bluuebunny/crossref_metadata_2025 huggingface dataset:
Long Non-Coding RNAs Associated with Ribosomes in Human Adipose-Derived Stem Cells: From RNAs to Microproteins
Authors: Bonilauri Bernardo , Holetz Fabiola Barbieri , Dallagiovanna Bruno
Published: November 2021

Ribosome profiling reveals the translational dynamics of mRNAs by capturing a ribosomal footprint snapshot. Growing evidence shows that several long non-coding RNAs (lncRNAs) contain small open reading frames (smORFs) that are translated into functional peptides. The difficulty in identifying bona-fide translated smORFs is a constant challenge in experimental and bioinformatics fields due to their unconventional characteristics. This motivated us to isolate human adipose-derived stem cells (hASC) from adipose tissue and perform a ribosome profiling followed by bioinformatics analysis of transcriptome, translatome, and ribosome-protected fragments of lncRNAs. Here, we demonstrated that 222 lncRNAs were associated with the translational machinery in hASC, including the already demonstrated lncRNAs coding microproteins. The ribosomal occupancy of some transcripts was consistent with the translation of smORFs. In conclusion, we were able to identify a subset of 15 lncRNAs containing 35 smORFs that likely encode functional microproteins, including four previously demonstrated smORF-derived microproteins, suggesting a possible dual role of these lncRNAs in hASC self-renewal.
Sgt1 Regulates α-Synuclein Subcellular Localization and Expression of Parkinson’s Disease Related Genes, PINK1 and PARK9
Authors: Bohush Anastasiia , Góral Agnieszka , Sierant Małgorzata , Nawrot Barbara , Leśniak Wiesława , Filipek Anna
Published: November 2021

The SGT1 protein is highly expressed in the mammalian brain, particularly in neurons of the hippocampus and cortex, and in Purkinje cells of the cerebellum. There are literature data indicating that the protein may be involved in pathogenesis of neurodegenerative disorders such as Parkinson’s disease (PD). In the present work we have found that SGT1 protected cells from the toxicity of rotenone, an agent that evokes behavioral and histopathological symptoms of PD. To gain more insight into the possible mechanism underlying the protective action of SGT1 we looked at α-synuclein subcellular distribution in HEK293 cells with an altered SGT1 level. By immunofluorescent staining we have found that in HEK293 cells overexpressing SGT1 α-synuclein was mainly localized in the cytoplasm while in control cells it was present in the nucleus. Accordingly, when SGT1 expression was silenced, α-synuclein was predominantly present in the nucleus. These results were then confirmed by subcellular fractionation and Western blot analysis. Moreover, we have found that altered level of SGT1 in HEK293 cells influenced the expression of PD related genes, PINK1 and PARK9. Altogether, our results point to SGT1 as an important factor that might be involved in the pathogenesis of Parkinson’s disease (PD).
Glycine Transporters and Receptors as Targets for Analgesics
Authors: Harvey Robert J. , Vandenberg Robert J.
Published: November 2021

The suitability of modulating glycinergic neurotransmission for the treatment of inflammatory and chronic pain has gained widespread recognition, with glycine receptors (GlyRs) and glycine transporters (GlyT1 and GlyT2) now considered key therapeutic targets [...]
Structural Rearrangements of a Dodecameric Ketol-Acid Reductoisomerase Isolated from a Marine Thermophilic Methanogen
Authors: Lemaire Olivier Nicolas , Müller Marie-Caroline , Kahnt Jörg , Wagner Tristan
Published: November 2021

Ketol-acid reductoisomerase (KARI) orchestrates the biosynthesis of branched-chain amino acids, an elementary reaction in prototrophic organisms as well as a valuable process in biotechnology. Bacterial KARIs belonging to class I organise as dimers or dodecamers and were intensively studied to understand their remarkable specificity towards NADH or NADPH, but also to develop antibiotics. Here, we present the first structural study on a KARI natively isolated from a methanogenic archaea. The dodecameric structure of 0.44-MDa was obtained in two different conformations, an open and close state refined to a resolution of 2.2-Å and 2.1-Å, respectively. These structures illustrate the conformational movement required for substrate and coenzyme binding. While the close state presents the complete NADP bound in front of a partially occupied Mg2+-site, the Mg2+-free open state contains a tartrate at the nicotinamide location and a bound NADP with the adenine-nicotinamide protruding out of the active site. Structural comparisons show a very high conservation of the active site environment and detailed analyses point towards few specific residues required for the dodecamerisation. These residues are not conserved in other dodecameric KARIs that stabilise their trimeric interface differently, suggesting that dodecamerisation, the cellular role of which is still unknown, might have occurred several times in the evolution of KARIs.
FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro
Authors: Yeung Vincent , Sriram Sriniwas , Tran Jennifer A. , Guo Xiaoqing , Hutcheon Audrey E. K. , Zieske James D. , Karamichos Dimitrios , Ciolino Joseph B.
Published: November 2021

