bluuebunny/crossref_metadata_2025 huggingface dataset:
The Evolution of Antisense Oligonucleotide Chemistry—A Personal Journey
Authors: Agrawal Sudhir
Published: May 2021

Over the last four decades, tremendous progress has been made in use of synthetic oligonucleotides as therapeutics. This has been possible largely by introducing chemical modifications to provide drug like properties to oligonucleotides. In this article I have summarized twists and turns on use of chemical modifications and their road to success and highlight areas of future directions.
High Levels of Low-Density Lipoproteins Correlate with Improved Survival in Patients with Squamous Cell Carcinoma of the Head and Neck
Authors: Wilms Torben , Boldrup Linda , Gu Xiaolian , Coates Philip J. , Sgaramella Nicola , Nylander Karin
Published: May 2021

Circulating lipoproteins as risk factors or prognostic indicators for various cancers have been investigated previously; however, no clear consensus has been reached. In this study, we aimed at evaluating the impact of serum lipoproteins on the prognosis of patients with squamous cell carcinoma of the head and neck (SCCHN). Levels of total cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides and lipoprotein(a) were measured in serum samples from 106 patients and 28 healthy controls. We found that HDL was the only lipoprotein exhibiting a significant difference in concentration between healthy controls and patients (p = 0.012). Kaplan–Meier survival curves indicated that patients with high levels of total cholesterol or LDL had better overall survival than patients with normal levels (p = 0.028 and p = 0.007, respectively). Looking at patients without lipid medication (n = 89) and adjusting for the effects of TNM stage and weight change, multivariate Cox regression models indicated that LDL was an independent prognostic factor for both overall (p = 0.005) and disease-free survival (p = 0.013). In summary, our study revealed that high LDL level is beneficial for survival outcome in patients with SCCHN. Use of cholesterol-lowering medicines for prevention or management of SCCHN needs to be evaluated carefully.
Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug
Authors: Pérez-Hernández Marta , Cuscó Cristina , Benítez-García Cristina , Bonelli Joaquin , Nuevo-Fonoll Marina , Soriano Aroa , Martínez-García David , Arias-Betancur Alain , García-Valverde María , Segura Miguel F. , Quesada Roberto , Rocas Josep , Soto-Cerrato Vanessa , Pérez-Tomás Ricardo
Published: May 2021

Cancer is one of the leading causes of mortality worldwide due, in part, to limited success of some current therapeutic approaches. The clinical potential of many promising drugs is restricted by their systemic toxicity and lack of selectivity towards cancer cells, leading to insufficient drug concentration at the tumor site. To overcome these hurdles, we developed a novel drug delivery system based on polyurea/polyurethane nanocapsules (NCs) showing pH-synchronized amphoteric properties that facilitate their accumulation and selectivity into acidic tissues, such as tumor microenvironment. We have demonstrated that the anticancer drug used in this study, a hydrophobic anionophore named T21, increases its cytotoxic activity in acidic conditions when nanoencapsulated, which correlates with a more efficient cellular internalization. A biodistribution assay performed in mice has shown that the NCs are able to reach the tumor and the observed systemic toxicity of the free drug is significantly reduced in vivo when nanoencapsulated. Additionally, T21 antitumor activity is preserved, accompanied by tumor mass reduction compared to control mice. Altogether, this work shows these NCs as a potential drug delivery system able to reach the tumor microenvironment, reducing the undesired systemic toxic effects. Moreover, these nanosystems are prepared under scalable methodologies and straightforward process, and provide tumor selectivity through a smart mechanism independent of targeting ligands.
Effects of Sponge-Derived Alkaloids on Activities of the Bacterial α-D-Galactosidase and Human Cancer Cell α-N-Acetylgalactosaminidase
Authors: Utkina Natalia , Likhatskaya Galina , Malyarenko Olesya , Ermakova Svetlana , Balabanova Larisa , Slepchenko Lubov , Bakunina Irina
Published: May 2021

During a search for glycosidase inhibitors among marine natural products, we applied an integrated in vitro and in silico approach to evaluate the potency of some aaptamines and makaluvamines isolated from marine sponges on the hydrolyzing activity of α-N-acetylgalactosaminidase (α-NaGalase) from human cancer cells and the recombinant α-D-galactosidase (α-PsGal) from a marine bacterium Pseudoalteromonas sp. KMM 701. These alkaloids showed no direct inhibitory effect on the cancer α-NaGalase; but isoaaptamine (2), 9-demethylaaptamine (3), damirone B (6), and makaluvamine H (7) reduced the expression of the enzyme in the human colorectal adenocarcinoma cell line DLD-1 at 5 μM. Isoaaptamine (2), 9-demethylaaptamine (3), makaluvamine G (6), and zyzzyanone A (7) are slow-binding irreversible inhibitors of the bacterial α-PsGal with the inactivation rate constants (kinact) 0.12 min−1, 0.092 min−1, 0.079 min−1, and 0.037 min−1, as well as equilibrium inhibition constants (Ki) 2.70 µM, 300 µM, 411 µM, and 105 µM, respectively. Docking analysis revealed that these alkaloids bind in a pocket close to the catalytic amino acid residues Asp451 and Asp516 and form complexes, due to π-π interactions with the Trp308 residue and hydrogen bonds with the Lys449 residue. None of the studied alkaloids formed complexes with the active site of the human α-NaGalase.
Protein Expression Correlates Linearly with mRNA Dose over Up to Five Orders of Magnitude In Vitro and In Vivo
Authors: van Asbeck Alexander H. , Dieker Jürgen , Oude Egberink Rik , van den Berg Lennard , van der Vlag Johan , Brock Roland
Published: May 2021

