bluuebunny/crossref_metadata_2025 huggingface dataset:
Cadmium-Associated Molecular Signatures in Cancer Cell Models
Authors: Luparello Claudio
Published: June 2021

The exposure of cancer cells to cadmium and its compounds is often associated with the development of more malignant phenotypes, thereby contributing to the acceleration of tumor progression. It is known that cadmium is a transcriptional regulator that induces molecular reprogramming, and therefore the study of differentially expressed genes has enabled the identification and classification of molecular signatures inherent in human neoplastic cells upon cadmium exposure as useful biomarkers that are potentially transferable to clinical research. This review recapitulates selected studies that report the detection of cadmium-associated signatures in breast, gastric, colon, liver, lung, and nasopharyngeal tumor cell models, as specifically demonstrated by individual gene or whole genome expression profiling. Where available, the molecular, biochemical, and/or physiological aspects associated with the targeted gene activation or silencing in the discussed cell models are also outlined.
Toxicity, Response and Survival in Older Patients with Metastatic Melanoma Treated with Checkpoint Inhibitors
Authors: de Glas Nienke A. , Bastiaannet Esther , van den Bos Frederiek , Mooijaart Simon P. , van der Veldt Astrid A. M. , Suijkerbuijk Karlijn P. M. , Aarts Maureen J. B. , van den Berkmortel Franchette W. P. J. , Blank Christian U. , Boers-Sonderen Marye J. , van den Eertwegh Alfonsus J. M. , de Groot Jan-Willem B. , Haanen John B. A. G. , Hospers Geke A. P. , Jalving Hilde , Piersma Djura , van Rijn Rozemarijn S. , ten Tije Albert J. , Vreugdenhil Gerard , Wouters Michel W. J. M. , Portielje Johanneke E. A. , Kapiteijn Ellen W.
Published: June 2021

Background: Previous trials suggest no differences in immunotherapy treatment between older and younger patients, but mainly young patients with a good performance status were included. The aim of this study was to describe the treatment patterns and outcomes of “real-world” older patients with metastatic melanoma and to identify predictors of outcome. Methods: We included patients aged ≥65 years with metastatic melanoma from the Dutch Melanoma Treatment Registry. We described the reasons for hospital admissions and treatment discontinuation. Additionally, we assessed predictors of toxicity and response using logistic regression models and survival using Cox regression models. Results: We included 2216 patients. Grade ≥3 toxicity was not associated with age, comorbidities or WHO status. Patients aged ≥75 discontinued treatment due to toxicity more often, resulting in fewer treatment cycles. Response rates were similar to previous trials (40.3% and 43.6% in patients aged 65–75 and ≥75, respectively, for anti-PD1 treatment) and did not decrease with age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity. Conclusion: Response rates and toxicity outcomes of checkpoint inhibitors did not change with increasing age or comorbidity. However, the impact of grade I-II toxicity on quality of life deserves further study as older patients discontinue treatment more frequently.
Do Salivary Bypass Tubes Reduce the Risk of Pharyngocutaneous Fistula after Laryngopharyngectomy—A Systematic Review and Meta-Analysis
Authors: Marijić Blažen , Grasl Stefan , Grasl Matthaeus , Faisal Muhammad , Erovic Boban , Janik Stefan
Published: June 2021

To evaluate the effect of salivary bypass tube (SBT) usage on the occurrence of pharyngocutaneous fistula (PCF) in patients after a laryngopharyngectomy, a total of 20 studies, published between 1988 and 2021, were identified including 2946 patients. We performed a meta-analysis assessing the risk of PCF occurrence in patients after SBT application compared to those without. PCF occurred in 26.8% of cases (669/2496) and SBT was applied in 33.0% of patients (820/2483). There was an overall trend towards lower PCF rates when using SBTs (22.2% vs. 35.3%; p = 0.057). We further selected five studies, comprising 580 patients who underwent laryngopharyngectomies, for meta-analysis showing that application of SBT reduced the risk of PCF formation (OR 0.46; 95% CI 0.18–1.18; p = 0.11). The meta-analysis demonstrates a beneficial effect of SBT insertion on PCF formation in patients after laryngopharyngectomy.
Indications and Clinical Outcomes of Transoral Robotic Surgery and Free Flap Reconstruction
Authors: Gorphe Philippe , Temam Stéphane , Moya-Plana Antoine , Leymarie Nicolas , Kolb Frédéric , Bout-Roumazeilles Apolline , Qassemyar Quentin , Benmoussa Nadia , Honart Jean-François
Published: June 2021

We reviewed the indications, peroperative feasibility, and postoperative clinical outcomes of our first 50 consecutive patients who underwent free flap reconstruction after TORS for complex pharyngeal defects at our institution. We analyzed indications according to previous radiotherapy, the size of the resection, and the transoral exposure of critical structures. We reviewed surgical data, postoperative complications, and functional outcomes comprising tracheostomy and alimentation management. Indications were upfront surgery (34%), a second primary surgery after radiotherapy (28%), or salvage surgery after chemoradiotherapy failure (38%). Localizations were the tongue base (44%), tonsillar fossa (28%), pharyngeal wall (22%), and soft palate (6%). T-classifications were T1 (6%), T2 (52%), T3 (20%), and T4 (22%). The mean length of the surgery was 574 min. Two patients were intraoperatively converted to a conventional approach at the beginning of the learning curve. In conclusion, TORS and free flap reconstruction in complex situations were associated with low rates of postoperative complications and satisfactory functional outcomes. They were, however, associated with a renewed learning curve.
Two Complementarity Immunotherapeutics in Non-Small-Cell Lung Cancer Patients—Mechanism of Action and Future Concepts
Authors: Wojas-Krawczyk Kamila , Krawczyk Paweł , Gil Michał , Strzemski Maciej
Published: June 2021

