bluuebunny/crossref_metadata_2025 huggingface dataset:
Programmed Death-Ligand 1 (PD-L1) as Immunotherapy Biomarker in Breast Cancer
Authors: Núñez Abad Martín , Calabuig-Fariñas Silvia , Lobo de Mena Miriam , Torres-Martínez Susana , García González Clara , García García José Ángel , Iranzo González-Cruz Vega , Camps Herrero Carlos
Published: January 2022

Breast cancer constitutes the most common malignant neoplasm in women around the world. Approximately 12% of patients are diagnosed with metastatic stage, and between 5 and 30% of early or locally advanced BC patients will relapse, making it an incurable disease. PD-L1 ligation is an immune inhibitory molecule of the activation of T cells, playing a relevant role in numerous types of malignant tumors, including BC. The objective of the present review is to analyze the role of PD-L1 as a biomarker in the different BC subtypes, adding clinical trials with immune checkpoint inhibitors and their applicable results. Diverse trials using immunotherapy with anti-PD-1/PD-L1 in BC, as well as prospective or retrospective cohort studies about PD-L1 in BC, were included. Despite divergent results in the reviewed studies, PD-L1 seems to be correlated with worse prognosis in the hormone receptor positive subtype. Immune checkpoints inhibitors targeting the PD-1/PD-L1 axis have achieved great response rates in TNBC patients, especially in combination with chemotherapy, making immunotherapy a new treatment option in this scenario. However, the utility of PD-L1 as a predictive biomarker in the rest of BC subtypes remains unclear. In addition, predictive differences have been found in response to immunotherapy depending on the stage of the tumor disease. Therefore, a better understanding of tumor microenvironment, as well as identifying new potential biomarkers or combined index scores, is necessary in order to make a better selection of the subgroups of BC patients who will derive benefit from immune checkpoint inhibitors.
Surgery vs. Biopsy in the Treatment of Butterfly Glioblastoma: A Systematic Review and Meta-Analysis
Authors: Chawla Shreya , Kavouridis Vasileios K. , Boaro Alessandro , Korde Rasika , Amaral Medeiros Sofia , Edrees Heba , Mezzalira Elisabetta , Sala Francesco , Mekary Rania A. , Smith Timothy R.
Published: January 2022

Butterfly glioblastomas (bGBM) are grade IV gliomas that spread to bilateral hemispheres by infiltrating the corpus callosum. Data on the effect of surgery are limited to small case series. The aim of this meta-analysis was to compare resection vs. biopsy in terms of survival outcomes and postoperative complications. A systematic review of the literature was conducted using PubMed, EMBASE, and Cochrane databases through March 2021 in accordance with the PRISMA checklist. Pooled hazard ratios were calculated and meta-analyzed in a random-effects model including assessment of heterogeneity. Out of 3367 articles, seven studies were included with 293 patients. Surgical resection was significantly associated with longer overall survival (HR 0.39, 95%CI 0.2–0.55) than biopsy. Low heterogeneity was observed (I2: 0%). In further analysis, the effect persisted in extent of resection subgroups of both ≥80% and <80%. No statistically significant difference between surgery and biopsy was detected in terms of postoperative complications, although these were numerically larger for surgery. In patients with bGBM, surgical resection was associated with longer survival prospects compared with biopsy.
Hyperthermia: A Potential Game-Changer in the Management of Cancers in Low-Middle-Income Group Countries
Authors: Datta Niloy R. , Jain Bharati M. , Mathi Zatin , Datta Sneha , Johari Satyendra , Singh Ashok R. , Kalbande Pallavi , Kale Pournima , Shivkumar Vitaladevuni , Bodis Stephan
Published: January 2022

Loco-regional hyperthermia at 40–44 °C is a multifaceted therapeutic modality with the distinct triple advantage of being a potent radiosensitizer, a chemosensitizer and an immunomodulator. Risk difference estimates from pairwise meta-analysis have shown that the local tumour control could be improved by 22.3% (p < 0.001), 22.1% (p < 0.001) and 25.5% (p < 0.001) in recurrent breast cancers, locally advanced cervix cancer (LACC) and locally advanced head and neck cancers, respectively by adding hyperthermia to radiotherapy over radiotherapy alone. Furthermore, thermochemoradiotherapy in LACC have shown to reduce the local failure rates by 10.1% (p = 0.03) and decrease deaths by 5.6% (95% CI: 0.6–11.8%) over chemoradiotherapy alone. As around one-third of the cancer cases in low-middle-income group countries belong to breast, cervix and head and neck regions, hyperthermia could be a potential game-changer and expected to augment the clinical outcomes of these patients in conjunction with radiotherapy and/or chemotherapy. Further, hyperthermia could also be a cost-effective therapeutic modality as the capital costs for setting up a hyperthermia facility is relatively low. Thus, the positive outcomes evident from various phase III randomized trials and meta-analysis with thermoradiotherapy or thermochemoradiotherapy justifies the integration of hyperthermia in the therapeutic armamentarium of clinical management of cancer, especially in low-middle-income group countries.
Analysis of Survival and Response to Lenvatinib in Unresectable Hepatocellular Carcinoma
Authors: Amioka Kei , Kawaoka Tomokazu , Kosaka Masanari , Johira Yusuke , Shirane Yuki , Miura Ryoichi , Murakami Serami , Yano Shigeki , Naruto Kensuke , Ando Yuwa , Kosaka Yumi , Fujii Yasutoshi , Kodama Kenichiro , Uchikawa Shinsuke , Fujino Hatsue , Ono Atsushi , Nakahara Takashi , Murakami Eisuke , Okamoto Wataru , Yamauchi Masami , Imamura Michio , Mori Nami , Takaki Shintaro , Tsuji Keiji , Masaki Keiichi , Honda Yoji , Kouno Hirotaka , Kohno Hiroshi , Moriya Takashi , Naeshiro Noriaki , Nonaka Michihiro , Hyogo Hideyuki , Aisaka Yasuyuki , Azakami Takahiro , Hiramatsu Akira , Aikata Hiroshi
Published: January 2022