Corneal fibrosis (or scarring) occurs in response to ocular trauma or infection, and by reducing corneal transparency, it can lead to visual impairment and blindness. Studies highlight important roles for transforming growth factor (TGF)-β1 and -β3 as modulators in corneal wound healing and fibrosis, leading to increased extracellular matrix (ECM) components and expression of α-smooth muscle actin (αSMA), a myofibroblast marker. In this study, human corneal fibroblasts (hCF) were cultured as a monolayer culture (2D) or on poly-transwell membranes to generate corneal stromal constructs (3D) that were treated with TGF-β1, TGF-β3, or TGF-β1 + FAK inhibitor (FAKi). Results show that hCF 3D constructs treated with TGF-β1 or TGF-β3 impart distinct effects on genes involved in wound healing and fibrosis—ITGAV, ITGB1, SRC and ACTA2. Notably, in the 3D construct model, TGF-β1 enhanced αSMA and focal adhesion kinase (FAK) protein expression, whereas TGF-β3 did not. In addition, in both the hCF 2D cell and 3D construct models, we found that TGF-β1 + FAKi attenuated TGF-β1-mediated myofibroblast differentiation, as shown by abrogated αSMA expression. This study concludes that FAK signaling is important for the onset of TGF-β1-mediated myofibroblast differentiation, and FAK inhibition may provide a novel beneficial therapeutic avenue to reduce corneal scarring.
MicroRNAs as Critical Biomarkers of Major Depressive Disorder: A Comprehensive Perspective
Authors: Ortega Miguel A. , Alvarez-Mon Miguel Angel , García-Montero Cielo , Fraile-Martinez Oscar , Lahera Guillermo , Monserrat Jorge , Muñoz-Merida Luis , Mora Fernando , Rodríguez-Jiménez Roberto , Fernandez-Rojo Sonia , Quintero Javier , Álvarez-Mon Melchor
Published: November 2021

Major Depressive Disorder (MDD) represents a major global health concern, a body-mind malady of rising prevalence worldwide nowadays. The complex network of mechanisms involved in MDD pathophysiology is subjected to epigenetic changes modulated by microRNAs (miRNAs). Serum free or vesicles loaded miRNAs have starred numerous publications, denoting a key role in cell-cell communication, systematically and in brain structure and neuronal morphogenesis, activity and plasticity. Upregulated or downregulated expression of these signaling molecules may imply the impairment of genes implicated in pathways of MDD etiopathogenesis (neuroinflammation, brain-derived neurotrophic factor (BDNF), neurotransmitters, hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, circadian rhythms...). In addition, these miRNAs could serve as potential biomarkers with diagnostic, prognostic and predictive value, allowing to classify severity of the disease or to make decisions in clinical management. They have been considered as promising therapy targets as well and may interfere with available antidepressant treatments. As epigenetic malleable regulators, we also conclude emphasizing lifestyle interventions with physical activity, mindfulness and diet, opening the door to new clinical management considerations.
Sex Differences in the Effect of Diabetes on Cerebral Glucose Metabolism
Authors: Wu Chun-Yi , Lin Yu-Hsin , Hsieh Hsin-Hua , Lin Jia-Jia , Peng Shin-Lei
Published: November 2021

The neuroimaging literature indicates that brain structure and function both deteriorate with diabetes, but information on sexual dimorphism in diabetes-related brain alterations is limited. This study aimed to ascertain whether brain metabolism is influenced by sex in an animal model of diabetes. Eleven rats (male, n = 5; female, n = 6) received a single intraperitoneal injection of 70 mg/kg streptozotocin (STZ) to develop diabetes. Another 11 rats (male, n = 5; female, n = 6) received the same amount of solvent through a single intraperitoneal injection. Longitudinal positron emission tomography scans were used to assess cerebral glucose metabolism before and 4 weeks after STZ or solvent administration. Before STZ or solvent injections, there was no evidence of sexual dimorphism in cerebral metabolism (p > 0.05). Compared with healthy control animals, rats with diabetes had significantly decreased brain metabolism in all brain regions (all p < 0.05). In addition, female diabetic rats exhibited further reduction in cerebral metabolism, relative to male diabetic rats (p < 0.05). The results of this study may provide some biological evidence, supporting the existence of a sexual dimorphism in diabetes-related complications.
Effectiveness of Biofunctionalization of Titanium Surfaces with Phosphonic Acid
Authors: Aresti Ainhoa , Aragoneses Javier , López-Valverde Nansi , Suárez Ana , Aragoneses Juan Manuel
Published: November 2021

Surface functionalization of dental implant surfaces has been a developing field in biomaterial research. This study aimed to obtain self-assembled monolayers (SAMs) using carboxyethylphosphonic acid on the surface of titanium (Ti) screws, and assessed the surface characteristics, biomechanical, and cellular behavior on the obtained specimens. This study had three groups, i.e., a control (untreated screws), a test group treated with phosphonic acid, and a third group with treated acid and bone morphogenetic protein (BMP-2) for in vitro analysis of cell lines. The assessed parameters included surface wettability, surface characteristics using scanning electron microscopy (SEM), protein immobilization, and cellular behavior of fibroblasts and mesenchymal stem cells of adipose tissue (MSCat cells). For surface wettability, a Welch test was performed to compare the contact angles between control (67 ± 1.83) and test (18.84 ± 0.72) groups, and a difference was observed in the mean measurements, but was not statistically significant. The SEM analysis showed significant surface roughness on the test screws and the cellular behavior of fibroblasts, and MSCat cells were significantly improved in this group, with fibroblasts having a polygonal shape with numerous vesicles and MSCat cells stable and uniformly coating the test Ti surface. Surface biofunctionalization of Ti surfaces with phosphonic acid showed promising results in this study, but remains to be clinically validated for its applications.
The Role of the ACE2/MasR Axis in Ischemic Stroke: New Insights for Therapy
Authors: Barzegar Mansoureh , Stokes Karen Y. , Chernyshev Oleg , Kelley Roger E. , Alexander Jonathan S.
Published: November 2021

