bluuebunny/crossref_metadata_2025 huggingface dataset:
Zinc: Multidimensional Effects on Living Organisms
Authors: Cuajungco Math , Ramirez Maria , Tolmasky Marcelo
Published: February 2021

Zinc is a redox-inert trace element that is second only to iron in abundance in biological systems. In cells, zinc is typically buffered and bound to metalloproteins, but it may also exist in a labile or chelatable (free ion) form. Zinc plays a critical role in prokaryotes and eukaryotes, ranging from structural to catalytic to replication to demise. This review discusses the influential properties of zinc on various mechanisms of bacterial proliferation and synergistic action as an antimicrobial element. We also touch upon the significance of zinc among eukaryotic cells and how it may modulate their survival and death through its inhibitory or modulatory effect on certain receptors, enzymes, and signaling proteins. A brief discussion on zinc chelators is also presented, and chelating agents may be used with or against zinc to affect therapeutics against human diseases. Overall, the multidimensional effects of zinc in cells attest to the growing number of scientific research that reveal the consequential prominence of this remarkable transition metal in human health and disease.
Urinary Cyclophilin A as Marker of Tubular Cell Death and Kidney Injury
Authors: Cabello Ramio , Fontecha-Barriuso Miguel , Martin-Sanchez Diego , Lopez-Diaz Ana M. , Carrasco Susana , Mahillo Ignacio , Gonzalez-Enguita Carmen , Sanchez-Niño Maria D. , Ortiz Alberto , Sanz Ana B.
Published: February 2021

Background: Despite the term acute kidney injury (AKI), clinical biomarkers for AKI reflect function rather than injury and independent markers of injury are needed. Tubular cell death, including necroptotic cell death, is a key feature of AKI. Cyclophilin A (CypA) is an intracellular protein that has been reported to be released during necroptosis. We have now explored CypA as a potential marker for kidney injury in cultured tubular cells and in clinical settings of ischemia-reperfusion injury (IRI), characterized by limitations of current diagnostic criteria for AKI. Methods: CypA was analyzed in cultured human and murine proximal tubular epithelial cells exposed to chemical hypoxia, hypoxia/reoxygenation (H/R) or other cell death (apoptosis, necroptosis, ferroptosis) inducers. Urinary levels of CypA (uCypA) were analyzed in patients after nephron sparing surgery (NSS) in which the contralateral kidney is not disturbed and kidney grafts with initial function. Results: Intracellular CypA remained unchanged while supernatant CypA increased in parallel to cell death induction. uCypA levels were higher in NSS patients with renal artery clamping (that is, with NSS-IRI) than in no clamping (NSS-no IRI), and in kidney transplantation (KT) recipients (KT-IRI) even in the presence of preserved or improving kidney function, while this was not the case for urinary Neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, higher uCypA levels in NSS patients were associated with longer surgery duration and the incidence of AKI increased from 10% when using serum creatinine (sCr) or urinary output criteria to 36% when using high uCypA levels in NNS clamping patients. Conclusions: CypA is released by kidney tubular cells during different forms of cell death, and uCypA increased during IRI-induced clinical kidney injury independently from kidney function parameters. Thus, uCypA is a potential biomarker of kidney injury, which is independent from decreased kidney function.
The lncRNA 44s2 Study Applicability to the Design of 45-55 Exon Skipping Therapeutic Strategy for DMD
Authors: Gargaun Elena , Falcone Sestina , Solé Guilhem , Durigneux Julien , Urtizberea Andoni , Cuisset Jean Marie , Benkhelifa-Ziyyat Sofia , Julien Laura , Boland Anne , Sandron Florian , Meyer Vincent , Deleuze Jean François , Salgado David , Desvignes Jean-Pierre , Béroud Christophe , Chessel Anatole , Blesius Alexia , Krahn Martin , Levy Nicolas , Leturcq France , Pietri-Rouxel France
Published: February 2021

In skeletal muscle, long noncoding RNAs (lncRNAs) are involved in dystrophin protein stabilization but also in the regulation of myocytes proliferation and differentiation. Hence, they could represent promising therapeutic targets and/or biomarkers for Duchenne and Becker muscular dystrophy (DMD/BMD). DMD and BMD are X-linked myopathies characterized by a progressive muscular dystrophy with or without dilatative cardiomyopathy. Two-thirds of DMD gene mutations are represented by deletions, and 63% of patients carrying DMD deletions are eligible for 45 to 55 multi-exons skipping (MES), becoming BMD patients (BMDΔ45-55). We analyzed the genomic lncRNA presence in 38 BMDΔ45-55 patients and characterized the lncRNA localized in introns 44 and 55 of the DMD gene. We highlighted that all four lncRNA are differentially expressed during myogenesis in immortalized and primary human myoblasts. In addition, the lncRNA44s2 was pointed out as a possible accelerator of differentiation. Interestingly, lncRNA44s expression was associated with a favorable clinical phenotype. These findings suggest that lncRNA44s2 could be involved in muscle differentiation process and become a potential disease progression biomarker. Based on these results, we support MES45-55 therapy and propose that the design of the CRISPR/Cas9 MES45-55 assay consider the lncRNA sequences bordering the exonic 45 to 55 deletion.
Recent Advances in Nanotechnology-Based Diagnosis and Treatments of Human Osteosarcoma
Authors: Barani Mahmood , Mukhtar Mahwash , Rahdar Abbas , Sargazi Saman , Pandey Sadanand , Kang Misook
Published: February 2021