The association between radiological response and overall survival (OS) was retrospectively evaluated in patients treated with lenvatinib as a first-line systemic treatment for unresectable hepatocellular carcinoma. A total of 182 patients with Child–Pugh class A liver function and an Eastern Cooperative Oncology Group performance status of zero or one were enrolled. Radiological evaluation was performed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Initial radiological evaluation confirmed significant stratification of OS by efficacy judgment with both RECIST and mRECIST, and that initial radiological response was an independent prognostic factor for OS on multivariate analysis. Furthermore, in patients with stable disease (SD) at initial evaluation, macrovascular invasion at the initial evaluation on RECIST and modified albumin–bilirubin grade at initial evaluation on mRECIST were independent predictors of OS on multivariate analysis. In conclusion, if objective response is obtained at the initial evaluation, continuation of treatment appears desirable because prolonged OS can be expected; but, if SD is obtained at the initial evaluation, one should determine whether to continue or switch to the next treatment, with careful consideration of factors related to the tumor and hepatic reserve at the initial evaluation.
CRISPR-Cas9 Screen Identifies DYRK1A as a Target for Radiotherapy Sensitization in Pancreatic Cancer
Authors: Lan Bin , Zeng Siyuan , Zhang Shuman , Ren Xiaofan , Xing Yuming , Kutschick Isabella , Pfeffer Susanne , Frey Benjamin , Britzen-Laurent Nathalie , Grützmann Robert , Cordes Nils , Pilarsky Christian
Published: January 2022

Although radiation therapy has recently made great advances in cancer treatment, the majority of patients diagnosed with pancreatic cancer (PC) cannot achieve satisfactory outcomes due to intrinsic and acquired radioresistance. Identifying the molecular mechanisms that impair the efficacy of radiotherapy and targeting these pathways are essential to improve the radiation response of PC patients. Our goal is to identify sensitive targets for pancreatic cancer radiotherapy (RT) using the kinome-wide CRISPR-Cas9 loss-of-function screen and enhance the therapeutic effect through the development and application of targeted inhibitors combined with radiotherapy. We transduced pancreatic cancer cells with a protein kinase library; 2D and 3D library cells were irradiated daily with a single dose of up to 2 Gy for 4 weeks for a total of 40 Gy using an X-ray generator. Sufficient DNA was collected for next-generation deep sequencing to identify candidate genes. In this study, we identified several cell cycle checkpoint kinases and DNA damage related kinases in 2D- and 3D-cultivated cells, including DYRK1A, whose loss of function sensitizes cells to radiotherapy. Additionally, we demonstrated that the harmine-targeted suppression of DYRK1A used in conjunction with radiotherapy increases DNA double-strand breaks (DSBs) and impairs homologous repair (HR), resulting in more cancer cell death. Our results support the use of CRISPR-Cas9 screening to identify new therapeutic targets, develop radiosensitizers, and provide novel strategies for overcoming the tolerance of pancreatic cancer to radiotherapy.
Production of Hydroxypyruvic Acid by Glycerol Oxidation over Pt/CeO2-ZrO2-Bi2O3-PbO/SBA-16 Catalysts
Authors: Choi Yeon-Bin , Nunotani Naoyoshi , Morita Kunimitsu , Imanaka Nobuhito
Published: January 2022

Pt/CeO2-ZrO2-Bi2O3-PbO/SBA-16 (SBA-16: Santa Barbara Amorphous No. 16) catalysts were synthesized to produce hydroxypyruvic acid by glycerol oxidation. In the catalysts, the introduction of PbO into CeO2-ZrO2-Bi2O3 improved the oxygen release and storage abilities owing to the synergistic redox reaction of Pb2+/4+ and Ce3+/4+, which facilitated the oxidation ability of Pt. In addition, the oxidation of the secondary OH group in glycerol might be accelerated by the geometric effects of glycerol, Pt, and Bi3+ or Pb2+/4+. Furthermore, the moderate reaction conditions such as room temperature and open-air atmosphere enabled the suppression of further oxidation of hydroxypyruvic acid. The highest catalytic activity was obtained for 7 wt% Pt/16 wt% Ce0.60Zr0.15Bi0.20Pb0.05O2−δ/SBA-16, which provided a hydroxypyruvic acid yield maximum of 24.6%, after the reaction for 6 h at 30 °C in atmospheric air.
The H+ Transporter SLC4A11: Roles in Metabolism, Oxidative Stress and Mitochondrial Uncoupling
Authors: Bonanno Joseph A. , Shyam Raji , Choi Moonjung , Ogando Diego G.
Published: January 2022

