bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive Potential of Stone Moroko (Pseudorasbora parva, Temminck et Schlegel, 1846) (Teleostei: Cypriniformes: Gobionidae) Inhabiting Central Europe
Authors: Kirczuk Lucyna , Dziewulska Katarzyna , Czerniejewski Przemysław , Brysiewicz Adam , Rząd Izabella
Published: September 2021

Similar to other invasive species, stone moroko is extending its global distribution. The present study aimed to assess the reproductive potential of stone moroko fish in a new habitat in Poland based on analysing the sexual cycle and fecundity. Fish morphometric data, age, and gonadal structures were analysed. Fish age ranged from 0+ to 5+ years. Most females and males (93% and 60%, respectively) had reached sexual maturity in the first year of their life, with the smallest length of 25 mm and 28 mm, respectively. The mean, standard length of the body was 50 mm. The spawning season was spread over four months from late-April to mid-August. Females laid eggs in portions, and the absolute and relative fecundity was 1372 and 1691, respectively. Stone moroko males were ready to spawn for a longer time period than females. The present study shows greater reproductive potential of stone moroko population in the central Europe than the native population, suggesting its successful colonisation in the new habitat.
Understanding the Benefits, Challenges, and the Role of Pet Ownership in the Daily Lives of Community-Dwelling Older Adults: A Case Study
Authors: Obradović Nataša , Lagueux Émilie , Latulippe Karine , Provencher Véronique
Published: September 2021

Human–animal interactions may positively impact the health and well-being of older adults. Considering about one third of community-dwelling older adults report owning a pet, better understanding the benefits, challenges, and the role of pet ownership may help support the relationships between older adults and their pets. This case study aims to better understand the role of pet ownership in the daily lives of older adults and explore the benefits and the challenges of owning a pet for this population. Interviews were conducted with Violet, a 77-year-old dog owner and her healthcare provider. Qualitative data were analyzed by two evaluators and validated by the participants. Both participants agree that the benefits outweigh the challenges for both the older adult and her pet. The benefits and challenges were the following: Violet, taking care of her dog (Jack), (1) could provide Violet with a sense of safety and positively influence her mood; (2) may introduce a slight fall risk; (3) includes financial costs to consider. Ensuring Jack’s well-being is important for Violet and her dog benefits from Violet’s continual presence and care. The findings suggest that improving the fit between characteristics of the owner and their pet may support the meaningful role of pet ownership within the context of aging-in-place.
A Preliminary Investigation into Ridden Water Submersion Training as an Adjunct to Current Condition Training Protocols in Performance Horses
Authors: O’ Brien Claire , Pegg Josephine
Published: September 2021

This observational study aimed to elucidate the effects of RWST on the cardiovascular and musculoskeletal systems of horses and concurrently determine whether RWST limits distal limb temperature increases previously reported during gallop training on land. A group of 15 clinically sound international event horses were recruited, and heart rate (HR), speed (km/h) and thermal images of the distal limb were analysed at set intervals during RWST training. Intervals of RWST produced a total mean HRmax value of 65.18 ± 3.76%, which is within the parameters for increased aerobic stamina. Mean HR increased significantly (p < 0.01) while mean distal limb temperature decreased significantly (p < 0.01) between warm-up and RWST, which contrasts with positive correlations previously reported during gallop training on land. These preliminary results suggest that RWST can be classed as a moderate submaximal intensity exercise in elite international event horses whilst restricting an increase in temperature of the distal limb that is commonly associated with tendon rupture. Horses competing at very elite levels of eventing only represent a small percentage of the total performance population; therefore, further research is needed to ascertain the physiological effects of RWST in non-elite performance horses, as well as horses competing across various equestrian disciplines.
High Prevalence of Antibiotic Resistance among Opportunistic Pathogens Isolated from Patients with COVID-19 under Mechanical Ventilation: Results of a Single-Center Study
Authors: Temperoni Chiara , Caiazzo Luca , Barchiesi Francesco
Published: September 2021

The effect of the COVID-19 pandemic on antibiotic resistance diffusion in healthcare settings has not been fully investigated. In this study we evaluated the prevalence of antibiotic resistance among opportunistic pathogens isolated from patients with COVID-19 under mechanical ventilation. An observational, retrospective, analysis was performed on confirmed cases of COVID-19 patients who were admitted to the ICU department of San Salvatore Hospital in Pesaro, Italy, from 1 February 2021 to 31 May 2021. We considered all consecutive patients aged ≥ 18, under mechanical ventilation for longer than 24 h. Eighty-nine patients, 66 (74.1%) men and 23 (25.9%) women, with a median age of 67.1 years, were recruited. Sixty-eight patients (76.4%) had at least one infection, and 11 patients (12.3%) were colonized, while in the remaining 10 patients (11.2%) neither colonization nor infection occurred. In total, 173 microorganisms were isolated. There were 73 isolates (42.2%) causing bacterial or fungal infections while the remaining 100 isolates (57.8%) were colonizers. Among Gram-negative bacteria, E. coli, A. baumannii and K. pneumoniae were the most common species. Among Gram-positive bacteria, S. aureus and E. faecalis were the most common species. Overall, there were 58/105 (55.2%) and 22/59 (37.2%) MDR isolates among Gram-negative and Gram-positive bacteria, respectively. The prevalence of an MDR microorganism was significantly higher in those patients who had been exposed to empiric antibiotic treatment before ICU admission. In conclusion, we found a high prevalence of antibiotic resistance among opportunistic pathogens isolated from patients with COVID-19 under mechanical ventilation.
Efficacies of Colistin–Carbapenem versus Colistin–Tigecycline in Critically Ill Patients with CR-GNB-Associated Pneumonia: A Multicenter Observational Study
Authors: Wang Sheng-Huei , Yang Kuang-Yao , Sheu Chau-Chyun , Chen Wei-Cheng , Chan Ming-Cheng , Feng Jia-Yih , Chen Chia-Min , Wu Biing-Ru , Zheng Zhe-Rong , Chou Yu-Ching , Peng Chung-Kan ,   on behalf of the T-CARE (Taiwan Critical Care Infection) Group
Published: September 2021