Messenger RNA is rapidly gaining significance as a therapeutic modality. Here, we address the dependence of dose–response functions on the type of delivery vehicle, cell line, and incubation time. Knowledge of these characteristics is crucial for the application of mRNA. As delivery vehicles, a lipid-based formulation and the cell-penetrating peptide Pepfect14 (PF14) were employed. As cell lines, we included a glomerular endothelial cell line (mGEnC) as a model for differentiated cells, HeLa cells, and SKOV-3 ovarian carcinoma cells. Uptake and expression were detected by flow cytometry, using a Cy5-labelled mRNA coding for enhanced green fluorescent protein (EGFP). There was a linear correlation of dose, uptake, and expression, and this correlation was maintained for over up to 72 h. Through application of a multistep kinetic model, we show that differences in expression levels can already be explained by the number of mRNAs packaged per delivery vehicle. Using luciferase as a reporter protein, linearity of expression was observed over 5 orders of magnitude in vitro and 3 orders of magnitude in vivo. Overall, the results demonstrate that mRNA provides excellent quantitative control over protein expression, also over extended periods of time.
Chemical Manipulation of the Endosome Trafficking Machinery: Implications for Oligonucleotide Delivery
Authors: Juliano Rudolph L.
Published: May 2021

Antisense oligonucleotides (ASOs), siRNA and splice switching oligonucleotides (SSOs) all have immense potential as therapeutic agents, potential that is now being validated as oligonucleotides enter the clinic. However, progress in oligonucleotide-based therapeutics has been limited by the difficulty in delivering these complex molecules to their sites of action in the cytosol or nucleus of cells within specific tissues. There are two aspects to the delivery problem. The first is that most types of oligonucleotides have poor uptake into non-hepatic tissues. The second is that much of the oligonucleotide that is taken up by cells is entrapped in endosomes where it is pharmacologically inert. It has become increasingly recognized that endosomal trapping is a key constraint on oligonucleotide therapeutics. Thus, many approaches have been devised to address this problem, primarily ones based on various nanoparticle technologies. However, recently an alternative approach has emerged that employs small molecules to manipulate intracellular trafficking processes so as to enhance oligonucleotide actions. This review presents the current status of this chemical biology approach to oligonucleotide delivery and seeks to point out possible paths for future development.
Levodopa-Based Changes on Vocalic Speech Movements during Prosodic Prominence Marking
Authors: Thies Tabea , Mücke Doris , Dano Richard , Barbe Michael T.
Published: May 2021

The present study investigates speech changes in Parkinson’s disease on the acoustic and articulatory level with respect to prosodic prominence marking. To display movements of the underlying articulators, speech data from 16 patients with Parkinson’s disease were recorded using electromagnetic articulography. Speech tasks focused on strategies of prominence marking. Patients’ ability to encode prominence in the laryngeal and supra-laryngeal domain is tested in two conditions to examine the influence of motor performance on speech production further: without dopaminergic medication and with dopaminergic medication. The data reveal that patients with Parkinson’s disease are able to highlight important information in both conditions. They maintain prominence relations across- and within-accentuation by adjusting prosodic markers, such as vowel duration and pitch modulation, while the acoustic vowel space remains the same. For differentiating across-accentuation, not only intensity but also all temporal and spatial parameters related to the articulatory tongue body movements during the production of vowels are modulated to signal prominence. In response to the levodopa intake, gross motor performance improved significantly by 42%. The improvement in gross motor performance was accompanied by an improvement in speech motor performance in terms of louder speech and shorter, larger and faster tongue body movements. The tongue body is more agile under levodopa increase, a fact that is not necessarily detectable on the acoustic level but important for speech therapy.
Aromatic-Turmerone Analogs Protect Dopaminergic Neurons in Midbrain Slice Cultures through Their Neuroprotective Activities
Authors: Hori Yuria , Tsutsumi Reiho , Nasu Kento , Boateng Alex , Ashikari Yasuhiko , Sugiura Masaharu , Nakajima Makoto , Kurauchi Yuki , Hisatsune Akinori , Katsuki Hiroshi , Seki Takahiro
Published: May 2021

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. The inflammatory activation of microglia participates in dopaminergic neurodegeneration in PD. Therefore, chemicals that inhibit microglial activation are considered to have therapeutic potential for PD. Aromatic (ar)-turmerone is a main component of turmeric oil extracted from Curcuma longa and has anti-inflammatory activity in cultured microglia. The aims of the present study are (1) to investigate whether naturally occurring S-enantiomer of ar-turmerone (S-Tur) protects dopaminergic neurons in midbrain slice cultures and (2) to examine ar-turmerone analogs that have higher activities than S-Tur in inhibiting microglial activation and protecting dopaminergic neurons. R-enantiomer (R-Tur) and two analogs showed slightly higher anti-inflammatory effects in microglial BV2 cells. S- and R-Tur and these two analogs reversed dopaminergic neurodegeneration triggered by microglial activation in midbrain slice cultures. Unexpectedly, this neuroprotection was independent of the inhibition of microglial activation. Additionally, two analogs more potently inhibited dopaminergic neurodegeneration triggered by a neurotoxin, 1-methyl-4-phenylpyridinium, than S-Tur. Taken together, we identified two ar-turmerone analogs that directly and potently protected dopaminergic neurons. An investigation using dopaminergic neuronal precursor cells suggested the possible involvement of nuclear factor erythroid 2-related factor 2 in this neuroprotection.
Analysing Educational Interventions with Gifted Students. Systematic Review
Authors: García-Martínez Inmaculada , Gutiérrez Cáceres Rafaela , Luque de la Rosa Antonio , León Samuel P.
Published: May 2021