Due to the limited effectiveness of immunotherapy used as first-line monotherapy in patients with non-small-cell lung cancer (NSCLC), the concepts of combining classical immunotherapy based on immune checkpoint antibodies with other treatment methods have been developed. Pembrolizumab and atezolizumab were registered in combination with chemotherapy for the treatment of metastatic NSCLC, while durvalumab found its application in consolidation therapy after successful chemoradiotherapy in patients with locally advanced NSCLC. Exceptionally attractive, due to their relatively low toxicity and high effectiveness, are treatment approaches in which a combination of two different immunotherapy methods is applied. This method is based on observations from clinical trials in which nivolumab and ipilimumab were used as first-line therapy for advanced NSCLC. It turned out that the dual blockade of immune checkpoints activated T lymphocytes in different compartments of the immune response, at the same time affecting the downregulation of immune suppressor cells (regulatory T cells). These experiments not only resulted in the registration of combination therapy with nivolumab and ipilimumab, but also initiated other clinical trials using immune checkpoint inhibitors (ICIs) in combination with other ICIs or activators of costimulatory molecules found on immune cells. There are also studies in which ICIs are associated with molecules that modify the tumour environment. This paper describes the mechanism of the synergistic effect of a combination of different immunotherapy methods in NSCLC patients.
Identification of Nucleolin as a Novel AEG-1-Interacting Protein in Breast Cancer via Interactome Profiling
Authors: Lee Seong-Jae , Choi Kyoung-Min , Bang Geul , Park Seo-Gyu , Kim Eun-Bi , Choi Jin-Woong , Chung Young-Ho , Kim Jinyoung , Lee Seok-Geun , Kim Eunjung , Kim Jae-Young
Published: June 2021

Breast cancer is one of the most common malignant diseases worldwide. Astrocyte elevated gene-1 (AEG-1) is upregulated in breast cancer and regulates breast cancer cell proliferation and invasion. However, the molecular mechanisms by which AEG-1 promotes breast cancer have yet to be fully elucidated. In order to delineate the function of AEG-1 in breast cancer development, we mapped the AEG-1 interactome via affinity purification followed by LC-MS/MS. We identified nucleolin (NCL) as a novel AEG-1 interacting protein, and co-immunoprecipitation experiments validated the interaction between AEG-1 and NCL in breast cancer cells. The silencing of NCL markedly reduced not only migration/invasion, but also the proliferation induced by the ectopic expression of AEG-1. Further, we found that the ectopic expression of AEG-1 induced the tyrosine phosphorylation of c-Met, and NCL knockdown markedly reduced this AEG-1 mediated phosphorylation. Taken together, our report identifies NCL as a novel mediator of the oncogenic function of AEG-1, and suggests that c-Met could be associated with the oncogenic function of the AEG-1-NCL complex in the context of breast cancer.
Elevated Expression of the RAGE Variant-V in SCLC Mitigates the Effect of Chemotherapeutic Drugs
Authors: Madhavan Bindhu K. , Han Zhe , Singh Bishal , Bordt Nico , Kaymak Serap , Bandapalli Obul Reddy , Kihm Lars , Shahzad Khurrum , Isermann Berend , Herzig Stephan , Nawroth Peter , Kumar Varun
Published: June 2021

Small cell lung carcinoma (SCLC) is a highly aggressive malignancy with a very high mortality rate. A prominent part of this is because these carcinomas are refractory to chemotherapies, such as etoposide or cisplatin, making effective treatment almost impossible. Here, we report that elevated expression of the RAGE variant-V in SCLC promotes homology-directed DNA DSBs repair when challenged with anti-cancer drugs. This variant exclusively localizes to the nucleus, interacts with members of the double-strand break (DSB) repair machinery and thus promotes the recruitment of DSBs repair factors at the site of damage. Increased expression of this variant thus, promotes timely DNA repair. Congruently, the tumor cells expressing high levels of variant-V can tolerate chemotherapeutic drug treatment better than the RAGE depleted cells. Our findings reveal a yet undisclosed role of the RAGE variant-V in the homology-directed DNA repair. This variant thus can be a potential target to be considered for future therapeutic approaches in advanced SSLC.
Molecular Classification to Prognosticate Response in Medically Managed Endometrial Cancers and Endometrial Intraepithelial Neoplasia
Authors: Puechl Allison M. , Spinosa Daniel , Berchuck Andrew , Secord Angeles Alvarez , Drury Kerry E. , Broadwater Gloria , Wong Janice , Whitaker Regina , Devos Nicolas , Corcoran David L. , Strickland Kyle C. , Previs Rebecca A.
Published: June 2021