Solute-linked cotransporter, SLC4A11, a member of the bicarbonate transporter family, is an electrogenic H+ transporter activated by NH3 and alkaline pH. Although SLC4A11 does not transport bicarbonate, it shares many properties with other members of the SLC4 family. SLC4A11 mutations can lead to corneal endothelial dystrophy and hearing deficits that are recapitulated in SLC4A11 knock-out mice. SLC4A11, at the inner mitochondrial membrane, facilitates glutamine catabolism and suppresses the production of mitochondrial superoxide by providing ammonia-sensitive H+ uncoupling that reduces glutamine-driven mitochondrial membrane potential hyperpolarization. Mitochondrial oxidative stress in SLC4A11 KO also triggers dysfunctional autophagy and lysosomes, as well as ER stress. SLC4A11 expression is induced by oxidative stress through the transcription factor NRF2, the master regulator of antioxidant genes. Outside of the corneal endothelium, SLC4A11’s function has been demonstrated in cochlear fibrocytes, salivary glands, and kidneys, but is largely unexplored overall. Increased SLC4A11 expression is a component of some “glutamine-addicted” cancers, and is possibly linked to cells and tissues that rely on glutamine catabolism.
Native and Oxidized Low-Density Lipoproteins Increase the Expression of the LDL Receptor and the LOX-1 Receptor, Respectively, in Arterial Endothelial Cells
Authors: Catar Rusan , Chen Lei , Zhao Hongfan , Wu Dashan , Kamhieh-Milz Julian , Lücht Christian , Zickler Daniel , Krug Alexander W. , Ziegler Christian G. , Morawietz Henning , Witowski Janusz
Published: January 2022

Atherosclerotic artery disease is the major cause of death and an immense burden on healthcare systems worldwide. The formation of atherosclerotic plaques is promoted by high levels of low-density lipoproteins (LDL) in the blood, especially in the oxidized form. Circulating LDL is taken up by conventional and non-classical endothelial cell receptors and deposited in the vessel wall. The exact mechanism of LDL interaction with vascular endothelial cells is not fully understood. Moreover, it appears to depend on the type and location of the vessel affected and the receptor involved. Here, we analyze how native LDL (nLDL) and oxidized LDL (oxLDL) modulate the expression of their receptors—classical LDLR and alternative LOX-1—in endothelial cells derived from human umbilical artery (HUAECs), used as an example of a medium-sized vessel, which is typically affected by atherosclerosis. Exposure of HUAECs to nLDL resulted in moderate nLDL uptake and gradual increase in LDLR, but not LOX-1, expression over 24 h. Conversely, exposure of HUAECs to oxLDL, led to significant accumulation of oxLDL and rapid induction of LOX-1, but not LDLR, within 7 h. These activation processes were associated with phosphorylation of protein kinases ERK1/2 and p38, followed by activation of the transcription factor AP-1 and its binding to the promoters of the respective receptor genes. Both nLDL-induced LDLR mRNA expression and oxLDL-induced LOX-1 mRNA expression were abolished by blocking ERK1/2, p-38 or AP-1. In addition, oxLDL, but not nLDL, was capable of inducing LOX-1 through the NF-κB-controlled pathway. These observations indicate that in arterial endothelial cells nLDL and oxLDL signal mainly via LDLR and LOX-1 receptors, respectively, and engage ERK1/2 and p38 kinases, and AP-1, as well as NF-κB transcription factors to exert feed-forward regulation and increase the expression of these receptors, which may perpetuate endothelial dysfunction in atherosclerosis.
Establishment and Characterization of NCC-MFS5-C1: A Novel Patient-Derived Cell Line of Myxofibrosarcoma
Authors: Tsuchiya Ryuto , Yoshimatsu Yuki , Noguchi Rei , Sin Yooksil , Ono Takuya , Akiyama Taro , Sugaya Jun , Kobayashi Eisuke , Kojima Naoki , Yoshida Akihiko , Ohtori Seiji , Kawai Akira , Kondo Tadashi
Published: January 2022

Myxofibrosarcoma (MFS) is a highly aggressive malignancy with complex karyotypes and a postoperative recurrence tendency, owing to its strong invasiveness. Although systemic chemotherapy is considered in patients with unresectable MFS, the efficacy of conventional chemotherapy is hitherto unclear. Recently, drug screening analysis using a large number of tumor cell lines has been attempted to discover novel therapeutic candidate drugs for common cancers. However, the number of MFS cell lines is extremely small because of its low incidence—this hinders the conduction of screening studies and slows down the development of therapeutic drugs. To overcome this problem, we established a novel MFS cell line, NCC-MFS5-C1, which was shown to harbor typical MFS genetic abnormalities and thus had useful properties for in vitro studies. We conducted the largest integrated screening analysis of 210 drugs using NCC-MFS5-C1 cells along with four MFS cell lines, which we previously reported. Bortezomib (a proteasome inhibitor) and romidepsin (a histone deacetylase inhibitor) showed stronger antitumor effects than the standard drug, doxorubicin. Therefore, the NCC-MFS5-C1 cell line can potentially contribute to elucidating MFS pathogenesis and developing a novel MFS treatment.
Techno-Economic Analysis and Modelling of the Feasibility of Wind Energy in Kuwait
Authors: Khajah Ali M. H. A. , Philbin Simon P.
Published: January 2022