Osteosarcoma (OSA) is a type of bone cancer that begins in the cells that form bones. OSA is a rare mesenchymal bone neoplasm derived from mesenchymal stem cells. Genome disorganization, chromosomal modifications, deregulation of tumor suppressor genes, and DNA repair defects are the factors most responsible for OSA development. Despite significant advances in the diagnosing and treatment of OSA, patients’ overall survival has not improved within the last twenty years. Lately, advances in modern nanotechnology have spurred development in OSA management and offered several advantages to overcome the drawbacks of conventional therapies. This technology has allowed the practical design of nanoscale devices combined with numerous functional molecules, including tumor-specific ligands, antibodies, anti-cancer drugs, and imaging probes. Thanks to their small sizes, desirable drug encapsulation efficiency, and good bioavailability, functionalized nanomaterials have found wide-spread applications for combating OSA progression. This review invokes the possible utility of engineered nanomaterials in OSA diagnosis and treatment, motivating the researchers to seek new strategies for tackling the challenges associated with it.
Visual Cortex Transcranial Direct Current Stimulation for Proliferative Diabetic Retinopathy Patients: A Double-Blinded Randomized Exploratory Trial
Authors: de Venecia Angelito Braulio F. , Fresnoza Shane M.
Published: February 2021

Proliferative diabetic retinopathy (PDR) is a severe complication of diabetes. PDR-related retinal hemorrhages often lead to severe vision loss. The main goals of management are to prevent visual impairment progression and improve residual vision. We explored the potential of transcranial direct current stimulation (tDCS) to enhance residual vision. tDCS applied to the primary visual cortex (V1) may improve visual input processing from PDR patients’ retinas. Eleven PDR patients received cathodal tDCS stimulation of V1 (1 mA for 10 min), and another eleven patients received sham stimulation (1 mA for 30 s). Visual acuity (logarithm of the minimum angle of resolution (LogMAR) scores) and number acuity (reaction times (RTs) and accuracy rates (ARs)) were measured before and immediately after stimulation. The LogMAR scores and the RTs of patients who received cathodal tDCS decreased significantly after stimulation. Cathodal tDCS has no significant effect on ARs. There were no significant changes in the LogMAR scores, RTs, and ARs of PDR patients who received sham stimulation. The results are compatible with our proposal that neuronal noise aggravates impaired visual function in PDR. The therapeutic effect indicates the potential of tDCS as a safe and effective vision rehabilitation tool for PDR patients.
C—Journal of Carbon Research: 300th Publications Milestone
Authors: Banks Craig E. , Abot Jandro L.
Published: February 2021

The C—Journal of Carbon Research (ISSN 2311-5629) is quite pleased to announce the publication of its 300th article [...]
Control of Cell Growth and Proliferation by the Tribbles Pseudokinase: Lessons from Drosophila
Authors: Dobens Leonard L. , Nauman Christopher , Fischer Zachary , Yao Xiaolan
Published: February 2021

The Tribbles (Trib) family of pseudokinase proteins regulate cell growth, proliferation, and differentiation during normal development and in response to environmental stress. Mutations in human Trib isoforms (Trib1, 2, and 3) have been associated with metabolic disease and linked to leukemia and the formation of solid tumors, including melanomas, hepatomas, and lung cancers. Drosophila Tribbles (Trbl) was the first identified member of this sub-family of pseudokinases and shares a conserved structure and similar functions to bind and direct the degradation of key mediators of cell growth and proliferation. Common Trib targets include Akt kinase (also known as protein kinase B), C/EBP (CAAT/enhancer binding protein) transcription factors, and Cdc25 phosphatases, leading to the notion that Trib family members stand athwart multiple pathways modulating their growth-promoting activities. Recent work using the Drosophila model has provided important insights into novel facets of conserved Tribbles functions in stem cell quiescence, tissue regeneration, metabolism connected to insulin signaling, and tumor formation linked to the Hippo signaling pathway. Here we highlight some of these recent studies and discuss their implications for understanding the complex roles Tribs play in cancers and disease pathologies.
Antitumor Activity of Protons and Molecular Hydrogen: Underlying Mechanisms
Authors: Rochette Luc , Zeller Marianne , Cottin Yves , Vergely Catherine
Published: February 2021

Understanding the structure and dynamics of the various hydrogen forms has been a subject of numerous studies. Protons (H+) and molecular hydrogen (H2) in the cell are critical in a wide variety of processes. A new cancer treatment uses H2, a biologically inactive gas. Due to its small molecular weight, H2 can rapidly penetrate cell membranes and reach subcellular components to protect nuclear DNA and mitochondria. H2 reduces oxidative stress, exerts anti-inflammatory effects, and acts as a modulator of apoptosis. Exogenous H2, administered by inhalation, drinking H2-rich water, or injecting H2-rich saline solution, is a protective therapy that can be used in multiple diseases, including cancer. In particle therapy, cyclotrons and synchrotrons are the accelerators currently used to produce protons. Proton beam radiotherapy (PBT) offers great promise for the treatment of a wide variety of cancers due to the sharp decrease in the dose of radiation at a defined point. In these conditions, H2 and different types of H2 donors may represent a novel therapeutic strategy in cancer treatment.
Another One Bites the Gut: Nuclear Receptor LRH-1 in Intestinal Regeneration and Cancer
Authors: Zerlotin Roberta , Arconzo Maria , Piccinin Elena , Moschetta Antonio
Published: February 2021