Background: The aim of this study was to evaluate whether molecular classification prognosticates treatment response in women with endometrial cancers and endometrial intraepithelial neoplasia (EIN) treated with levonorgestrel intrauterine system (LNG-IUS). Methods: Patients treated with LNG-IUS for endometrial cancer or EIN from 2013 to 2018 were evaluated. Using immunohistochemistry and single gene sequencing of POLE, patients were classified into four groups as per the Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE): POLE-mutated, mismatch repair-deficient (MMRd), p53 wild type (p53wt), and p53-abnormal (p53abn). Groups were assessed relative to the primary outcome of progression or receipt of definitive treatment. Results: Fifty-eight subjects with endometrioid endometrial cancer or EIN treated with LNG-IUS were included. Of these, 22 subjects (37.9%) had endometrial cancer and 36 subjects (62.1%) had EIN. Per the ProMisE algorithm, 44 patients (75.9%) were classified as p53wt, 6 (10.3%) as MMRd, 4 (6.9%) as p53abn, and 4 (6.9%) as POLE-mutated. Of the 58 patients, 11 (19.0%) progressed or opted for definitive therapy. Median time to progression or definitive therapy was 7.5 months, with p53abn tumors having the shortest time to progression or definitive therapy. Conclusions: Molecular classification of endometrial cancer and EIN prior to management with LNG-IUS is feasible and may predict patients at risk of progression.
Identification of a Two-MicroRNA Signature in Plasma as a Novel Biomarker for Very Early Diagnosis of Breast Cancer
Authors: Adam-Artigues Anna , Garrido-Cano Iris , Carbonell-Asins Juan Antonio , Lameirinhas Ana , Simón Soraya , Ortega-Morillo Belén , Martínez María Teresa , Hernando Cristina , Constâncio Vera , Burgues Octavio , Bermejo Begoña , Henrique Rui , Lluch Ana , Jerónimo Carmen , Eroles Pilar , Cejalvo Juan Miguel
Published: June 2021

The early diagnosis of breast cancer is essential to improve patients’ survival rate. In this context, microRNAs have been described as potential diagnostic biomarkers for breast cancer. Particularly, circulating microRNAs have a strong value as non-invasive biomarkers. Herein, we assessed the potential of a microRNA signature based on miR-30b-5p and miR-99a-5p levels in plasma as a diagnostic biomarker for breast cancer. This two-microRNA signature was constructed by Principal Component Analysis and its prognostic value was assessed in a discovery cohort and blindly validated in a second cohort from an independent institution. ROC curve analysis and biomarker performance parameter evaluation demonstrated that our proposed signature presents a high value as a non-invasive biomarker for very early detection of breast cancer. In addition, pathway enrichment analysis identified three of the well-known pathways involved in cancer as targets of the two microRNAs.
Trends in Sustainable Synthesis of Organics by Gold Nanoparticles Embedded in Polymer Matrices
Authors: Buonerba Antonio , Grassi Alfonso
Published: June 2021

Gold nanoparticles (AuNPs) have emerged in recent decades as attractive and selective catalysts for sustainable organic synthesis. Nanostructured gold is indeed environmentally friendly and benign for human health; at the same time, it is active, under different morphologies, in a large variety of oxidation and reduction reactions of interest for the chemical industry. To stabilize the AuNPs and optimize the chemical environment of the catalytic sites, a wide library of natural and synthetic polymers has been proposed. This review describes the main routes for the preparation of AuNPs supported/embedded in synthetic organic polymers and compares the performances of these catalysts with those of the most popular AuNPs supported onto inorganic materials applied in hydrogenation and oxidation reactions. Some examples of cascade coupling reactions are also discussed where the polymer-supported AuNPs allow for the attainment of remarkable activity and selectivity.
The PINK1-Mediated Crosstalk between Neural Cells and the Underlying Link to Parkinson’s Disease
Authors: Leites Elvira Pequeno , Morais Vanessa Alexandra
Published: June 2021

Mitochondrial dysfunction has a fundamental role in the development of idiopathic and familiar forms of Parkinson’s disease (PD). The nuclear-encoded mitochondrial kinase PINK1, linked to familial PD, is responsible for diverse mechanisms of mitochondrial quality control, ATP production, mitochondrial-mediated apoptosis and neuroinflammation. The main pathological hallmark of PD is the loss of dopaminergic neurons. However, novel discoveries have brought forward the concept that a disruption in overall brain homeostasis may be the underlying cause of this neurodegeneration disease. To sustain this, astrocytes and microglia cells lacking PINK1 have revealed increased neuroinflammation and deficits in physiological roles, such as decreased wound healing capacity and ATP production, which clearly indicate involvement of these cells in the physiopathology of PD. PINK1 executes vital functions within mitochondrial regulation that have a detrimental impact on the development and progression of PD. Hence, in this review, we aim to broaden the horizon of PINK1-mediated phenotypes occurring in neurons, astrocytes and microglia and, ultimately, highlight the importance of the crosstalk between these neural cells that is crucial for brain homeostasis.
Targeting HDACs in Pancreatic Neuroendocrine Tumor Models
Authors: Schmitz Rosa Lynn , Weissbach Julia , Kleilein Jan , Bell Jessica , Hüttelmaier Stefan , Viol Fabrice , Clauditz Till , Grabowski Patricia , Laumen Helmut , Rosendahl Jonas , Michl Patrick , Schrader Jörg , Krug Sebastian
Published: June 2021