Background: Evaluating the options for antibiotic treatment for carbapenem-resistant Gram-negative bacteria (CR-GNB)-associated pneumonia remains crucial. We compared the therapeutic efficacy and nephrotoxicity of two combination therapies, namely, colistin + carbapenem (CC) versus colistin + tigecycline (CT), for treating CR-GNB-related nosocomial pneumonia in critically ill patients. Methods: In this multicenter, retrospective, and cohort study, we recruited patients admitted to intensive care units and diagnosed with CR-GNB-associated nosocomial pneumonia. We divided the enrolled patients into CC (n = 62) and CT (n = 59) groups. After propensity score matching (n = 39), we compared the therapeutic efficacy by mortality, favorable outcome, and microbiological eradication and compared nephrotoxicity by acute kidney injury between groups. Results: There was no significant difference between the CC and CT groups regarding demographic characteristics and disease severities as assessed using the Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, and other organ dysfunction variables. Therapeutic efficacy was non-significantly different between groups in all-cause mortality, favorable outcomes, and microbiological eradication at days 7, 14, and 28; as was the Kaplan-Meier analysis of 28-day survival. For nephrotoxicity, both groups had similar risks of developing acute kidney injury, evaluated using the Kidney Disease Improving Global Outcomes criteria (p = 1.000). Conclusions: Combination therapy with CC or CT had similar therapeutic efficacy and risk of developing acute kidney injury for treating CR-GNB-associated nosocomial pneumonia in critically ill patients.
Analytical Methods for Exploring Nutraceuticals Based on Phenolic Acids and Polyphenols
Authors: Vidal-Casanella Oscar , Núñez Oscar , Granados Mercè , Saurina Javier , Sentellas Sonia
Published: September 2021

Phenolic compounds such as phenolic acids, flavonoids, and stilbenes comprise an enormous family of bioactive molecules with a range of positive properties, including antioxidant, antimicrobial, or anti-inflammatory effects. As a result, plant extracts are often purified to recover phenolic compound-enriched fractions to be used to develop nutraceutical products or dietary supplements. In this article, we review the properties of some remarkable plant-based nutraceuticals in which the active molecules are mainly polyphenols and related compounds. Methods for the characterization of these extracts, the chemical determination of the bioactivities of key molecules, and the principal applications of the resulting products are discussed in detail.
Is There a Significant Difference in Accuracy of Four Intraoral Scanners for Short-Span Fixed Dental Prosthesis? A Comparative In Vitro Study
Authors: Jivănescu Anca , Bara Adrian , Faur Andrei-Bogdan , Rotar Raul Nicolae
Published: September 2021

Is the accuracy of the older generation of IOSs an impediment for obtaining a quality intraoral digital impression? The aim of this study was to evaluate the differences in accuracy between four intraoral scanners (two of the latest IOSs and two older IOSs) in the scenario of a short span fixed partial denture, and to determine if these differences have a major impact on the quality of the final digital impression. Four intraoral scanners: Cerec PrimeScan, Medit i700, Cerec Omnicam and Planmeca PlanScan and one laboratory scanner were used in this study. The scanned data were processed with the help of Geomagic Control X, a metrology software. For the statistical data analysis, the level of significance was set as 0.05 (α = 0.05). The Medit i700 group displayed the best level of trueness with the median value of 23.25 µm, PrimeScan group with a median of 25.55 µm, Omnicam group with a median of 32.3 µm and the PlanScan group which displayed the lowest level of trueness with a median value of 75.8 µm. From the precision data analysis, it was concluded that the PrimeScan group showed the best results, followed by Medit i700, Omnicam and the PlanScan group which showed the lowest precision. Even if there are some significant differences in accuracy between old and new IOSs, in the in vitro scenario of short span dental prostheses, the accuracy values were within the clinically acceptable range and may present important clinical implications.
Students’ Perceptions of Verbal and Non-Verbal Communication Behaviors during and after the COVID-19 Pandemic
Authors: Dragomir Gabriel-Mugurel , Fărcașiu Marcela Alina , Șimon Simona
Published: September 2021