There continues to be significant attention and investment in wind power generation, which can supply a high percentage of the global demand for renewable energy if harvested efficiently. The research study is based on a techno-economic analysis of the feasibility of implementing wind power generation in Kuwait for 105 MW of electricity generation based on 50 wind turbines, which is a major requirement for clean energy. The study focused on three main areas of analysis and numerical modelling using the RETScreen software tool. The first area involved evaluating the performance and efficacy of generating wind power by collecting, analysing, and modelling data on observed wind levels, wind turbine operation, and wind power generation. The second area comprised an environmental impact report to assess the environmental benefits of implementing wind power. The third area involved economic analysis of installing wind power in Kuwait. The analysis was undertaken to determine the energy recovery time for wind energy and determine the mitigation of global warming and pollution levels, the decrease of toxic emissions, and any cost savings from implementing clean energy systems in Kuwait. Additionally, sensitivity analysis was undertaken to determine the impact of certain variables in the modelling process. The results were used to estimate that the energy price would be $0.053 per kWh for a power generation capacity of 105 MWh based on an initial cost of US $168 million and O&M of $5 million for 214,000 MWh of electricity exported to the grid. Moreover, the wind turbine farm will potentially avoid the emission of approximately 1.8 million t of carbon dioxide per year, thereby saving about $9 million over 20 years spent through installing carbon capture systems for conventional power plants. The wind farm is estimated to have a payback time of 9.1 years.
Plasma Rich in Growth Factors in Macular Hole Surgery
Authors: Sánchez-Ávila Ronald M. , Robayo-Esper Carlos A. , Villota-Deleu Eva , Fernández-Vega Sanz Álvaro , Fernández-Vega González Álvaro , de la Sen-Corcuera Borja , Anitua Eduardo , Merayo-Lloves Jesús
Published: January 2022

The aim of this study was to evaluate the use of PRGF (plasma rich in growth factors) as an adjuvant to PPV (pars plana vitrectomy) in recurrent, persistent, or poor prognosis MH (macular hole). Patients with MH were treated with PPV plus adjuvant therapy (PRGF membrane (mPRGF) and injectable liquid PRGF (iPRGF)). The anatomical closure of MH and postoperative BCVA (best-corrected visual acuity) were evaluated. Eight eyes (eight patients) were evaluated: myopic MH (MMH, n = 4), idiopathic MH (IMH, n = 2), iatrogenic n = 1, traumatic n = 1. The mean age was 53.1 ± 19.3 years. Hence, 66.7% (n = 4) of patients previously had internal limiting membrane peeling. Five patients (62.5%) received mPRGF and iPRGF, and three patients (37.5%) received iPRGF. Gas tamponade (C3F8) was placed in seven cases and one case of silicone oil. Anatomic closure of MH was achieved in seven eyes (87.5%) and BCVA improved in six cases. In the MMH group, visual acuity improved in two lines of vision. Follow-up time was 27.2 ± 9.0 months. No adverse events or MH recurrences were recorded during follow-up. The use of PRGF as an adjuvant therapy to PPV can be useful to improve anatomical closure and visual acuity in MH surgery.
Investigation of Accelerated Degradation Methods to Cause Blisters for Non-Defective Vinyl Ester Resin Glass Flake Organic Coatings
Authors: Tokutake Koya , Okazaki Shinji , Kodama Shintaro
Published: January 2022

Organic coatings are applied as a corrosion prevention measure, but their effectiveness may degrade over time. In this study, the acceleration effects of typical degradation methods in non-defective vinyl ester resin organic coatings containing glass flakes such as high-temperature immersion and immersion in chemical accelerators are clarified using physiochemical techniques. Immersion in an acetic acid (AcOH) aqueous solution causes resin swelling, and the behaviors are quantitatively evaluated through gravimetric, thickness, and electrochemical impedance spectroscopy (EIS) measurements. Furthermore, a combined process of immersion in hydrofluoric acid and an AcOH aqueous solution reduces the electrical properties and eventually blisters the thick coating surface. This result suggests that an appropriate combination of the resin swelling and the glass degradation (glass dissolution and/or formation of the gap between glass and resin) decrease mechanical properties of the glass flake coating and causes blisters. In order to help the health diagnosis of the visually non-defective aged glass flake coating, the relationship between the electrical characteristic values and the invisible degradation by accelerated tests is finally indicated.
Approximator: A Software Tool for Automatic Generation of Approximate Arithmetic Circuits
Authors: Balasubramanian Padmanabhan , Nayar Raunaq , Min Okkar , Maskell Douglas L.
Published: January 2022

Approximate arithmetic circuits are an attractive alternative to accurate arithmetic circuits because they have significantly reduced delay, area, and power, albeit at the cost of some loss in accuracy. By keeping errors due to approximate computation within acceptable limits, approximate arithmetic circuits can be used for various practical applications such as digital signal processing, digital filtering, low power graphics processing, neuromorphic computing, hardware realization of neural networks for artificial intelligence and machine learning etc. The degree of approximation that can be incorporated into an approximate arithmetic circuit tends to vary depending on the error resiliency of the target application. Given this, the manual coding of approximate arithmetic circuits corresponding to different degrees of approximation in a hardware description language (HDL) may be a cumbersome and a time-consuming process—more so when the circuit is big. Therefore, a software tool that can automatically generate approximate arithmetic circuits of any size corresponding to a desired accuracy would not only aid the design flow but also help to improve a designer’s productivity by speeding up the circuit/system development. In this context, this paper presents ‘Approximator’, which is a software tool developed to automatically generate approximate arithmetic circuits based on a user’s specification. Approximator can automatically generate Verilog HDL codes of approximate adders and multipliers of any size based on the novel approximate arithmetic circuit architectures proposed by us. The Verilog HDL codes output by Approximator can be used for synthesis in an FPGA or ASIC (standard cell based) design environment. Additionally, the tool can perform error and accuracy analyses of approximate arithmetic circuits. The salient features of the tool are illustrated through some example screenshots captured during different stages of the tool use. Approximator has been made open-access on GitHub for the benefit of the research community, and the tool documentation is provided for the user’s reference.
Between Harmonic Crystal and Glass: Solids with Dimpled Potential-Energy Surfaces Having Multiple Local Energy Minima
Authors: Zarkevich Nikolai , Johnson Duane
Published: January 2022