(1) Background: Educational attention to gifted students has not been a well-established line of research due to the multiple conceptions about their characterisation. While educational attention has tended to respond to students who present learning difficulties due to their limitations, it has been observed that gifted students may also fail in their studies. The purpose of this study is to examine educational interventions carried out with this population worldwide; (2) Methods: The methodological design is a systematic review, following the PRISMA guidelines, in the Scopus and WOS databases on educational interventions and gifted students; (3) Results: The papers were studied through a qualitative content analysis based on a population of 557 articles, with a final sample of 14, finding a great variety of didactic strategies and models oriented to meet the needs of this group. In relation to the quality of the studies, the lack of pre-post methodological designs focused on performance stands out; (4) Conclusions: Educational research with gifted population demands more interventions personalised to the specific characteristics of the students. In addition, there is a need for further research with quasi-experimental designs with this population to identify quality, not generalised, interventions to meet these needs and replace them with individualised adaptations regarding the needs and interests of these students in order to increase their motivation and reduce failure.
Body Fat Mass, Percent Body Fat, Fat-Free Mass, and Skeletal Muscle Mass Reference Curves for Czech Children Aged 6–11 Years
Authors: Zbořilová Vendula , Přidalová Miroslava , Kaplanová Tereza
Published: May 2021

Background: Negative lifestyle trends are reflected in overweight and obese children, in which their lack of physical activity results in decreased muscle mass. This study aimed to define age- and sex-specific reference curves for body fat mass (BFM), skeletal muscle mass (SMM), fat-free mass (FFM), and percent body fat (%BF) in Czech children. Methods: Body composition was measured by segmental bioelectrical impedance (BIA, InBody 720). The research sample included 2093 children aged 6–11 years (1008 boys and 1085 girls). Only children whose parents provided informed consent were included. Statistical analysis was performed using SPSS v. 22. The statistical analysis was performed separately by age and sex. Anthropometric data were summarized as means and standard deviation. The percentile curves (P3, P10, P25, P50, P75, P90, and P97) of BFM, FFM, %BF, and SMM were calculated using the gamlss package in R 3.4.2 (R Foundation for Statistical Computing, Vienna, Austria). Results: This study developed age- and gender-specific percentile curves of SMM, FFM, BFM, and %BF for Czech children aged 6–11 years. During childhood, BFM and %BF increased in boys, peaking at approximately 11 years of age. Girls displayed a different pattern of age-related changes in BFM and %BF compared to that in boys. These parameters gradually increased during childhood. This pattern was also observed for SMM and FFM in both sexes. Conclusions: The purpose of this study was to serve as a reference to improve methods to evaluate body composition in Czech children and for comparison with studies worldwide.
Does Parenting Style Affect Adolescent IBD Transition Readiness and Self-Efficacy Scores?
Authors: Zuar Lynsey R. , Chien Kimberley , Lentine Jennifer , Cooley Victoria , Gerber Linda M. , Ward Mary J. , Keefer Laurie
Published: May 2021

Background: Transition to adult-centered care requires adolescents with inflammatory bowel disease (IBD) to acquire a set of independent self-management skills. Transition success can be affected by maturity, cognitive development, and many other factors. Our hypothesis was that parenting style would be associated with increased self-efficacy and therefore transitions readiness. Methods: A prospective cohort survey study of adolescents with IBD and their parents from October 2018 to October 2019 was performed. Participants completed the IBD-Self-Efficacy Scale- Adolescent questionnaire (IBD-SES-A) and the Transition Readiness Assessment Questionnaire (TRAQ). Parents completed the Parent Styles and Dimensions Questionnaire (PSDQ-short form). Demographic and disease information were also collected. Results: Sixty-nine participants were included for full analysis (36 males and 33 females); mean age was 18.2 years, and average age of IBD diagnosis 13 years. Overall, 83% of participants were non-Hispanic Caucasian, and 84% reported parental annual income over USD 100,000. All 69 parents reported an authoritative parenting style. Females have significantly higher TRAQ scores than males (p = 0.0004). TRAQ scores differed significantly between age groups, with 20 to 22 years old having higher scores (p ≤ 0.0001). TRAQ and IBD-SES-A scores did not differ by parental education or parenting style. Conclusion: Given the inability to delineate different parenting, this study was unable to demonstrate a protective parenting style associated with better transitions readiness and self-efficacy scores in adolescents with IBD. Within the context of authoritative parenting, we did find that females and older adolescents had higher transition readiness scores. Additional research into psychosocial determinants of transition readiness, and the importance of multidisciplinary management with an integrated team including psychologist and social workers, can help improve IBD transition outcomes.
Mindfulness-Based Virtual Reality Intervention for Children and Young Adults with Inflammatory Bowel Disease: A Pilot Feasibility and Acceptability Study
Authors: Wren Anava A. , Neiman Nicole , Caruso Thomas J. , Rodriguez Samuel , Taylor Katherine , Madill Martine , Rives Hal , Nguyen Linda
Published: May 2021