The process of self-renewal in normal intestinal epithelium is characterized by a fine balance between proliferation, differentiation, migration, and cell death. When even one of these aspects escapes the normal control, cellular proliferation and differentiation are impaired, with consequent onset of tumorigenesis. In humans, colorectal cancer (CRC) is the main pathological manifestation of this derangement. Nowadays, CRC is the world’s fourth most deadly cancer with a limited survival after treatment. Several conditions can predispose to CRC development, including dietary habits and pre-existing inflammatory bowel diseases. Given their extraordinary ability to interact with DNA, it is widely known that nuclear receptors play a key role in the regulation of intestinal epithelium, orchestrating the expression of a series of genes involved in developmental and homeostatic pathways. In particular, the nuclear receptor Liver Receptor Homolog-1 (LRH-1), highly expressed in the stem cells localized in the crypts, promotes intestine cell proliferation and renewal in both direct and indirect DNA-binding manner. Furthermore, LRH-1 is extensively correlated with diverse intestinal inflammatory pathways. These evidence shed a light in the dynamic intestinal microenvironment in which increased regenerative epithelial cell turnover, mutagenic insults, and chronic DNA damages triggered by factors within an inflammatory cell-rich microenvironment act synergistically to favor cancer onset and progression.
Neoadjuvant Endocrine Therapy in Breast Cancer Management: State of the Art
Authors: Lerebours Florence , Cabel Luc , Pierga Jean-Yves
Published: February 2021

Endocrine therapy is the mainstay of treatment in HR+/HER2- breast cancers, which represent about 70% of all breast cancers. Neoadjuvant therapy has been developed since the 1990s to address several issues, including breast-conserving surgery (BCS) and improvement of survival rates. For a long time, neoadjuvant endocrine therapy (NET) was confined to frail patients in order to improve surgery outcome. Since the 2000s, NET now plays a central role as a research tool for predictive endocrine sensitivity biomarkers and targeted therapies. One of the major issues in early HR+/HER2- breast cancer is to identify patients in whom chemotherapy can be safely withheld. In vivo assessment of response to NET might be the best treatment strategy to address this issue.
Novel Gene Signatures Predictive of Patient Recurrence-Free Survival and Castration Resistance in Prostate Cancer
Authors: A Jun , Zhang Baotong , Zhang Zhiqian , Hu Hailiang , Dong Jin-Tang
Published: February 2021

Molecular signatures predictive of recurrence-free survival (RFS) and castration resistance are critical for treatment decision-making in prostate cancer (PCa), but the robustness of current signatures is limited. Here, we applied the Robust Rank Aggregation (RRA) method to PCa transcriptome profiles and identified 287 genes differentially expressed between localized castration-resistant PCa (CRPC) and hormone-sensitive PCa (HSPC). Least absolute shrinkage and selection operator (LASSO) and stepwise Cox regression analyses of the 287 genes developed a 6-gene signature predictive of RFS in PCa. This signature included NPEPL1, VWF, LMO7, ALDH2, NUAK1, and TPT1, and was named CRPC-derived prognosis signature (CRPCPS). Interestingly, three of these 6 genes constituted another signature capable of distinguishing CRPC from HSPC. The CRPCPS predicted RFS in 5/9 cohorts in the multivariate analysis and remained valid in patients stratified by tumor stage, Gleason score, and lymph node status. The signature also predicted overall survival and metastasis-free survival. The signature’s robustness was demonstrated by the C-index (0.55–0.74) and the calibration plot in all nine cohorts and the 3-, 5-, and 8-year area under the receiver operating characteristic curve (0.67–0.77) in three cohorts. The nomogram analyses demonstrated CRPCPS’ clinical applicability. The CRPCPS thus appears useful for RFS prediction in PCa.
Detection of Tumor-Associated Membrane Receptors on Extracellular Vesicles from Non-Small Cell Lung Cancer Patients via Immuno-PCR
Authors: Stiller Christiane , Viktorsson Kristina , Paz Gomero Elizabeth , Hååg Petra , Arapi Vasiliki , Kaminskyy Vitaliy O. , Kamali Caroline , De Petris Luigi , Ekman Simon , Lewensohn Rolf , Karlström Amelie Eriksson
Published: February 2021

Precision cancer medicine for non-small-cell lung cancer (NSCLC) has increased patient survival. Nevertheless, targeted agents towards tumor-associated membrane receptors only result in partial remission for a limited time, calling for approaches which allow longitudinal treatment monitoring. Rebiopsy of tumors in the lung is challenging, and metastatic lesions may have heterogeneous signaling. One way ahead is to use liquid biopsies such as circulating tumor DNA or small extracellular vesicles (sEVs) secreted by the tumor into blood or other body fluids. Herein, an immuno-PCR-based detection of the tumor-associated membrane receptors EGFR, HER2, and IGF-1R on CD9-positive sEVs from NSCLC cells and pleural effusion fluid (PE) of NSCLC patients is developed utilizing DNA conjugates of antibody mimetics and affibodies, as detection agents. Results on sEVs purified from culture media of NSCLC cells treated with anti-EGFR siRNA, showed that the reduction of EGFR expression can be detected via immuno-PCR. Protein profiling of sEVs from NSCLC patient PE samples revealed the capacity to monitor EGFR, HER2, and IGF-1R with the immuno-PCR method. We detected a significantly higher EGFR level in sEVs derived from a PE sample of a patient with an EGFR-driven NSCLC adenocarcinoma than in sEVs from PE samples of non-EGFR driven adenocarcinoma patients or in samples from patients with benign lung disease. In summary, we have developed a diagnostic method for sEVs in liquid biopsies of cancer patients which may be used for longitudinal treatment monitoring to detect emerging bypassing resistance mechanisms in a noninvasive way.
A Computational Method to Predict Effects of Residue Mutations on the Catalytic Efficiency of Hydrolases
Authors: Li Yun , Song Kun , Zhang Jian , Lu Shaoyong
Published: February 2021

