclonal antibody, isatuximab, the first BCMA-targeting therapy and first-in-class antibody–drug conjugate (ADC) belantamab mafodotin, the first BCMA-targeting CAR T cell product Idecabtagen-Vicleucel (bb2121, Ide-Cel), the first in-class XPO-1 inhibitor selinexor, as well as the first-in-class anti-tumor peptide-drug conjugate, melflufen. The present introductory article of the Special Issue on “Advances in the Treatment of Relapsed and Refractory Multiple Myeloma: Novel Agents, Immunotherapies and Beyond” summarizes the most recent registration trials and emerging immunotherapies in RRMM, gives an overview on latest insights on MM genomics and on tumor-induced changes within the MM microenvironment, and presents some of the most promising rationally derived future therapeutic strategies.
A Cardiac Mitochondrial FGFR1 Mediates the Antithetical Effects of FGF2 Isoforms on Permeability Transition
Authors: Srisakuldee Wattamon , Nickel Barbara E. , Fandrich Robert R. , Zhang Feixong , Pasumarthi Kishore B. S. , Kardami Elissavet
Published: October 2021

Mitochondria, abundant organelles in high energy demand cells such as cardiomyocytes, can determine cell death or survival by regulating the opening of mitochondrial permeability transition pore, mPTP. We addressed the hypothesis that the growth factor FGF2, known to reside in intracellular locations, can directly influence mitochondrial susceptibility to mPTP opening. Rat cardiac subsarcolemmal (SSM) or interfibrillar (IFM) mitochondrial suspensions exposed directly to rat 18 kDa low molecular weight (Lo-) FGF2 isoform displayed increased resistance to calcium overload-induced mPTP, measured spectrophotometrically as “swelling”, or as cytochrome c release from mitochondria. Inhibition of mitochondrial protein kinase C epsilon abrogated direct Lo-FGF2 mito-protection. Exposure to the rat 23 kDa high molecular weight (Hi) FGF2 isoform promoted cytochrome c release from SSM and IFM under nonstressed conditions. The effect of Hi-FGF2 was prevented by mPTP inhibitors, pre-exposure to Lo-FGF2, and okadaic acid, a serine/threonine phosphatase inhibitor. Western blotting and immunoelectron microscopy pointed to the presence of immunoreactive FGFR1 in cardiac mitochondria in situ. The direct mito-protective effect of Lo-FGF2, as well as the deleterious effect of Hi-FGF2, were prevented by FGFR1 inhibitors and FGFR1 neutralizing antibodies. We propose that intracellular FGF2 isoforms can modulate mPTP opening by interacting with mito-FGFR1 and relaying isoform-specific intramitochondrial signal transduction.
Plectin in Skin Fragility Disorders
Authors: Kiritsi Dimitra , Tsakiris Leonidas , Schauer Franziska
Published: October 2021

Plectin is a multi-faceted, 500 kDa-large protein, which due to its expression in different isoforms and distinct organs acts diversely as a cytoskeletal crosslinker and signaling scaffold. It functions as a mediator of keratinocyte mechanical stability in the skin, primarily through linking intermediate filaments to hemidesmosomes. Skin fragility may occur through the presence of mutations in the gene encoding for plectin, PLEC, or through the presence of autoantibodies against the molecule. Below, we review the cutaneous manifestations of plectinopathies as well as their systemic involvement in specific disease subtypes. We summarize the known roles of plectin in keratinocytes and fibroblasts and provide an outlook on future perspectives for plectin-associated skin disorders.
The Roles of Extracellular Vesicles in Malignant Melanoma
Authors: Cheng Ying-Chen , Chang Yu-An , Chen Yi-Jen , Sung Hsu-Min , Bogeski Ivan , Su Hong-Lin , Hsu Ya-Ling , Wang Hui-Min David
Published: October 2021