The aim of this pilot study was to assess: (1) the feasibility and acceptability of a Mindfulness-Based Virtual Reality (MBVR) intervention among children and young adults with Inflammatory Bowel Disease (IBD), and (2) the preliminary efficacy of MBVR on key psychological (anxiety) and physical (pain) outcomes. Participants were 62 children to young adults with IBD (M = 15.6 years; 69.4% Crohn’s disease; 58% male) recruited from an outpatient pediatric IBD clinic. Participants completed a baseline assessment, underwent the 6-min MBVR intervention, completed a post-intervention assessment and study satisfaction survey, and provided qualitative feedback. Results suggest strong feasibility and acceptability. Participants reported high levels of satisfaction with MBVR including high levels of enjoyment (M = 4.38; range 1–5) and relaxation (M = 4.35; range 1–5). Qualitative data revealed several key themes including participants interest in using MBVR in IBD medical settings (e.g., hospitalizations, IBD procedures, IBD treatments), as well as in their daily lives to support stress and symptom management. Preliminary analyses demonstrated improvements in anxiety (t = 4.79, p = 0.001) and pain (t = 3.72, p < 0.001) following MBVR. These findings provide initial support for the feasibility and acceptability of MBVR among children and young adults with IBD. Results also suggest MBVR may improve key IBD outcomes (e.g., anxiety, pain) and highlight the importance of conducting a randomized controlled trial and more rigorous research to determine intervention efficacy.
Crystal Structure, Topological and Hirshfeld Surface Analysis of a Zn(II) Zwitterionic Schiff Base Complex Exhibiting Nonlinear Optical (NLO) Properties Using Z-Scan Technique
Authors: Kamaal Saima , Mehkoom Mohd , Muslim Mohd , Afzal Syed Mohammad , Alarifi Abdullah , Afzal Mohd , Alowais Ahmad , Muddassir Mohd , Albalwi Awad Naseer , Ahmad Musheer
Published: May 2021

A mononuclear Zn(II) complex of (Zn(H2L) (CH3OH) Cl2) (1) has been synthesized by using a nonlinear optically active Zwitterionic Schiff base which is 4-((2-hydroxy-3-methoxybenzylidene) amino) benzoic acid (H2L). Complex 1 has been structurally analyzed by FTIR and UV spectroscopy, TGA, Powder-XRD and single crystal X-ray diffraction. X-Ray crystallographic studies revealed Zn(II) complex crystallizes in a P21/c space group and exists in a distorted trigonal bipyramidal geometry (τ = 0.68). The topological analysis of complex 1 showed that the underlying net is characterized by an unknown topological type and point symbol {342.468.510}, and multilevel analysis of complex packing as dimer gives a 18-c uninodal net with unknown topological type and point symbol {348.499.56}. The calculation results of a Hirshfeld surface analysis have been investigated to explore the H-bonding within the crystal. Third-order non-linear properties were also studied, which revealed that the lower input power (5.0 mM) for the material shows full transparency; however, it becomes opaque for higher input power. Such limiting behavior of complex 1 suggests its potential for instrumental protective devices against high laser illuminations.
Is There a Right Way? Productive Patterns of Interaction during Collaborative Problem Solving
Authors: Webb Noreen M. , Ing Marsha , Burnheimer Eric , Johnson Nicholas C. , Franke Megan L. , Zimmerman Joy
Published: May 2021

Compelling research evidence shows benefits for student learning from explaining one’s ideas and engaging with the ideas of others. However, whether certain patterns of group interaction may engender this productive student participation is unknown. Using data from two third grade mathematics classrooms, and over the course of six days during a five-month span, we investigated how students interacted with each other to solve problems when the teacher was not driving the interaction. We identified multiple profiles of group interaction that yielded highly-detailed participation for some or all students in the group. These profiles varied in terms of whether students interacted in an ongoing, sustained manner or interacted periodically but not continually, whether one or multiple students initiated problem-solving strategies, and whether group members worked jointly or largely separately on their strategies. No single profile of group interaction was either necessary or sufficient to lead to highly-detailed participation for all students in the group.
A Low-Complexity Edward-Curve Point Multiplication Architecture
Authors: Sajid Asher , Rashid Muhammad , Imran Malik , Jafri Atif Raza
Published: May 2021

The Binary Edwards Curves (BEC) are becoming more and more important, as compared to other forms of elliptic curves, thanks to their faster operations and resistance against side channel attacks. This work provides a low-complexity architecture for point multiplication computations using BEC over GF(2233). There are three major contributions in this article. The first contribution is the reduction of instruction-level complexity for unified point addition and point doubling laws by eliminating multiple operations in a single instruction format. The second contribution is the optimization of hardware resources by minimizing the number of required storage elements. Finally, the third contribution is to reduce the number of required clock cycles by incorporating a 32-bit finite field digit-parallel multiplier in the datapath. As a result, the achieved throughput over area ratio over GF(2233) on Virtex-4, Virtex-5, Virtex-6 and Virtex-7 Xilinx FPGA (Field Programmable Gate Array) devices are 2.29, 19.49, 21.5 and 20.82, respectively. Furthermore, on the Virtex-7 device, the required computation time for one point multiplication operation is 18 µs, while the power consumption is 266 mW. This reveals that the proposed architecture is best suited for those applications where the optimization of both area and throughput parameters are required at the same time.
Network Slicing for Beyond 5G Systems: An Overview of the Smart Port Use Case
Authors: Sohaib Rana Muhammad , Onireti Oluwakayode , Sambo Yusuf , Imran Muhammad Ali
Published: May 2021