Solids with dimpled potential-energy surfaces are ubiquitous in nature and, typically, exhibit structural (elastic or phonon) instabilities. Dimpled potentials are not harmonic; thus, the conventional quasiharmonic approximation at finite temperatures fails to describe anharmonic vibrations in such solids. At sufficiently high temperatures, their crystal structure is stabilized by entropy; in this phase, a diffraction pattern of a periodic crystal is combined with vibrational properties of a phonon glass. As temperature is lowered, the solid undergoes a symmetry-breaking transition and transforms into a lower-symmetry phase with lower lattice entropy. Here, we identify specific features in the potential-energy surface that lead to such polymorphic behavior; we establish reliable estimates for the relative energies and temperatures associated with the anharmonic vibrations and the solid–solid symmetry-breaking phase transitions. We show that computational phonon methods can be applied to address anharmonic vibrations in a polymorphic solid at fixed temperature. To illustrate the ubiquity of this class of materials, we present a range of examples (elemental metals, a shape-memory alloy, and a layered charge-density-wave system); we show that our theoretical predictions compare well with known experimental data.
Abnormal Shear Performance of Microscale Ball Grid Array Structure Cu/Sn–3.0Ag–0.5Cu/Cu Solder Joints with Increasing Current Density
Authors: Wang Bo , Li Wangyun , Pan Kailin
Published: January 2022

The shear performance and fracture behavior of microscale ball grid array structure Cu/Sn–3.0Ag–0.5Cu/Cu solder joints with increasing electric current density (from 1.0 × 103 to 6.0 × 103 A/cm2) at various test temperatures (25 °C, 55 °C, 85 °C, 115 °C, 145 °C, and 175 °C) were investigated systematically. Shear strength increases initially, then decreases with increasing current density at a test temperature of no more than 85 °C; the enhancement effect of current stressing on shear strength decreases and finally diminishes with increasing test temperatures. These changes are mainly due to the counteraction of the athermal effect of current stressing and Joule heating. After decoupling and quantifying the contribution of the athermal effect to the shear strength of solder joints, the results show that the influence of the athermal effect presents a transition from an enhancement state to a deterioration state with increasing current density, and the critical current density for the transition decreases with increasing test temperatures. Joule heating is always in a deterioration state on the shear strength of solder joints, which gradually becomes the dominant factor with increasing test temperatures and current density. In addition, the fracture location changes from the solder matrix to the interface between the solder matrix and the intermetallic compound (IMC) layer (the solder/IMC layer interface) with increasing current density, showing a ductile-to-brittle transition. The interfacial fracture is triggered by current crowding at the groove of the IMC layer and driven by mismatch strain at the solder/IMC layer interface, and the critical current density for the occurrence of interfacial fracture decreases with increasing test temperatures.
Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence
Authors: Attili Ilaria , Passaro Antonio , Pisapia Pasquale , Malapelle Umberto , de Marinis Filippo
Published: January 2022

Compound epidermal growth factor receptor (EGFR) mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations. We conducted a systematic review to investigate the available data on this patients’ subgroup. Overall, we found a high heterogeneity in the incidence of compound mutations (4–26% of total EGFR mutant cases), which is dependent on the different testing methods adopted and the specific mutations considered. In addition, the relative incidence of distinct compound subclasses identified is reported with extreme variability in different studies. Preclinical and clinical data, excluding de novoEGFR exon 20 p.T790M compound mutations, show good responses with EGFR tyrosine kinase inhibitors (TKIs) (combined common mutations: response rate (RR) ≥ 75% with either first- or second-generation TKIs; combined common plus uncommon: RR 40–80% and 100% with first-generation TKIs and afatinib, respectively; combined uncommon: RR 20–70%, ~80% and ~75% with first-generation TKIs, afatinib and osimertinib, respectively). Overall, data are consistent in supporting the use of EGFR TKIs in treating compound EGFR mutations, taking into account different sensitivity profile of accompanying EGFR mutations for selecting the most adequate EGFR TKI for individual patients.
Dental Disorders and Salivary Changes in Patients with Laryngopharyngeal Reflux
Authors: Casciaro Sabrina , Gelardi Matteo , Giancaspro Rossana , Quaranta Vitaliano Nicola , Porro Giuseppe , Sterlicchio Brigida , Abbinante Antonia , Corsalini Massimo
Published: January 2022

Background: Laryngopharyngeal reflux (LPR) is a common inflammatory condition of the upper aerodigestive tract tissues related to the effects of gastroduodenal content reflux, characterized by a wide variety of clinical manifestations. The aim of our study was to evaluate the possible association between dental disorders and LRP, focusing on the role of salivary changes. Methods: Patient’s dental status was evaluated according to Schiff Index Sensitivity Scale (SISS), Basic Erosive Wear Examination (BEWE) and Decayed, Missing, and Filled Teeth (DMFT) scores. Reflux-associated symptoms were assessed according to Reflux symptom index (RSI). A qualitative and quantitative examination of saliva was performed. Results: Patients suffering from LPR had a higher incidence of dental disorders, regardless the presence of salivary pepsin, and thus, statistically significant higher scores of RSI (p = 0.0001), SISS (p = 0.001), BEWE (p < 0.001) and VAS (p < 0.001). Moreover, they had lower salivary flow compared with healthy patients. Conclusions: The finding of demineralization and dental caries on intraoral evaluation must raise the suspicion of LRP. Reflux treatments should also be aimed at correcting salivary alterations, in order to preserve the buffering capacity and salivary pH, thus preventing mucosal and dental damage.
Physical Activity Experiences of People with Multiple Sclerosis during the COVID-19 Pandemic
Authors: Koopmans Alanna , Pelletier Chelsea
Published: January 2022