Ischemic stroke remains the leading cause of neurologically based morbidity and mortality. Current stroke treatment is limited to two classes of FDA-approved drugs: thrombolytic agents (tissue plasminogen activator (tPA)) and antithrombotic agents (aspirin and heparin), which have a narrow time-window (<4.5 h) for administration after onset of stroke symptoms. While thrombolytic agents restore perfusion, they carry serious risks for hemorrhage, and do not influence damage responses during reperfusion. Consequently, stroke therapies that can suppress deleterious effects of ischemic injury are desperately needed. Angiotensin converting enzyme-2 (ACE2) has been recently suggested to beneficially influence experimental stroke outcomes by converting the vasoconstrictor Ang II into the vasodilator Ang 1–7. In this review, we extensively discuss the protective functions of ACE2-Ang (1–7)-MasR axis of renin angiotensin system (RAS) in ischemic stroke.
Role of Enteric Glia as Bridging Element between Gut Inflammation and Visceral Pain Consolidation during Acute Colitis in Rats
Authors: Lucarini Elena , Seguella Luisa , Vincenzi Martina , Parisio Carmen , Micheli Laura , Toti Alessandra , Corpetti Chiara , Del Re Alessandro , Squillace Silvia , Maftei Daniela , Lattanzi Roberta , Ghelardini Carla , Di Cesare Mannelli Lorenzo , Esposito Giuseppe
Published: November 2021

Acute inflammation is particularly relevant in the pathogenesis of visceral hypersensitivity associated with inflammatory bowel diseases. Glia within the enteric nervous system, as well as within the central nervous system, contributes to neuroplasticity during inflammation, but whether enteric glia has the potential to modify visceral sensitivity following colitis is still unknown. This work aimed to investigate the occurrence of changes in the neuron–glial networks controlling visceral perception along the gut–brain axis during colitis, and to assess the effects of peripheral glial manipulation. Enteric glia activity was altered by the poison fluorocitrate (FC; 10 µmol kg−1 i.p.) before inducing colitis in animals (2,4-dinitrobenzenesulfonic acid, DNBS; 30 mg in 0.25 mL EtOH 50%), and visceral sensitivity, colon damage, and glia activation along the pain pathway were studied. FC injection significantly reduced the visceral hyperalgesia, the histological damage, and the immune activation caused by DNBS. Intestinal inflammation is associated with a parallel overexpression of TRPV1 and S100β along the gut–brain axis (colonic myenteric plexuses, dorsal root ganglion, and periaqueductal grey area). This effect was prevented by FC. Peripheral glia activity modulation emerges as a promising strategy for counteracting visceral pain induced by colitis.
Antimicrobial, Immunomodulatory and Anti-Inflammatory Potential of Liposomal Thymoquinone: Implications in the Treatment of Bacterial Pneumonia in Immunocompromised Mice
Authors: Allemailem Khaled S. , Almatroudi Ahmad , Alrumaihi Faris , Aljaghwani Aseel , Alnuqaydan Abdullah M. , Khalilullah Habibullah , Younus Hina , El-Kady Asmaa M. , Aldakheel Fahad M. , Khan Amjad Ali , Khan Arif , Khan Masood Alam
Published: November 2021

Acinetobacter baumannii has recently been increasing as an aggressive pathogen in immunocompromised persons. In the present study, we determined the in vitro antibacterial and anti-biofilm activity of thymoquinone (TQ) against A. baumannii. A liposomal formulation of TQ (Lip-TQ) was prepared and its therapeutic potential was investigated in the treatment of A. baumannii infection in immunocompromised mice. Leukopenia was induced in mice by injecting cyclophosphamide (CYP) at a dose of 200 mg/kg and the leukopenic mice were infected with 1 × 106 CFUs of A. baumannii. The effectiveness of free TQ or Lip-TQ against A. baumannii infection was assessed by analyzing the survival rate and bacterial burden. Moreover, the efficacy of Lip-TQ was also studied by examining the systemic inflammatory markers and the histological changes in the lung tissues. The results showed that the mice in the group treated with Lip-TQ at a dose of 10 mg/kg exhibited a 60% survival rate on day 40 post-infection, whereas all the mice treated with free TQ at the same dose died within this duration. Likewise, the lowest bacterial burden was found in the lung tissue of mice treated with Lip-TQ (10 mg/kg). Besides, Lip-TQ treatment remarkably alleviated the infection-associated inflammation, oxidative stress, and histological changes in the lung tissues. Based on the findings of the present study, we recommend considering Lip-TQ as a valuable therapeutic formulation in the treatment of A. baumannii-associated pneumonia in immunocompromised subjects.
Editorial to the Special Issue “MicroRNA in Solid Tumor and Hematological Diseases”
Authors: Lovat Francesca
Published: November 2021

In the last two decades, the roles of microRNAs in the biology and progression of human cancer have been extensively studied; at present, these small non-coding RNAs are considered powerful gene regulators [...]
Mechanism Study of Thermally Induced Anti-Tumor Drug Loading to Engineered Human Heavy-Chain Ferritin Nanocages Aided by Computational Analysis
Authors: Yin Shuang , Liu Yongdong , Dai Sheng , Zhang Bingyang , Qu Yiran , Zhang Yao , Choe Woo-Seok , Bi Jingxiu
Published: November 2021