As the idea of a new wireless communication standard (5G) started to circulate around the world, there was much speculation regarding its performance, making it necessary to carry out further research by keeping in view the challenges presented by it. 5G is considered a multi-system support network due to its ability to provide benefits to vertical industries. Due to the wide range of devices and applications, it is essential to provide support for massively interconnected devices. Network slicing has emerged as the key technology to meet the requirements of the communications network. In this paper, we present a review of the latest achievements of 5G network slicing by comparing the architecture of The Next Generation Mobile Network Alliance’s (NGMN’s) and 5G-PPP, using the enabling technologies software-defined networking (SDN) and network function virtualization (NFV). We then review and discuss machine learning (ML) techniques and their integration with network slicing for beyond 5G networks and elaborate on how ML techniques can be useful for mobility prediction and resource management. Lastly, we propose the use case of network slicing based on ML techniques in a smart seaport environment, which will help to manage the resources more efficiently.
Antimicrobial Polyamide-Alginate Casing Incorporated with Nisin and ε-Polylysine Nanoparticles Combined with Plant Extract for Inactivation of Selected Bacteria in Nitrite-Free Frankfurter-Type Sausage
Authors: Alirezalu Kazem , Yaghoubi Milad , Poorsharif Leila , Aminnia Shadi , Kahve Halil Ibrahim , Pateiro Mirian , Lorenzo José M. , Munekata Paulo E. S.
Published: May 2021

The effects of combining a polyamide-alginate casing incorporated with nisin (100 ppm and 200 ppm) and ε-polylysine (500 ppm and 1000 ppm) nanoparticles and a mixed plant extract as ingredient in sausage formulation (500 ppm; composed of olive leaves (OLE), green tea (GTE) and stinging nettle extracts (SNE) in equal rates) were studied to improve the shelf life and safety of frankfurter-type sausage. The film characteristics and microbiological properties of sausage samples were evaluated. Sausage samples were packaged in polyethylene bags (vacuum condition) and analysed during 45 days of storage at 4 °C. Control sausages were also treated with 120 ppm sodium nitrite. Polyamide-alginate films containing 100 ppm nisin and 500 ε-PL nanoparticles had the highest ultimate tensile strength compared to other films. However, 100 ppm nisin and 500 ε-PL nanoparticles decreased water vapour permeability of films. The results also revealed that nisin nanoparticles had significantly (p < 0.05) low inhibitory effects against Escherichia coli, Staphylococcus aureus, molds and yeasts and total viable counts compared to control and ε-PL nanoparticles. Furthermore, 1000 ppm ε-PL nanoparticles displayed the highest antimicrobial activity. Based on the obtained results, the films containing ε-PL nanoparticle could be considered as a promising packaging for frankfurter-type sausages.
Herbal Medicine Must Be Treated with Care—A Case Report on Aconitine
Authors: Theofel Nadine , Wagner Marlene , Vejmelka Elke , Scholtis Stefan , Tsokos Michael
Published: May 2021

Pathologists usually only request a screening for natural toxic substances if plant material has been observed during autopsy or if there exists a hint in the police investigation file. This situation is aggravated by the fact that most toxins are not covered by typical immunoassays and gas chromatography–mass spectrometry (GC–MS) profiling systems. In addition, only a few forensic toxicological libraries based on liquid chromatography coupled to high-resolution tandem mass spectrometry (LC–HRMS/MS) exist. In the following case, femoral blood and urine were applied to systematic toxicological analysis (STA). However, the concentrations determined in blood did not lead to death. Consequently, a liquid chromatography high-resolution tandem mass spectrometry (LC–HRMS/MS) screening approach was applied. Aconitine was quantitated in all specimens taken during autopsy and urine and bile fluid screened for aconitine metabolites. Aconitine, jesaconitine, hypaconitine, and mesaconitine were found in the root piece collected from the duodenum. Apart from aconitine, no other alkaloids were detected in the urine or in the femoral blood sample. The highest concentrations of aconitine were found in gastric content (55.2 μg/mL), bile fluid (11.7 μg/mL), and liver (9.14 μg/g), and least in femoral blood (0.15 μg/mL) and cerebrospinal fluid (0.07 μg/mL). The liver/peripheral blood ratio amounted to 61 L/kg and indicated that aconitine undergoes postmortem redistribution. During our metabolism investigation, we found 3-dehydrogen-aconitine in the urine and bile fluid sample and N-deethyl-aconitine only in the bile fluid sample. If the routine GC–MS screening approach does not come up with a toxin, then LC–HRMS/MS profiling could represent the method of choice. In this case aconitine was identified. The concentrations determined were compared to those reported in literature and clearly indicate that the deceased died due to an aconitine overdose.
Tectono-Sedimentary Evolution of Cenozoic Basins
Authors: Martín-Martín Manuel
Published: May 2021

The study of the tectono-sedimentary evolution of basins is a capital topic with many scientific and economic derivations [...]
Assessment of the Photosynthetic Response of Posidonia oceanica (Linneaus) Delile, 1813 along a Depth Gradient in the Northern Tyrrhenian Sea (Latium, Italy)
Authors: Madonia Alice , Caporale Giulia , Penna Marina , Bonamano Simone , Marcelli Marco
Published: May 2021