With scientific and technological advances, growing research has focused on engineering enzymes that acquire enhanced efficiency and activity. Thereinto, computer-based enzyme modification makes up for the time-consuming and labor-intensive experimental methods and plays a significant role. In this study, for the first time, we collected and manually curated a data set for hydrolases mutation, including structural information of enzyme-substrate complexes, mutated sites and Kcat/Km obtained from vitro assay. We further constructed a classification model using the random forest algorithm to predict the effects of residue mutations on catalytic efficiency (increase or decrease) of hydrolases. This method has achieved impressive performance on a blind test set with the area under the receiver operating characteristic curve of 0.86 and the Matthews Correlation Coefficient of 0.659. Our results demonstrate that computational mutagenesis has an instructive effect on enzyme modification, which may expedite the design of engineering hydrolases.
The Pleiotropic Function of Human Sirtuins as Modulators of Metabolic Pathways and Viral Infections
Authors: Alqarni Mohammed Hamed , Foudah Ahmed Ibrahim , Muharram Magdy Mohamed , Labrou Nikolaos E.
Published: February 2021

Sirtuins (SIRTs) are nicotinamide adenine dinucleotide-dependent histone deacetylases that incorporate complex functions in the mechanisms of cell physiology. Mammals have seven distinct members of the SIRT family (SIRT1-7), which play an important role in a well-maintained network of metabolic pathways that control and adapt the cell to the environment, energy availability and cellular stress. Until recently, very few studies investigated the role of SIRTs in modulating viral infection and progeny. Recent studies have demonstrated that SIRT1 and SIRT2 are promising antiviral targets because of their specific connection to numerous metabolic and regulatory processes affected during infection. In the present review, we summarize some of the recent progress in SIRTs biochemistry and their emerging function as antiviral targets. We also discuss the potential of natural polyphenol-based SIRT modulators to control their functional roles in several diseases including viral infections.
DNA or Protein Methylation-Dependent Regulation of Activator Protein-1 Function
Authors: Kim Eunji , Ahuja Akash , Kim Mi-Yeon , Cho Jae Youl
Published: February 2021

Epigenetic regulation and modification govern the transcriptional mechanisms that promote disease initiation and progression, but can also control the oncogenic processes, cell signaling networks, immunogenicity, and immune cells involved in anti-inflammatory and anti-tumor responses. The study of epigenetic mechanisms could have important implications for the development of potential anti-inflammatory treatments and anti-cancer immunotherapies. In this review, we have described the key role of epigenetic progression: DNA methylation, histone methylation or modification, and protein methylation, with an emphasis on the activator protein-1 (AP-1) signaling pathway. Transcription factor AP-1 regulates multiple genes and is involved in diverse cellular processes, including survival, differentiation, apoptosis, and development. Here, the AP-1 regulatory mechanism by DNA, histone, or protein methylation was also reviewed. Various methyltransferases activate or suppress AP-1 activities in diverse ways. We summarize the current studies on epigenetic alterations, which regulate AP-1 signaling during inflammation, cancer, and autoimmune diseases, and discuss the epigenetic mechanisms involved in the regulation of AP-1 signaling.
Utilisation of Chick Embryo Chorioallantoic Membrane as a Model Platform for Imaging-Navigated Biomedical Research
Authors: Chen Lei , Wang Shuncong , Feng Yuanbo , Zhang Jinyong , Du Yuqing , Zhang Jiang , Ongeval Chantal Van , Ni Yicheng , Li Yue
Published: February 2021

The fertilised chick egg and particularly its chorioallantoic membrane (CAM) have drawn continuing interest in biomedicine and bioengineering fields, especially for research on vascular study, cancer, drug screening and development, cell factors, stem cells, etc. This literature review systemically introduces the CAM’s structural evolution, functions, vascular features and the circulation system, and cell regulatory factors. It also presents the major and updated applications of the CAM in assays for pharmacokinetics and biodistribution, drug efficacy and toxicology testing/screening in preclinical pharmacological research. The time course of CAM applications for different assays and their advantages and limitations are summarised. Among these applications, two aspects are emphasised: (1) potential utility of the CAM for preclinical studies on vascular-disrupting agents (VDAs), promising for anti-cancer vascular-targeted therapy, and (2) modern imaging technologies, including modalities and their applications for real-time visualisation, monitoring and evaluation of the changes in CAM vasculature as well as the interactions occurring after introducing the tested medical, pharmaceutical and biological agents into the system. The aim of this article is to help those working in the biomedical field to familiarise themselves with the chick embryo CAM as an alternative platform and to utilise it to design and optimise experimental settings for their specific research topics.
Compartmentalized Signaling in Aging and Neurodegeneration
Authors: Di Benedetto Giulietta , Iannucci Liliana F. , Surdo Nicoletta C. , Zanin Sofia , Conca Filippo , Grisan Francesca , Gerbino Andrea , Lefkimmiatis Konstantinos
Published: February 2021