Diverse drug loading approaches for human heavy-chain ferritin (HFn), a promising drug nanocarrier, have been established. However, anti-tumor drug loading ratio and protein carrier recovery yield are bottlenecks for future clinical application. Mechanisms behind drug loading have not been elaborated. In this work, a thermally induced drug loading approach was introduced to load anti-tumor drug doxorubicin hydrochloride (DOX) into HFn, and 2 functionalized HFns, HFn-PAS-RGDK, and HFn-PAS. Optimal conditions were obtained through orthogonal tests. All 3 HFn-based proteins achieved high protein recovery yield and drug loading ratio. Size exclusion chromatography (SEC) and transmission electron microscopy (TEM) results showed the majority of DOX loaded protein (protein/DOX) remained its nanocage conformation. Computational analysis, molecular docking followed by molecular dynamic (MD) simulation, revealed mechanisms of DOX loading and formation of by-product by investigating non-covalent interactions between DOX with HFn subunit and possible binding modes of DOX and HFn after drug loading. In in vitro tests, DOX in protein/DOX entered tumor cell nucleus and inhibited tumor cell growth.
Fiber Optic Distributed Sensing Network for Shape Sensing-Assisted Epidural Needle Guidance
Authors: Amantayeva Aida , Adilzhanova Nargiz , Issatayeva Aizhan , Blanc Wilfried , Molardi Carlo , Tosi Daniele
Published: November 2021

Epidural anesthesia is a pain management process that requires the insertion of a miniature needle through the epidural space located within lumbar vertebrae. The use of a guidance system for manual insertion can reduce failure rates and provide increased efficiency in the process. In this work, we present and experimentally assess a guidance system based on a network of fiber optic distributed sensors. The fibers are mounted externally to the needle, without blocking its inner channel, and through a strain-to-shape detection method reconstruct the silhouette of the epidural device in real time (1 s). We experimentally assessed the shape sensing methods over 25 experiments performed in a phantom, and we observed that the sensing system correctly identified bending patterns typical in epidural insertions, characterized by the different stiffness of the tissues. By studying metrics related to the curvatures and their temporal changes, we provide identifiers that can potentially serve for the (in)correct identification of the epidural space, and support the operator through the insertion process by recognizing the bending patterns.
A Fluorescent Biosensor for Sensitive Detection of Salmonella Typhimurium Using Low-Gradient Magnetic Field and Deep Learning via Faster Region-Based Convolutional Neural Network
Authors: Hu Qiwei , Wang Siyuan , Duan Hong , Liu Yuanjie
Published: November 2021

In this study, a fluorescent biosensor was developed for the sensitive detection of Salmonella typhimurium using a low-gradient magnetic field and deep learning via faster region-based convolutional neural networks (R-CNN) to recognize the fluorescent spots on the bacterial cells. First, magnetic nanobeads (MNBs) coated with capture antibodies were used to separate target bacteria from the sample background, resulting in the formation of magnetic bacteria. Then, fluorescein isothiocyanate fluorescent microspheres (FITC-FMs) modified with detection antibodies were used to label the magnetic bacteria, resulting in the formation of fluorescent bacteria. After the fluorescent bacteria were attracted against the bottom of an ELISA well using a low-gradient magnetic field, resulting in the conversion from a three-dimensional (spatial) distribution of the fluorescent bacteria to a two-dimensional (planar) distribution, the images of the fluorescent bacteria were finally collected using a high-resolution fluorescence microscope and processed using the faster R-CNN algorithm to calculate the number of the fluorescent spots for the determination of target bacteria. Under the optimal conditions, this biosensor was able to quantitatively detect Salmonella typhimurium from 6.9 × 101 to 1.1 × 103 CFU/mL within 2.5 h with the lower detection limit of 55 CFU/mL. The fluorescent biosensor has the potential to simultaneously detect multiple types of foodborne bacteria using MNBs coated with their capture antibodies and different fluorescent microspheres modified with their detection antibodies.
Stable in Biocompatible Buffers Silver Nanoisland Films for SERS
Authors: Skvortsov Alexey , Babich Ekaterina , Redkov Alexey , Lipovskii Andrey , Zhurikhina Valentina
Published: November 2021

We investigated the stability of silver nanoisland films, which were formed on glass surface by the method of out-diffusion, in biocompatible buffers and the applicability of the films in surface enhanced Raman scattering (SERS). We have shown that silver nanoisland films are stable in one of the most widespread in biological studies buffer—phosphate buffer saline (PBS), and in 1:100 water-diluted PBS, in the PBS-based buffer, in which NaCl is replaced by the same amount of NaClO4, and in acidic phosphate buffer. At the same time, the replacement of NaCl in PBS by N(CH3)4Cl leads to the degradation of the nanoislands. It was shown that after exposure to PBS the nanoisland films provided a good SERS signal from a monolayer of 1,2-di(4-pyridyl)ethylene (BPE), which makes silver nanoisland films promising for biosensor applications. Additionally, in our experiments, we registered for the first time that silver nanoparticles formed in the bulk of the samples dissolved after exposing to PBS, while nanoislands on the glass surface stayed unchanged. We associate this phenomenon with the interaction of ions contained in PBS solution with silver, which results in the shift of corresponding chemical equilibrium.
Multiplexed Liquid Biopsy and Tumor Imaging Using Surface-Enhanced Raman Scattering
Authors: Dell’Olio Francesco
Published: November 2021