Different types of cells, such as endothelial cells, tumor-associated fibroblasts, pericytes, and immune cells, release extracellular vesicles (EVs) in the tumor microenvironment. The components of EVs include proteins, DNA, RNA, and microRNA. One of the most important functions of EVs is the transfer of aforementioned bioactive molecules, which in cancer cells may affect tumor growth, progression, angiogenesis, and metastatic spread. Furthermore, EVs affect the presentation of antigens to immune cells via the transfer of nucleic acids, peptides, and proteins to recipient cells. Recent studies have also explored the potential application of EVs in cancer treatment. This review summarizes the mechanisms by which EVs regulate melanoma development, progression, and their potentials to be applied in therapy. We initially describe vesicle components; discuss their effects on proliferation, anti-melanoma immunity, and drug resistance; and finally focus on the effects of EV-derived microRNAs on melanoma pathobiology. This work aims to facilitate our understanding of the influence of EVs on melanoma biology and initiate ideas for the development of novel therapeutic strategies.
Comparison of Differentiation Pattern and WNT/SHH Signaling in Pluripotent Stem Cells Cultured under Different Conditions
Authors: Świerczek-Lasek Barbara , Dudka Damian , Bauer Damian , Czajkowski Tomasz , Ilach Katarzyna , Streminska Władysława , Kominek Agata , Piwocka Katarzyna , Ciemerych Maria A. , Archacka Karolina
Published: October 2021

Pluripotent stem cells (PSCs) are characterized by the ability to self-renew as well as undergo multidirectional differentiation. Culture conditions have a pivotal influence on differentiation pattern. In the current study, we compared the fate of mouse PSCs using two culture media: (1) chemically defined, free of animal reagents, and (2) standard one relying on the serum supplementation. Moreover, we assessed the influence of selected regulators (WNTs, SHH) on PSC differentiation. We showed that the differentiation pattern of PSCs cultured in both systems differed significantly: cells cultured in chemically defined medium preferentially underwent ectodermal conversion while their endo- and mesodermal differentiation was limited, contrary to cells cultured in serum-supplemented medium. More efficient ectodermal differentiation of PSCs cultured in chemically defined medium correlated with higher activity of SHH pathway while endodermal and mesodermal conversion of cells cultured in serum-supplemented medium with higher activity of WNT/JNK pathway. However, inhibition of either canonical or noncanonical WNT pathway resulted in the limitation of endo- and mesodermal conversion of PSCs. In addition, blocking WNT secretion led to the inhibition of PSC mesodermal differentiation, confirming the pivotal role of WNT signaling in this process. In contrast, SHH turned out to be an inducer of PSC ectodermal, not mesodermal differentiation.
Unzipping the Secrets of Amyloid Disassembly by the Human Disaggregase
Authors: Franco Aitor , Velasco-Carneros Lorea , Alvarez Naiara , Orozco Natalia , Moro Fernando , Prado Adelina , Muga Arturo
Published: October 2021

Neurodegenerative diseases (NDs) are increasingly positioned as leading causes of global deaths. The accelerated aging of the population and its strong relationship with neurodegeneration forecast these pathologies as a huge global health problem in the upcoming years. In this scenario, there is an urgent need for understanding the basic molecular mechanisms associated with such diseases. A major molecular hallmark of most NDs is the accumulation of insoluble and toxic protein aggregates, known as amyloids, in extracellular or intracellular deposits. Here, we review the current knowledge on how molecular chaperones, and more specifically a ternary protein complex referred to as the human disaggregase, deals with amyloids. This machinery, composed of the constitutive Hsp70 (Hsc70), the class B J-protein DnaJB1 and the nucleotide exchange factor Apg2 (Hsp110), disassembles amyloids of α-synuclein implicated in Parkinson’s disease as well as of other disease-associated proteins such as tau and huntingtin. We highlight recent studies that have led to the dissection of the mechanism used by this chaperone system to perform its disaggregase activity. We also discuss whether this chaperone-mediated disassembly mechanism could be used to solubilize other amyloidogenic substrates. Finally, we evaluate the implications of the chaperone system in amyloid clearance and associated toxicity, which could be critical for the development of new therapies.
Directed Differentiation of Human Pluripotent Stem Cells toward Skeletal Myogenic Progenitors and Their Purification Using Surface Markers
Authors: Xu Nasa , Wu Jianbo , Ortiz-Vitali Jose L. , Li Yong , Darabi Radbod
Published: October 2021