Aiming at shedding light on the implications the COVID-19 pandemic has had on the students’ social and personal lives, this study has focused on the verbal and non-verbal communication and on the surveyees’ personal lives during the pandemic as well as on the perspective of changing their communication behaviors after the pandemic. The 409 respondents, students at Politehnica University of Timisoara, took part in a survey, conducted between 1 April and 30 May 2021, that was posted on isondaje.ro, a Romanian online survey platform. The research has suggested the following results: the adjustment of the verbal communication by speaking in a more articulated manner or more loudly; the overuse of the upper part of the face to compensate for the concealed parts of the face due to face mask wearing; the analysis of the factors underlying the respondents’ actions, i.e., relational attitudes, various greeting forms, various non-verbal reactions, which are aspects that are likely to change even after the pandemic. The results have also presented the changes that interpersonal communication could go through under the pressure of the restrictions imposed by the pandemic, but also the ways through which people try to protect their most valuable asset, i.e., communication, which defines humanity and makes us unique as human beings.
Carbon Lock-In and Contradictions—Applied Guide to Academic Teaching of Mexico’s Energy Transition
Authors: Hernandez Ariel Macaspac , Pacheco Rojas Daniel Alejandro , Barrón Villaverde Diana
Published: September 2021

The energy sector plays an important role in Mexico’s development trajectory. Mexico makes an interesting case study because it shows how difficult it is to reduce fossil energy dependence despite geographic and climatic conditions that favour renewable energy deployment and use. Resolving path dependencies and the related carbon lock-in are key to Mexico’s sustainable energy transition. This applied teaching guide contemplates the use of a case-illustration typology to identify and discuss how the politics about carbon lock-in affects Mexico’s sustainable energy transition. This methodology is an innovative endeavour that aims to apply the case study in classrooms with the intention to encourage discussions and solution-oriented approaches when tangible actions are identified by the educator and students. This methodology elevates the case study to a “living” case study that leads to recommended actions. The applied teaching guide allows educators, who are mostly researchers, to reflect on how Mexico’s case study could be explained not only to promote the students’ understanding of the challenges, but also to provide educators/researchers the skills on how to effectively disseminate knowledge. Mexico’s carbon lock-in involves oil and oil-run power plants that are costly to build but relatively inexpensive to operate. To conclude, this case study identifies potential entry points for transitioning towards sustainable energy in Mexico—resources that can promote the use of clean energy despite carbon lock-in. For example, focusing on electrification—particularly the carbon-intensive sectors—can help Mexico transit towards sustainable energy despite institutional constraints. Complementing this case study is a teaching guide with recommendations for using Mexico’s energy transition in courses on sustainability. By understanding how to explain the case study, the educator/researcher can better structure the complexity of the case study. This approach introduces a “learning activation framework” to identify emerging opportunities that can advance sustainable energy transitions in different cases of carbon lock-in. The framework also gives students a chance to help dismantle or cope with carbon lock-ins. Mexico’s energy transition makes a valuable teaching example because its energy transition is part of a broader developmental goal. This teaching guide’s systematic approach can maximise the students’ learning experience.
Design and Verification of Multi-Agent Systems with the Use of Bigraphs
Authors: Cybulski Piotr , Zieliński Zbigniew
Published: September 2021

Widespread access to low-cost, high computing power allows for increased computerization of everyday life. However, high-performance computers alone cannot meet the demands of systems such as the Internet of Things or multi-agent robotic systems. For this reason, modern design methods are needed to develop new and extend existing projects. Because of high interest in this subject, many methodologies for designing the aforementioned systems have been developed. None of them, however, can be considered the default one to which others are compared to. Any useful methodology must provide some tools, versatility, and capability to verify its results. This paper presents an algorithm for verifying the correctness of multi-agent systems modeled as tracking bigraphical reactive systems and checking whether a behavior policy for the agents meets non-functional requirements. Memory complexity of methods used to construct behavior policies is also discussed, and a few ways to reduce it are proposed. Detailed examples of algorithm usage have been presented involving non-functional requirements regarding time and safety of behavior policy execution.
Experiment-Based Fatigue Behaviors and Damage Detection Study of Headed Shear Studs in Steel–Concrete Composite Beams
Authors: Xu Jun , Sun Huahuai , Chen Weizhen , Guo Xuan
Published: September 2021

Many in-service bridges with steel–concrete composite beams are currently aging and experiencing performance deterioration. Under long-term cyclic loads from traffic on bridges, headed shear studs in steel–concrete composite beams are vulnerable to fatigue damage. The comprehensive understanding of fatigue behaviors and the feasible detection of fatigue damage of headed shear studs is, thus, crucial for the accurate numerical simulation of the fatigue crack propagation process. The paper, thus, experimentally investigates the fatigue behaviors of headed shear studs through push-out tests of three specimens. The fatigue failure modes and cyclic strain evolution of specimens are analyzed. The fatigue lives of headed shear studs are compared with the S–N curves of the AASHTO, Eurocode 4 and BS5400 codes. The fatigue crack details of shear studs in push-out tests are then detected using the ultrasonic non-destructive testing. The results show that the root fracture is the main fatigue failure mode of shear studs under fatigue loading. The fatigue life estimations based on the three current codes (i.e., AASHTO, Eurocode 4 and BS5400) can be safely guaranteed only with different safety redundancies. The strain at the shear stud with fatigue damage shows a consistent increasing trend followed by decreasing behavior after reaching the peak value with the loading cycles. Moreover, the feasibility of the ultrasonic non-destructive testing with the combination of a strain measurement for fatigue crack details detection of headed shear studs in composite beams is proved.
Academic Insights and Perspectives in 3D Printing: A Bibliometric Review
Authors: Bai Wenyu , Fang Hui , Wang Yawen , Zeng Qiang , Hu Guangyao , Bao Guanjun , Wan Yuehua
Published: September 2021