During the COVID-19 pandemic, government and health officials introduced measures such as social distancing and facility closures that amplified barriers to physical activity. Certain groups, including people with multiple sclerosis (MS), have been underserved during the pandemic. In this qualitative study we aimed to: (1) explore the physical activity experiences of people with MS during the COVID-19 pandemic; (2) identify the facilitators and barriers to physical activity during COVID-19 for people with MS; and (3) make recommendations for inclusive physical activity policy and programming. We conducted semi-structured interviews with 11 adults (9 women) with MS during January and February 2021. Following an inductive thematic analysis, three themes were developed: (1) changing opportunities and adapting to new opportunities; (2) social isolation and physical activity; and (3) adapting physical activity to stay safe from COVID-19. Common facilitators identified included having knowledge and resources to adapt activities, social connections, and access to outdoor recreation opportunities. Identified barriers included fear and anxiety related to the spread of the virus, a loss of in-person activity options, and the closure of physical activity spaces. Online and at-home opportunities for physical activity were a valued and accessible way to address barriers to physical activity for people with MS, and should be maintained post-pandemic while considering flexibility to accommodate variable support needs.
Anonymous Mutual and Batch Authentication with Location Privacy of UAV in FANET
Authors: Rajasekaran Arun Sekar , Maria Azees , Al-Turjman Fadi , Altrjman Chadi , Mostarda Leonardo
Published: January 2022

As there has been an advancement in avionic systems in recent years, the enactment of unmanned aerial vehicles (UAV) has upgraded. As compared to a single UAV system, multiple UAV systems can perform operations more inexpensively and efficiently. As a result, new technologies between user/control station and UAVs have been developed. FANET (Flying Ad-Hoc Network) is a subset of the MANET (Mobile Ad-Hoc Network) that includes UAVs. UAVs, simply called drones, are used for collecting sensitive data in real time. The security and privacy of these data are of priority importance. Therefore, to overcome the privacy and security threats problem and to make communication between the UAV and the user effective, a competent anonymous mutual authentication scheme is proposed in this work. There are several methodologies addressed in this work such as anonymous batch authentication in FANET which helps to authenticate a large group of drones at the same time, thus reducing the computational overhead. In addition, the integrity preservation technique helps to avoid message alteration during transmission. Moreover, the security investigation section discusses the resistance of the proposed work against different types of possible attacks. Finally, the proposed work is related to the prevailing schemes in terms of communication and computational cost and proves to be more efficient.
Design and Analysis of a Voltage-Mode Non-Linear Control of a Non-Minimum-Phase Positive Output Elementary Luo Converter
Authors: Chincholkar Satyajit H. , Malge Sangmesh V. , Patil Sanjaykumar L.
Published: January 2022

The positive output elementary Luo (POEL) converter is a fourth-order DC–DC converter having highly non-linear dynamic characteristics. In this paper, a new dynamic output voltage feedback controller is proposed to achieve output voltage regulation of the POEL converter. In contrast to the state-of-the-art current-mode controllers for the high-order boost converters, the proposed control strategy uses only the output voltage state variable for feedback purposes. This eliminates the need for the inductor current sensor to reduce the cost and complexity of implementation. The controller design is accompanied by a strong theoretical foundation and detailed stability analyses to obtain some insight into the controlled system. The performance of the proposed controller is then compared with a multi-loop hysteresis-based sliding-mode controller (SMC) to achieve the output voltage-regulation of the same POEL converter. The schemes are compared concerning ease of implementation, in particular, the number of state variables and current sensors required for implementation and the closed-loop dynamic performance. Experimental results illustrating the features of both controllers in the presence of input reference and load changes are presented.
The Tracking and Frequency Measurement of the Sway of Leafless Deciduous Trees by Adaptive Tracking Window Based on MOSSE
Authors: Wang Achuan , Yang Xinnian , Xin Dabo
Published: January 2022

The tree sway frequency is an important part of the dynamic properties of trees. In order to obtain trees sway frequency in wind, a method of tracking and measuring the sway frequency of leafless deciduous trees by adaptive tracking window based on MOSSE was proposed. Firstly, an adaptive tracking window is constructed for the observed target. Secondly, the tracking method based on Minimum Output Sum Of Squared Error Filter (MOSSE) is used to track tree sway. Thirdly, Fast Fourier transform was used to analyze the horizontal sway velocity of the target area on the trees, and the sway frequency was determined. Finally, comparing the power spectral densities (PSDs) of the x axis acceleration measured by the accelerometer and PSDs of the x axis velocity measured by the video, the fundamental sway frequency measured by the accelerometer is equal to the fundamental sway frequency measured by video. The results show that the video-based method can be used successfully for measuring the sway frequency of leafless deciduous trees.
Fungal Perspective of Pine and Oak Colonization in Mediterranean Degraded Ecosystems
Authors: Adamo Irene , Dashevskaya Svetlana , Alday Josu G.
Published: January 2022