The recent improvements in diagnosis enabled by advances in liquid biopsy and oncological imaging significantly better cancer care. Both these complementary approaches, which are used for early tumor detection, characterization, and monitoring, can benefit from applying techniques based on surface-enhanced Raman scattering (SERS). With a detection sensitivity at the single-molecule level, SERS spectroscopy is widely used in cell and molecular biology, and its capability for the in vitro detection of several types of cancer biomarkers is well established. In the last few years, several intriguing SERS applications have emerged, including in vivo imaging for tumor targeting and the monitoring of drug release. In this paper, selected recent developments and trends in SERS applications in the field of liquid biopsy and tumor imaging are critically reviewed, with a special emphasis on results that demonstrate the clinical utility of SERS.
Testing the Effects of a Virtual Reality Game for Aggressive Impulse Management: A Preliminary Randomized Controlled Trial among Forensic Psychiatric Outpatients
Authors: Smeijers Danique , Bulten Erik H. , Verkes Robbert-Jan , Koole Sander L.
Published: November 2021

Prior laboratory experiments among healthy samples found that training avoidance movements to angry faces may lower anger and aggression, especially people high in trait anger. To enrich this training and make it more suitable for clinical applications, the present researchers developed it into a Virtual Reality Game for Aggressive Impulse Management (VR-GAIME). The current study examined the effects of this training in a randomized controlled trial among forensic psychiatric outpatients with aggression regulation problems (N = 30). In addition to the aggression replacement training, patients played either the VR-GAIME or a control game. Aggressive behavior was measured pre-, half-way, and post-treatment via self-report and clinicians ratings. No difference was found between the VR-GAIME and the control game. However, the participants reported gaining more insight into their own behavior and that of others. Future VR intervention tools in clinical settings may capitalize more on their benefits for self-reflection within interpersonal settings.
The Mammalian Locus Coeruleus Complex—Consistencies and Variances in Nuclear Organization
Authors: Manger Paul R. , Eschenko Oxana
Published: November 2021

Descriptions of the nuclear parcellation of the locus coeruleus complex have been provided in approximately 80 mammal species spanning the phylogenetic breadth of this class. Within the mammalian rostral hindbrain, noradrenergic neurons (revealed with tyrosine hydroxylase and dopamine-ß-hydroxylase immunohistochemistry) have been observed within the periventricular grey matter (A4 and A6 nuclei) and parvicellular reticular nucleus (A5 and A7 nuclei), with the one exception to date being the tree pangolin, where no A4/A6 neurons are observed. The alphanumeric nomenclature system, developed in laboratory rodent brains, has been adapted to cover the variation observed across species. Cross-species homology is observed regarding the nuclear organization of noradrenergic neurons located in the parvicellular reticular nucleus (A5 and A7). In contrast, significant variations are observed in the organization of the A6 neurons of the locus coeruleus proper. In most mammals, the A6 is comprised of a moderate density of neurons, but in Murid rodents, primates, and megachiropteran bats, the A6 exhibits a very high density of neurons. In primates and megachiropterans, there is an additional moderate density of A6 neurons located rostromedial to the high-density portion. These variations are of importance in understanding the translation of findings in laboratory rodents to humans.
The Human Cerebellum as a Hub of the Predictive Brain
Authors: Gatti Daniele , Rinaldi Luca , Ferreri Laura , Vecchi Tomaso
Published: November 2021

Although the cerebellum has long been believed to be involved uniquely in sensorimotor processes, recent research works pointed to its participation in a wide range of cognitive predictive functions. Here, we review the available evidence supporting a generalized role of the cerebellum in predictive computation. We then discuss the anatomo-physiological properties that make the cerebellum the ideal hub of the predictive brain. We further argue that cerebellar involvement in cognition may follow a continuous gradient, with higher cerebellar activity occurring for tasks relying more on predictive processes, and outline the empirical scenarios to probe this hypothesis.
Effect of 6-Week Balance Exercise by Real-Time Postural Feedback System on Walking Ability for Patients with Chronic Stroke: A Pilot Single-Blind Randomized Controlled Trial
Authors: Komiya Makoto , Maeda Noriaki , Narahara Taku , Suzuki Yuta , Fukui Kazuki , Tsutsumi Shogo , Yoshimi Mistuhiro , Ishibashi Naoki , Shirakawa Taizan , Urabe Yukio
Published: November 2021

Stroke causes balance dysfunction, leading to decreased physical activity and increased falls. Thus, effective balance exercises are needed to improve balance dysfunction. This single-blind, single-center randomized controlled trial evaluated the long-term and continuous effects of balance exercise using a real-time postural feedback system to improve balancing ability safely. Thirty participants were randomized into intervention (n = 15) and control (n = 15) groups; 11 in each group completed the final evaluation. The effect of the intervention was evaluated by muscle strength of knee extension, physical performance (short physical performance battery, the center of pressure trajectory length per second, and Timed Up and Go test [TUG]), and self-reported questionnaires (modified Gait Efficacy Scale [mGES] and the Fall Efficacy Scale) at pre (0 week), post (6-week), and at follow-up (10-week) visits. The TUG and mGES showed a significant interactive (group * time) effect (p = 0.007 and p = 0.038, respectively). The intervention group showed significant decreasing time to perform TUG from pre- to post-intervention (p = 0.015) and pre-intervention to follow-up (p = 0.016); mGES showed a significant change from pre-intervention to follow-up (p = 0.036). Thus, balance exercise using a real-time postural feedback system can confer a positive effect on the walking ability in patients with chronic stroke and increase their self-confidence in gait performance.
Head Accelerations during a 1-on-1 Rugby Tackling Drill Performed by Experienced Rugby Union Players
Authors: Reha Tahere , McNabb Colm , Netto Kevin , Davey Paul , Lavender Andrew P.
Published: November 2021