Research interest in three-dimensional (3D) printing has been greatly aroused since 1990 due to its outstanding merits, such as freedom of design, mass customization, waste minimization and fast prototyping complex structures. To formally elaborate the research status of the 3D printing field, a bibliometric analysis is applied to evaluate the related publications from 1990 to 2020 based on the Science Citation Index Expanded database and Social Science Citation Index database. The overview with detailed discussions is cataloged by keywords, citation, h-index, year, journal, institution, country, author, patent and review. The statistical results show that the United States plays a dominant role in this research field, followed by China and the UK. Singapore is the most productive country with the highest average citations per publication (ACPP), and the second most cooperative country. Among all the institutions, Chinese Academy of Sciences is most productive, and Harvard University has the highest ACPP and h-index. Among all the journals, Materials ranks first in the number of publications in this field. The most attractive research area is “Materials science, Multidisciplinary”, with 4053 publications. Moreover, the major hot topics derived from authors’ keywords are “3D printing”, “additive manufacturing” and “tissue engineering”. Commercial and medical applications appear to be the initial driving force and end goal for the development of the 3D printing technology.
Integrated Electromagnetic-Thermal Approach to Simulate a GaN-Based Monolithic Half-Bridge for Automotive DC-DC Converter
Authors: Mauromicale Giuseppe , Sitta Alessandro , Calabretta Michele , Oliveri Salvatore Massimo , Sequenzia Gaetano
Published: September 2021

New technological and packaging solutions are more and more being employed for power semiconductor switches in an automotive environment, especially the SiC- and GaN-based ones. In this framework, new front-end and back-end solutions have been developed, and many more are in the design stage. New and more integrated power devices are useful to guarantee the performances in electric vehicles, in terms of thermal management, size reduction, and low power losses. In this paper, a GaN-based system in package solution is simulated to assess the structure temperature submitted to a Joule heating power loss. The monolithic package solution involves a half-bridge topology, as well as a driver logic. A novel integrated electromagnetic and thermal method, based on finite element simulations, is proposed in this work. More specifically, dynamic electric power losses of the copper interconnections are computed in the first simulation stage, by an electromagnetic model. In the second stage, the obtained losses’ geometrical map is imported in the finite element thermal simulation, and it is considered as the input. Hence, the temperature distribution of the package’s copper traces is computed. The simulation model verifies the proper design of copper traces. The obtained temperature swing avoids any thermal-related reliability bottleneck.
Correction: Orsi et al. Carbon Nanotubes under Scrutiny: Their Toxicity and Utility in Mesothelioma Research. Appl. Sci. 2020, 10, 4513
Authors: Orsi Micaela , Al Hatem Chafik , Leinardi Riccardo , Huaux François
Published: September 2021

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Chemical Fractionation of Trace Elements in Arctic PM10 Samples
Authors: Conca Eleonora , Malandrino Mery , Giacomino Agnese , Inaudi Paolo , Giordano Annapaola , Ardini Francisco , Traversi Rita , Abollino Ornella
Published: September 2021

In this study, the information potential of a two-step sequential extraction procedure was evaluated. For this purpose, first of all the elemental composition of Arctic PM10 samples collected in Ny-Ålesund (Svalbard Islands) from 28 February 2015 to 21 October 2015 was investigated. Enrichment Factors, Principal Component Analysis and Hierarchical Cluster Analysis were performed to identify PM10 sources and to understand the effects of short- and long-range transport processes. The investigation of the potential source areas was also aided by taking into account back-trajectories. Then, the sequential extraction procedure was applied to some of the samples in order to obtain more information on these sources. This approach allowed us to establish that most of the elements prevalently having an anthropogenic origin not only were present in higher concentrations, but they were also more easily extractable in late winter and early spring. This confirms the common statement that the anthropogenic portion of the elements present in a sample is generally loosely bound to the particulate matter structure, and so it is more easily extractable and releasable on the Arctic snowpack. Moreover, in the samples collected in late winter and early spring, even the elements prevalently having a crustal origin were more easily extractable, probably due to the particle size selection occurred during the long-range transport.
Phenotype Switching in Metal-Tolerant Bacteria Isolated from a Hyperaccumulator Plant
Authors: Banach Artur , Kuźniar Agnieszka , Marzec-Grządziel Anna , Gałązka Anna , Wolińska Agnieszka
Published: September 2021

As an adaptation to unfavorable conditions, microorganisms may represent different phenotypes. Azolla filiculoides L. is a hyperaccumulator of pollutants, but the functions of its microbiome have not been well recognized to date. We aimed to reveal the potential of the microbiome for degradation of organic compounds, as well as its potential to promote plant growth in the presence of heavy metals. We applied the BiologTM Phenotypic Microarrays platform to study the potential of the microbiome for the degradation of 96 carbon compounds and stress factors and assayed the hydrolytic potential and auxin production by the microorganisms in the presence of Pb, Cd, Cr (VI), Ni, Ag, and Au. We found various phenotype changes depending on the stress factor, suggesting a possible dual function of the studied microorganisms, i.e., in bioremediation and as a biofertilizer for plant growth promotion. Delftia sp., Staphylococcus sp. and Microbacterium sp. exhibited high efficacy in metabolizing organic compounds. Delftia sp., Achromobacter sp. and Agrobacterium sp. were efficient in enzymatic responses and were characterized by metal tolerant. Since each strain exhibited individual phenotype changes due to the studied stresses, they may all be beneficial as both biofertilizers and bioremediation agents, especially when combined in one biopreparation.
In Silico Characterization of Calcineurin from Pathogenic Obligate Intracellular Trypanosomatids: Potential New Biological Roles
Authors: Orrego Patricio R. , Serrano-Rodríguez Mayela , Cortez Mauro , Araya Jorge E.
Published: September 2021