Compared to pancreatic adenocarcinoma (PDAC), pancreatic neuroendocrine tumors (PanNET) represent a rare and heterogeneous tumor entity. In addition to surgical resection, several therapeutic approaches, including biotherapy, targeted therapy or chemotherapy are applicable. However, primary or secondary resistance to current therapies is still challenging. Recent genome-wide sequencing efforts in PanNET identified a large number of mutations in pathways involved in epigenetic modulation, including acetylation. Therefore, targeting epigenetic modulators in neuroendocrine cells could represent a new therapeutic avenue. Detailed information on functional effects and affected signaling pathways upon epigenetic targeting in PanNETs, however, is missing. The primary human PanNET cells NT-3 and NT-18 as well as the murine insulinoma cell lines beta-TC-6 (mouse) and RIN-T3 (rat) were treated with the non-selective histone-deacetylase (HDAC) inhibitor panobinostat (PB) and analyzed for functional effects and affected signaling pathways by performing Western blot, FACS and qPCR analyses. Additionally, NanoString analysis of more than 500 potentially affected targets was performed. In vivo immunohistochemistry (IHC) analyses on tumor samples from xenografts and the transgenic neuroendocrine Rip1Tag2-mouse model were investigated. PB dose dependently induced cell cycle arrest and apoptosis in neuroendocrine cells in human and murine species. HDAC inhibition stimulated redifferentiation of human primary PanNET cells by increasing mRNA-expression of somatostatin receptors (SSTRs) and insulin production. In addition to hyperacetylation of known targets, PB mediated pleitropic effects via targeting genes involved in the cell cycle and modulation of the JAK2/STAT3 axis. The HDAC subtypes are expressed ubiquitously in the existing cell models and in human samples of metastatic PanNET. Our results uncover epigenetic HDAC modulation using PB as a promising new therapeutic avenue in PanNET, linking cell-cycle modulation and pathways such as JAK2/STAT3 to epigenetic targeting. Based on our data demonstrating a significant impact of HDAC inhibition in clinical relevant in vitro models, further validation in vivo is warranted.
Friend or Foe: Paradoxical Roles of Autophagy in Gliomagenesis
Authors: Batara Don Carlo Ramos , Choi Moon-Chang , Shin Hyeon-Uk , Kim Hyunggee , Kim Sung-Hak
Published: June 2021

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor in adults, with a poor median survival of approximately 15 months after diagnosis. Despite several decades of intensive research on its cancer biology, treatment for GBM remains a challenge. Autophagy, a fundamental homeostatic mechanism, is responsible for degrading and recycling damaged or defective cellular components. It plays a paradoxical role in GBM by either promoting or suppressing tumor growth depending on the cellular context. A thorough understanding of autophagy’s pleiotropic roles is needed to develop potential therapeutic strategies for GBM. In this paper, we discussed molecular mechanisms and biphasic functions of autophagy in gliomagenesis. We also provided a summary of treatments for GBM, emphasizing the importance of autophagy as a promising molecular target for treating GBM.
Towards Goals to Refine Prophylactic and Therapeutic Strategies Against COVID-19 Linked to Aging and Metabolic Syndrome
Authors: Shin Chong-Hyun , Kim Ki-Hye , Jeeva Subbiah , Kang Sang-Moo
Published: June 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gave rise to the coronavirus disease 2019 (COVID-19) pandemic. A strong correlation has been demonstrated between worse COVID-19 outcomes, aging, and metabolic syndrome (MetS), which is primarily derived from obesity-induced systemic chronic low-grade inflammation with numerous complications, including type 2 diabetes mellitus (T2DM). The majority of COVID-19 deaths occurs in people over the age of 65. Individuals with MetS are inclined to manifest adverse disease consequences and mortality from COVID-19. In this review, we examine the prevalence and molecular mechanisms underlying enhanced risk of COVID-19 in elderly people and individuals with MetS. Subsequently, we discuss current progresses in treating COVID-19, including the development of new COVID-19 vaccines and antivirals, towards goals to elaborate prophylactic and therapeutic treatment options in this vulnerable population.
ACE2-Independent Interaction of SARS-CoV-2 Spike Protein with Human Epithelial Cells Is Inhibited by Unfractionated Heparin
Authors: Partridge Lynda J. , Urwin Lucy , Nicklin Martin J. H. , James David C. , Green Luke R. , Monk Peter N.
Published: June 2021

Coronaviruses such as SARS-CoV-2, which is responsible for COVID-19, depend on virus spike protein binding to host cell receptors to cause infection. The SARS-CoV-2 spike protein binds primarily to ACE2 on target cells and is then processed by membrane proteases, including TMPRSS2, leading to viral internalisation or fusion with the plasma membrane. It has been suggested, however, that receptors other than ACE2 may be involved in virus binding. We have investigated the interactions of recombinant versions of the spike protein with human epithelial cell lines that express low/very low levels of ACE2 and TMPRSS2 in a proxy assay for interaction with host cells. A tagged form of the spike protein containing the S1 and S2 regions bound in a temperature-dependent manner to all cell lines, whereas the S1 region alone and the receptor-binding domain (RBD) interacted only weakly. Spike protein associated with cells independently of ACE2 and TMPRSS2, while RBD required the presence of high levels of ACE2 for interaction. As the spike protein has previously been shown to bind heparin, a soluble glycosaminoglycan, we tested the effects of various heparins on ACE2-independent spike protein interaction with cells. Unfractionated heparin inhibited spike protein interaction with an IC50 value of <0.05 U/mL, whereas two low-molecular-weight heparins were less effective. A mutant form of the spike protein, lacking the arginine-rich putative furin cleavage site, interacted only weakly with cells and had a lower affinity for unfractionated and low-molecular-weight heparin than the wild-type spike protein. This suggests that the furin cleavage site might also be a heparin-binding site and potentially important for interactions with host cells. The glycosaminoglycans heparan sulphate and dermatan sulphate, but not chondroitin sulphate, also inhibited the binding of spike protein, indicating that it might bind to one or both of these glycosaminoglycans on the surface of target cells.
Role of FGF15 in Hepatic Surgery in the Presence of Tumorigenesis: Dr. Jekyll or Mr. Hyde?
Authors: Caballeria-Casals Albert , Micó-Carnero Marc , Rojano-Alfonso Carlos , Maroto-Serrat Cristina , Casillas-Ramírez Araní , Álvarez-Mercado Ana I. , Gracia-Sancho Jordi , Peralta Carmen
Published: June 2021