The cyclic AMP (cAMP) signalling cascade is necessary for cell homeostasis and plays important roles in many processes. This is particularly relevant during ageing and age-related diseases, where drastic changes, generally decreases, in cAMP levels have been associated with the progressive decline in overall cell function and, eventually, the loss of cellular integrity. The functional relevance of reduced cAMP is clearly supported by the finding that increases in cAMP levels can reverse some of the effects of ageing. Nevertheless, despite these observations, the molecular mechanisms underlying the dysregulation of cAMP signalling in ageing are not well understood. Compartmentalization is widely accepted as the modality through which cAMP achieves its functional specificity; therefore, it is important to understand whether and how this mechanism is affected during ageing and to define which is its contribution to this process. Several animal models demonstrate the importance of specific cAMP signalling components in ageing, however, how age-related changes in each of these elements affect the compartmentalization of the cAMP pathway is largely unknown. In this review, we explore the connection of single components of the cAMP signalling cascade to ageing and age-related diseases whilst elaborating the literature in the context of cAMP signalling compartmentalization.
Children’s Views and Experiences of Treatment Adherence and Parent/Child Co-Management in Eczema: A Qualitative Study
Authors: Teasdale Emma , Sivyer Katy , Muller Ingrid , Ghio Daniela , Roberts Amanda , Lawton Sandra , Santer Miriam
Published: February 2021

Eczema affects one in five children and can have a substantial impact on quality of life. This qualitative study aimed to explore children’s views and experiences of eczema and what may affect treatment adherence from their perspective. We conducted semi-structured, face-to-face interviews with children with eczema aged 6–12 years from March to July 2018. Interviews were transcribed verbatim and analysed using inductive thematic analysis. We found that children do not typically view eczema as a long-term condition, and topical treatments (predominately emollients) were seen to provide effective symptom relief. Uncertainty around co-managing at home was expressed as children typically felt that parental reminders and assistance with applying different types of topical treatments were still needed. For some children, eczema can be difficult to manage at school due to a lack of convenient access and appropriate spaces to apply creams and psychosocial consequences such as attracting unwanted attention from peers and feeling self-conscious. Treatment adherence could be supported by reinforcing that eczema is a long-term episodic condition, providing clear information about regular emollient use, practical advice such as setting reminders to support co-management at home, and working with schools to facilitate topical treatment use when necessary.
Behavioral Inhibition in Childhood: European Portuguese Adaptation of an Observational Measure (Lab-TAB)
Authors: Faísca Luís , Ferreira Laura I. , Fernandes Catarina C. , Gagne Jeffrey R. , Martins Ana T.
Published: February 2021

The assessment of behaviorally inhibited children is typically based on parent or teacher reports, but this approach has received criticisms, mainly for being prone to bias. Several researchers proposed the additional use of observational methods because they provide a direct and more objective description of the child's functioning in different contexts. The lack of a laboratory assessment of temperament for Portuguese children justifies the adaptation of some episodes of the Laboratory Temperament Assessment Battery (Lab-TAB) as an observational measure for behavioral inhibition. Method: In our study, we included 124 children aged between 3 and 9 years and their parents. The evaluation of child behavioral inhibition was made by parent report (Behavioral Inhibition Questionnaire) and through Lab-TAB episodes. Parental variables with potential influence on parents’ reports were also collected using the Social Interaction and Performance Anxiety and Avoidance Scale (SIPAAS) and the Parental Overprotection Measure (POM). Results and Discussion: The psychometric analyses provided evidence that Lab-TAB is a reliable instrument and can be incorporated in a multi-method approach to assess behavioral inhibition in studies involving Portuguese-speaking children. Moderate convergence between observational and parent report measures of behavioral inhibition was obtained. Mothers’ characteristics, as well as child age, seem to significantly affect differences between measures, being potential sources of bias in the assessment of child temperament.
Sleep and the General Behavior of Infants and Parents during the Closure of Schools as a Result of the COVID-19 Pandemic: Comparison with 2019 Data
Authors: Shinomiya Yasuaki , Yoshizaki Arika , Murata Emi , Fujisawa Takashi , Taniike Masako , Mohri Ikuko
Published: February 2021

This study compared cross-sectional data from online surveys describing the sleep behavior of infants and caregivers in March 2020 (the school closure period during the early stages of the COVID-19 pandemic; n = 295, 23.8 ± 3.8 months old) and March 2019 (before the pandemic; n = 2017, 24.2 ± 3.8 months old). In comparing those two points in time, no significant differences were found in wake-up times (2019: 7:19 ± 0:46 am vs. 2020: 7:18 ± 0:47 am, p = 0.289), bedtimes (21:01 ± 0:48 pm vs. 21:04 ± 0:53 pm, p = 0.144), or nocturnal sleep times (593.7 ± 43.9 min vs. 588.1 ± 50.3 min, p = 0.613). Regarding the caregivers, in 2020, wake-up times (2019: 6:46 ± 0:50 am vs. 2020: 6:39 ± 0:50 am, p = 0.017) and bedtimes (22:53 ± 1:17 pm vs. 22:42 ± 1:04 pm, p = 0.016) became significantly earlier compared to 2019. Among infants staying at home, total sleep time and percentage of outdoor play decreased significantly, and media use increased significantly in 2020. Lower levels of exercise and more frequent media viewing may have caused prolonged sleep latency in these children. The percentage of caregivers responding with “negative childcare feelings” was significantly higher in the group with less than three nursery school attendance days. Caregivers and infants staying at home are a high-risk group during the pandemic.
Physical, Optical, and Visual Performance of Coated Cross-Laminated Timber during Natural and Artificial Weathering
Authors: Bobadilha Gabrielly dos Santos , Stokes C. Elizabeth , Ohno Katie M. , Kirker Grant , Lopes Dercilio Junior Verly , Nejad Mojgan
Published: February 2021