Posidonia oceanica (L.) Delile meadows are recognized to be one of the most productive ecosystems of the Mediterranean basin. Due to the impacts of human activities in coastal areas, seagrasses are experiencing a critical decline. In this context, the understanding of the dynamics of production and photosynthesis in response to the environmental factors is essential to address efficient conservation strategies that limit this trend and to assess the ecological status of marine ecosystems. Pulse Amplitude Modulated (PAM) fluorometry has been widely implemented to assess seagrass health and productivity. Here we analyzed the photosynthetic dynamics of P. oceanica according to its bathymetric distribution and daily light availability along a depth gradient to be used as baseline for monitoring purposes on the health status of the seagrass meadows in the Northern Tyrrhenian Sea. Moreover, to investigate the effects of the environmental factors on the health status of P. oceanica within the study area through a multidisciplinary approach, the models contained in the Civitavecchia Coastal Environmental Monitoring System were used. In this study, significant photo-physiological changes have been observed among the investigated meadows. Moreover, the integration of physiological and hydrodynamic information allowed the description of how P. oceanica modulates its photosynthetic capacity at different environmental conditions.
Feasibility of a Portable Electronic Nose for Detection of Oral Squamous Cell Carcinoma in Sudan
Authors: Mohamed Nazar , van de Goor Rens , El-Sheikh Mariam , Elrayah Osman , Osman Tarig , Nginamau Elisabeth Sivy , Johannessen Anne Christine , Suleiman Ahmed , Costea Daniela Elena , Kross Kenneth W.
Published: May 2021

Background: Oral squamous cell carcinoma (OSCC) is increasing at an alarming rate particularly in low-income countries. This urges for research into noninvasive, user-friendly diagnostic tools that can be used in limited-resource settings. This study aims to test and validate the feasibility of e-nose technology for detecting OSCC in the limited-resource settings of the Sudanese population. Methods: Two e-nose devices (Aeonose™, eNose Company, Zutphen, The Netherlands) were used to collect breath samples from OSCC (n = 49) and control (n = 35) patients. Patients were divided into a training group for building an artificial neural network (ANN) model and a blinded control group for model validation. The Statistical Package for the Social Sciences (SPSS) software was used for the analysis of baseline characteristics and regression. Aethena proprietary software was used for data analysis using artificial neural networks based on patterns of volatile organic compounds. Results: A diagnostic accuracy of 81% was observed, with 88% sensitivity and 71% specificity. Conclusions: This study demonstrates that e-nose is an efficient tool for OSCC detection in limited-resource settings, where it offers a valuable cost-effective strategy to tackle the burden posed by OSCC.
Geospatial Analysis of Solar Energy in Riyadh Using a GIS-AHP-Based Technique
Authors: Albraheem Lamya , Alabdulkarim Leena
Published: May 2021

In recent years, spatial multi-criteria decision analysis (MCDA) has been applied to different types of spatial problems, such as solar power site suitability. MCDA can be used to support the process of identifying suitable regions for solar energy projects. To the best of our knowledge, no study has addressed the problem of site evaluation for solar photovoltaic PV systems in the Riyadh region. Therefore, a spatial MCDA framework is proposed to perform a geospatial analysis of solar energy in the Riyadh region, which includes data collection, spatial analysis, a spatial decision support system and visualization. The methodology that was used to solve the site suitability problem is described. It involved the combination of a Geographical Information System (GIS) and the Analytic Hierarchy Process (GIS-AHP). The results show that the most suitable sites are in the north and northwest of the Riyadh region, with an area that represents 16,748 Km2 with an 80% suitability degree. In addition, it was proven that Afif is the largest suitable city. It has high solar radiation, at an average of 2.631687 MWh/m2/year, and low temperatures, at an average of 26.3 °C, as well as having flat areas with a slope under 5°. The results were validated using a sensitivity analysis model and also compared with those for ground-based stations.
Assessment of Surface Water Availability under Climate Change Using Coupled SWAT-WEAP in Hongshui River Basin, China
Authors: Touseef Muhammad , Chen Lihua , Yang Wenzhe
Published: May 2021

Climate change adversely affects the hydrological cycle at the basin level. This study integrated two models, the Soil and Water Assessment Tool (SWAT) for future climate prediction, and Water Evaluation and Planning (WEAP) for the simulation of water quantity in the Hongshui River Basin (HRB), to evaluate the impacts of climate change, which plays a significant role in the lives of inhabitants downstream of the basin. Downscaled monthly rainfalls and temperatures under four Representative Concentration Pathways (RCPs) emission scenarios from five global circulation models (GCMs) were used to generate streamflow using the SWAT model. Streamflow data (1991–2001) were used to calibrate and validate, with the period of 1991–1997 used for calibration and that of 1998–2001 used for validation. Six scenarios were established to evaluate the response of the basin under socio-economic scenarios. The simulated results show that precipitation and streamflow would likely undergo a slight increase. The available water resources would be sufficient to meet the existing needs until 2050. The results indicated that no water shortages exist under socio-economic, low, and medium climate change emission scenarios, however the basin will experience a water shortage under the high climate change emission scenario (RCP-8.5). The study proposed that, to ensure the sustainability of water resources, better long-term management policies are required to be implemented in the basin and to meet future downstream water needs.
A Study on Prediction Model of Gully Volume Based on Morphological Features in the JINSHA Dry-Hot Valley Region of Southwest China
Authors: Yang Dan , Mu Kai , Yang Hui , Luo Mingliang , Lv Wei , Zhang Bin , Liu Hui , Wang Zhicheng
Published: May 2021