Rugby Union is a popular sport played by males and females worldwide, from junior to elite levels. The highly physical skill of tackling occurs every few seconds throughout a match and various injuries associated with tackling are relatively common. Of particular interest are head injuries that result in a concussion. Recently, repeated non-injurious head impacts in sport have attracted the attention of researchers interested in brain health. Therefore, this study assessed head movement during repeated rugby tackle drills among experienced Rugby Union players. Experienced male and female participants performed 15 1-on-1 tackles in a motion analysis laboratory to measure the head movements of the ball carrier and tackler during each tackle, using three-dimensional motion capture. The average peak acceleration of the head for ball carriers was 28.9 ± 24.08 g and 36.67 ± 28.91 g for the tacklers. This study found that the type of head impacts common while performing a tackle in Rugby Union are similar to those experienced by soccer players during heading, which has been found to alter brain function that lasts hours after the event. This has important implications for player health and suggests that mitigation strategies should be considered for Rugby Union.
Geopolymers as Sustainable Material for Strengthening and Restoring Unreinforced Masonry Structures: A Review
Authors: Abulencia Anabel B. , Villoria Ma. Beatrice D. , Libre Roneh Glenn D. , Quiatchon Pauline Rose J. , Dollente Ithan Jessemar R. , Guades Ernesto J. , Promentilla Michael Angelo B. , Garciano Lessandro Estelito O. , Ongpeng Jason Maximino C.
Published: November 2021

Unreinforced masonry (URM) structures are vulnerable to earthquakes; thus, materials and techniques for their strengthening and restoration should be developed. However, the materials used in some of the existing retrofitting technologies for URM and the waste produced at its end-of-life are unsustainable. The production of ordinary Portland cement (OPC) worldwide has enormously contributed to the global carbon footprint, resulting in persistent environmental problems. Replacing OPC with geopolymers, which are more sustainable and environmentally friendly, presents a potential solution to these problems. Geopolymers can replace the OPC component in engineering cementitious composites (ECC), recommended to strengthen and restore URM structures. In the present paper, the state-of-the-art knowledge development on applying geopolymers in URM structures is discussed. The discussion is focused on geopolymers and their components, material characterization, geopolymers as a strengthening and restoration material, and fiber-reinforced geopolymers and their application to URM structures. Based on this review, it was found that the mechanical properties of geopolymers are on par with that of OPC; however, there are few studies on the mentioned applications of geopolymers. The characterization of geopolymers’ mechanical and physical properties as a restoration material for URM structures is still limited. Therefore, other properties such as chemical interaction with the substrate, workability, thixotropic behavior, and aesthetic features of geopolymers need to be investigated for its wide application. The application method of geopolymer-based ECC as a strengthening material for a URM structure is by grouting injection. It is also worth recommending that other application techniques such as deep repointing, jacketing, and cement-plastering be explored.
The Function and Potential of Innovative Reinforced Concrete Prefabrication Technologies in Achieving Residential Construction Goals in Germany and Poland
Authors: Kirschke Paweł , Sietko Dagmara
Published: November 2021

This paper presents the role and potential of housing built using innovative reinforced concrete prefabrication technologies. The subject was presented by investigating the share of such buildings in the achievement of housing goals in Germany and Poland, where they currently constitute one of the most dynamically developing housing sector branches. The phenomenon has been presented via comparative analyses of selected designs by manufacturers from the sector and development companies. Prefabrication is essentially based on optimising architectural and structural solutions and leads to lowering financial and material cost; decreasing project completion time. At present, these goals are achieved by systematising the design and construction process and using the potential offered by building information modelling technology (BIM). This enables coordination between design specialisations and reduces the number of errors, increasing manufacturing and assembly efficiency. Innovative prefabricated technologies are solutions that are either new or are considerably improved in terms of technical specifications, components and materials, that use the latest software, are easy to assemble, durable, energy efficient, can be disassembled and reused and have a low carbon footprint and can be considered aesthetically pleasing. Contemporary prefabricated housing architecture is a combination of innovative technological solutions that enables constructing sustainable architecture and emphasizes the aesthetic features of structural solutions and solutions.
Interconnections: An Analysis of Disassemblable Building Connection Systems towards a Circular Economy
Authors: O’Grady Timothy M. , Minunno Roberto , Chong Heap-Yih , Morrison Greg M.
Published: November 2021

This study investigates the interconnection methods used to create a circular economy building featuring modularity and designed for disassembly and relocation. Designing modular buildings for disassembly and reuse can decrease waste production and material depletion, in line with the circular economy framework. Disassemblable buildings require connections to be easily accessible. Visible connections may be unpopular features; however, concealing these, yet leaving these accessible, presents a substantial design challenge. This study demonstrates solutions to this challenge by analyzing a purposely designed case study: the Legacy Living Lab. The challenges of disguising and sealing, such as by waterproofing, two types of connections are analysed: structural and non-structural. This study details the materials and connections used across the two analyzed connection types and compares the weights and reusability of components. Thus, a necessary case study is provided for practitioners to advance circular economy theory in the building industry. Notably, all connections in the Legacy Living Lab can be easily accessed with standard building tools, facilitating its disassembly and fostering component reusability.
Chemokine Pathways in Cutaneous Melanoma: Their Modulation by Cancer and Exploitation by the Clinician
Authors: Adams Rebecca , Moser Bernhard , Karagiannis Sophia N. , Lacy Katie E.
Published: November 2021