Advancements in reprogramming somatic cells into induced pluripotent stem cells (iPSCs) have provided a strong framework for in vitro disease modeling, gene correction and stem cell-based regenerative medicine. In cases of skeletal muscle disorders, iPSCs can be used for the generation of skeletal muscle progenitors to study disease mechanisms, or implementation for the treatment of muscle disorders. We have recently developed an improved directed differentiation method for the derivation of skeletal myogenic progenitors from hiPSCs. This method allows for a short-term (2 weeks) and efficient skeletal myogenic induction (45–65% of the cells) in human pluripotent stem cells (ESCs/iPSCs) using small molecules to induce mesoderm and subsequently myotomal progenitors, without the need for any gene integration or modification. After initial differentiation, skeletal myogenic progenitors can be purified from unwanted cells using surface markers (CD10+CD24−). These myogenic progenitors have been extensively characterized using in vitro gene expression/differentiation profiling as well as in vivo engraftment studies in dystrophic (mdx) and muscle injury (VML) rodent models and have been proven to be able to engraft and form mature myofibers as well as seeding muscle stem cells. The current protocol describes a detailed, step-by-step guide for this method and outlines important experimental details and troubleshooting points for its application in any human pluripotent stem cells.
Mercaptosuccinic-Acid-Functionalized Gold Nanoparticles for Highly Sensitive Colorimetric Sensing of Fe(III) Ions
Authors: Komova Nadezhda S. , Serebrennikova Kseniya V. , Berlina Anna N. , Pridvorova Svetlana M. , Zherdev Anatoly V. , Dzantiev Boris B.
Published: October 2021

The development of reliable and highly sensitive methods for heavy metal detection is a critical task for protecting the environment and human health. In this study, a qualitative colorimetric sensor that used mercaptosuccinic-acid-functionalized gold nanoparticles (MSA-AuNPs) to detect trace amounts of Fe(III) ions was developed. MSA-AuNPs were prepared using a one-step reaction, where mercaptosuccinic acid (MSA) was used for both stabilization, which was provided by the presence of two carboxyl groups, and functionalization of the gold nanoparticle (AuNP) surface. The chelating properties of MSA in the presence of Fe(III) ions and the concentration-dependent aggregation of AuNPs showed the effectiveness of MSA-AuNPs as a sensing probe with the use of an absorbance ratio of A530/A650 as an analytical signal in the developed qualitative assay. Furthermore, the obvious Fe(III)-dependent change in the color of the MSA-AuNP solution from red to gray-blue made it possible to visually assess the metal content in a concentration above the detection limit with an assay time of less than 1 min. The detection limit that was achieved (23 ng/mL) using the proposed colorimetric sensor is more than 10 times lower than the maximum allowable concentration for drinking water defined by the World Health Organization (WHO). The MSA-AuNPs were successfully applied for Fe(III) determination in tap, spring, and drinking water, with a recovery range from 89.6 to 126%. Thus, the practicality of the MSA-AuNP-based sensor and its potential for detecting Fe(III) in real water samples were confirmed by the rapidity of testing and its high sensitivity and selectivity in the presence of competing metal ions.
Oxidized Cell-Free DNA Rapidly Skews the Transcriptional Profile of Brain Cells toward Boosting Neurogenesis and Neuroplasticity
Authors: Filev Anton D. , Kostyuk Svetlana V. , Umriukhin Pavel E. , Pisarev Vladimir M.
Published: October 2021