Forest restoration has become one of the most important challenges for restoration ecology in the recent years. In this regard, soil fungi are fundamental drivers of forest ecosystem processes, with significant implications for plant growth and survival. However, the post-disturbance recovery of belowground communities has been rarely assessed, especially in highly degraded systems such as mines. Our aim was to compare forests and mined systems for biomass and structure of fungal communities in soil during early stages of tree establishment after disturbance. We performed ergosterol analysis and PacBio and Illumina sequencing of internal transcribed spacer 2 amplicons across soil layers in P. sylvestris, Q. robur and Q. ilex (holm oak) forests and naturally revegetated mined sites. In pine forests, total fungal biomass was significantly higher in litter and humus compared to mineral layers, with dominance of the mycorrhizal genera Tomentella, Inocybe and Tricholoma. Conversely, in oak forests the most abundant mycorrhizal genera were Tomentella, Cortinarius and Sebacina, but the biomass of saprotrophic fungi was greater in the litter layer compared to mycorrhizal fungi, with the genus Preussia being the most abundant. In the revegetated mined sites, ectomycorrhizal fungi dominated in the humus and mineral layers, with the mycorrhizal genus Oidiodendron being dominant. In contrast, in holm oak forests saprotrophic fungi dominated both soil humus and mineral layers, with the genera of Alternaria, Bovista and Mycena dominating the soil humus forest layer, while the genus Cadophora dominated the mineral layer. The habitat-specific differences in soil fungal community composition and putative functions suggest that an understanding of soil–plant–microbial interactions for different tree species and use of specific soil/litter inoculum upon planting/seeding might help to increase the effectiveness of tree restoration strategies in Mediterranean degraded sites.
Gönpa Gang—The First Application of Dendrochronological Dating to Study the Traditional Architecture of Upper Mustang (Nepal)
Authors: Gmińska-Nowak Barbara , Tiwari Achyut , Ważny Tomasz
Published: January 2022

Gönpa Gang is an example of the traditional Buddhist architecture of Upper Mustang. It is also the first monument in Upper Mustang to be studied using the dendrochronological dating method. The gönpa is a two-story building of imposing size, made from simple elements of Tibetan architecture, namely masonry walls, timber posts, and beams. A total of 14 samples were collected from elements on both the ground and the first floor. The limited number of samples results from the cultural and religious character of the object under study. Only the elements consistent with the structure and the space arrangement, interpreted as original features, were examined. Microscopic observation and the analysis of the anatomical features of all 14 samples resulted in the identification of Himalayan pine (blue pine), Pinus wallichiana A.B. Jacks. Intra-annual density fluctuation, false rings, and missing rings were detected. From 14 samples collected in Gönpa Gang, 18 series were worked out. Thus, 15 series from 12 samples were synchronized and used for the development of the mean chronology, UMGG_m, with a total length of 160 rings. The chronology covers the period from 1524 to 1683. Examination of the Gang Gönpa wood resulted in the age determination of 13 elements. The results were compared with architectural stratification by Harrison and historical data from written sources. The timber used in the gönpa comes from the Southern Mustang area. The examined wood demonstrates a correlation with the timber used in the Upper Mustang historical buildings further north.
A Queueing-Based Model Performance Evaluation for Internet of People Supported by Fog Computing
Authors: Rodrigues Laécio , Rodrigues Joel J. P. C. , Serra Antonio de Barros , Silva Francisco Airton
Published: January 2022

Following the Internet of Things (IoT) and the Internet of Space (IoS), we are now approaching IoP (Internet of People), or the Internet of Individuals, with the integration of chips inside people that link to other chips and the Internet. Low latency is required in order to achieve great service quality in these ambient assisted living facilities. Failures, on the other hand, are not tolerated, and assessing the performance of such systems in a real-world setting is difficult. Analytical models may be used to examine these types of systems even in the early phases of design. The performance of aged care monitoring systems is evaluated using an M/M/c/K queuing network. The model enables resource capacity, communication, and service delays to be calibrated. The proposed model was shown to be capable of predicting the system’s MRT (mean response time) and calculating the quantity of resources required to satisfy certain user requirements. To analyze data from IoT solutions, the examined architecture incorporates cloud and fog resources. Different circumstances were analyzed as case studies, with four main characteristics taken into consideration. These case studies look into how cloud and fog resources differ. Simulations were also run to test various routing algorithms with the goal of improving performance metrics. As a result, our study can assist in the development of more sophisticated health monitoring systems without incurring additional costs.
The Effects of Silkworm-Derived Polysaccharide (Silkrose) on Ectoparasitic Infestations in Yellowtail (Seriola quinqueradiata) and White Trevally (Pseudocaranx dentex)
Authors: Miura Takeshi , Nishikawa Munenori , Otsu Yuki , Ali Muhammad Fariz Zahir , Hashizume Atsushi , Miura Chiemi
Published: January 2022