Calcineurin (CaN) is present in all eukaryotic cells, including intracellular trypanosomatid parasites such as Trypanosoma cruzi (Tc) and Leishmania spp. (Lspp). In this study, we performed an in silico analysis of the CaN subunits, comparing them with the human (Hs) and looking their structure, post-translational mechanisms, subcellular distribution, interactors, and secretion potential. The differences in the structure of the domains suggest the existence of regulatory mechanisms and differential activity between these protozoa. Regulatory subunits are partially conserved, showing differences in their Ca2+-binding domains and myristoylation potential compared with human CaN. The subcellular distribution reveals that the catalytic subunits TcCaNA1, TcCaNA2, LsppCaNA1, LsppCaNA1_var, and LsppCaNA2 associate preferentially with the plasma membrane compared with the cytoplasmic location of HsCaNAα. For regulatory subunits, HsCaNB-1 and LsppCaNB associate preferentially with the nucleus and cytoplasm, and TcCaNB with chloroplast and cytoplasm. Calpain cleavage sites on CaNA suggest differential processing. CaNA and CaNB of these trypanosomatids have the potential to be secreted and could play a role in remote communication. Therefore, this background can be used to develop new drugs for protozoan pathogens that cause neglected disease.
Identification of a Region in the Common Amino-terminal Domain of Hendra Virus P, V, and W Proteins Responsible for Phase Transition and Amyloid Formation
Authors: Salladini Edoardo , Gondelaud Frank , Nilsson Juliet , Pesce Giulia , Bignon Christophe , Murrali Maria , Fabre Roxane , Pierattelli Roberta , Kajava Andrey , Horvat Branka , Gerlier Denis , Mathieu Cyrille , Longhi Sonia
Published: September 2021

Henipaviruses are BSL-4 zoonotic pathogens responsible in humans for severe encephalitis. Their V protein is a key player in the evasion of the host innate immune response. We previously showed that the Henipavirus V proteins consist of a long intrinsically disordered N-terminal domain (NTD) and a β-enriched C-terminal domain (CTD). The CTD is critical for V binding to DDB1, which is a cellular protein that is a component of the ubiquitin ligase E3 complex, as well as binding to MDA5 and LGP2, which are two host sensors of viral RNA. Here, we serendipitously discovered that the Hendra virus V protein undergoes a liquid-to-hydrogel phase transition and identified the V region responsible for this phenomenon. This region, referred to as PNT3 and encompassing residues 200–310, was further investigated using a combination of biophysical and structural approaches. Congo red binding assays, together with negative-staining transmisison electron microscopy (TEM) studies, show that PNT3 forms amyloid-like fibrils. Fibrillation abilities are dramatically reduced in a rationally designed PNT3 variant in which a stretch of three contiguous tyrosines, falling within an amyloidogenic motif, were replaced by three alanines. Worthy to note, Congo red staining experiments provided hints that these amyloid-like fibrils form not only in vitro but also in cellula after transfection or infection. The present results set the stage for further investigations aimed at assessing the functional role of phase separation and fibrillation by the Henipavirus V proteins.
Exploring the Mechanism of Shikimate Kinase through Quantum Mechanical and Molecular Mechanical (QM/MM) Methods
Authors: Ojeda-May Pedro
Published: September 2021

The chemical step of Shikimate Kinase Helicobacter pylori, involving the transfer of a phosphoryl group, has been studied by using quantum mechanical and molecular mechanical (QM/MM) methods. Understanding the mechanism of this chemical step, present in bacteria and other microorganisms but absent in humans, can lead to the development of novel drugs for the treatment of common diseases caused by those pathogenic organisms. Different mechanisms including associative, dissociative, and concerted have been proposed up to now but there is not a consensus on the type of pathway that the reaction follows. Herein, we found that the mechanism has features from the associative and concerted types. An analysis of the free energy landscape of the chemical step reveals that the reaction is a two-step process without a well-defined intermediate state.
The Current State of Traumatic Brain Injury Biomarker Measurement Methods
Authors: Krausz Alyse D. , Korley Frederick K. , Burns Mark A.
Published: September 2021

Traumatic brain injury (TBI) is associated with high rates of morbidity and mortality partially due to the limited tools available for diagnosis and classification. Measuring panels of protein biomarkers released into the bloodstream after injury has been proposed to diagnose TBI, inform treatment decisions, and monitor the progression of the injury. Being able to measure these protein biomarkers at the point-of-care would enable assessment of TBIs from the point-of-injury to the patient’s hospital bedside. In this review, we provide a detailed discussion of devices reported in the academic literature and available on the market that have been designed to measure TBI protein biomarkers in various biofluids and contexts. We also assess the challenges associated with TBI biomarker measurement devices and suggest future research directions to encourage translation of these devices to clinical use.
Simultaneous Detection of Dihydroxybenzene Isomers Using Electrochemically Reduced Graphene Oxide-Carboxylated Carbon Nanotubes/Gold Nanoparticles Nanocomposite
Authors: Domínguez-Aragón Angélica , Dominguez Rocio B. , Zaragoza-Contreras Erasto Armando
Published: September 2021