Cell-free DNA (cfDNA) is liberated and accumulated in neural tissue due to cell damage. The oxidative and nitrosative stress in the brain that accompanies various pathological conditions has been shown to increase the oxidation of cellular and cell-free DNA. Whether the high concentration of non-oxidized and oxidized cfDNA may affect the transcriptome response of brain cells has not been studied. In the current work, we studied whether cfDNA fragments affect several key pathways, including neurogenesis, at the level of gene expression in brain cells. In the study, primary rat cerebellum cell cultures were used to assess the effects of oxidized and non-oxidized cfDNA on the expression of 91 genes in brain cells. We found that only oxidized cfDNA, not non-oxidized cfDNA, significantly altered the transcription in brain cells in 3 h. The pattern of change included all 10 upregulated genes (S100A8, S100A9, S100b, TrkB, Ngf, Pink1, Aqp4, Nmdar, Kcnk2, Mapk1) belonging to genes associated with neurogenesis and neuroplasticity. The expression of inflammatory and apoptosis genes, which oppose neurogenesis, decreased. The results show that the oxidized form of cfDNA positively regulates early gene expression of neurogenesis and neuroplasticity. At the same time, the question of whether chronic elevation of cfDNA concentration alters brain cells remains unexplored.
Strain Localization Modes within Single Crystals Using Finite Deformation Strain Gradient Crystal Plasticity
Authors: Cai Lei , Jebahi Mohamed , Abed-Meraim Farid
Published: October 2021

The present paper aims at providing a comprehensive investigation of the abilities and limitations of strain gradient crystal plasticity (SGCP) theories in capturing different kinds of localization modes in single crystals. To this end, the small deformation Gurtin-type SGCP model recently proposed by the authors, based on non-quadratic defect energy and the uncoupled dissipation assumption, is extended to finite deformation. The extended model is then applied to simulate several single crystal localization problems with different slip system configurations. These configurations are chosen in such a way as to obtain idealized slip and kink bands as well as general localization bands, i.e., with no particular orientation with respect to the initial crystallographic directions. The obtained results show the good abilities of the applied model in regularizing various kinds of localization bands, except for idealized slip bands. Finally, the model is applied to reproduce the complex localization behavior of single crystals undergoing single slip, where competition between kink and slip bands can take place. Both higher-order energetic and dissipative effects are considered in this investigation. For both effects, mesh-independent results are obtained, proving the good capabilities of SGCP theories in regularizing complex localization behaviors. The results associated with higher-order energetic effects are in close agreement with those obtained using a micromorphic crystal plasticity approach. Higher-order dissipative effects led to different results with dominant slip banding.
A Brief Study on Optical and Mechanical Properties of an Organic Material: Urea Glutaric Acid (2/1)—A Third Order Nonlinear Optical Single Crystal
Authors: Kumari C. , Al Otaibi Ahmed , Kamaraj T. , Nageshwari M. , Mathubala G. , Manikandan Ayyar , Caroline M. , Sudha S. , Kashmery Heba , Madhu P. , Khan Anish , Marwani Hadi , Asiri Abdullah
Published: October 2021

Urea glutaric acid (UGA), an organic crystal, was synthesized and grown using a low temperature solution technique. Single crystal XRD revealed a monoclinic structure with a C2/C space group. The various cell data were identified. The optical parameters were calculated from UV-visible spectrum. The transmittance spectra showed the cutoff wavelength as 240 nm (low) and the energy gap determined from the spectra was compared with the theoretical energy gap. The transition number revealed the electron transition, which corresponded to direct allowed transition. The diverse optical parameters like reflectance, extinction coefficient, refractive index and optical susceptibility were determined. The least value of Urbach energy caused less defects and a good crystalline nature. The steepness value and electron phonon interaction were calculated. The positions of lower and higher band energy levels were identified. Electronic polarizability was found using the Clausius–Mossoti relation and tabulated. The mechanical fitness was measured from Vickers hardness analysis. The nonlinear optical property was measured from Z-scan analysis. Thus, the optical results support the material suitability and fitness for optical and electronic domain applications.
Halogen Bonding in N-Alkyl-3-halogenopyridinium Salts
Authors: Fotović Luka , Stilinović Vladimir
Published: October 2021