The incidence of cutaneous malignant melanoma is rising globally and is projected to continue to rise. Advances in immunotherapy over the last decade have demonstrated that manipulation of the immune cell compartment of tumours is a valuable weapon in the arsenal against cancer; however, limitations to treatment still exist. Cutaneous melanoma lesions feature a dense cell infiltrate, coordinated by chemokines, which control the positioning of all immune cells. Melanomas are able to use chemokine pathways to preferentially recruit cells, which aid their growth, survival, invasion and metastasis, and which enhance their ability to evade anticancer immune responses. Aside from this, chemokine signalling can directly influence angiogenesis, invasion, lymph node, and distal metastases, including epithelial to mesenchymal transition-like processes and transendothelial migration. Understanding the interplay of chemokines, cancer cells, and immune cells may uncover future avenues for melanoma therapy, namely: identifying biomarkers for patient stratification, augmenting the effect of current and emerging therapies, and designing specific treatments to target chemokine pathways, with the aim to reduce melanoma pathogenicity, metastatic potential, and enhance immune cell-mediated cancer killing. The chemokine network may provide selective and specific targets that, if included in current therapeutic regimens, harbour potential to improve outcomes for patients.
Gastric Cancers Missed at Upper Endoscopy in Central Norway 2007 to 2016—A Population-Based Study
Authors: Beck Marianne , Bringeland Erling A. , Qvigstad Gunnar , Fossmark Reidar
Published: November 2021

Background: The rates of missed gastric cancers (MGC) at upper endoscopy (UE) has been reported at 5–10% in Western countries. We aimed to calculate the rate of MGC and identify factors associated with MGC. Methods: Retrospective population-based cohort study including 730 patients diagnosed with gastric adenocarcinoma in Central Norway 2007–2016. MGCs were incident gastric adenocarcinomas diagnosed 6–36 months after a previous UE. Factors associated with MGC were examined. Definitely missed (UE 6–12 months prior) and potentially missed (UE 12–36 months prior) MGCs were compared. Results: Sixty-seven (9.2%) of 730 gastric cancers were MGC. MGC were associated with localization (p = 0.009) and more frequent in the corpus, Lauren’s histological type (p = 0.028) and diffuse type more prevalent, and previous Billroth 2-operation (14.9% vs. 4.7%, p = 0.001). MGCs were diagnosed at earlier stages (p = 0.037). An ulceration was more common in patients with definitely missed than potentially MGC (40.9% vs. 17.8%, p = 0.041). Conclusions: MGC accounted for 9.2% of gastric cancers in Central Norway. MGC were associated with localization in the corpus, Lauren´s diffuse type and previous Billroth-2-operation. Intensified follow-up and adequate biopsy sampling of patients with gastric ulcerations could reduce the rate of missed gastric cancers.
Prognostic Effect of Preoperative Psoas Muscle Hounsfield Unit at Radical Cystectomy for Bladder Cancer
Authors: Sugino Yusuke , Sasaki Takeshi , Kato Manabu , Masui Satoru , Nishikawa Kouhei , Okamoto Takashi , Kajiwara Shinya , Shibahara Takuji , Onishi Takehisa , Tanaka Shiori , Kanda Hideki , Matsuura Hiroshi , Inoue Takahiro
Published: November 2021

Radical cystectomy (RC) is the standard treatment for patients with advanced bladder cancer. Since RC is a highly invasive procedure, the surgical indications in an aging society must be carefully judged. In recent years, the concept of “frailty” has been attracting attention as a term used to describe fragility due to aging. We focused on the psoas muscle Hounsfield unit (PMHU) and analyzed its appropriateness as a prognostic factor together with other clinical factors in patients after RC. We retrospectively analyzed the preoperative prognostic factors in 177 patients with bladder cancer who underwent RC between 2008 and 2020. Preoperative non-contrast computed tomography axial image at the third lumbar vertebral level was used to measure the mean Hounsfield unit (HU) and cross-sectional area (mm2) of the psoas muscle. Univariate analysis showed significant differences in age, sex, clinical T stage, and PMHU. In multivariate analysis using the Cox proportional hazards model, age (hazard ratio (HR) = 1.734), sex (HR = 2.116), cT stage (HR = 1.665), and PMHU (HR = 1.758) were significant predictors for overall survival. Furthermore, using these four predictors, it was possible to stratify the prognosis of patients after RC. Finally, PMHU was useful as a simple and significant preoperative factor that correlated with prognosis after RC.
Head and Neck Cancers Are Not Alike When Tarred with the Same Brush: An Epigenetic Perspective from the Cancerization Field to Prognosis
Authors: Camuzi Diego , Simão Tatiana de Almeida , Dias Fernando , Ribeiro Pinto Luis Felipe , Soares-Lima Sheila Coelho
Published: November 2021