An electrochemical sensor based on electrochemically reduced graphene oxide (ErGO), carboxylated carbon nanotubes (cMWCNT), and gold nanoparticles (AuNPs) (GCE/ErGO-cMWCNT/AuNPs) was developed for the simultaneous detection of dihidroxybenzen isomers (DHB) hydroquinone (HQ), catechol (CC), and resorcinol (RS) using differential pulse voltammetry (DPV). The fabrication and optimization of the system were evaluated with Raman Spectroscopy, SEM, cyclic voltammetry, and DPV. Under optimized conditions, the GCE/ErGO-cMWCNT/AuNPs sensor exhibited a linear concentration range of 1.2–170 μM for HQ and CC, and 2.4–400 μM for RS with a detection limit of 0.39 μM, 0.54 μM, and 0.61 μM, respectively. When evaluated in tap water and skin-lightening cream, DHB multianalyte detection showed an average recovery rate of 107.11% and 102.56%, respectively. The performance was attributed to the synergistic effects of the 3D network formed by the strong π–π stacking interaction between ErGO and cMWCNT, combined with the active catalytic sites of AuNPs. Additionally, the cMWCNT provided improved electrocatalytic properties associated with the carboxyl groups that facilitate the adsorption of the DHB and the greater amount of active edge planes. The proposed GCE/ErGO-cMWCNT/AuNPs sensor showed a great potential for the simultaneous, precise, and easy-to-handle detection of DHB in complex samples with high sensitivity.
Development of Multi-Scale X-ray Fluorescence Tomography for Examination of Nanocomposite-Treated Biological Samples
Authors: Chen Si , Lastra Ruben Omar , Paunesku Tatjana , Antipova Olga , Li Luxi , Deng Junjing , Luo Yanqi , Wanzer Michael Beau , Popovic Jelena , Li Ya , Glasco Alexander D. , Jacobsen Chris , Vogt Stefan , Woloschak Gayle E.
Published: September 2021

Research in cancer nanotechnology is entering its third decade, and the need to study interactions between nanomaterials and cells remains urgent. Heterogeneity of nanoparticle uptake by different cells and subcellular compartments represent the greatest obstacles to a full understanding of the entire spectrum of nanomaterials’ effects. In this work, we used flow cytometry to evaluate changes in cell cycle associated with non-targeted nanocomposite uptake by individual cells and cell populations. Analogous single cell and cell population changes in nanocomposite uptake were explored by X-ray fluorescence microscopy (XFM). Very few nanoparticles are visible by optical imaging without labeling, but labeling increases nanoparticle complexity and the risk of modified cellular uptake. XFM can be used to evaluate heterogeneity of nanocomposite uptake by directly imaging the metal atoms present in the metal-oxide nanocomposites under investigation. While XFM mapping has been performed iteratively in 2D with the same sample at different resolutions, this study is the first example of serial tomographic imaging at two different resolutions. A cluster of cells exposed to non-targeted nanocomposites was imaged with a micron-sized beam in 3D. Next, the sample was sectioned for immunohistochemistry as well as a high resolution “zoomed in” X-ray fluorescence (XRF) tomography with 80 nm beam spot size. Multiscale XRF tomography will revolutionize our ability to explore cell-to-cell differences in nanomaterial uptake.
Somatic Disease in Survivors of Childhood Malignant Bone Tumors in the Nordic Countries
Authors: Pedersen Camilla , Rechnitzer Catherine , Andersen Elisabeth Anne Wreford , Kenborg Line , Norsker Filippa Nyboe , Bautz Andrea , Baad-Hansen Thomas , Tryggvadottir Laufey , Madanat-Harjuoja Laura-Maria , Holmqvist Anna Sällfors , Hjorth Lars , Hasle Henrik , Winther Jeanette Falck ,   on behalf of the ALiCCS Study Group
Published: September 2021

Survivors of malignant bone tumors in childhood are at risk of long-term adverse health effects. We comprehensively reviewed cases of somatic diseases that required a hospital contact in survivors of osteosarcoma and Ewing sarcoma. In a population-based cohort study, 620 five-year survivors of osteosarcoma (n = 440) or Ewing sarcoma (n = 180), diagnosed before the age of 20 years in Denmark, Finland, Iceland, and Sweden during 1943–2008, were followed in the national hospital registers. Overall rates of hospital contacts for any somatic disease and for 12 main diagnostic groups and 120 specific disease categories were compared with those in a matched comparison cohort (n = 3049) randomly selected from the national population registers. The rate of hospital contact for any somatic disease was 80% higher in survivors of malignant bone tumors than in comparisons and remained elevated up to 30 years after diagnosis. The rate of hospital contacts was higher after Ewing sarcoma (rate ratio (RR) 2.24; 95% confidence interval (CI) 1.76–2.85) than after osteosarcoma (RR 1.67; 95% CI 1.41–1.98). Elevated rates were observed for 11 main diagnostic groups, including infections, second malignant neoplasms, and diseases of the skin, bones, and circulatory, digestive, endocrine, and urinary systems. Survivors of malignant bone tumors in childhood are at increased risk of somatic diseases many years after diagnosis. This comprehensive study contributes new insight into the risk of late effects in survivors of osteosarcoma and Ewing sarcoma, which is an essential basis for optimal patient counseling and follow-up care.
Tackling Refractory Metastatic Colorectal Cancer: Future Perspectives
Authors: Personeni Nicola , Smiroldo Valeria , Giunta Emilio Francesco , Prete Maria Giuseppina , Rimassa Lorenza , Bregni Giacomo , Sclafani Francesco
Published: September 2021