We performed a structural study of N-alkylated halogenopyridinium cations to examine whether choice of the N-substituent has any considerable effect on the halogen bonding capability of the cations. For that purpose, we prepared a series of N-ethyl-3-halopyridinium iodides and compared them with their N-methyl-3-halopyridinium analogues. Structural analysis revealed that N-ethylated halogenopyridinium cations form slightly shorter C−X⋯I− halogen bonds with iodide anion. We have also attempted synthesis of ditopic symmetric bis-(3-iodopyridinium) dications. Although successful in only one case, the syntheses have afforded two novel ditopic asymmetric monocations with an iodine atom bonded to the pyridine ring and another on the aliphatic N-substituent. Here, the C−I⋯I− halogen bond lengths involving pyridine iodine atom were notably shorter than those involving an aliphatic iodine atom as a halogen bond donor. This trend in halogen bond lengths is in line with the charge distribution on the Hirshfeld surfaces of the cations—the positive charge is predominantly located in the pyridine ring making the pyridine iodine atom σ-hole more positive than the one on the alkyl chan.
A Literature Review on High-Performance Photocatalysts for Sustainable Cancer Therapy
Authors: Yi Hanxi , Cheng Zeneng
Published: October 2021

Since cancer is a serious threat to public health worldwide, the development of novel methods and materials for treating cancer rapidly and thoroughly is of great significance. This review summarizes the mechanism and application of photocatalytic materials used to kill cancer cells. The photosensitivity and toxicological properties of several common photcatalysts used in anti-cancer treatment are discussed in detail. The ideal photocatalyst must possess the following characteristics: a highly stable production of active oxygen species and high selectivity to cancer cells without causing any damage to healthy tissues. This work concluded the existing photocatalytic materials used to treat cancer, as well as the current challenges in the application of cancer therapy. We aim to provide a basis for the development of new photocatalytic anti-cancer materials with high stability and selectivity while maintaining high photodynamic reaction performance.
Haplogroup Distribution of 309 Thais from Admixed Populations across the Country by HVI and HVII Sanger-Type Sequencing
Authors: Areesirisuk Prapatsorn , Srikulnath Kornsorn , Onsod Preyaporn , Jaroensuk Juthamas , Rerkamnuaychoke Budsaba
Published: October 2021

The mitochondrial DNA (mtDNA) control region sequences for the hypervariable regions I (HVI) and II (HVII) of 309 Thai citizens were investigated using Sanger-type sequencing to generate an mtDNA reference dataset for forensic casework, and the haplogroup distribution within geographically proximal Asian populations was analyzed. The population sample set contained 264 distinct haplotypes and showed high haplotype diversity, low matching probability, and high powers of discrimination, at 0.9985, 0.4744%, and 0.9953, respectively, compared with previous reports. Subhaplogroup F1a showed the highest frequency in the Thai population, similar to Southeast Asian populations. The haplotype frequencies in the northern, northeastern, and southern populations of Thailand illustrate the relevance of social, religious, and historical factors in the biogeographical origin of the admixed Thai population as a whole. The HVI and HVII reference datasets will be useful for forensic casework applications, with improved genetic information content and discriminatory power compared to currently available techniques.
Margin Status Post Cervical Conization Predicts Residual Adenocarcinoma In Situ (AIS) and Occult Adenocarcinoma in a Predominantly Hispanic Population
Authors: Hong Linda J. , Huynh Sandy , Kim Joy , Denham Laura , Momeni Mazdak , Ioffe Yevgeniya J. M.
Published: October 2021