The pro-tumorigenic activity of fibroblast growth factor (FGF) 19 (FGF15 in its rodent orthologue) in hepatocellular carcinoma (HCC), as well as the unsolved problem that ischemia-reperfusion (IR) injury supposes in liver surgeries, are well known. However, it has been shown that FGF15 administration protects against liver damage and regenerative failure in liver transplantation (LT) from brain-dead donors without tumor signals, providing a benefit in avoiding IR injury. The protection provided by FGF15/19 is due to its anti-apoptotic and pro-regenerative properties, which make this molecule a potentially beneficial or harmful factor, depending on the disease. In the present review, we describe the preclinical models currently available to understand the signaling pathways responsible for the apparent controversial effects of FGF15/19 in the liver (to repair a damaged liver or to promote tumorigenesis). As well, we study the potential pharmacological use that has the activation or inhibition of FGF15/19 pathways depending on the disease to be treated. We also discuss whether FGF15/19 non-pro-tumorigenic variants, which have been developed for the treatment of liver diseases, might be promising approaches in the surgery of hepatic resections and LT using healthy livers and livers from extended-criteria donors.
Growth Kinetics of the (110) Faces of Complex Potassium Cobalt–Nickel Sulphate K2CoxNi1−x(SO4)2·6H2O Crystals
Authors: Vorontsov Dmitry A. , Grebenev Vadim V. , Vasilyeva Natalia A. , Rudneva Elena B. , Manomenova Vera L. , Kim Ekaterina L. , Voloshin Alexey E.
Published: June 2021

The normal growth rate, the steepness of polygonized growth hillocks and the velocity of step movement on the (110) faces of potassium cobalt–nickel sulphate crystals in aqueous solutions with cobalt to nickel ratios of 1:1 and 1:2 were investigated as a function of supersaturation by the geometry of growth hillocks using laser interferometry. It was found that the morphologies of growth hillocks on the (110) faces of the crystals grown from 1:1 and 1:2 solutions are similar and that the growth hillocks are formed by multiple screw dislocation sources. The experimental data on the growth kinetics of the (110) faces of the crystals were analyzed by using the Burton–Cabrera–Frank theory. It was found that (1) there is a critical supersaturation for the growth of the (110) faces, and the value of this supersaturation in the 1:2 solution is higher than that in the 1:1 solution, and (2) the kinetic coefficient of the step movement in the sectors of growth hillocks is highly anisotropic, and the values of this coefficient are larger in 1:2 solution than in 1:1 solution. These results are discussed in the presented work.
Allele Surfing and Holocene Expansion of an Australian Fig (Ficus—Moraceae)
Authors: Wilde Brendan C. , Rutherford Susan , Yap Jia-Yee S. , Rossetto Maurizio
Published: June 2021

The creek sandpaper fig of southeastern Australia, Ficus coronata Spin, is culturally significant to Australian traditional owners who made use of the leaves to smooth timber and ate the fruit. The species is thought to have a long history on the continent, with some suggesting a Gondwanan origin. However, distributional patterns and overall ecology suggest a recent expansion across suitable habitats. We used landscape genomic techniques and environmental niche modelling to reconstruct its history and explore whether the species underwent a recent and rapid expansion along the east coast of New South Wales. Genomic analysis of 178 specimens collected from 32 populations throughout the species’ New South Wales distribution revealed a lack of genetic diversity and population structure. Some populations at the species’ southern and western range limits displayed unexpected diversity, which appears to be the result of allele surfing. Field work and genetic evidence suggest a Holocene expansion which may have increased since European colonisation. We also present a novel method for detecting allele surfing—MAHF (minor allele at highest frequency).
Turbid Coral Reefs: Past, Present and Future—A Review
Authors: Zweifler (Zvifler) Adi , O’Leary Michael , Morgan Kyle , Browne Nicola K.
Published: June 2021

Increasing evidence suggests that coral reefs exposed to elevated turbidity may be more resilient to climate change impacts and serve as an important conservation hotspot. However, logistical difficulties in studying turbid environments have led to poor representation of these reef types within the scientific literature, with studies using different methods and definitions to characterize turbid reefs. Here we review the geological origins and growth histories of turbid reefs from the Holocene (past), their current ecological and environmental states (present), and their potential responses and resilience to increasing local and global pressures (future). We classify turbid reefs using new descriptors based on their turbidity regime (persistent, fluctuating, transitional) and sources of sediment input (natural versus anthropogenic). Further, by comparing the composition, function and resilience of two of the most studied turbid reefs, Paluma Shoals Reef Complex, Australia (natural turbidity) and Singapore reefs (anthropogenic turbidity), we found them to be two distinct types of turbid reefs with different conservation status. As the geographic range of turbid reefs is expected to increase due to local and global stressors, improving our understanding of their responses to environmental change will be central to global coral reef conservation efforts.
The Cerebellum Is a Common Key for Visuospatial Execution and Attention in Parkinson’s Disease
Authors: Sako Wataru , Abe Takashi , Matsumoto Yuki , Nakamura Kazumi , Haji Shotaro , Osaki Yusuke , Harada Masafumi , Izumi Yuishin
Published: June 2021