Cross-laminated timber (CLT) market demand is on the rise in the United States. Adequate protective measures have not been extensively studied. The objective of this study was to investigate the weathering performance of exterior wood coatings. We evaluated coated CLT sample surfaces based on visual appearance, color change (CIE*L*a*b), gloss changes, and water intrusion. From the five exterior wood coatings evaluated, only two showed adequate performance after twelve months field exposure. Based on visual ratings following the ASTM procedures, coating failure occurs more quickly in Mississippi than in Wisconsin, due to its greater decay zone. Both location and coating type impacted the aging of the samples. Artificial weathering results were consistent with natural weathering indicating the two adequate coatings were the most resistant to failure, color, and gloss change. For future studies, new coatings designed for the protection of end-grain in CLT panels should be a target of research and development.
Modified ALNS Algorithm for a Processing Application of Family Tourist Route Planning: A Case Study of Buriram in Thailand
Authors: Khamsing Narisara , Chindaprasert Kantimarn , Pitakaso Rapeepan , Sirirak Worapot , Theeraviriya Chalermchat
Published: February 2021

This research presents a solution to the family tourism route problem by considering daily time windows. To find the best solution for travel routing, the modified adaptive large neighborhood search (MALNS) method, using the four destructions and the four reconstructions approach, is applied here. The solution finding performance of the MALNS method is compared with an exact method running on the Lingo program. As shown by various solutions, the MALNS method can balance travel routing designs, including when many tourist attractions are present in each path. Furthermore, the results of the MALNS method are not significantly different from the results of the exact method for small problem sizes. For medium and large problem sizes, the MALNS method shows a higher performance and a smaller processing time for finding solutions. The values for the average total travel cost and average travel satisfaction rating derived by the MALNS method are approximately 0.18% for a medium problem and 0.05% for a large problem, 0.24% for a medium problem, and 0.21% for a large problem, respectively. The values derived from the exact method are slightly different. Moreover, the MALNS method calculation requires less processing time than the exact method, amounting to approximately 99.95% of the time required for the exact method. In this case study, the MALNS algorithm result shows a suitable balance of satisfaction and number of tourism places in relation to the differences between family members of different ages and genders in terms of satisfaction in tour route planning. The proposed solution methodology presents an effective high-quality solution, suggesting that the MALNS method has the potential to be a great competitive algorithm. According to the empirical results shown here, the MALNS method would be useful for creating route plans for tourism organizations that support travel route selection for family tours in Thailand.
Bis (Diamines) Cu and Zn Complexes of Flurbiprofen as Potential Cholinesterase Inhibitors: In Vitro Studies and Docking Simulations
Authors: Jamil Muhammad , Sultana Nargis , Ashraf Rizwan , Bashir Maryam , Rehman Muhammad Fayyaz ur , Kanwal Fariha , Ellahi Humna , Lu Changrui , Zhang Wei Xing , Tariq Muhammad Ilyas
Published: February 2021

Alzheimer’s disease (AD) causes dementia and continuous damage to brain cells. Cholinesterase inhibitors can alleviate the condition by increasing communication between the nerve cells and reducing the risk of dementia. In an effort to treat Alzheimer’s disease, we synthesized flurbiprofen-based diamines (1,2 diaminoethane and 1,3 diaminopropane) Zn(II), Cu(II) metal complexes and characterized them by single-crystal X-ray analysis, NMR, (FT)-IR, UV-Vis, magnetic susceptibility, elemental analysis and conductivities measurements. Synthesized diamine metal complexes appeared in ionic forms and have distorted octahedral geometry based on conductivity studies, magnetic susceptibility and electronic studies. Single crystal X-ray diffraction analysis confirmed (2b) Cu(H2O)2(L1)2(L2)2 complex formation. Moreover, we tested all synthesized metal complexes against the cholinesterase enzyme that showed higher inhibition potential. In general, copper metal complexes showed higher inhibitory activities than simple metal complexes with flurbiprofen. These synthesized metal complexes may derive more effective and safe inhibitors for cholinesterases.
Alternative Development Strategies of Clinostomum chabaudi (Digenea) Metacercariae in Frog Hosts (Hyperolius spp.)
Authors: Sinsch Ulrich , Dehling J. Maximilian , Scheid Patrick , Balczun Carsten
Published: February 2021