Gully erosion is well-developed in the Jinsha dry-hot valley region, which has caused serious soil losses. Gully volume is regarded as an effective indicator that can reflect the development intensity of gully erosion, and the evolutionary processes of gullies can be predicted based on the dynamic variation in gully volume. Establishing an effective prediction model of gully volume is essential to determine gully volume accurately and conveniently. Therefore, in this work, an empirical prediction model of gully volume was constructed and verified based on detailed morphological features acquired by elaborate field investigations and measurements in 134 gullies. The results showed the mean value of gully length, width, depth, cross-section area, volume, and vertical gradient decreased with the weakness of the activity degree of the gully, although the decrease in processes of these parameters had some differences. Moreover, a series of empirical prediction models of gully volume was constructed, and gully length was demonstrated to be a better predictor than other morphological features. Lastly, the effectiveness test showed the model of V = aL^b was the most effective in predicting gully volume among the different models established in this study. Our results provide a useful approach to predict gully volume in dry-hot valley regions.
Spatial Pattern of Highway Transport Dominance in Qinghai–Tibet Plateau at the County Scale
Authors: Wang Zhiheng , Fan Hongkui , Wang Daikun , Xing Tao , Wang Dongchuan , Guo Qiaozhen , Xiu Lina
Published: May 2021

The highway is an important mode of transportation in the Qinghai–Tibet Plateau, and can be regarded as a major contributor to the high-quality and sustainable development of the Qinghai–Tibet Plateau. It is of great significance to explore its spatial distribution and characteristics for understanding the regional and geographical process. Although Qinghai–Tibet Plateau’s highway transportation infrastructure has been experiencing rapid development in recent years, there lacks a systematic examination of the whole Qinghai–Tibet Plateau from the perspective of supportive capacity for its socio-economic activities. This paper applies geospatial analysis methods, such as network analysis, spatial statistics, and weighted overlay, to model the highway transport dominance in the Qinghai–Tibet Plateau in 2015 at the county scale and reveals the basic characteristics of the highway transport dominance’s spatial pattern. The results are mainly of four aspects: 1) there is a significant difference between the east and west of the highway in the Qinghai–Tibet Plateau, showing an irregular circle structure of gradual attenuation from the east to west; 2) at the county scale, the highway transport dominance in the Qinghai–Tibet Plateau shows strong spatial autocorrelation and a certain extent of spatial heterogeneity, presenting a spatial distribution pattern of High–High and Low–Low clustering; 3) the urban locations of Lhasa, Xining and other center cities have obvious spatial constraints on the distribution of highway transport dominance and generally have a logarithmic decline trend; and 4) there are obvious differences in distribution among the three Urban Agglomerations in the Qinghai–Tibet Plateau. Due to the influence of traffic location, topography, construction of national trunk lines, and level of socio-economic development., the traffic conditions of Lan-Xi Urban Agglomeration and Lhasa Urban Agglomeration are better than Kashgar Urban Agglomeration. This study can be used to guide the optimization of the highway network structure and provide a macro decision-making reference for the planning and evaluation of major highway projects in the Qinghai–Tibet Plateau.
Use of Random Forest Model to Identify the Relationships among Vegetative Species, Salt Marsh Soil Properties, and Interstitial Water along the Atlantic Coast of Georgia
Authors: Hikouei Iman Salehi , Christian Jason , Kim S. Sonny , Sutter Lori A. , Durham Stephan A. , Yang Jidong J. , Vickery Charles Gray
Published: May 2021

Saltmarshes, known to be ecologically sensitive areas, face disturbances such as vegetation dieback due to anthropogenic activities such as construction. The current construction specifications recommended by state highway agencies do not specifically require documenting or restoring any prior saltmarsh soil/interstitial water properties, nor do they require re-establishing saltmarsh vegetation; restoring the abiotic properties and appropriate vegetation would enhance the long-term functionality and ecology of a disturbed area. In order to have a successful restoration of disturbed saltmarshes with healthy vegetation, the relationship between vegetative species and the properties of saltmarsh soils and interstitial water must be fully understood. In this study, field and laboratory tests were conducted for the soil samples from eight different saltmarsh sites in the Southeastern US Atlantic coastal region, followed by the development of a random forest model; the aim is to identify correlation among saltmarsh predominant vegetation types, redox potential, and salinity. The results reveal that moisture content and sand content are two main drivers for the bulk density of saltmarsh soils, which directly affect plant growth and likely root development. Moreover, it is concluded that deploying modern machine learning algorithms, such as random forest, can help to identify desirable saltmarsh soil/water properties for re-establishing vegetative cover with the reduced time after construction activities.
Deletion of a Hand1 lncRNA-Containing Septum Transversum Enhancer Alters lncRNA Expression but Is Not Required for Hand1 Expression
Authors: George Rajani M. , Firulli Anthony B.
Published: May 2021