Cognitive decline affects the clinical course in patients with Parkinson’s disease (PD) and contributes to a poor prognosis. However, little is known about the underlying network-level abnormalities associated with each cognitive domain. We aimed to identify the networks related to each cognitive domain in PD using resting-state functional magnetic resonance imaging (MRI). Forty patients with PD and 15 normal controls were enrolled. All subjects underwent MRI and the Mini-Mental State Examination. Furthermore, the cognitive function of patients with PD was assessed using the Montreal Cognitive Assessment (MoCA). We used independent component analysis of the resting-state functional MRI for functional segmentation, followed by reconstruction to identify each domain-related network, to predict scores in PD using multiple regression models. Six networks were identified, as follows: the visuospatial-executive-domain-related network (R2 = 0.54, p < 0.001), naming-domain-related network (R2 = 0.39, p < 0.001), attention-domain-related network (R2 = 0.86, p < 0.001), language-domain-related network (R2 = 0.64, p < 0.001), abstraction-related network (R2 = 0.10, p < 0.05), and orientation-domain-related network (R2 = 0.64, p < 0.001). Cerebellar lobule VII was involved in the visuospatial-executive-domain-related and attention-domain-related networks. These two domains are involved in the first three listed nonamnestic cognitive impairment in the diagnostic criteria for PD with dementia (PDD). Furthermore, Brodmann area 10 contributed most frequently to each domain-related network. Collectively, these findings suggest that cerebellar lobule VII may play a key role in cognitive impairment in nonamnestic types of PDD.
The Role of Cytology in the Diagnosis of Subcentimeter Thyroid Lesions
Authors: Fiorentino Vincenzo , Dell’ Aquila Marco , Musarra Teresa , Martini Maurizio , Capodimonti Sara , Fadda Guido , Curatolo Mariangela , Traini Emanuela , Raffaelli Marco , Lombardi Celestino Pio , Pontecorvi Alfredo , Larocca Luigi Maria , Pantanowitz Liron , Rossi Esther Diana
Published: June 2021

Thyroid nodules are common and typically detected by palpation and/or ultrasound (US). Guidelines have defined the management of large nodules, but controversy exists regarding nodules ≤ 1 cm. We evaluated a cohort of patients with subcentimeter nodules to determine their rate of malignancy (ROM). A total of 475 thyroid FNAs of lesions ≤ 1 cm with available follow-up were identified from January 2015–December 2019. For comparative analysis, we added a control series of 606 thyroid lesions larger than 1 cm from the same reference period. All aspirates were processed with liquid-based cytology and classified according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Subcentimeter nodules were stratified as 35 category I—non-diagnostic cases (ND; 7.3%), 144 category II—benign lesions (BL; 30.3%), 12 category III—atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS; 2.5%), 12 category IV—follicular neoplasm/suspicious for follicular neoplasm (FN/SFN; 2.5%), 124 category V—suspicious for malignancy (SM; 26.1%), and 148 category VI—positive for malignancy (PM; 31.1%). A total of 307 cases (64.6%) underwent subsequent surgery. Only one ND and three BLs had a malignant outcome. ROM for indeterminate lesions (III + IV) was 3.2%; with 1.6% for category III and 3.2% for category IV. ROM for the malignant categories (V + VI) was 88.2%. The control cohort of lesions demonstrated a higher number of benign histological diagnoses (67.3%). We documented that 57.2% of suspected subcentimeter lesions were malignant, with a minor proportion that belonged in indeterminate categories. There were very few ND samples, suggesting that aspirates of subcentimeter lesions yield satisfactory results. Suspected US features in subcentimeter lesions should be evaluated and followed by an interdisciplinary team for appropriate patient management.
The Effect of CAG Repeats within the Non-Pathological Range in the HTT Gene on Cognitive Functions in Patients with Subjective Cognitive Decline and Mild Cognitive Impairment
Authors: Bessi Valentina , Mazzeo Salvatore , Bagnoli Silvia , Giacomucci Giulia , Ingannato Assunta , Ferrari Camilla , Padiglioni Sonia , Franchi Virginia , Sorbi Sandro , Nacmias Benedetta
Published: June 2021

The Huntingtin gene (HTT) is within a class of genes containing a key region of CAG repeats. When expanded beyond 39 repeats, Huntington disease (HD) develops. Individuals with less than 35 repeats are not associated with HD. Increasing evidence has suggested that CAG repeats play a role in modulating brain development and brain function. However, very few studies have investigated the effect of CAG repeats in the non-pathological range on cognitive performances in non-demented individuals. In this study, we aimed to test how CAG repeats’ length influences neuropsychological scores in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). We included 75 patients (46 SCD and 29 MCI). All patients underwent an extensive neuropsychological battery and analysis of HTT alleles to quantify the number of CAG repeats. Results: CAG repeat number was positively correlated with scores of tests assessing for executive function, visual–spatial ability, and memory in SCD patients, while in MCI patients, it was inversely correlated with scores of visual–spatial ability and premorbid intelligence. When we performed a multiple regression analysis, we found that these relationships still remained, also when adjusting for possible confounding factors. Interestingly, logarithmic models better described the associations between CAG repeats and neuropsychological scores. CAG repeats in the HTT gene within the non-pathological range influenced neuropsychological performances depending on global cognitive status. The logarithmic model suggested that the positive effect of CAG repeats in SCD patients decreases as the number of repeats grows.
A Simple Parallel Chaotic Circuit Based on Memristor
Authors: Zhang Xiefu , Tian Zean , Li Jian , Cui Zhongwei
Published: June 2021