Clinostomum metacercariae are common endoparasites of fish and frogs. In this study, we examine taxonomic identity and developmental strategy of Clinostomum metacercariae infesting reed frogs Hyperolius kivuensis and H. viridiflavus in Rwanda. Moreover, we evaluate the impact of infestation on demographic and morphological life-history traits of the hosts. Morphological and molecular features, particularly genital morphology and COX1 sequences, provided evidence that the metacercariae belong to C. chabaudi Vercammen-Grandjean, 1960. Depending on the host’s defensive behavior and the availability of resources, metacercariae develop either as sedentary “yellow grubs” encysted in the lymphatic sacs or mouth of the host or as initially encysted, but later free-ranging individuals invading the host´s body cavity. Nutrition on lymphatic fluid within the cyst leads to yellow-colored gut content, feeding on blood or host tissue, to brownish green gut content in free-ranging individuals. Almost all metacercariae opted for the first developmental strategy in H. kivuensis, whereas the second strategy dominated in metacercariae infesting H. viridiflavus. Hyperolius kivuensis suffered significant morphological modifications, when infested with encysted metacercariae. Both developmental modes permitted a coexistence with the host of less than one year. We hypothesize that the presence of alternative development modes is an adaptation of C. chabaudi to cope with resource limitation within host-produced cysts.
Ecology of Predation and Scavenging and the Interface: A Special Issue
Authors: Moleón Marcos
Published: February 2021

Predation and scavenging are pervasive ecological interactions in both terrestrial and aquatic environments [...]
Assessment of PSIM (Prostatic Systemic Inflammatory Markers) Score in Predicting Pathologic Features at Robotic Radical Prostatectomy in Patients with Low-Risk Prostate Cancer Who Met the Inclusion Criteria for Active Surveillance
Authors: Ferro Matteo , Musi Gennaro , Matei Deliu Victor , Mistretta Alessandro Francesco , Luzzago Stefano , Cozzi Gabriele , Bianchi Roberto , Di Trapani Ettore , Cioffi Antonio , Lucarelli Giuseppe , Busetto Gian Maria , Del Giudice Francesco , Russo Giorgio Ivan , Di Mauro Marina , Porreca Angelo , Renne Giuseppe , Catellani Michele , Bottero Danilo , Brescia Antonio , Cordima Giovanni , de Cobelli Ottavio
Published: February 2021

Background: circulating levels of lymphocytes, platelets and neutrophils have been identified as factors related to unfavorable clinical outcome for many solid tumors. The aim of this cohort study is to evaluate and validate the use of the Prostatic Systemic Inflammatory Markers (PSIM) score in predicting and improving the detection of clinically significant prostate cancer (csPCa) in men undergoing robotic radical prostatectomy for low-risk prostate cancer who met the inclusion criteria for active surveillance. Methods: we reviewed the medical records of 260 patients who fulfilled the inclusion criteria for active surveillance. We performed a head-to-head comparison between the histological findings of specimens after radical prostatectomy (RP) and prostate biopsies. The PSIM score was calculated on the basis of positivity according to cutoffs (neutrophil-to-lymphocyte ratio (NLR) 2.0, platelets-to-lymphocyte ratio (PLR) 118 and monocyte-to-lymphocyte-ratio (MLR) 5.0), with 1 point assigned for each value exceeding the specified threshold and then summed, yielding a final score ranging from 0 to 3. Results: median NLR was 2.07, median PLR was 114.83, median MLR was 3.69. Conclusion: we found a significantly increase in the rate of pathological International Society of Urological Pathology (ISUP) ≥ 2 with the increase of PSIM. At the multivariate logistic regression analysis adjusted for age, prostate specific antigen (PSA), PSA density, prostate volume and PSIM, the latter was found the sole independent prognostic variable influencing probability of adverse pathology.
Motor Pathophysiology Related to Dyspnea in COPD Evaluated by Cardiopulmonary Exercise Testing
Authors: Miki Keisuke
Published: February 2021

In chronic obstructive pulmonary disease (COPD), exertional dyspnea, which increases with the disease’s progression, reduces exercise tolerance and limits physical activity, leading to a worsening prognosis. It is necessary to understand the diverse mechanisms of dyspnea and take appropriate measures to reduce exertional dyspnea, as COPD is a systemic disease with various comorbidities. A treatment focusing on the motor pathophysiology related to dyspnea may lead to improvements such as reducing dynamic lung hyperinflation, respiratory and metabolic acidosis, and eventually exertional dyspnea. However, without cardiopulmonary exercise testing (CPET), it may be difficult to understand the pathophysiological conditions during exercise. CPET facilitates understanding of the gas exchange and transport associated with respiration-circulation and even crosstalk with muscles, which is sometimes challenging, and provides information on COPD treatment strategies. For respiratory medicine department staff, CPET can play a significant role when treating patients with diseases that cause exertional dyspnea. This article outlines the advantages of using CPET to evaluate exertional dyspnea in patients with COPD.
A Multi-Center, Multi-Vendor Study to Evaluate the Generalizability of a Radiomics Model for Classifying Prostate cancer: High Grade vs. Low Grade
Authors: Castillo T. Jose M. , Starmans Martijn P. A. , Arif Muhammad , Niessen Wiro J. , Klein Stefan , Bangma Chris H. , Schoots Ivo G. , Veenland Jifke F.
Published: February 2021