We have previously identified a Hand1 transcriptional enhancer that drives expression within the septum transversum, the origin of the cells that contribute to the epicardium. This enhancer directly overlaps a common exon of a predicted family of long non-coding RNAs (lncRNA) that are specific to mice. To interrogate the necessity of this Hand1 enhancer, as well as the importance of these novel lncRNAs, we deleted the enhancer sequences, including the common exon shared by these lncRNAs, using genome editing. Resultant homozygous Hand1 enhancer mutants (Hand1ΔST/ΔST) present with no observable phenotype. Assessment of lncRNA expression reveals that Hand1ΔST/ΔST mutants effectively eliminate detectable lncRNA expression. Expression analysis within Hand1ΔST/ΔST mutant hearts indicates higher levels of Hand1 than in controls. The generation of Hand1 compound heterozygous mutants with the Hand1LacZ null allele (Hand1ΔST/LacZ) also did not reveal any observable phenotypes. Together these data indicate that deletion of this Hand1 enhancer and by consequence a family of murine-specific lncRNAs does not impact embryonic development in observable ways.
The Spectrum of COVID-19-Associated Myocarditis: A Patient-Tailored Multidisciplinary Approach
Authors: Peretto Giovanni , Villatore Andrea , Rizzo Stefania , Esposito Antonio , De Luca Giacomo , Palmisano Anna , Vignale Davide , Cappelletti Alberto Maria , Tresoldi Moreno , Campochiaro Corrado , Sartorelli Silvia , Ripa Marco , De Gaspari Monica , Busnardo Elena , Ferro Paola , Calabrò Maria Grazia , Fominskiy Evgeny , Monaco Fabrizio , Cavalli Giulio , Gianolli Luigi , De Cobelli Francesco , Margonato Alberto , Dagna Lorenzo , Scandroglio Mara , Camici Paolo Guido , Mazzone Patrizio , Della Bella Paolo , Basso Cristina , Sala Simone
Published: May 2021

Background. Myocarditis lacks systematic characterization in COVID-19 patients. Methods. We enrolled consecutive patients with newly diagnosed myocarditis in the context of COVID-19 infection. Diagnostic and treatment strategies were driven by a dedicated multidisciplinary disease unit for myocarditis. Multimodal outcomes were assessed during prospective follow-up. Results. Seven consecutive patients (57% males, age 51 ± 9 y) with acute COVID-19 infection received a de novo diagnosis of myocarditis. Endomyocardial biopsy was of choice in hemodynamically unstable patients (n = 4, mean left ventricular ejection fraction (LVEF) 25 ± 9%), whereas cardiac magnetic resonance constituted the first exam in stable patients (n = 3, mean LVEF 48 ± 10%). Polymerase chain reaction (PCR) analysis revealed an intra-myocardial SARS-CoV-2 genome in one of the six cases undergoing biopsy: in the remaining patients, myocarditis was either due to other viruses (n = 2) or virus-negative (n = 3). Hemodynamic support was needed for four unstable patients (57%), whereas a cardiac device implant was chosen in two of four cases showing ventricular arrhythmias. Medical treatment included immunosuppression (43%) and biological therapy (29%). By the 6-month median follow-up, no patient died or experienced malignant arrhythmias. However, two cases (29%) were screened for heart transplantation. Conclusions. Myocarditis associated with acute COVID-19 infection is a spectrum of clinical manifestations and underlying etiologies. A multidisciplinary approach is the cornerstone for tailored management.
Comparison of Premixed Human Insulin 30/70 to Biphasic Aspart 30 in Well-Controlled Patients with Type 2 Diabetes Using Continuous Glucose Monitoring
Authors: Margaritidis Charalampos , Karlafti Eleni , Kotzakioulafi Evangelia , Kantartzis Konstantinos , Tziomalos Konstantinos , Kaiafa Georgia , Savopoulos Christos , Didangelos Triantafyllos
Published: May 2021

Aim: To compare in terms of glycemic variability two premixed insulins, Premixed Human Insulin 30/70 (PHI) and Biphasic Aspart 30 (BiAsp30), using Continuous Glucose Monitoring (CGM) and to estimate the correlation of Glycated Albumin (GA) and Fructosamine (FA) with CGM data. Patients-Data: A total of 36 well-controlled patients with type 2 Diabetes Mellitus (T2DM) underwent 7-day CGM with PHI and subsequently with BiAsp30. GA and FA were measured at the first and last day of each week of CGM. Results: BiAsp30 was associated with lower Average Blood Glucose (ABG) during the 23:00–03:00 period (PHI: 135.08 ± 28.94 mg/dL, BiAsp30: 117.75 ± 21.24 mg/dL, p < 0.001) and the 00:00–06:00 period (PHI: 120.42 ± 23.13 mg/dL, BiAsp30: 111.17 ± 14.74 mg/dL, p = 0.008), as well as with more time below range (<70 mg/dL) (TBR) during the 23:00–03:00 period in the week (PHI: 3.65 ± 5.93%, BiAsp30: 11.12 ± 16.07%, p = 0.005). PHI was associated with lower ABG before breakfast (PHI: 111.75 ± 23.9 mg/dL, BiAsp30: 128.25 ± 35.9 mg/dL, p = 0.013). There were no differences between the two groups in ABG, Time In Range and Time Below Range during the entire 24-h period for 7 days, p = 0.502, p = 0.534, and p = 0.258 respectively, and in TBR for the 00:00–06:00 period p = 0.253. Total daily insulin requirements were higher for BiAsp30 (PHI: 47.92 ± 12.18 IU, BiAsp30: 49.58 ± 14.12 IU, p = 0.001). GA and FA correlated significantly with ABG (GA: r = 0.512, p = 0.011, FA: r = 0.555, p = 0.005). Conclusions: In well-controlled patients with T2DM, BiAsp30 is an equally effective alternative to PHI.