Head and neck squamous cell carcinomas (HNSCC) are among the ten most frequent types of cancer worldwide and, despite all efforts, are still diagnosed at late stages and show poor overall survival. Furthermore, HNSCC patients often experience relapses and the development of second primary tumors, as a consequence of the field cancerization process. Therefore, a better comprehension of the molecular mechanisms involved in HNSCC development and progression may enable diagnosis anticipation and provide valuable tools for prediction of prognosis and response to therapy. However, the different biological behavior of these tumors depending on the affected anatomical site and risk factor exposure, as well as the high genetic heterogeneity observed in HNSCC are major obstacles in this pursue. In this context, epigenetic alterations have been shown to be common in HNSCC, to discriminate the tumor anatomical subsites, to be responsive to risk factor exposure, and show promising results in biomarker development. Based on this, this review brings together the current knowledge on alterations of DNA methylation and microRNA expression in HNSCC natural history, focusing on how they contribute to each step of the process and on their applicability as biomarkers of exposure, HNSCC development, progression, and response to therapy.
The Large GTPase, GBP-2, Regulates Rho Family GTPases to Inhibit Migration and Invadosome Formation in Breast Cancer Cells
Authors: Nyabuto Geoffrey O. , Wilson John P. , Heilman Samantha A. , Kalb Ryan C. , Kopacz Jonathan P. , Abnave Ankita V. , Vestal Deborah J.
Published: November 2021

Breast cancer is the most common cancer in women. Despite advances in early detection and treatment, it is predicted that over 43,000 women will die of breast cancer in 2021. To lower this number, more information about the molecular players in breast cancer are needed. Guanylate-Binding Protein-2 has been correlated with better prognosis in breast cancer. In this study, we asked if the expression of GBP-2 in breast cancer merely provided a biomarker for improved prognosis or whether it actually contributed to improving outcome. To answer this, the 4T1 model of murine breast cancer was used. 4T1 cells themselves are highly aggressive and highly metastatic, while 67NR cells, isolated from the same tumor, do not leave the primary site. The expression of GBP-2 was examined in the two cell lines and found to be inversely correlated with aggressiveness/metastasis. Proliferation, migration, and invadosome formation were analyzed after altering the expression levels of GBP-2. Our experiments show that GBP-2 does not alter the proliferation of these cells but inhibits migration and invadosome formation downstream of regulation of Rho GTPases. Together these data demonstrate that GBP-2 is responsible for cell autonomous activities that make breast cancer cells less aggressive.
Extracellular Vesicles in Lung Cancer Metastasis and Their Clinical Applications
Authors: Saviana Michela , Romano Giulia , Le Patricia , Acunzo Mario , Nana-Sinkam Patrick
Published: November 2021

Extracellular vesicles (EVs) are heterogenous membrane-encapsulated vesicles secreted by every cell into the extracellular environment. EVs carry bioactive molecules, including proteins, lipids, DNA, and different RNA forms, which can be internalized by recipient cells, thus altering their biological characteristics. Given that EVs are commonly found in most body fluids, they have been widely described as mediators of communication in several physiological and pathological processes, including cancer. Moreover, their easy detection in biofluids makes them potentially useful candidates as tumor biomarkers. In this manuscript, we review the current knowledge regarding EVs and non-coding RNAs and their role as drivers of the metastatic process in lung cancer. Furthermore, we present the most recent applications for EVs and non-coding RNAs as cancer therapeutics and their relevance as clinical biomarkers.
Comment on Hosmann et al. 5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)—Experience at Two Specialized Centers. Cancers 2021, 13, 2540
Authors: Stummer Walter , Thomas Christian
Published: November 2021

With great interest, we have read the paper by Hosmann et al. [...]
A Targeted Catalytic Nanobody (T-CAN) with Asparaginolytic Activity
Authors: Maggi Maristella , Pessino Greta , Guardamagna Isabella , Lonati Leonardo , Pulimeno Cristina , Scotti Claudia
Published: November 2021

E. coli L-asparaginase is an amidohydrolase (EC 3.5.1.1) which has been successfully used for the treatment of Acute Lymphoblastic Leukemia for over 50 years. Despite its efficacy, its side effects, and especially its intrinsic immunogenicity, hamper its usage in a significant subset of cases, thus limiting therapeutic options. Innovative solutions to improve on these drawbacks have been attempted, but none of them have been truly successful so far. In this work, we fully replaced the enzyme scaffold, generating an active, miniaturized form of L-asparaginase by protein engineering of a camel single domain antibody, a class of antibodies known to have a limited immunogenicity in humans. We then targeted it onto tumor cells by an antibody scFv fragment directed onto the CD19 B-cell surface receptor expressed on ALL cells. We named this new type of nanobody-based antibody-drug conjugate “Targeted Catalytic Nanobody” (T-CAN). The new molecule retains the catalytic activity and the binding capability of the original modules and successfully targets CD19 expressing cells in vitro. Thanks to its theoretically reduced immunogenic potential compared to the original molecule, the T-CAN can represent a novel approach to tackle current limitations in L-asparaginase usage.
Dysregulation of Microtubule Nucleating Proteins in Cancer Cells
Authors: Dráber Pavel , Dráberová Eduarda
Published: November 2021

In cells, microtubules typically nucleate from microtubule organizing centers, such as centrosomes. γ-Tubulin, which forms multiprotein complexes, is essential for nucleation. The γ-tubulin ring complex (γ-TuRC) is an efficient microtubule nucleator that requires additional centrosomal proteins for its activation and targeting. Evidence suggests that there is a dysfunction of centrosomal microtubule nucleation in cancer cells. Despite decades of molecular analysis of γ-TuRC and its interacting factors, the mechanisms of microtubule nucleation in normal and cancer cells remains obscure. Here, we review recent work on the high-resolution structure of γ-TuRC, which brings new insight into the mechanism of microtubule nucleation. We discuss the effects of γ-TuRC protein dysregulation on cancer cell behavior and new compounds targeting γ-tubulin. Drugs inhibiting γ-TuRC functions could represent an alternative to microtubule targeting agents in cancer chemotherapy.