Background: Adenocarcinoma in situ (AIS) of the cervix, is increasing in incidence, particularly in women of reproductive age. Fertility preservation is often desired. In a predominantly Hispanic population, we sought to determine the incidence of occult cervical cancer co-existing with AIS, and evaluate how conization margin status correlates with residual disease upon hysterectomy. Methods: A retrospective study utilizing a comprehensive cancer center database was conducted. Data from patients with histologically proven AIS of the cervix were abstracted. Results: Of 47 patients that met the criteria, 23 (49%) were Hispanic, 21 (45%) were White, two (4%) were Asian, and one (2%) was Black. The median age was 37. Forty-two patients underwent cervical conizations; 13/42 (48%) had positive margins upon conization; 28/42 (67%) underwent hysterectomies. Furthermore, 6/13 (46%) patients with positive conization margins had residual disease in hysterectomy specimens, with 2/13 (15%) found to have invasive cancer. In contrast, 0/14 (0%) of patients with negative margins had residual disease (p = 0.036, Chi-squared 4.41, df = 1). In total, 2/27 (7%) patients who underwent hysterectomies had invasive cancer (7%). Conclusions: Positive margins upon cervical conization for AIS of the cervix were correlated with a relatively high rate of residual AIS and occult invasive cancer. Negative conization margins were correlated with no residual disease. Those patients may be candidates for fertility-sparing treatment.
Improving Blood Flow Visualization of Recirculation Regions at Carotid Bulb in 4D Flow MRI Using Semi-Automatic Segmentation with ITK-SNAP
Authors: Ngo Minh Tri , Lee Ui Yun , Ha Hojin , Jung Jinmu , Lee Dong Hwan , Kwak Hyo Sung
Published: October 2021

Assessment of carotid bulb hemodynamics using four-dimensional (4D) flow magnetic resonance imaging (MRI) requires accurate segmentation of recirculation regions that is frequently hampered by limited resolution. This study aims to improve the accuracy of 4D flow MRI carotid bulb segmentation and subsequent recirculation regions analysis. Time-of-flight (TOF) MRI and 4D flow MRI were performed on bilateral carotid artery bifurcations in seven healthy volunteers. TOF-MRI data was segmented into 3D geometry for computational fluid dynamics (CFD) simulations. ITK-SNAP segmentation software was included in the workflow for the semi-automatic generation of 4D flow MRI angiographic data. This study compared the velocities calculated at the carotid bifurcations and the 3D blood flow visualization at the carotid bulbs obtained by 4D flow MRI and CFD. By applying ITK-SNAP segmentation software, an obvious improvement in the 4D flow MRI visualization of the recirculation regions was observed. The 4D flow MRI images of the recirculation flow characteristics of the carotid artery bulbs coincided with the CFD. A reasonable agreement was found in terms of velocity calculated at the carotid bifurcation between CFD and 4D flow MRI. However, the dispersion of velocity data points relative to the local errors of measurement in 4D flow MRI remains. Our proposed strategy showed the feasibility of improving recirculation regions segmentation and the potential for reliable blood flow visualization in 4D flow MRI. However, quantitative analysis of recirculation regions in 4D flow MRI with ITK-SNAP should be enhanced for use in clinical situations.
Assessing Parkinson’s Disease at Scale Using Telephone-Recorded Speech: Insights from the Parkinson’s Voice Initiative
Authors: Arora Siddharth , Tsanas Athanasios
Published: October 2021

Numerous studies have reported on the high accuracy of using voice tasks for the remote detection and monitoring of Parkinson’s Disease (PD). Most of these studies, however, report findings on a small number of voice recordings, often collected under acoustically controlled conditions, and therefore cannot scale at large without specialized equipment. In this study, we aimed to evaluate the potential of using voice as a population-based PD screening tool in resource-constrained settings. Using the standard telephone network, we processed 11,942 sustained vowel /a/ phonations from a US-English cohort comprising 1078 PD and 5453 control participants. We characterized each phonation using 304 dysphonia measures to quantify a range of vocal impairments. Given that this is a highly unbalanced problem, we used the following strategy: we selected a balanced subset (n = 3000 samples) for training and testing using 10-fold cross-validation (CV), and the remaining (unbalanced held-out dataset, n = 8942) samples for further model validation. Using robust feature selection methods we selected 27 dysphonia measures to present into a radial-basis-function support vector machine and demonstrated differentiation of PD participants from controls with 67.43% sensitivity and 67.25% specificity. These findings could help pave the way forward toward the development of an inexpensive, remote, and reliable diagnostic support tool for PD using voice as a digital biomarker.
From Zygote to Blastocyst: Application of Ultrashort Lasers in the Field of Assisted Reproduction and Developmental Biology
Authors: Ilina Inna , Sitnikov Dmitry
Published: October 2021