This paper reports a simple parallel chaotic circuit with only four circuit elements: a capacitor, an inductor, a thermistor, and a linear negative resistor. The proposed system was analyzed with MATLAB R2018 through some numerical methods, such as largest Lyapunov exponent spectrum (LLE), phase diagram, Poincaré map, dynamic map, and time-domain waveform. The results revealed 11 kinds of chaotic attractors, 4 kinds of periodic attractors, and some attractive characteristics (such as coexistence attractors and transient transition behaviors). In addition, spectral entropy and sample entropy are adopted to analyze the phenomenon of coexisting attractors. The theoretical analysis and numerical simulation demonstrate that the system has rich dynamic characteristics.
ATMP-CA: Optimising Mixed-Criticality Systems Considering Criticality Arithmetic
Authors: Fadlelseed Sajid , Kirner Raimund , Menon Catherine
Published: June 2021

Many safety-critical systems use criticality arithmetic, an informal practice of implementing a higher-criticality function by combining several lower-criticality redundant components or tasks. This lowers the cost of development, but existing mixed-criticality schedulers may act incorrectly as they lack the knowledge that the lower-criticality tasks are operating together to implement a single higher-criticality function. In this paper, we propose a solution to this problem by presenting a mixed-criticality mid-term scheduler that considers where criticality arithmetic is used in the system. As this scheduler, which we term ATMP-CA, is a mid-term scheduler, it changes the configuration of the system when needed based on the recent history of deadline misses. We present the results from a series of experiments that show that ATMP-CA’s operation provides a smoother degradation of service compared with reference schedulers that do not consider the use of criticality arithmetic.
Factors for the Automation of the Creation of Virtual Reality Experiences to Raise Awareness of Occupational Hazards on Construction Sites
Authors: Mora-Serrano Javier , Muñoz-La Rivera Felipe , Valero Ignacio
Published: June 2021

Two of the differential characteristics of the AECO sector (architecture, engineering, construction and operation) are barriers for the mass creation of training materials for its workers. On the one hand, the workplace is unique and changing over time; on the other, the aging trend of its workers and the unattractive nature of the industry for new generations of professionals. These two problems can be tackled by virtual reality technologies, which allow the agile creation of all kinds of scenarios, while their current technology may be attractive to young people and intuitive for everyone. This work shows the results of an investigation that seeks to provide automated tools based on virtual reality experiences to support learning in occupational risk prevention. This objective is part of the development of a culture for prevention, which allows the treatment of the human factor, with all its complexity and casuistry. The proposal includes the development of a process and tools that allow replicating the specific scenario where the work will be carried out, incorporating risks and probable incidents, systematically establishing cause-effect relationships, incorporating a narrative (storytelling) that provides emotional meaning to users and Lastly, the creation of a workflow that facilitates the agile development of these virtual reality experiences for each specific work.
Cross-Compiler Bipartite Vulnerability Search
Authors: Black Paul , Gondal Iqbal
Published: June 2021

Open-source libraries are widely used in software development, and the functions from these libraries may contain security vulnerabilities that can provide gateways for attackers. This paper provides a function similarity technique to identify vulnerable functions in compiled programs and proposes a new technique called Cross-Compiler Bipartite Vulnerability Search (CCBVS). CCBVS uses a novel training process, and bipartite matching to filter SVM model false positives to improve the quality of similar function identification. This research uses debug symbols in programs compiled from open-source software products to generate the ground truth. This automatic extraction of ground truth allows experimentation with a wide range of programs. The results presented in the paper show that an SVM model trained on a wide variety of programs compiled for Windows and Linux, x86 and Intel 64 architectures can be used to predict function similarity and that the use of bipartite matching substantially improves the function similarity matching performance.
Autonomous Haulage Systems in the Mining Industry: Cybersecurity, Communication and Safety Issues and Challenges
Authors: Gaber Tarek , El Jazouli Yassine , Eldesouky Esraa , Ali Ahmed
Published: June 2021

The current advancement of robotics, especially in Cyber-Physical Systems (CPS), leads to a prominent combination between the mining industry and connected-embedded technologies. This progress has arisen in the form of state-of-the-art automated giant vehicles with Autonomous Haulage Systems (AHS) that can transport ore without human intervention. Like CPS, AHS enable autonomous and/or remote control of physical systems (e.g., mining trucks). Thus, similar to CPS, AHS are also susceptible to cyber attacks such as Wi-Fi De-Auth and GPS attacks. With the use of the AHS, several mining activities have been strengthened due to increasing the efficiency of operations. Such activities require ensuring accurate data collection from which precise information about the state of the mine should be generated in a timely and consistent manner. Consequently, the presence of secure and reliable communications is crucial in making AHS mines safer, productive, and sustainable. This paper aims to identify and discuss the relation between safety of AHS in the mining environment and both cybersecurity and communication as well as highlighting their challenges and open issues. We survey the literature that addressed this aim and discuss its pros and cons and then highlight some open issues. We conclude that addressing cybersecurity issues of AHS can ensure the safety of operations in the mining environment as well as providing reliable communication, which will lead to better safety. Additionally, it was found that new communication technologies, such 5G and LTE, could be adopted in AHS-based systems for mining, but further research is needed to considered related cybersecurity issues and attacks.
Hygrothermal Analysis of a Museum Storage Room for Metal Cultural Artifacts: Quantification of Factors Influencing High Humidity
Authors: Ishikawa Kazuki , Iba Chiemi , Ogura Daisuke , Hokoi Shuichi , Yokoyama Misao
Published: June 2021