Substantial improvements have characterized the systemic treatment of metastatic colorectal cancer (mCRC) over the past 20 years. Besides strong evidence that supports the use of RAS and BRAF status as prognostic and predictive indicators of disease and response, novel technologies have made possible the incorporation of emerging biomarkers for the management of mCRC. On one hand, the discovery of point mutations, amplifications, fusions, and gene expression profiles highlights the genomic and dynamic complexity of CRC. On the other, such discoveries are leading to newer biomarker-driven strategies that add to existing anti-epidermal growth factor receptor (EGFR) and anti-angiogenic approaches. In addition, the availability of a wide molecular profiling has relevant implications for patient prognosis and treatment benefits. Here, we will review the molecular underpinnings and clinical data supporting novel targeted treatments under development for refractory mCRC harboring BRAF mutations, KRAS G12C mutations, HER2 amplification, and less common molecular alterations, such as the re-arrangements of NTRK, ALK, and ROS1. Additionally, we will discuss novel strategies driving the rechallenge of EGFR antibodies and the incorporation of newer anti-angiogenic agents in the therapeutic armamentarium.
Phosphate Enrichment of Niobium-Based Catalytic Surfaces in Relation to Reactions of Carbohydrate Biomass Conversion: The Case Studies of Inulin Hydrolysis and Fructose Dehydration
Authors: Catrinck Mariana N. , Campisi Sebastiano , Carniti Paolo , Teófilo Reinaldo F. , Bossola Filippo , Gervasini Antonella
Published: September 2021

In this work, some physical mixtures of Nb2O5·nH2O and NbOPO4 were prepared to study the role of phosphate groups in the total acidity of samples and in two reactions involving carbohydrate biomass: hydrolysis of polyfructane and dehydration of fructose/glucose to 5-hydroxymethylfurfural (HMF). The acid and catalytic properties of the mixtures were dominated by the phosphate group enrichment. Lewis and Brønsted acid sites were detected by FT-IR experiments with pyridine adsorption/desorption under dry and wet conditions. Lewis acidity decreased with NbP in the composition, while total acidity of the samples, measured by titrations with phenylethylamine in cyclohexane (~3.5 μeq m−2) and water (~2.7 μeq m−2), maintained almost the same values. Inulin conversion took advantage of the presence of surfaces rich in Brønsted sites, and NbOPO4 showed the best hydrolysis activity with glucose/fructose formation. The catalyst with a more phosphated surface showed less deactivation during the dehydration of fructose/glucose into HMF.
Endothelial Heterogeneity in Development and Wound Healing
Authors: Gurevich David B. , David Deena T. , Sundararaman Ananthalakshmy , Patel Jatin
Published: September 2021

The vasculature is comprised of endothelial cells that are heterogeneous in nature. From tissue resident progenitors to mature differentiated endothelial cells, the diversity of these populations allows for the formation, maintenance, and regeneration of the vascular system in development and disease, particularly during situations of wound healing. Additionally, the de-differentiation and plasticity of different endothelial cells, especially their capacity to undergo endothelial to mesenchymal transition, has also garnered significant interest due to its implication in disease progression, with emphasis on scarring and fibrosis. In this review, we will pinpoint the seminal discoveries defining the phenotype and mechanisms of endothelial heterogeneity in development and disease, with a specific focus only on wound healing.
Systems Biology Applied to the Study of Papaya Fruit Ripening: The Influence of Ethylene on Pulp Softening
Authors: Soares Caroline Giacomelli , do Prado Samira Bernardino Ramos , Andrade Sónia C. S. , Fabi João Paulo
Published: September 2021

Papaya is a fleshy fruit that undergoes fast ethylene-induced modifications. The fruit becomes edible, but the fast pulp softening is the main factor that limits the post-harvest period. Papaya fast pulp softening occurs due to cell wall disassembling coordinated by ethylene triggering that massively expresses pectinases. In this work, RNA-seq analysis of ethylene-treated and non-treated papayas enabled a wide transcriptome overview that indicated the role of ethylene during ripening at the gene expression level. Several families of transcription factors (AP2/ERF, NAC, and MADS-box) were differentially expressed. ACO, ACS, and SAM-Mtase genes were upregulated, indicating a high rate of ethylene biosynthesis after ethylene treatment. The correlation among gene expression and physiological data demonstrated ethylene treatment can indeed simulate ripening, and regulation of changes in fruit color, aroma, and flavor could be attributed to the coordinated expression of several related genes. Especially about pulp firmness, the identification of 157 expressed genes related to cell wall metabolism demonstrated that pulp softening is accomplished by a coordinated action of several different cell wall-related enzymes. The mechanism is different from other commercially important fruits, such as strawberry, tomato, kiwifruit, and apple. The observed behavior of this new transcriptomic data confirms ethylene triggering is the main event that elicits fast pulp softening in papayas.
Regulation of the Hypoxia-Inducible Factor (HIF) by Pro-Inflammatory Cytokines
Authors: Malkov Mykyta I. , Lee Chee Teik , Taylor Cormac T.
Published: September 2021