Although the use of lasers in medical diagnosis and therapies, as well as in fundamental biomedical research is now almost routine, advanced laser sources and new laser-based methods continue to emerge. Due to the unique ability of ultrashort laser pulses to deposit energy into a microscopic volume in the bulk of a transparent material without disrupting the surrounding tissues, the ultrashort laser-based microsurgery of cells and subcellular components within structurally complex and fragile specimens such as embryos is becoming an important tool in developmental biology and reproductive medicine. In this review, we discuss the mechanisms of ultrashort laser pulse interaction with the matter, advantages of their application for oocyte and preimplantation embryo microsurgery (e.g., for oocyte/blastomere enucleation and embryonic cell fusion), as well as for nonlinear optical microscopy for studying the dynamics of embryonic development and embryo quality assessment. Moreover, we focus on ultrashort laser-based approaches and techniques that are increasingly being applied in the fundamental research and have the potential for successful translation into the IVF (in vitro fertilization) clinics, such as laser-mediated individual embryo labelling and controlled laser-assisted hatching.
Spondylodiscitis Caused by Aspergillus Species
Authors: Koutserimpas Christos , Chamakioti Ifigeneia , Naoum Symeon , Raptis Konstantinos , Alpantaki Kalliopi , Kofteridis Diamantis P. , Samonis George
Published: October 2021

Background: Spondylodiscitis caused by Aspergillus spp. is a rare but life-threatening clinical entity. However, a consensus on diagnostic criteria and most effective medical management is still missing. The present study is a review of all published cases of spondylodiscitis caused by Aspergillus spp., in an effort to elucidate epidemiology, patients’ characteristics, andand the medical and surgical treatment options and their effectiveness. Methods: A thorough review of all existing spondylodiscitis cases caused by Aspergillus was performed. Data regarding demographics, responsible fungus, time between symptoms’ onset and firm diagnosis, antifungal treatment (AFT), surgical intervention, andand the infection’s outcome were investigated. Results: A total of 118 Aspergillus spondylodiscitis cases, yielding 119 Aspergillus spp. isolates, were identified in the literature. The patients’ mean age was 40.6 years. Magnetic resonance imaging (MRI) (after its introduction) indicated the diagnosis in most cases (66.7%), while definite diagnosis was established through cultures in the majority of cases (73.7%). Aspergillus fumigatus was isolated in most cases (73; 61.3%), followed by Aspergillus flavus (15; 12.6%) andand Aspergillus nidulans and terreus (7; 5.9%, each). The mean time between symptoms’ onset and diagnosis was 5.7 months. Amphotericin B was the preferred antifungal regiment (84 cases; 71.2%), followed by voriconazole (31; 26.3%), and the mean AFT duration was 6.1 months. The final outcome was successful in 93 cases (78.8%). Furthermore, 77 patients (65.3%) underwent surgery. Conclusions: Spondylodiscitis caused by Aspergillus spp. represents a clinical challenge, requiring a multidisciplinary approach. The present review has shown that prolonged AFT has been the standard of care of the studied cases, while surgical treatment seems to play an important role in selected patents.
The Behavioural Outcomes of Children with Autism Spectrum Disorder and Other Developmental Disabilities as Perceived by Parents during the COVID-19 Lockdown
Authors: Franz Kathleen , Kelly Michelle E.
Published: October 2021