The effect of silkworm-derived polysaccharide silkrose on fish ectoparasites was investigated. When juvenile yellowtail (Seriola quinqueradiata) fed diets containing silkrose were artificially infected with Benedenia seriolae, a fish ectoparasite, the numbers of parasitized B. seriolae were significantly lower compared to that in fish in the control group without silkrose treatment. Furthermore, when juvenile yellowtails were severely infected with B. seriolae, no mortality was observed in the silkrose-treated group, compared to more than 60% in the control group. In field studies carried out at a fish farm with yellowtail and white trevally (Pseudocaranx dentex), oral treatment with silkrose significantly reduced B. seriolae parasitism in yellowtail and Caligus longipedis and Neobenedenia girellae parasitism in white trevally. Silkrose treatment also reduced blood levels of cortisol, a stress hormone in both species. The changes in gene expression in the epidermis of yellowtail by silkrose treatment were also investigated, showing that the expression of various genes, including factors involved in immunity, stress response, and wound healing, was changed by the treatment. These findings indicate that silkworm-derived silkrose effectively prevents infection by external parasites in yellowtail and white trevally.
Molecular Investigation of miRNA Biomarkers as Chemoresistance Regulators in Melanoma: A Protocol for Systematic Review and Meta-Analysis
Authors: Shaw Peter , Raymond Greg , Tzou Katherine S. , Baxi Siddhartha , Mani Ravishankar Ram , Kumar Govind Suresh , Chandramoorthy Harish C. , Sivanandy Palanisamy , Rajagopal Mogana , Samiappan Suja , Krishnan Sunil , Jayaraj Rama
Published: January 2022

Introduction: Melanoma is a global disease that is predominant in Western countries. However, reliable data resources and comprehensive studies on the theragnostic efficiency of miRNAs in melanoma are scarce. Hence, a decisive study or comprehensive review is required to collate the evidence for profiling miRNAs as a theragnostic marker. This protocol details a comprehensive systematic review and meta-analysis on the impact of miRNAs on chemoresistance and their association with theragnosis in melanoma. Methods and analysis: The articles will be retrieved from online bibliographic databases, including Cochrane Review, EMBASE, MEDLINE, PubMed, Scopus, Science Direct, and Web of Science, with different permutations of ‘keywords’. To obtain full-text papers of relevant research, a stated search method will be used, along with selection criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Protocols 2015 (PRISMA-P) standards were used to create this study protocol. The hazard ratio (HR) with a 95% confidence interval will be analyzed using Comprehensive Meta-Analysis (CMA) software 3.0. (CI). The pooled effect size will be calculated using a random or fixed-effects meta-analysis model. Cochran’s Q test and the I2 statistic will be used to determine heterogeneity. Egger’s bias indicator test, Orwin’s and the classic fail-safe N tests, the Begg and Mazumdar rank collection test, and Duval and Tweedie’s trim and fill calculation will all be used to determine publication bias. The overall standard deviation will be evaluated using Z-statistics. Subgroup analyses will be performed according to the melanoma participants’ clinicopathological and biological characteristics and methodological factors if sufficient studies and retrieved data are identified and available. The source of heterogeneity will be assessed using a meta-regression analysis. A pairwise matrix could be developed using either a pairwise correlation or expression associations of miRNA with patients’ survival for the same studies.
Role of Actionable Genes in Pursuing a True Approach of Precision Medicine in Monogenic Diabetes
Authors: Marucci Antonella , Rutigliano Irene , Fini Grazia , Pezzilli Serena , Menzaghi Claudia , Di Paola Rosa , Trischitta Vincenzo
Published: January 2022

Monogenic diabetes is a genetic disorder caused by one or more variations in a single gene. It encompasses a broad spectrum of heterogeneous conditions, including neonatal diabetes, maturity onset diabetes of the young (MODY) and syndromic diabetes, affecting 1–5% of patients with diabetes. Some of these variants are harbored by genes whose altered function can be tackled by specific actions (“actionable genes”). In suspected patients, molecular diagnosis allows the implementation of effective approaches of precision medicine so as to allow individual interventions aimed to prevent, mitigate or delay clinical outcomes. This review will almost exclusively concentrate on the clinical strategy that can be specifically pursued in carriers of mutations in “actionable genes”, including ABCC8, KCNJ11, GCK, HNF1A, HNF4A, HNF1B, PPARG, GATA4 and GATA6. For each of them we will provide a short background on what is known about gene function and dysfunction. Then, we will discuss how the identification of their mutations in individuals with this form of diabetes, can be used in daily clinical practice to implement specific monitoring and treatments. We hope this article will help clinical diabetologists carefully consider who of their patients deserves timely genetic testing for monogenic diabetes.
Thirteen Independent Genetic Loci Associated with Preserved Processing Speed in a Study of Cognitive Resilience in 330,097 Individuals in the UK Biobank
Authors: Fitzgerald Joan , Fahey Laura , Holleran Laurena , Ó Broin Pilib , Donohoe Gary , Morris Derek W.
Published: January 2022

Cognitive resilience is the ability to withstand the negative effects of stress on cognitive functioning and is important for maintaining quality of life while aging. The UK Biobank does not have measurements of the same cognitive phenotype at distal time points. Therefore, we used education years (EY) as a proxy phenotype for past cognitive performance and current cognitive performance was based on processing speed. This represented an average time span of 40 years between past and current cognitive performance in 330,097 individuals. A confounding factor was that EY is highly polygenic and masked the genetics of resilience. To overcome this, we employed Genomics Structural Equation Modelling (GenomicSEM) to perform a genome-wide association study (GWAS)-by-subtraction using two GWAS, one GWAS of EY and resilience and a second GWAS of EY but not resilience, to generate a GWAS of Resilience. Using independent discovery and replication samples, we found 13 independent genetic loci for Resilience. Functional analyses showed enrichment in several brain regions and specific cell types. Gene-set analyses implicated the biological process “neuron differentiation”, the cellular component “synaptic part” and the “WNT signalosome”. Mendelian randomisation analysis showed a causative effect of white matter volume on cognitive resilience. These results may contribute to the neurobiological understanding of resilience.