Hypoxia and inflammation are frequently co-incidental features of the tissue microenvironment in a wide range of inflammatory diseases. While the impact of hypoxia on inflammatory pathways in immune cells has been well characterized, less is known about how inflammatory stimuli such as cytokines impact upon the canonical hypoxia-inducible factor (HIF) pathway, the master regulator of the cellular response to hypoxia. In this review, we discuss what is known about the impact of two major pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), on the regulation of HIF-dependent signaling at sites of inflammation. We report extensive evidence for these cytokines directly impacting upon HIF signaling through the regulation of HIF at transcriptional and post-translational levels. We conclude that multi-level crosstalk between inflammatory and hypoxic signaling pathways plays an important role in shaping the nature and degree of inflammation occurring at hypoxic sites.
Phytochemicals from Rhizophora mucronata Propagules, Its In Vitro Anti-Cancer and In Silico Drug-Likeness Potential
Authors: Yunos Nurhanan Murni , Ling Sui Kiong , Osman Asiah , Abdullah Zunoliza , Sallehudin Nor Jannah
Published: September 2021

This is the first report to identify the presence of 3-O-caffeoyl quinic acid (1), 4-O-caffeoyl quinic acid (2), 5-O-caffeoyl quinic acid (3), epi-catechin (4), and procyanidin B2 (5) in the young propagules of Rhizophora mucronata. Compounds 2–5 were purified and then treated against breast, colorectal, and ovarian cancer cell lines for 72 h and the results of the Sulphorhodomine-B (SRB) assay were evaluated for percent cell viability and IC50 values. Epi-catechin, 4-O-caffeoyl quinic acid, 5-O-caffeoyl quinic acid and procyanidin B2 showed strong to moderate inhibitory effects when treated on breast (T47D), colorectal (HT29), and ovarian (A2780, SKOV3) cancer cell lines with IC50 values ranging from 16.77 ± 0.58 to 28.28 ± 0.89 μg/mL. In silico evaluation was performed to evaluate the drug-likeness and toxicological effects of these compounds using Molinspiration calculation and OSIRIS program. It was found that compounds 2, 3, and 4 have the potential to be orally active and have a low risk in exerting the mutagenic, tumorigenic, irritant, and reproductive effects.
Electrochemical Sensing and Removal of Cesium from Water Using Prussian Blue Nanoparticle-Modified Screen-Printed Electrodes
Authors: Pandey Prem. C. , Yadav Hari Prakash , Shukla Shubhangi , Narayan Roger J.
Published: September 2021

Selective screening followed by the sensing of cesium radionuclides from contaminated water is a challenging technical issue. In this study, the adsorption functionality of Prussian blue (PB) nanoparticles was utilized for the detection and efficient removal of cesium cations. An efficient PB nanoparticle-modified screen-printed electrode (SPE) in the three-electrode configuration was developed for the electrochemical sensing and removal of Cs+. PB nanoparticles inks were obtained using a facile two-step process that was previously described as suitable for dispensing over freshly prepared screen-printed electrodes. The PB nanoparticle-modified SPE induced a cesium adsorption-dependent chronoamperometric signal based on ion exchange as a function of cesium concentration. This ion exchange, which is reversible and rapid, is associated with electron transfer in the PB nanoparticle-modified SPE. Using this electrochemical adsorption system (EAS) based on chronoamperometry, the maximum adsorption capacity (Qmax) of Cs+ ions in the PB nanoparticle-modified SPE reached up to 325 ± 1 mg·g−1 in a 50 ± 0.5 μM Cs+ solution, with a distribution coefficient (Kd) of 580 ± 5 L·g−1 for Cs+ removal. The cesium concentration-dependent adsorption of PB nanoparticles was also demonstrated by fluorescence spectroscopy based on fluorescence quenching of PB nanoparticles as a function of cesium concentration using a standard fluorophore like fluorescein in a manner analogous to that previously reported for As(III).
Resveratrol Ameliorates Aortic Calcification in Ovariectomized Rats via SIRT1 Signaling
Authors: Hammad Sally K. , Eissa Rana G. , Shaheen Mohamed A. , Younis Nahla N.
Published: September 2021

Postmenopausal women are at an increased risk of vascular calcification which is defined as the pathological deposition of minerals in the vasculature, and is strongly linked with increased cardiovascular disease risk. Since estrogen-replacement therapy is associated with increased cancer risk, there is a strong need for safer therapeutic approaches. In this study we aimed to investigate the protective and therapeutic effects of the phytoestrogen resveratrol against vascular calcification in ovariectomized rats, a preclinical model of postmenopause. Furthermore, we aimed to compare the effects of resveratrol to those of estrogen and to explore the mechanisms underpinning those effects. Treatment with resveratrol or estrogen ameliorated aortic calcification in ovariectomized rats, as shown by reduced calcium deposition in the arterial wall. Mechanistically, the effects of resveratrol and estrogen were mediated via the activation of SIRT1 signaling. SIRT1 protein expression was downregulated in the aortas of ovariectomized rats, and upregulated in rats treated with resveratrol or estrogen. Moreover, resveratrol and estrogen reduced the levels of the osteogenic markers: runt-related transcription factor 2 (RUNX2), osteocalcin and alkaline phosphatase (ALP) which have been shown to play a role during vascular calcification. Additionally, the senescence markers (p53, p16 and p21) which were also reported to play a role in the pathogenesis of vascular calcification, were reduced upon treatment with resveratrol and estrogen. In conclusion, the phytoestrogen resveratrol may be a safer alternative to estrogen, as a therapeutic approach against the progression of vascular calcification during postmenopause.