The COVID-19 lockdown and closure of schools, clinics, and community-based services put children with autism spectrum disorders (ASDs) and other developmental disabilities (DDs) at increased risk of negative outcomes. This study aimed to investigate parents’ perceptions of their children’s behavioural outcomes during the COVID-19 lockdown, parents’ satisfaction with services during this time, and willingness to engage in telehealth. A cross-sectional study was conducted in Ireland. Parents (n = 89) completed an online questionnaire that included the strengths and difficulties questionnaire (SDQ-P). Results demonstrated that children with ASD/DDs were vulnerable to negative outcomes including hyperactivity, emotional symptoms, problems with peers and fewer prosocial behaviors. Children’s behavioral outcomes (‘current sample’, n = 89) were also compared with pre-COVID-19 data taken from the Growing Up in Ireland Study (‘GUI sample’, n = 327). The current sample exhibited significantly more behavioral difficulties than the pre-COVID GUI sample (p < 0.001). For the current sample, scores on each of the five SDQ subscales were significantly associated with a total impact score, and parents reported dissatisfaction with support services provided and willingness to engage in behavioral telehealth. Commitment is required to identify barriers to services faced by families in Ireland and to address the need for adapted behavior support services during periods of emergency.
Quantifiers in Natural Language: Efficient Communication and Degrees of Semantic Universals
Authors: Steinert-Threlkeld Shane
Published: October 2021

While the languages of the world vary greatly, they exhibit systematic patterns, as well. Semantic universals are restrictions on the variation in meaning exhibit cross-linguistically (e.g., that, in all languages, expressions of a certain type can only denote meanings with a certain special property). This paper pursues an efficient communication analysis to explain the presence of semantic universals in a domain of function words: quantifiers. Two experiments measure how well languages do in optimally trading off between competing pressures of simplicity and informativeness. First, we show that artificial languages which more closely resemble natural languages are more optimal. Then, we introduce information-theoretic measures of degrees of semantic universals and show that these are not correlated with optimality in a random sample of artificial languages. These results suggest both that efficient communication shapes semantic typology in both content and function word domains, as well as that semantic universals may not stand in need of independent explanation.
Assessment of Digital Competencies of University Faculty and Their Conditioning Factors: Case Study in a Technological Adoption Context
Authors: Jorge-Vázquez Javier , Náñez Alonso Sergio Luis , Fierro Saltos Washington Raúl , Pacheco Mendoza Silvia
Published: October 2021

The rise of digital technologies and their educational applications increasingly require the development of digital skills among university faculty. This study focuses on examining the level of digital competencies of university faculty and identifying their conditioning factors. To achieve this objective, an ex post facto methodological design with surveys is used. A sample of 216 university teachers from different regions of Ecuador was used. The non-parametric Chi-square test was used to validate the hypothesis of independence of the variables. The results obtained show that university faculty have a mostly intermediate level of digital skills, which is independent of gender, but dependent on the generational cohort. In particular, it is found that younger teachers (millennials) have a more advanced level of digital skills, although this relationship is not very strong. On the other hand, we observe the positive influence of the university’s strategic leadership in terms of technological adoption on the development of teachers’ digital skills. Universities with better technological resources and with training plans focused on the pedagogical application of technology have teachers with a more advanced level of digital skills. All of this leads to the recommendation that education policies should prioritise actions that promote the development of digital competencies among university faculty
The Effects of Using Socio-Scientific Issues and Technology in Problem-Based Learning: A Systematic Review
Authors: Hernández-Ramos José , Pernaa Johannes , Cáceres-Jensen Lizethly , Rodríguez-Becerra Jorge
Published: October 2021

Currently, a growing number of learning institutions at all educational levels are including problem-based learning (PBL) in their curricula. PBL scenarios often utilise technology and socio-scientific Issues (SSI), which enables the simultaneous learning of content and creative thinking and working skills needed in generating new knowledge for the future. In this sense, using SSI and technological tools in PBL learning environments can be viewed as a starting point for acquiring and integrating new knowledge. However, there is no comprehensive knowledge regarding the possibilities of this approach. The objective of this systematic review is to produce this knowledge via the PRISMA method. The strategy is used to explore the effects of the described approach through implementations conducted at secondary and undergraduate levels. The data consisted of 33 research articles that were categorised via qualitative content analysis. According to the results, PBL scenarios exploit mainly local SSIs that link scientific knowledge with a meaningful context for students. Technology is principally used in offering technical support for teaching tasks. Lastly, these results are discussed from the technological pedagogical science knowledge (TPASK) framework perspective, which proposes guidelines for achieving the Sustainable Development Goals (SDG).