Radiomics applied in MRI has shown promising results in classifying prostate cancer lesions. However, many papers describe single-center studies without external validation. The issues of using radiomics models on unseen data have not yet been sufficiently addressed. The aim of this study is to evaluate the generalizability of radiomics models for prostate cancer classification and to compare the performance of these models to the performance of radiologists. Multiparametric MRI, photographs and histology of radical prostatectomy specimens, and pathology reports of 107 patients were obtained from three healthcare centers in the Netherlands. By spatially correlating the MRI with histology, 204 lesions were identified. For each lesion, radiomics features were extracted from the MRI data. Radiomics models for discriminating high-grade (Gleason score ≥ 7) versus low-grade lesions were automatically generated using open-source machine learning software. The performance was tested both in a single-center setting through cross-validation and in a multi-center setting using the two unseen datasets as external validation. For comparison with clinical practice, a multi-center classifier was tested and compared with the Prostate Imaging Reporting and Data System version 2 (PIRADS v2) scoring performed by two expert radiologists. The three single-center models obtained a mean AUC of 0.75, which decreased to 0.54 when the model was applied to the external data, the radiologists obtained a mean AUC of 0.46. In the multi-center setting, the radiomics model obtained a mean AUC of 0.75 while the radiologists obtained a mean AUC of 0.47 on the same subset. While radiomics models have a decent performance when tested on data from the same center(s), they may show a significant drop in performance when applied to external data. On a multi-center dataset our radiomics model outperformed the radiologists, and thus, may represent a more accurate alternative for malignancy prediction.
Has the Flood Entered the Basement? A Systematic Literature Review about Machine Learning in Laboratory Medicine
Authors: Ronzio Luca , Cabitza Federico , Barbaro Alessandro , Banfi Giuseppe
Published: February 2021

This article presents a systematic literature review that expands and updates a previous review on the application of machine learning to laboratory medicine. We used Scopus and PubMed to collect, select and analyse the papers published from 2017 to the present in order to highlight the main studies that have applied machine learning techniques to haematochemical parameters and to review their diagnostic and prognostic performance. In doing so, we aim to address the question we asked three years ago about the potential of these techniques in laboratory medicine and the need to leverage a tool that was still under-utilised at that time.
Molecular Approaches Using Body Fluid for the Early Detection of Pancreatic Cancer
Authors: Satoh Kennichi
Published: February 2021

Pancreatic ductal adenocarcinoma (PDAC) is the most malignant form of gastrointestinal tumor and is the fourth leading cause of deaths due to cancer in Japan. This cancer shows a poor outcome due to the difficulty of its early diagnosis and its rapid growth. Once this disease becomes clinically evident, it is frequently accompanied by distant metastasis at the time of diagnosis. A recent multicenter study in Japan revealed that patients with the early stage of this disease (stage 0 and I) showed favorable prognosis after surgical resection, indicating the importance of early detection for improvement of PDAC prognosis. PDAC develops through a stepwise progression from the precursor lesion, and over the last few decades molecular analyses have shown the detailed genetic alterations that occur in this process. Since advances in molecular technologies have enabled the detection of genetic changes from a very small quantity of samples, a large number of non-invasive molecular approaches have been utilized in an attempt to find precursor or non-invasive carcinoma lesions. In this review, the current efforts in terms of the molecular approaches applied for the early detection of PDAC—especially using body fluids such as pancreatic juice, blood, and saliva—are summarized.
A Simulation-Based Methodology of Developing 3D Printed Anthropomorphic Phantoms for Microwave Imaging Systems
Authors: Abedi Soroush , Joachimowicz Nadine , Phillips Nicolas , Roussel Hélène
Published: February 2021

This work is devoted to the development and manufacturing of realistic benchmark phantoms to evaluate the performance of microwave imaging devices. The 3D (3 dimensional) printed phantoms contain several cavities, designed to be filled with liquid solutions that mimic biological tissues in terms of complex permittivity over a wide frequency range. Numerical versions (stereolithography (STL) format files) of these phantoms were used to perform simulations to investigate experimental parameters. The purpose of this paper is two-fold. First, a general methodology for the development of a biological phantom is presented. Second, this approach is applied to the particular case of the experimental device developed by the Department of Electronics and Telecommunications at Politecnico di Torino (POLITO) that currently uses a homogeneous version of the head phantom considered in this paper. Numerical versions of the introduced inhomogeneous head phantoms were used to evaluate the effect of various parameters related to their development, such as the permittivity of the equivalent biological tissue, coupling medium, thickness and nature of the phantom walls, and number of compartments. To shed light on the effects of blood circulation on the recognition of a randomly shaped stroke, a numerical brain model including blood vessels was considered.
CBCT Radiological Features as Predictors of Nerve Injuries in Third Molar Extractions: Multicenter Prospective Study on a Northeastern Italian Population
Authors: Bigagnoli Stefano , Greco Christian , Costantinides Fulvia , Porrelli Davide , Bevilacqua Lorenzo , Maglione Michele
Published: February 2021

Background: Neurological alterations are one of the main complications occurring after the third molar extractions. The aim of this prospective multicenter cohort study was to find out Cone Beam Computed Tomography (CBCT) features and distribution of neurological complications in patients undergoing lower third molar surgery and to determine the radiological and patient-related factors that could be correlated to the occurrence of inferior alveolar and lingual nerves injury. Material and Methods: 378 patients who underwent lower third molar extraction from March 2018 to March 2019 were included. Clinical and radiological data were collected. CBCT features were recorded following Maglione et al. classification. Symptoms and characteristics of patients who experienced neurological alterations were evaluated. Results: 193 patients needed a second-level radiological exam (CBCT). In these patients, the most common feature was Maglione class 3: a higher frequency of apical or buccal mandibular canals in direct contact with the tooth was observed. 3.17% of the patients developed a neurological complication. Maglione class 4, increased age, and operative time were all positively correlated with neurological alterations. Conclusions: while the buccal or apical position of the mandibular canal was the more common findings, the lingual position was found to have a higher correlation with a negative outcome. Age and operative time were also found to be risk factors for developing nerve injury in the considered population.