Several methods for appropriate control of the hygrothermal environment in museums to prevent the deterioration of cultural artifacts were presented in previous studies. However, few detailed hygrothermal simulation models have been used considering the hygrothermal performance of building components and airflow through gaps. Furthermore, hygrothermal properties of a type of storage facility with buffer spaces prevailing in Japan have not been quantitatively evaluated. The objectives of this study were to develop a detailed numerical model of a museum storage room with buffer spaces exhibiting high humidity during summer and to quantitatively evaluate the potential factors causing it; the inflow of humid outdoor air and indirect cooling caused by the air-conditioning system of a surrounding room. We analyzed the simulated temperature and humidity for various cases in which each influencing factor was suppressed. The humidity was reduced when the exhaust fan for the surrounding rooms was stopped or the windows were made airtight, but it hardly changed when the cooling ducts and the reinforced concrete beams were insulated. Thus, the high humidity in the room was attributed to the inflow of humid outdoor air accelerated by the ventilation of surrounding rooms. Although indirect cooling had a small impact on high humidity, its impact on energy loss could still be significant.
Evaluating Latency in Multiprocessing Embedded Systems for the Smart Grid
Authors: Alonso Sara , Lázaro Jesús , Jiménez Jaime , Bidarte Unai , Muguira Leire
Published: June 2021

Smart grid endpoints need to use two environments within a processing system (PS), one with a Linux-type operating system (OS) using the Arm Cortex-A53 cores for management tasks, and the other with a standalone execution or a real-time OS using the Arm Cortex-R5 cores. The Xen hypervisor and the OpenAMP framework allow this, but they may introduce a delay in the system, and some messages in the smart grid need a latency lower than 3 ms. In this paper, the Linux thread latencies are characterized by the Cyclictest tool. It is shown that when Xen hypervisor is used, this scenario is not suitable for the smart grid as it does not meet the 3 ms timing constraint. Then, standalone execution as the real-time part is evaluated, measuring the delay to handle an interrupt created in programmable logic (PL). The standalone application was run in A53 and R5 cores, with Xen hypervisor and OpenAMP framework. These scenarios all met the 3 ms constraint. The main contribution of the present work is the detailed characterization of each real-time execution, in order to facilitate selecting the most suitable one for each application.
Performance Evaluation of Photovoltaic Modules by Combined Damp Heat and Temperature Cycle Test
Authors: Park Hyeonwook , So Wonshoup , Kim Woo Kyoung
Published: June 2021

Standard damp heat (DH), temperature cycle (TC), and combined DH-TC tests were performed using monocrystalline Si 72-cell modules with a conventional ethylene vinyl acetate (EVA) encapsulant, and their module performance and electroluminescence images were investigated. During the DH test, a significant drop (~20%) in the maximum output power of the module was noticed, primarily because of the degradation of fill factor and an increase in series resistance at 5500 h of DH testing (DH5500), presumably due to the corrosion of metal electrodes by moisture ingress. Conversely, it was revealed that temperature cycling did not seriously degrade module performance until 1400 cycles. However, the combined DH5000-TC600 test suggested in this study, with a sequence of DH1000-TC200-DH1000-TC200-DH1000-TC200-DH2000, was confirmed to provide harsher conditions than the DH-only test by causing a 20% decrease in maximum output power (Pmax) after DH3000/TC400. Promisingly, we confirmed that the module with a polyolefin elastomer encapsulant showed better durability than the module with EVA even in the combined DH-TC test, showing a limited decrease in Pmax (~10%) even after the DH5500/TC600 test.
Deep Convolutional Feature-Based Probabilistic SVDD Method for Monitoring Incipient Faults of Batch Process
Authors: Wang Xiaohui , Wang Yanjiang , Deng Xiaogang , Zhang Zheng
Published: June 2021

Support vector data description (SVDD) has been widely applied to batch process fault detection. However, it often performs poorly, especially when incipient faults occur, because it only considers the shallow data feature and omits the probabilistic information of features. In order to provide better monitoring performance on incipient faults in batch processes, an improved SVDD method, called deep probabilistic SVDD (DPSVDD), is proposed in this work by integrating the convolutional autoencoder and the probability-related monitoring indices. For mining the hidden data features effectively, a deep convolutional features extraction network is designed by a convolutional autoencoder, where the encoder outputs and the reconstruction errors are used as the monitor features. Furthermore, the probability distribution changes of these features are evaluated by the Kullback-Leibler (KL) divergence so that the probability-related monitoring indices are developed for indicating the process status. The applications to the benchmark penicillin fermentation process demonstrate that the proposed method has a better monitoring performance on the incipient faults in comparison to the traditional SVDD methods.